Cardiovascular E n g i n e e r i n g

145 CHANGES IN ACTIVE AND PASSIVE MECHANICAL PROPERTIES OF STUNNED MYOCARDIUM T.J. Schmeling, D.A. Hettrick, P.S. Pagel, D.C. Warltier Medical College of Wisconsin and Marquette University, Milwaukee, WI, The time-course of changes in mechanical properties of reperfused, postischemic (stunned) myocardium is poorly understood. We appfied a modified Voigt model incorporating an active non-linear spring [KA(t)] in parallel with a passive non-linear spring (KP) and a viscous damper (V) before, during and after occlusion of the left anterior descending coronary artery (LAD). Open-chested dogs (n=14) were instrumented for measurement of left ventricular pressure (LVP) and segment length (L). A series of five LAD occlusions and reperfusions was performed at 5 minute intervals followed by a 3 hr reperfusion period. Measured LVP and L were input to the model which was then solved for KP, KA(t) and V. Dogs which recovered more than 50% of baseline shortening during reperfusion (Group R, n=7) and dogs which did not recover (Group N, n=7) both showed significant (P<0.05; student's t-test) increases in V, KP, and decreases in KA(t) during occlusion. Changes in mechanical properties were maintained throughout the reperfusion period in Group N, while values gradually returned to baseline in Group R. We conclude that the degree of injury and rate and extent of recovery of regional function of stunned myocardium is directly related to specific changes in active and passive mechanical properties.

146 CHANGES IN PASSIVE LEFT VENTRICULAR CHAMBER STIFFNESS DUE TO A MUTATION IN TYPE I COLLAGEN SM Vaplon, JL Emery, D McBride*, JH Omens, AD McCulloch Depts of Bioengineering & Medicine, U.C. San Diego, La Jolla, CA *Geriatric Medicine & Gerontology, Johns Hopkins, Baltimore MD Recent research suggests collagen contributes to passive myocardial stiffness particularly at high passive loads. We hypothesize that alterations in the amount and organization of collagen in the myocardium will likely affect diastolic ventricular mechanics. We used the osteogenesis imperfecta routine (oim) model harboring a Type I collagen mutation to relate myocardial collagen fiber content with passive mechanical function. 15-Bm transverse sections of left ventricle (LV) free wall stained with picrosirius red were imaged using laser scanning confocal microscopy (60x, 1.4 NA). The homozygous oim group had a 35% smaller collagen area fraction and a 38% reduction in fiber number density than the wild type group (P<0.07). In arrested isolated hearts, we measured the effects of changes in collagen content on the LV pressure-volume (P-V) relation by inflating an intraventricular balloon. The slopes of the P-V relation for cavity pressures in the range 10-60 mmHg were 23-29% lower for the oim group (P<0.08). Thus reductions in myocardial collagen content in the oim model are associated with parallel reductions in diastolic chamber stiffness, suggesting that collagen defects may predispose the heart to LV dilatation. (Supported by: NSF, NIJ-I, The Whitaker Foundation.)

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148 THREE-DIMENSIONAL GEOMETRIC MODELING OF CARDIAC RIGHT AND LEFT VENTRICLES FROM MULTI-VIEW, MULTISLICE MRI IMAGE E. Haber, D.N. Metaxas, and L. Axel University of Pennsylvania Unlike the left ventricle (LV), the right ventricle (RV) cannot be described by any predefined three-dimensional shape: it has a crescentic inflow tract and a tubular outflow tract. As a result of the projected difficulty in combining results from separate ventricular models and because the two ventricles share a septal wall, we have built an integrated ventricular model. An automated computer program finds important landmarks, such as extrema in the short-axis crescent shape of the RV, and samples epicardial and endocardial contour data to build the initial RV-LV model. Long-axis views (rotated along the LV long axis) provide information to define the apex of each ventricle, the outflow tract, and the wall curvature between slices. Higher-dimensional, hexahedral, finite elements are used to represent the wall tissue and provide continuity between slices. Customized computer graphics tools are used to visualize the model. This model will be used for motion reconstruction and analysis of the ventricles, based on MRI contour and spatial modulation of magnetization tagging (SPAMM) data. This approach can be extended to model the atria and geometric changes due to disease or surgery.

149 A 2-D NON-LINEAR FINITE ELEMENT (FE) MODEL OF THE

INTERVENTRICULAR SEPTUM UNDER NORMAL AND ABNORMAL LOADING CONDITIONS IN DIASTOLE G.S. Nelson, EY. Sayed-Ahmed, J.V. Tyberg, and N.G. Shrive University of Calgary, Depts. of Physiology & Biophysics and Civil Engineering, Calgary, AB, CANADA. The interventricular septum (IVS) is shared by both left and right ventricles and, together with the pericardium, it mediates diastolic and systolic ventricular interaction. The function of the IVS under normal conditions is complex, and more so under various abnormal conditions when the diastolic transseptal gradient (P~s) reverses causing the IVS to flatten and subsequently invert. This motion pattern is viewed by many as being similar to the flapping of an unstressed sail (ie, a thin-walled membrane). However, investigation using a 2-D non-linear hyperelastic FE model of the IVS (effects of residual stress and sarcomere lengthening included) suggests that the behaviour may really be more like that of a thick-walled beam structure subject to lateral pressure and end-bending moments. Also, compressive stresses which develop in the IVS prior to mitral valve opening may have important implications with respect to the phenomenon of diastolic suction.

Poster Presentations 147 PASSIVE MATERIAL PROPERTIES OF INTACT VENTRICULAR WALL DETERMINED USING EPICARDIAL SUCTION R.J. Okamoto, M.J. Moulton, M.K. Pasque, and J.M. Guccione Washington University, Depts. of ME and Surgery, St. Louis, MO Passive material properties of the ventricular walls are needed for accurate prediction of regional stress and strain distributions during diastole and systole. We used a new technique ("epicardial suction") to create a bending and shearing mode of deformation in the lateral free wall of the left ventricle (LV) in three isolated arrested dog hearts. Myocardial deformation was measured using magnetic resonance imaging tissue tagging. Material parameters in anisotropic, exponential constitutive relations were optimized using these measurements and a finite element (FE) model. The optimized material properties were then used in an FE model of passive inflation of the canine LV. Good agreement between experimental and model-predicted transmural distributions of 3-D finite strain was obtained only when the intact epicardium was significantly stiffer than the myocardium. Previous biaxial test results indicate that ventricular epicardium is qualitatively different from passive myocardium, but it is not possible to determine where on the measured stressstretch curves the epicardium acts in vivo. Our epicardial suction results suggest that the epicardium is prestretched in the unloaded heart, and indicate the need to perform multiple testing protocols when studying mechanical properties of potentially heterogeneous materials.

150

"Unsteady Coupled Fluid Flow and Elastic Wall Calculations for the Aorta". Thomas Rutaganira% Harry A. Dwyer+, Angela Cheer*, Abdul Barakat § *Department of Mathematics, +Depar~ent of Mechanical Engineering, University of California, Davis, California 95616 It has been a goal for many decades to develop a detailed model of the aortic artery that includes a coupled fluid/wall interaction that is time dependent and three-dimensional. Simple models of the large arteries have yielded valuable information, but the complications of coupled time dependencies, three dimensionaiity, and wall elasticity are needed to compare with actual diseased states. Our paper presents some o f the first results for the fully unsteady and three-dimensional Navier-Stokes numerical calculations. These calculations are for a curved pipe which is coupled to an elastic model for the wall of the thoracic aorta. The numerical model we have developed have the capability to include with increasing fidelity a detailed description of a large part of the aortic flow system. The calculations show significant differences between the input flow and the flow out of the curved pipe. These differences are directly due to the wall elasticity. The results in the paper are an important step in making a complete model of the aortic flow system.

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Cardiovascular Engineering - Posters

151 IDENTIFIABILITY OF TUBE-MODELS OF DESCENDING AORTIC CIRCULATION R. Burattini~ and K, B. Campbell* ~ of Electronics and Automatica, Umversity of Ancona, Italy. *Dept. of V.C.A.P.P., WashingtonState University, Pullman, WA. We addressed the problem in uniqueness of parameter estimates in two competing tube-medels of descending aortic circulation: a uniform, frictionless elastic tube, terminating in a first-order low-pass filter load (model A) and a uniform, frictional elastic tube terminating in a pure resistor (model B). We analysed the identifiability of these models making use of measurementsof high descending aortic pressure and flow taken from three anaesthetised, open-chest dogs (23.9 + 1.7 kg). A multiplicity of solutions for the wave transit time along the transmission tubes, and the related tube-lengths, satisfied the criteria for minimum error in descending aortic flow-fit. However, with aid of an extrameasurement of terminal aortic pressure, we found that the lowest estimate of the wave transit time provided by model A, 46.4 +_5.5 ms, was the only one solution compatible with the real system. This solution a) located the effective reflecting site, from which reflections appear to originate, in the abdominal aorta nearby the origin of renal arteries, and b) yielded a physiologically relevant discrimination between proximal and distal properties of descending aortic circulation. By contrast, the model B showed significant limitations in both mathematical and physiological assessment.

152 MORPHOMETRY AND MICROSTRUCTUREOF THE HUMAN AORTIC ARCH Z.L. Jiang and G.J. Cai Department of Anatomy, Second Military Medical University,Shanghai 200433. The aortic arch is a curved and branched vessel with complex geometrical morphology and microstructure. In order to provide essential morphological data for research concerning biomechanics and hemodynamics of the vessel, a quantitative study was conducted systematically on 5 ascending aorta and aortic arch specimens of normal adult human cadaver by continuous vascular sections and computer image analysis. A series of data were gained of the lumen size, wall thickness and cross-sectionalarea of the vessel wall, so as to develop a curve of the varying geometrical morphology of the haman ascending aorta and aortic arch. The relative area (Aa%) of smooth muscle cells, elastin and collagen was also measured in four different circumferential directions of the continuous vascular sections. At the site of the proximalto the origin of the innominate artery, the Aa% of the elastin content in superior (19.77%), anterior (18.32%), inferior (15.85%), and posterior (18.69%) of the cross section differed significantly (p<0.01). It is shown that the quantity of the microstructural components is unequal in both longitudinal and circumferential directions of the aortic arch, which reflects the inequality of the vascular stress and strain.These morphological data have important applications in development of the biomechanical models, and in further research on the law of growth and remodelingof the human aortic arch.

153

FACTORS INFLUENCING CORONARY BLOOD F L O W IN AORTOMYOPLSTY Dirk R. Thompson, Brian L. Cmolik, Alexander S. Geha, David T. George, School of Medicine, Case Western Reserve University, Cleveland, Ohio. A goal of our laboratory is to maximize the benefits of aortomyoplasty (AMP) by maximizing blood displacement from the muscle-wrapped aorta. In dogs (n=6), AMP was performed and the heart placed into failure by rapid ventricular pacing. Wrap stroke volume (WSV), calculated from two aortic flow probes positioned above and below the wrapped region correlated with mean diastolic aortic pressure and endocardial viability ratio: Pearson Product Moment Correlation of 0.54 (p<0.05) and 0.51 (p<0.05), respectively. Coronary blood flow did not correlate with WSV. Examination of aortic flows pattern during muscle contraction revealed that wrap ejection was completed early during diastole. Maintaining muscle contraction for longer than needed to complete wrap ejection does not contribute to additional flow but maintains the elevated diastolic resistance of the aorta. These results suggest that, in addition to active displacement, a mechanism of aortomyoplasty is a time-varying aortic resistance causing the blood volume stored in the windkessel compliance chamber of the ascending aorta during cardiac systole to maintain elevated root aortic pressure and thereby augment coronary blood flow.

154 SENSITIVITY OF THE FLOW FIELD IN THE RABBIT ABDOMINAL AORTA TO VARIOUS FLOW PARAMETERS A.Y. Cheer, H.A. Dwyer, A.I. Barakat and M. Bice University of California, Depts. of Math. and M.E., Davis, CA. Atherosclerotic disease of the coronary arteries and the large vessels is the leading cause of death in industrialized countries. Early atherosclerotic lesions are more frequently found in regions of arterial branching and curvature where the flow field is "disturbed". This has long motivated the notion that arterial fluid mechanics may act as a localizing factor forearly atherosclerotic lesions. Despite intense study over the past three decades, the precise role of hemodynarnics in atherogenesis remains incompletely understood. The objective of the current study is to investigate the impact of a range of physiologically-relevant fluid mechanical parameters on the flow field within the rabbit abdominal aorta in the vicinity of the celiac artery. This is accomplished using experimentally-validated finite volume numerical techniques. The current study represents the most systematic investigation to date of the sensitivity of the computed flow field to a number of flow parameters including Re, flow division ratios, and frequency of pulsatility. The computed results have been validated against experimental data and have revealed particularly large pressure and shear stress gradients in the immediate vicinity of the celiac artery.

155 NUMERICAL SIMULATION OF BLOOD FLOW AND LIPID TRANSPORT IN THE HUMAN CAROTID ARTERY WALL Nasser Fatouraee, Deng, X.Y., De Champlain, A., Guidoin, R. Departments of Surgery and Mechanical Engineering, Laval University, and Quebec Biomaterials Institute, Inc., Pavilion St-Francois d'Assise, CHUQ, Quebec, Qc, Canada The lipid concentration at the luminal surface of a blood vessel may vary according to its location in the arterial tree because of regional differences in wall shear rate, blood pressure, and vascular permeability. These local variations in the luminal surface lipid concentration may contribute to the localization of atherosclerosis. To verify this hypothesis, we studied numerically lipid transport from flowing blood to the arterial wall under both steady-state and pulsatile flow conditions. Numerical analysis predicted that the time-average value of the luminal surface low-density lipoproteins concentration (LDL) was 6% to 17% grater than the bulk concentration in a straight segment of an artery. The luminal surface LDL concentration at the arterial wall was flow-dependent, varying linearly with the filtration rate through the vessel wall and inversely with wall shear rate.

156 STRUCTURAL AND HISTOLOGICAL ANALYSIS OF RUPTURED CORONARY LESIONS D.L.Thompson, S. Krucinski, D.G. Vince, C.M. Sanscrainte, D. Cao, M.J. Bennish, E.E. Herderick, LF. Cornhill. Biomedical Eng. Dept., Cleveland Clinic Foundation, Cleveland, OH. Rupture of the fibrous cap of an atherosclerotic lesion is the most common initial event leading to acute coronary syndromes. Pathology observations suggest that rupture is a consequence of the mechanical failure. This study investigates ruptured plaques by examining the stress characteristics and cell distribution in ruptured lesions. Histological sections from nine ruptured arteries were obtained at autopsy. The lumen, internal elastic lamina, external elastic lamina (EEL), and necrotic core were traced on histology images using custom software. These outlines provided the input data for custom developed Patran PCL code that automatically generates plane strain fnite element models of the arteries with circular EEL. Displacement of EEL measured with IVUS were used to impose the realistic kinematic boundary conditions~ When compared to the histology, 88% of cases were found to have ruptured at areas of highest major principal stress. Most of the plaques ruptured at the point within the fibrous cap where smooth muscle cells encroachment ceased.

Cardiovascular Engineering - Posters

157 POROELASTIC TUMOR MODEL WITH COLLAPSIBLE VASCULATURE D. Allan Farrow, Anne Hoger, and Richard Skalak Department of Bioengineering, University of California, San Diego Solid tumors present an environment that inhibits the delivery of anti cancer drugs in quantities sufficient to produce a significant response. Monoclonal antibodies, for instance, have been shown to accumulate mainly in the regions surrounding the vasculature and the tumors' periphery. This non uniform distribution of therapeutic agents has been attributed to the heterogeneous vasculature and the elevated interstitial pressure that exists in solid tumors. To facilitate the goal of improved drug delivery in solid tumors a model is constructed that describes the movement of fluid through a tumors' vasculature network and interstitial space as well as the exchange of fluid between these two spaces. The vasculature is modeled as a collapsible network of vessels with permeable walls. The tumors' interstitium is treated as a two phase poroelastic media by utilizing equations originally postulated by Biot. It has recently been postulated that a periodic modulation of blood pressure may increase the delivery of anti cancer agents in solid tumors. This comprehensive model of a solid tumor and its vasculature will allow the optimum frequency and wave form of modulation to be examined. It will also be possible to study the effects of vascular development and tumor size on fluid transport through the tumors vasculature and interstitium.

158 HEMODYNAMICS IN A WOVEN WIRE VASCULAR STENT James E. Moore Jr., Aland Santamarina & Joel L. Berry* Florida International University, Miami, Florida *Bowman Gray School of Medicine, Winston-Salem North Carolina Flow patterns in intravascular devices such as stents may be related to their subsequent failure due to restenosis. Restenosis occurs due to the accumulation of blood-borne materials such as platelets and the reaction of the wall to the presence of the stent. Increased flow stagnation due to stent structure may be an important determinant of stent patency. The flow patterns in a woven wire vascular stent were analyzed using both dye injection flow visualization and numerical modeling. The numerical study consisted of a two-dimensional pulsatile near-wall flow featuring overlapping circular shaped stent struts. Pulsatile flow waveforms indicative of 2 mm and 4 mm coronary artery resting conditions were applied in both studies. The flow visualization study demonstrated that more flow stagnation occurred when the spacing between the wires was smallest. In the numerical study, stagnation zones were noted upstream and downstream of the struts. For the cases where the strut spacing was less than six strut diameters, the stagnation zone downstream of one strut merged with the stagnation zone upstream of the next strut, forming a continuous zone of flow stagnation. For larger strut spacings, the stagnation zones were separate for at least part of the cardiac cycle. These studies may help explain previous observations of neointimal formation in stented arteries, where it was noted that strut spacing had an important effect on neointimal thickness. The observation that stagnation is continuous in stents with strut spacings of less than six strut diameters may provide a criterion for future stent design.

159 I N VIVO PERFORMANCE OF ELECTROSTATIC ENDOTHELIAL

CELL SEEDED 4 mm I.D. e-lrrFE VASCULAR PROSTHESES L. Bowlin, Stanley E. Rht~gers , Jeffrey Bulgrin, and Rick Sims Summa Health System and ~The University of Akron, Akron, Ohio In v~vo (canine) evaluation of an electrostatic seeding technique (Patent

Pending) used autologons jugular vein endothelial cells (EC) harvested ushlg a 0.2% collagenase solution. These ECs were electrostatically seeded (16 minutes) onto 4.0 ram I.D. GORF~TEX| (W.L Gore & Associates) grafts (L= 6 cm) and then implanted into a femoral artery along with a contralateral untreated control gratt (n=5) for six weeks. Aspirin therapy (325 mg/day) was admini~ered for the first two weeks post-operation and discontinued for the remaining four week~ The electrostatically seeded gra~s resulted in a 100% patency rate while the control gra~s had a patency rate of 80%. The electrostatically seeded gralts experienced minimal gra/i e~capsulation while the conUrol grafts demonstrated a high degree of tissue ingrowth. The internal visual examination of the electrostatically EC seeded gra~ luminal surfaces revealed minimal to no thrombus formation with neointimal development while the control grafts demonstrated minimal pannus EC ingrowth and extensive thrombus formation on all b~minal surface~ FFlstological examination verified the visual e~,amination showing the development of the neointima and media hi the seeded grafts. Thus, the electrostafically seeded gralis demonstrated high thromboresistance despite discon"tmuation of the aspirin therapy.

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160 INTRAMURAL DRUG DELIVERY:THE NEXT INTERVENTIONAL FRONTIER Robert E. Reiss InterVentional Technologies Inc. Simple balloon dilatation angioplasty in 20 years has culminated in intra-arterial reconstructive surgery via stent implantation. Looming on the horizon is Erlich's magic bullet delivered to the atherosclerotic site utilizing direct intramural injection with a new class of devices named the INFILTRATOR ~. Lesion-Site--specific drugs and transvected genes are thought to be the next wave of treatment for atherosclerotic disease, and will provide opportunity for those preparations that exhibit intolerable systemic side effects. Utilizing equipment familiar to the practitioner, microliter quantities of drugs can be precisely injected into the lesion and underlying medial aspect of the artery in 10 seconds with 90% plus delivery efficiency and near zero luminal blood stream loss.

161 A NOVEL INVARIANT BASIS FOR MYOCARDIAL RESPONSE ALLOWS UNIFICATION OF BIAXIAL AND TORSIONAL DATA John C. Criscione, Jay D. Humphrey, and William C. Hunter Dept BME Johns Hopkins Univ., Dept ME UMBC, Baltimore, MD A complete basis for an incompressible, transversely isotropic strainenergy function depends on 4 scalar invariants of C (I1,I2,I4,I5). However, current experiments only measure the material response via a dual basis. Yet, by combining results of different tests, the myocardial response can be formulated in terms of a complete basis. To enable such a union, we developed a new basis (J1,J2,J4,J5) in which each Ji has a physical meaning related to a specific mode of deformation. In terms of Ii the Ji basis is: Jt=(Ii-I4)/2; J2=(I1+I4)2/4-I2-I5; J4=I4; J5=I5-I42. Physically, J1 is the mean squared stretch in the transverse plane, J2 is the squared shear in the transverse plane, J4 is the squared fiber stretch, and J5 is the squared shear along the fiber. Whereas every common test produces significant variation in most Ii, the Ji variation is tested more selectively, as follows: for papillary muscle stretch, variation occurs primarily in J4, Jl is secondary, J2=0, J5=0; for papillary torsion, J5 is 1~ J4 is 2% Jl is constant, J2=0; for biaxial stretch transverse to fibers, J2 is 1~ Jl is 2 ~ J4 is constant, Js=0. Most importantly, by employing the Ji basis, we have been able to develop a constitutive relation which encompasses both the biaxial data of Humphrey et al.(1990) as well as recent papillary extension and torsion data from our laboratory.

162 DETERMINATION OF MATERIAL PROPERTIES FOB. THE PASSIVELY FILLING CANINE LEFT VENTRICLE WG O'Dell, WC Hunter*, ER McVeigh* and AD McCulloch Departments of Bioengineering, UCSD and *Biomedical Engineering, Johns Hopkins University Purpose: Determine the material properties for passive canine left ventricular (LV) myocardium from MRI tagging data. Methods: High resolution, 3D MR imaging with cardiac tagging [Zerhouni88, McVeigh92] was performed on a cyclically inflated, isolated, arrested canine heart. Displacement field-fitting [O'Del195] was used to reconstruct 3D strains accnrately over the LV at a physiologic end-diastolic cavity pressure. A constitutive relation for a transversely isotropic (along the fibers), exponential (in fiber and cross fiber strains), compressible material was derived from an existing strain-energy model[Guccione91]. Results: The six material model parameters were optimized by rainimizing the difference between computed bmmdary reaction forces and known endo- and epicardial surface tractions. Discussion: This represents a new way to determine myocardial stresses, material properties and energy expenditures in ~Ji~Jo.

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Cardiovascular Engineering - Posters

163 REGIONAL STRAIN-FLOW RELATION DURING ACUTE MYOCARDIAL ISCHEMIA: A MODEL-BASED APPROACH Reza Mazhari, Jeffrey H. Omens, Andrew D. McCulloch Department of Bioengineering, UC San Diego, La Jolla, CA.

166 VISCOELASTIC PROPERTIES IN THE TRABECULATED EMBRYONIC HEART C.E. Miller, M.A. Vanni, C.A. Wong Div. of Pediatric Cardiology, University of Rochester, Rochester, NY

To relate the nonhomogeneous regional epicardial strain variations of the left ventricle (LV) in normal and ischemic myocardium to regional perfusion, myocardial geometry, and fiber structure, a new method has been developed. An array of 42 radiopaque markers was sewn on the anterior wall of the LV of 12 anesthetized open-chested canines and their positions recorded using biplane fluoroscopy before and 2 minutes after either left anterior descending (LAD) or left circumflex (LCx) coronary a~ery occlusion. Regional myocardial blood flows were measured using fluorescent microspheres. The three-dimensional (3D) geometry of the LV, coronary vessel anatomy, the perfusion boundary, and epicardial fiber angles were measured post mortem using a 3D probe. A prelate spheroidal finite element surface was fitted to geometry (< 0.2 mm error). Fiber angles (< 5~ error) and blood flows (< 0.3 mI..hnin/g error) were also fitted into the model. Nonhomogeneous strains were computed with respect to end-diastole by allowing the model to deform according to the recorded motion of the epicardial markers. Strains as a function of both regional myocardial blood flow and distance from the perfusion boundary showed differences between LAD and LCx perfusion beds that may be associated with difference in orientation of perfusion boundaries. (Supported by: NIH Grant HL41603)

The stage-21 and 24 (3-1/2 and 4-day) chick ventricular myocardium contains a large inner trabeculated layer of dorsoventral orientation. We examined the hypothesis that short-term viscoelastic events in the trabeculated embryonic heart are insensitive to stretch level and myocardial architecture. We subjected stage-21 and -24 left ventricular sections of longitudinal and circumferential orientation, i.e., perpendicular and parallel to trabeculae orientation, to ramp-and-hold stress relaxation tests of 20 ms ramp time, 5, 10, 20, and 30% extension, and 5 min. duration. Resulting normalized relaxation curves were fit to a quasi-linear viscoelastic model. Consistent variation occurred with stage, orientation, and stretch level, the most significant differences based on stretch level. Fast time constant decreased in all groups from 5 to 20% stretch but rose at 30%. Decay rate increased monotonically with stretch while final relaxation decreased with stretch. The small (4-9 ms)time constant and stretch dependence differ from results on earlier, non-trabeculated embryonic myocardium. The intertrabecular spaces likely permit faster fluid motion than is possible through a more compact extracellular matrix.

164 NON-HOMOGENEOUS EPICARDIAL STRAIN ANALYSIS OF THE ISOLATED EJECTING MOUSE HEART W.J. Karlon, A.D. McCulloch, J.W. Covell, J.H. Omens UCSD, Departments. of Bioengineering and Medicine, La Jolla, CA

167 A NEW TIME SCALEFOR VENTRICULARFILLINGEFFICIENCY Mory Gharib,EdmondRambod,TakahiroShiota*, DavidJ. Sahn Calif Inst Tech, Pasadena. CA & Oregon Hlth Sci Univ, Portland, OR*

Transgenic mice used as a model of familial hypertrophic cardiomyopathy (FHC) exhibit local areas of myofiber disarray and fibrosis which may result in non-homogeneous ventricular deformation. To relate local disarray to regional variations in epicardial function, we developed methods to measure non-homogeneous strain of the isolated ejecting mouse heart. Titanium dioxide markers placed on the epicardium were recorded to video tape and digitized for calculation of non-homogeneous strains using a finite element fit. Peak systolic septal strains of approximately 10-15% were measured in normal hearts. Sensitivity of the strain analysis system was tested by damaging a small area of otherwise normal hearts with a needle puncture. Strain analysis was capable of detecting an area of needle damage approximately 0.25 mm 2 in diameter indicated by a gradient in strain. Epicardial septal strain measurement of isolated FHC transgenic hearts indicates that peak systolic principal strain is more non-uniform than in normal mice possibly due to underlying structural abnormalities. Our results indicate non-homogeneous strain analysis is a sensitive method for measuring regional function in the mouse heart.

165 A NOVEL ACTIVE CONTOUR METHOD FOR RECONSTRUCTING INTRAVASCULAR MEDICAL DEVICES I N VIVO WW Baxter, AD McCulloch Department of Bioengineering, U.C. San Diego, La Jolla, CA

Purpose: To develop a better understandingof the left ventricular filling events during the early diastolic phase of a cardiac cycle. The goal of the study was to identify a single universal time scale which may characterize the early transmittal vortex formationprocessin the left ventricularcavity by mapping the time resolved velocity field obtainedby in-vivo2D echocardiography. Methods: Two-dimensionalDoppler echoeardiography and color flow mapping were performed using commercially available ultrasound machines. Transmittal flows in a four chamber view wererecordedfor analysis and measurementof mitral annular diameter (D), diastolic transmitral averaged velocity (U,vs), and diastolic duration of |he E-wave(T) usinga calibrated track ball. A non-dimensionalnumber knownas "FormationNumber"was defined as follows: F=(TU,vg)/D. A population of 70 volunteerswith a broadspectrumof age and physicalconditions were examined to estimate the valuesof "'F". Results: A powerlaw curve presents the general behaviorof "F" as a function of age. The asymptoticbehaviorof the curve indicates that a single approximate value of F=4 is the best representation of the average filling time scale for a healthy population. Conclusion: Throughwell-controlled in-vitro experiments using the method of Digital Particle ImageVelocimetry (DPIV) it was shown that this value of "F" is related to maximumenergy attainable by the vortex formed in the left ventricular cavity. Therefore,the "Formation Number" can be used as an indicative of the maximumefficiency of the left ventricularfilling cycle.

168 TRANSPARENT COMPLIANT LEFT VENTRICLE FOR FLOW VISUALIZATION OF APICAL CANNULATION Alison S. Curtis, Jon Wu, and James F. Antaki University of Pittsburgh Artificial Heart and Lung Program

While engineers perform bench testing of intravascular medical devices (such as catheters and leads) to predict in vivo mechanical performance, clinicians frequently rely upon radiographic images to assess the mechanical integrity of a Source Error device in vivo. A new method for device PixelResolution 0.16mm reconstruction from biplane x-ray images Calibration 0.21ram provides a framework for testing the validity Correspondence 0.30mm of bench analyses and diagnosing ParametricFit 0.12mm mechanical complications such as fracture. By incorporating a priori information into the analysis, reconstruction errors are minimized (see table above). The method minimizes imagebased energies for a single set of 3-D centerline coordinates from two independent views of the device. Contour points are attracted to the darkest region in each image plane while minimizing the energy associated with a deforming thin beam. The active contour converges to the target in approximately 4 seconds on an SGI workstation. The proposed method is an important step towards integrating ex vivo mechanical analysis and in vivo imaging of implanted intravascular medical devices.

Geometrical design of cannulas for left ventricular circulatory support can significantly affect flow in both the ventricle and in the blood pump. In-vitro experiments were performed on transparent, compliant casts of bovine left ventricles to evaluate the anatomic interaction and fluid dynamics of apical cannulation. The casts were made in a two-part molding process. A cannulated left ventricle was used to make sacrificial endocardial pattern and epicardial mold. A transparent two-part silicone rubber was injected and cured at 35C. The result was an anatomically accurate, transparent replica of theventricular cavity, intraventricular structures, and ventricular walls. The wall thickness was thinned to obtain the desired compliance, and a gloss coat was added to increase optical characteristics. Flow visualization techniques including particle path tracing, dye dilution, and oil-film surface techniques were performed on various casts cannulated with a novel ltrumpeti" mouth cannula tip as well as conventional cannula tips. Initial studies verify that the novel tip provides suitable placement and stenting and reduces apical stasis. Future work is directed towards using a pressure chamber to simulate the active wall motion of the heart and extending the studies to human ventricles.

Cardiovascular Engineering - Posters

169 ANALYZING HEART SOUNDS USING A FAST ALGORITHM OF CWT BASED ON MERLIN TRANSFORM Aiwen Gut, Xiaorong Gao, Fusheng Yang Biomedical Engineering and Instrumentation Divsion Tsinghua University, Beijing, China In this paper, a fast algorithm of Continuous Wavelet Transform based on Merlin transform is introduced and used for analyzing heart sounds. However, due to the alias problem, which may be carried by the unique geometric sampling of Merlin transform, the performance of this fast algorithm will become worse when the analyzed signals have higher frequency and larger scale range. In order to solve this problem, an equal proportion expansion method is proposed. The theory and method are verified by the simulation results. Not only the whole computation time can be decreased significantly, but also the conflict between the computation time and the performance of this fast algorithm can be avoided. This fast algorithm can thus be used more widely. Through the analysis of normal and abnormal heart sound signals of several patients, some encouraging results are obtained. With these results, more useful information contained in heart sounds can be extracted and diagnosis performance will be improved.

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172 INVESTIGATION OF THE EFFECT OF VALVE TYPE AND ORIENTATION ON FLUID MECHANICAL WORK AND ENERGY LOSS IN AN IN VITRO MODEL OF VENTRICULAR HYPERTROPHY Brandon Travis, Russell Heinrich, Ann Ensley, David Gibson, and Ajit Yoganathan; Georgia Institute of Technology When choosing a prosthetic replacement for a natural heart valve, one objective should be to minimize the workload placed on the heart. This workload can be raised by fluid mechanical energy losses imposed by the valve. This study used a control volume analysis to investigate the effects of prosthetic mechanical aortic valve type and orientation on fluid mechanical energy losses in an in vitro model of ventricular hypertrophy (VH). This model differed from a previous study in that a cylindrical obstruction was placed proximal to the valve, simulating VH that commonly occurs in patients. Experiments were performed in pulsatile flow at a constant heart rate of 60 bpm for 5 valve type/orientation combinations. The stroke volume was varied between 40 and 100 ml for each valve/orientation studied. Results indicate that the hypertrophy may cause as much energy loss as the valve itself, and that some valve/orientation combinations in this model caused over 50% more energy loss than others. The observed differences in energy losses between valve/orientation combinations are supported by previous energy loss and flow visualization studies. Thus, valve type and orientation should be considered when replacing aortic valves of patients with VH.

170 QUANTITATIVE ANALYSIS OF COLLAGEN FIBER ORIENTATION IN DILATED CARDIOMYOPATHY D Neth, KA Powell, DG Vince, P McCarthy, R White The Cleveland Clinic Foundation, Depts. of Biomedical Engineering, Cardiothoracic Surgery,and Radiology

173 MECHANICAL BEHAVIOUR OF BOVINE PERICARDIUM AS A HEART VALVE TISSUE Sebnem Ozupek*, Hengchu Cat** *Institute for Mechanics and Materials, UCSD; **CarboMedics, Inc.

An automated approach was developed for quantifying collagen fiber orientation in myocardium excised from patients with dilated cardiomyopathy. Tissue samples from five subjects were fixed in Histochoice and stained with Picrosirius Red stain. Representative regions from each of the myocardial cross;esections were digitized at 4X magnification and 4 uroJpixel resolution. The collagen fibers were segmented from the surrounding tissue using a competitive learning color segmentation algorithm. A two dimensional FFT was applied to the color-segmented image. The principal axis of the resulting frequency spectrum was determined for each image. The orientation of this axis corresponds to the fiber orientation in the original image. The fiber orientations generated by this technique were compared to those obtained manually. In the twelve samples with the most coherent fiber organization the average difference between calculated and observed orientation angles was approximately 2 degrees. When compared over 45 samples, the average difference between calculated and observed orientation angles was less than 10 degrees.

Long term durability of bioprosthetic heart valves is controlled mainly bythe mechanical properties of the leaflet material. Consequently,accurate description of the mechanical behavior of the tissue leaflet plays an important role in the evaluation of the valve performance.The objective of this work is to determine a suitable constitutive model for bovine pericardium as a bioprosthetic leaflet.Some models that have been developed for soft tissues were selected from the literature and were implemented in a finite element code.Experiments were conducted by uniformly stretching a rectangular tissue patch containing a central cut or circular hole under uniaxial tensile load.The deformation field surrounding the cut or the hole were determined using an image based deformation mapping system. A least-squares procedure was used to derive strains from the measured displacements. Numerical results for displacement and strain fields were compared with the experimental measurements to critically assess the performance of the constitutive models.

171 APPLICATION OF A SUBSPACE PROJECTION TECHNIQUE TO MINI-BOLUS CARDIAC OUTPUT ESTIMATION BY THERMODILUTION R. Semnani and B. Womack University of Texas at Austin, Biomedical Engineering, Austin, TX.

174 ASSESSMENT OF AUTONOMIC CONTROL OF HEART RATE VARIABILITY THROUGH THRESHOLD MODELING G.B. Stanley, K. Poolla, and R.A. Siegel University of California, Berkeley

Thermodilution techniques are routinely used in the measurement of hemodynamic parameters such as the cardiac output and stroke volume. In the Stewart-Hamilton equation, cardiac output is inversely related to the area of the transient decline in the pulmonary artery temperature caused by an injection of a cold saline solution into the venous return to the right heart. The major source of error in thermodilution is the background thermal noise in the pulmonary artery that correlates with respiration and is due to the pseudo-periodic flows and temperatures in the vena cavae. To reduce error and improve reproducibility, larger injected thermal signals and averaging several measurements are typically used. It is desirable, however, to use smaller volumes to reduce costs and risks to the patient. Due to frequency overlap with the signal, conventional filters do not effectively remove the respiratory artifacts. In the approach presented here, the noisy data is first decomposed into two orthogonal subspaces corresponding to the signal and the respiratory noise. Projection of the data onto the signal subspace effectively filters the respiratory noise from the mini-bolus thermodilution signals.

Even in the absence of external perturbation to the human cardiovascular system, measures of cardiac function vary with time in normal physiology. The primary source of the variation is regulation by a complex control system which modulates cardiac function through the autonomic nervous system (ANS). Traditionally, ANS control of the heart has been assessed through construction of an artificial "heart rate" from ECG R-wave event times. We propose that ANS activity can be assessed directly through R-wave point events. The sino-atrial node serves as the pacemaker for the heart, integrating ANS activity until reaching a threshold in potential, when the node "fires" and resets. It is quite natural, therefore, to model variability in heart rate through an integrate-to-threshold mechanism. We present methods of reconstructing statistical properties of noise processes in the absence of ANS input, as well as characterizing respiratory-related ANS input. The result is a direct analysis of autonomic control of heart rate variability providing methods for assessing ANS function in the normal and pathological states.

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Cardiovascular E n g i n e e r i n g - Posters

175 MODELING HEART RATE VARIATION USING MULTIPLE DATA SIGNALS AND A NEURO-FUZZY INFERENCE SYSTEM Rebecca A. Landes, Mingui Sun, and Robert J. Sclabassi Bioengineering Program and Dept. of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania A computational model of autonomic control of the heart rate is being developed and investigated. The model characterizes feedback mechanisms used by the body to maintain cardiac control. Data from patients in the Neuro Intensive Care Unit at the University of Pittsburgh Medical Center are used for analysis. By examining these biological signals, short and long term changes in blood pressure and respiratory activity can be identified. These changes can then be used to predict corresponding changes in heart rate. Because of the extreme complexities and non-linearities of this system, a neuro-fuzzy inference system (NFIS) is used for modeling purposes. The NFIS allows for model development through a combination of knowledge-based and data-based inputs. Results to date indicate that mean arterial pressure, peak arterial pressure, mean venous pressure, and respiratory values can all be used to predict subsequent changes in heart rate to a reasonable degree of accuracy. The final model will account for beat-to-beat variations in the heart rate, allow for a better understanding of the complex regulatory mechanism involved in autonomic control of the heart rate, and provide insights into the use of a NFIS in the study of physiologic data.

178 INCREASED ARTERIOLAR MICROPRESSURE INDUCED BY LEUKOCYTES B. R Helmke t, E A. DeLano, and G. W. Schmid-Sch6nbein Inst. for Biomedical Engineering, UCSD, La Jolla, CA and qnst. for Medicine and Engineering, Univ. of Pennsylvania, Philadelphia, PA Although leukocytes constitute less than 1% of circulating blood cells, they may significantly affect whole organ pressure-flow relationships, as demonstrated in the isolated perfused rat gracilis muscle. However, the location within the microvascular network where the effect of the leukocytes may be manifest is not known. In the present study, arteriolar micropressure and pressure at the arterial input to the muscle were measured simultaneously during perfusion with blood cell suspensions. At constant arterial flow rate, physiological concentrations of leukocytes were added to an erythrocyte suspension. The leukocytes induced a significant increase in the arteriolar micropressure. The relative magnitude of the additional arteriolar pressure drop attributable to the presence of leukocytes was similar to the relative additional pressure drop measured at the muscle input artery. These results suggest that elevation of organ resistance by leukocytes may involve a mechanism located primarily in the microcirculation downstream of the arcade arterioles, especially the capillary network. Supported by NSF Grant IBN-9512778.

176 TRANSPORTATION OF A NEW ULTRASOUND CONTRAST AGENT, DODECAFLUOROPENTANE MICROBUBBLES, IN THE MICROCIRCULATION T. Yasu, G.W. Schmid-Schrnbein, *A.N. DeMaria. The Department of Bioengineering and *Cardiology Division of the Department of Medicine, University of California, San Diego, La Jolla, CA 92093 A dodecafluoropentane (DDFP) emulsion, a new ultrasound contrast agent, produces myocardial echo-enhancement persisting longer than left ventricular cavity opacification. We tested the hypothesis that a subgroup of DDFP microbubbles resides for prolonged periods in the microvasculature without affecting erythrocyte velocity. The mesenteric microvessels in 16 Wistar rats were observed after injection of fluorescently labeled erythrocytes or DDFP microbubbles by fluorescence intravital microscopy. The majority of microbubbles passed without adhesion to the endothelium, and only a small number of bubbles attached transiently to arteriolar or capillary endothelium < 0.5 sec. About 10 % of the microbubbles adhered transiently to the venular endothelium for periods of 0.1 - 120.0 sec. Venules with enhanced 'eukocyte adhesion had increased number of adhesive microbubbles. In conclusion, transient adhesion of a subgroup of microbubbles to venular endothelium in the microcirculation is a potential mechanism for the persistent myocardial enhancement by DDFP microbubbles during contrast echocardiography. (Supported by HL-43026)

179 TRANSPORT OF C O L L O I D A L PARTICLES IN THE LYMPHATICS AND IN THE V A S C U L A T U R E AFTER SUBCUTANEOUS INJECTION M. Higuchi, G.W. Schmid-Sch6nbein, T.N. Masters, A. Fokin, F. Robicsek UCSD, Depts. of Bioengineering, San Diego, CA and Carolinas Medical Center, Heineman Medical Research Lab, Charlotte, NC The present study is designed to determine the time course of transport of subcutaneously injected viral size colloid particles into the lymph and the vascular system in the hind leg of the dog. Two different colloid particles were tested, average size 130 nm and 410 nm respectively, one set of experiments with leg rotation and the other experiments without leg rotation. Leg rotation serves to enhance the lymph flow rates. Under anesthesia, the right femoral vein, artery and lymph vessel were canulated for collection of samples. The samples were collected at regular intervals after subcutaneous injection of the particles at the right knee level. The number of particles in samples were counted under fluorescence microscopy by using a hemocytometer.Without regards to leg rotation, both particles sets were rapidly taken up into the venous blood and into the lymph fluid and were continuously seen during a 45 minutes observation period. Particles were also seen in arterial blood samples, suggesting reflow and a prolonged residence time in the blood. These results show that inert particles of the size of viruses are rapidly taken up into the lymphatics and blood vessels after subcutaneous deposition.

177 THE EFFECT OF ISOVOLEMIC HEMODILUTION ON RETINAL CAPILLARY HEMODYNAMICS IN THE CAT. PS Jensen and MR Glucksberg. Biomedical Engineering Dept., Northwestern University, Evanston, IL 60208.

180 INCREASED REGIONAL BLOOD FLOW HOMOGENEITY IN COLLATERAL-DEPENDENT MYOCARDIAL PERFUSION BEDS D.A. Hettrick, T.J. Schmeling, D.C. Warlfier Medical College of Wisconsin and Marquette University, Milwaukee, WI.

The effect of isovolemic hemodilution on retinal capillary hemodynamics was studied using GRIN (GRadient INdex of refraction) lens endoscopy in the cat. In each of two trials, erythrocyte motion within twelve randomly selected retinal capillary networks was recorded on video tape before and after hemodilution. Isovolemic hemodilution was accomplished by i.v. injection of Dextran while simultaneously withdrawing blood from the femoral artery until reaching a systemic hematocfit of 20. Red blood cell velocity and optical density (a measure of capillary hematocrit) were determined for each visible capillary using time based correlation techniques. Isovolemic hemodilution was found to significantly increase (p<0.001) retinal capillary erythrocyte velocity from 0.59 + 0.30 mrn/sec (N=75) to 0.76 + 0.32 mm/sec (N=60) while significantly (p<0.001) decreasing optical density from 0.515 +_ 0.003 (N=75) to 0.424 +_ 0.003 (N=60). These results suggest a reduction in retinal capillary hematocrit occurs when systemic hematocrit is reduced and that increased pre-retinal oxygen tension following isovolemic hemodilution (Graefes Arch Clin Exp Ophthalmol 234(11):688-94, 1996) could result from an overcompensating increase in retinal capillary velocity. Supported by The Hoover Foundation, Fight For Sight and NIH #EY09714.

Chronic regional myocardial ischemia can induce "collateral" vessel growth to an ischemic region from the normal region and thus prevent ischemic injury. We hypothesized that the collateralized perfusion network (CN) may possess functional differences from native perfusion networks (NN). Collateral growth was induced in 9 dogs via chronic placement of an ameroid constrictor around the left anterior descending coronary artery (LAD). After 10 weeks, the dogs were returned to the lab and the LAD was cannulated to allow measurement of retrograde flow. Radioactive microspheres were administered via the left atrium to measure regional blood flow. The fractal dimension of the regional flow distribution (D) of the CN region was determined from the collateralized dogs as well as from 5 control dogs using standard techniques. The results showed that the CN group had a significantly lower regional D (1.29-2_0.02 in collateralized dogs vs. 1.39L-0.03 SEM in control dogs, P<0.01; unpaired t-test). Decreased D implies more homogenous flow. We conclude that in collateral-dependent myocardium native microvascular networks perfused via large collateral vessels may be augmented by newly formed angiogenic networks to increase blood flow homogeneity.

Cardiovascular Engineering - Posters

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181 THE RELATION BETWEEN BLOOD DISTRIBUTION AND FREQUENCY CHARACTERISTICS OF BLOOD PRESSURE WAVEFORM T. C. Lee and S. T. Young Institute of Biomedical Engineering, National Yang-Ming University

184 A NEW PRINCIPLE FOR NONINVASIVELY DETECTING AND ANALYZING CARDIOVASCULAR FUNCTIONS OF HUMAN BODY S. G. Wu, A. K. Qiao and Y. H. Peng Beijing Polytechnic University, Beijing 100022, China

This paper deals with the frequency characteristics of blood pressure waveforms to systemic blood distribution in the context of developing a hydraulic model of the overall system. The elastic tubes simulated the aorta and its major branches. The small balloons with different stiffnesses were used as organs. The self-designed pump which can generate arbitrary pressure waves and pure sinusoidal waves is used to simulate the heart. For each different output waveforms of the pump, we measure the flow into each balloon by ultrasonic transducer and the pressure at the same sites by strain gauge transducer. Summary of the experiments showed that the distribution of flow is affected by the frequency characteristics of the pressure waveforms. And the flow patterns recorded near the entrances of the branches also suggest that each balloon has a specific relation to frequencies. The pump is also able to synchronize with an animal's ECG signal, in this way, this paper provides a framework for future efforts in hydraulic model and animal model experiments for the entire cardiovascular system.

A new hemodynamics principle and method for more accurately and noninvasively detecting an d analyzing cardiovascular functions of human body was put forward, based on the strict theory of nonlinear pulse wave propagation developed by the author. The new principle is expressed by a system of nonlinear ordinary differential equations respectively describing flow of blood in Ascending Aorta, deformations and motions of arterial walls, and heart work, etc. These equations involve the interactions and effects among the blood pressure and its gradient, the flow rate, the viscosity and the inertia of blood, and the diameter of blood vessels, as well as many other physiological variables and factors. A set of Model MHS-100 system has been developed by the author using the principle. The clinical test was carried out. It is shown that the measuring results of this method for the staple hemodynamic parameters(e.g. CO, SV, etc.) were in good agreement with ones of the invasive thermal dilution method. It strongly proved that the new principle and method were available and reliable and it could be expected for a wide use.

182 GENDER DIFFERENCES IN CV RESPONSE TO LBNP AS MEASURED THROUGH MR ANGIOGRAPHY. V. Pothini, J. Evans, A. Griffin, L. Hilaire, G. Robson, C. Knapp University of Kentucky Center for Biomedical Engineering

185 A NONINVASIVE DETECTION METHOD OF HUMAN BLOOD VISCOSITY S.G. Wu, A.K. Qiao, Y. L. Jiang, Y. H. Peng, M. Zhou and L. M. Hu Beijing Polytechnic University, Beijing 100022, China

Twenty-one spin echo, ECG-gated, coronal images of the heart were obtained during rest and -35mmHg lower body negative pressure (LBNP) for each of nine women (70.9+I-2.9kg) and eight men (77.6+I-3.4kg). Six coronal images (time-of-flight) of the vena cava at the level of the portal vein were obtained during rest and LBNP for end-expiration and end-inspiration breath holds. At rest, men had larger hearts than women (p<0.01). LBNP caused heart size to decrease (p<0.000) in both groups, but men had a larger decrease than did women (p<0.005). At rest, the size of the vena cava was not significantly different between the sexes for either breath hold. During LBNP, however, men's average vena cava size was larger than women's (p<0.025). LBNP caused vena cava size to decrease (p<0.005); however, three men showed an increase during inspiration while only one showed an increase during expiration. Women's vena cava size decreased more than men's during inspiration (p<0.05). These results indicated that men and women responded differently to LBNP: men decreased heart size (36+/-3.4%) more than women (26+/-2.8%), but the decrease in vena cava size was more consistent in women than in men. Supported by NASA EPSCoR WKU 52261 l and NIH GCRC MO1 RR262.

Blood viscosity is an important hemodynamic and physiological parameter for diagnosing cardiovascular diseases of human. A noninvasive method to measure the in-vivo blood viscosity of human body is presented. The principle of method is established on the base of the nonlinear pulse wave theory proposed by Wu-Lee. A nonlinear differential equation system for calculating the viscosity, flow shear rate and flowrate waveform of blood in arteries is derived. This equation system can be solved by using the numerical iterative procedure after having the arterial pressure gradient waveforms. The waveforms of arterial pressure and its gradient are evaluated in terms of noninvasively detecting pulse waves of the human radial artery. A medical system for noninvasively detecting and analysing the blood viscosity and cardiovascular function of human was developed. The clinical comparative tests on 200 cases of cardiovascular patients have shown that the coherence precision and reliability of the present noninvasive detection method of human blood viscosity. It can reflect the distinctions in rheological characteristics of cardiovascular system for individuation under different physiological and pathological conditions.

183 TREATMENT OF ARTERIOVENOUS MALFORMATIONS WITH ENDOVASCULAR COPOLYMERS Timothy A. Becker; Daryl R. Kipke; Ph.D.; Michael T. Lawton, M.D. Arizona State University, Barrow Neurological Institute

186 NONLINEAR ELASTIC ANALYSIS OF CURVED BLOOD VESSELS S.G. Wu, X. Y. Li and A. K. Qiao Beijing Polytechnic University, Beijing 100022, China

An arteriovenous malformation (AVM) is a congenital defect of the cerebral circulation in which large arteries of the brain connect directly with their respective veins without an intervening capillary bed. The AVM acts as a low resistance shunt which produces abnormal hemodynamic conditions associated with hemorrhages and neurological deficits. The specific aim of this project was to create a bench-scale model of the AVM and the surrounding branches of the cerebrovascular system. The resulting model consisted of compliant and distensible Teflon vascular grafts supplied by lmpra, Inc. (Tempe, AZ). The vascular grafts varied from 3 mm to I6 mm I.D. to approximate the 50:1 ratio of flow resistances between the high resistance capillary bed and the low resistance AVM shunt. The components of a copolymer was bidirectionally injected from positions both proximal and distal to the AVM site during local circulatory arrest. The bench-scale model was used to optimize the injection pressure, injection rate, and polymer viscosity to obtain focal delivery of the embolizing polymer to the AVM.

Mechanical characterization of the blood vessels is an important prerequisite for quantitative description of the propagation of pulse waves in cardiovascular vessels. The constitutive equations of curved vessels like the aortic arch have not yet established theoretically. In this study, a theoretical method for the analysis of the nonlinear elastic characteristics of curved blood vessels is presented. The curved blood vessels are modeled to be a circularly toroidal, incompressible, and elastic thickwailed tube with anisotropy and local triclinicity. On these assumptions, the deformations and strains of curved vessel walls are analyzed in detail, and a pseudo-strain energy function of 3-d exponential type is introduced to establish the constitutive relationships of nonlinear elasticity of curved vessel walls. The residual stresses and strains of curved vessel walls are studied. How to generalize the constitutive equations obtained to involve residual stresses and strains is also discussed. These results can serve as the theoretical bases for the establishment of constitutive equations and the analysis of residual stresses and strains of curved vessel walls, as well as the numerical study of pulse wave propagation in curved blood vessels.

Funded by the Arizona Affiliate of the American Heart Association.

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Cardiovascular Engineering - Posters

187 AN ULTRASOUND TRANSDUCER SYSTEM FOR BLOOD VOLUME MEASUREMENT J.S. Lee, L.P. Lee and S.H. Wang Dept. of BME, Univ. VA and CardioResearch Inc. Charlottesville, VA.

190 PERFUSION RECOVERY DURING BOWEL OBSTRUCTION IS MAINLY GOVERNED BY INTRAMURAL STRESS RELAXATION D.E. Kanter, A.S. Douglas, And A.A. Shoukas Dept. of Biomed. Eng., Johns Hopkins University, Baltimore, MD.

The measurement of blood density reduction following saline infusion into the circulation has been used to assess the blood volume. We tested the ultrasound system with blood (37~ flowing through a chamber mounted with two ultrasound transducers (20 MHz central frequency). A pulser excited the first transducer at the rate of 100 pulse/s. Its transmission through the blood was received by the second transducer for digitization at 1 GHz to detect the time delay. Calibrated with saline to convert to sound velocity, the system averaged the time delays to report the sound velocity at 5 sample/s. By diluting the blood with saline and plasma, we measured the blood density 0 with a density measuring system and the sound velocity c with the ultrasound system. With the subscript p representing plasma, a linear fit 0 - 0p = 0.881(g/L)/(m/s) (c - %) + 0.84 g/L with a correlation coefficient of 0.999 was obtained. The good correlation indicates that the ultrasound system could have sufficient sensitivity to measure the blood volume. (Supported by HL 57136).

In simple mechanical small bowel obstruction (SMSBO), the mesenteric blood vessels remain patent while the proximal gut distends. To understand SMSBO's pathophysiology, we must know how distention impacts mural blood flow. In experimental models of SMSBO, transient mural perfusion recovery (TMPR) follows distention by intraluminal volume or transmural pressure. We hypothesized that intramural stresses primarily govern TMPR during volume distention, intramural stretches during pressure distention. To explore this hypothesis, we developed an in vivo experimental model of SMSBO in rat ileum, allowing for the quantification of transients in mural blood flow, as well as intramural stress and stretch. Our data suggest: 1) TMPR is not found over most of the physiological range of transmural pressure distention, although TMPR remains a prominent feature of intraluminal volume distention; and 2) intramural stresses primarily govern changes in total mural blood flow following either type of distention stimulus.

188 THE ROLE OF XANTHINE OXIDASE DERIVED OXYGEN FREE RADICALS IN THE DAHL HYPERTENSIVE RAT A. Swei, F. Lacy, F- A. DeLano and G. W. Schmid-Sch/3nbein University of California at San Diego, Department of Bioengineering, Institute for Biomedical Engineering, La Jolla, CA 92093-0412

191 VASCULAR CYLINDRICITY IN ANIMALS AND PLANTS S.S.Sobin and P.C-Y Chen. Dept. Bioengineering, Univ.Calif.,San Diego, La Jolla, CA 92093

Enhanced production of oxygen free radicals may play a role in hypertension by affecting vascular smooth muscle contraction and resistance to blood flow. The aim of this study was to determine if oxygen free radicals derived from xanthine oxidase are involved in the development of salt-induced hypertension. Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed either a low salt, high salt or high salt + tungsten diet for four weeks. The tungsten diet lowered the blood pressure of Dahl-S animals compared to high salt treated Dahl S animals but had no effect on blood pressure in Dahl-R animals. Reduction of a tetranitroblue tetrazolium (TNBT) dye was used to detect superoxide radicals (02) in the rat mesentery. Light absorption of formazan deposits revealed that tungsten treated Dahl-S animals had reduced staining along the endothelium of arterioles and venules compared to high salt treated Dahl-S animals. A Clark electrochemical electrode was used to measure hydrogen peroxide (H202) levels in fresh plasma. Tungsten treated DahlS animals had a lower plasma H202 concentration compared to high salt treated Dahl-S animals. These findings demonstrate that xanthine oxidase derived oxygen free radicals are involved in the pathogenesis of saltinduced hypertension. (Supported by NIH grant HL-10881)

189 RESONANCE PHENOMENA IN THE CAROTID CIRCULATION R. Burattini*, S. Natalucci*, F. Fantini*, V. Carrozzo* and D.R. Gross~ *Dept. of Electronics and Automatica, University of Ancona, Italy. ~ Veterinary Biosciences, University of Illinois, Urbana, IL.

of

With aid of an inertance-viscoelastic windkessel model we interpreted, in terms of resonance, the carotid imlxxlance of pigs. This model consists of an inductance, L, accounting for inertial properties of blood motion, in series with a viscoelastic windkessel (peripheral resistance in parallel with a complex and frequency-dependent compliance). Measurements of pressure and flow were taken from the origins of left and right carotid arteries in five anaesthetised pigs (46.6:1:0.7 kg), over a mean pressure range of 40 to 90 mmHg. The ratio of mean pressure to mean flow yielded carotid peripheral resistance values. The other model parameters were estimated by fitting to expea'imental flow. Estimates of inertance, L, showed a decrease with decreasing pressure that was consistent with a corresponding increase of the effective arterial diameter inferred from observed flow autoregulation. Due to the presence of tioth inductive and capacitive reactive properties, resonance occurred at the frequency, fo, where the impedance phase angle crossed zero. Estimates of fo increased with increasing pressure and showed a correlation with static elastic rnoduli, as a function of mean pressure, reported for carotid arteries. Major characteristics of pressure and flow pulse contours were related to resonance.

The change in dimension in the arterial system between consecutive branches has been described as conical segments (Marshall Hall, 1831) or taper, change in lumen dimension per unit length. Although initially of morphological interest, the significance of taper was important with the engineering analysis of pulsatile blood flow. Taper was considered a property of aortic length. Methods used to determine vascular geometry were faulty. We prepared in vivo silicone elastomer casts of the arterial vasculature, from the origin of the aorta to the terminal artrioles, of various laboratory animals: They demonstrate cylindricity of vascular segments between succesive branches; the reduction in vascular lumen dimension occurs immediately below each branch, limited to that immediate wall region. The arterial tree can thus be considerd a successive sequence of cylinders of reduced dimension. The geometry of trees both above and below ground, trunk and branches and roots, show identical structure: cylindrical segments betwen branches. Vascular cylindricity in animals, with local step reduction in lumen below a branch may promote turbulence and shear stress endothelial changes and play structural role in atherosclerosis.

192 EXPERIMENTAL STUDIES OF THE HEAT EXCHANGE IN PAIRED VESSELS USING THE RAT SPINOTRAPEZIUS MUSCLE Ji Song ~, Lisa X. Xu 3, Daniel E. Lemons2, and Sheldon Weinbaum ~ ~Dept. of Mechanical Engineering and 2Dept. of Biology, The City College, 3Dept. of Applied Sciences, The College of Staten Island, The Graduate School and University Center, The City University of New York The present study investigates the heat exchange in the thermally significant countercurrent paired vessels by the evaluation of the effective thermal conductivity (lgn) and vessel axial thermal equilibration length (Le) in the two-dimensional rat spinotrapezius muscle. The vascular geometry, blood flow rate and tissue surface temperature distribution were measured in an exteriorized rat spinotrapezius muscle. Based on the experimental measurements, k~r~was evaluated and Le was directly obtained from the temperature distribution. It was found that a large increase in blood flow resulted in a significant enhancement in I% and the total enhancement in ke, was due primarily to the IA vessel pair. It also was shown that the experimentally measured Le was close to the theoretical prediction. A better understanding of the mechanism of microvascular blood-tissue heat exchange in muscle tissue is obtained from this study.