Porcine aortic leaflet arrangement may contribute to clinical xenograft failure

Clinical experience with the first generation porcine xenograft shows significant deterioration and mechanical failure after 7-8 years post-implantation. Although many mechanisms of valve failure have been identified, the inherent differences between porcine and human aortic valves have not been emphasized. To determine if these differences are significant, the authors studied the anatomy of the aortic valve in 10 post-mortem porcine hearts. The authors found that the non-coronary leaflet was the smallest and the right leaflet was the largest based on the dimensions of area, perimeter, weight, and attached edge length (p < 0.05). These results differ from reported analyses of human aortic valves, in which the smallest cusp is generally the right the largest is the non-coronary. The authors believe that these differences between the human and porcine aortic valves may result in atypical mechanical stresses and the disruption of blood flow patterns in the sinuses of Valsalva, and may decrease the long-term stability of the porcine bioprostheses. In other words, the failure found with porcine bioprostheses after 8 years of implantation might be expected from the inherent structure (and associated fluid dynamics) of the porcine aortic valve positioned in the human aortic root.     

Re: Proportionate mortality among union members employed at three Texas refineries

OBJECTIVES:We established an in vitro model to investigate the effects of valve sizing on the hemodynamic characteristics and leaflet motion of the Toronto SPV valve (St Jude Medical, Inc, St Paul, Minn). METHODS: Nine valves were first implanted in fresh porcine aortic roots and then retested in glutaraldehyde-treated porcine aortic roots. Three valves were 1- to 2-mm oversized, 3 were 1- to 2-mm undersized, and there were 3 size-for-size implantations. The elasticities of the aortic roots and the composite roots were measured in the pressure range between 0 and 120 mm Hg, and the composite roots were then tested in a pulsatile flow simulator. The transvalvular gradient and regurgitation were measured and the effective orifice area and performance index were calculated for each root. Leaflet motion was recorded on videotape. RESULTS: The external diameter of the fresh root increased by 35% as the hydrostatic pressure rose from 0 to 120 mm Hg, as compared with 11% for the glutaraldehyde-treated root. Valve implantation in the fresh root reduced the distensibility to 22% but did not change distensibility in the glutaraldehyde-treated root. The effective orifice area was dependent on the valve size, with the transvalvular gradient decreasing as the valve size increased. For the same size of valve the hydrodynamic parameters were slightly better if the valve was undersized by 1 mm. A significant difference in favor of the undersized valves was found in open-leaflet bending deformation. CONCLUSION: Leaflet motion of the stentless porcine aortic valve in vitro is improved if the valve is slightly undersized, and this may be beneficial to the long-term durability of the prosthesis.     

Transcranial Doppler ultrasound signals associated with prosthetic heart valves: an in vitro study

The application of transcranial Doppler (TCD) ultrasonography to asymptomatic prosthetic heart valve patients can result in detection of localized bursts of high intensity signals, similar to those caused by the passage of emboli. The origin of these signals is not known. In order to investigate this phenomenon in a simplified, more controllable environment, a TCD machine was used to record flow downstream from mechanical prosthetic heart valves in a mock circulatory loop. The model, which uses a saline solution seeded with silk particles (< 15 micrometers) as the circulatory fluid, recreates the principal hydrodynamic characteristics of the left heart and systemic circulation. Reproducibility of the system was established through repeated testing of a Monostrut valve. Three different mechanical valve types, (Monostrut, Medtronic Hall, St. Jude Medical) were tested over a range of simulated cardiac outputs, and the effect of valve size was investigated with four Omniscience tilting disc valves (21, 23, 25 and 29 mm). Average energy of the reflected Doppler signal was used to quantify the amount of high intensity Doppler signal, QTCD. TCD signals recorded in vitro were visually and aurally similar to those found in prosthetic heart valve patients. All valve types generated exponentially more QTCD with increasing simulated cardiac output. Differences amongst valve types were only significant at higher flow outputs, with the Monostrut valve producing the greatest QTCD. Larger valves consistently generated greater QTCD than smaller valves. In conclusion, TCD signals found in prosthetic heart valve patients can be reproduced, at least qualitatively, using a mock circulatory loop which does not incorporate the formed elements of blood.(ABSTRACT TRUNCATED AT 250 WORDS)     

Three-dimensional coupled fluid-structure simulation of pericardial bioprosthetic aortic valve function

A computational, three-dimensional coupled fluid-structure dynamics model was developed for a generic pericardial aortic valve in a rigid aortic root graft with physiologic sinuses. Valve geometry was based on that of the natural valve. Blood flow was modeled as pulsatile, laminar, Newtonian, incompressible flow. The structural model accounted for material and geometric nonlinearities and also simulated leaflet coaptation. A body fitted grid was used to subdivide the flow domain into computational finite volume cells. Shell finite elements were used to discretize the leaflet volume. A finite volume computational fluid dynamics code and finite element structure dynamics code were used to solve the flow and structure equations, respectively. The fluid flow and structural equations were coupled using an implicit "influence coefficient" technique. Physiologic ventricular and aortic pressure waveforms were prescribed as the flow boundary conditions. The aortic flow field, valve structural configuration, and leaflet stresses were computed at 2 msec intervals. Model predictions on aortic flow and transient variation in valve orifice area were in close agreement with corresponding experimental in vitro data. These findings suggest that the computer model has potential for being a powerful design tool for bioprosthetic aortic valves.     

Experience with surgery of the heart valves

A review is given of a 15 year experience of valve replacement with Teflon cusps, pericardial cusps, Starr-Edwards, Key-Shiley, Wada-Cutter and Bj?rk-Shiley artificial valve prosthesis. The Bj?rk-Shiley tilting disc valves have shown the lowest gradient and blood trauma and excellent durability in more than 1 000 implantations during a 7 year period. Anticoagulation therapy is considered necessary with all types of artificial heart valves. Thrombo-embolism is negligible after aortic valve replacement (1 episode in 4 000 patient months) but still a problem in the mitral position (4 episodes in 1 000 patient months).     

3D CFD Predictions and Experimental Comparisons of Pressure Drop in a Ball Valve at Different Partial Openings in Turbulent Flow

A three dimensional computational fluid dynamics model, using the STAR-CD software, has been developed to simulate fluid flow in a commonly used flanged ball valve at different partially open settings. The Reynolds number (Re) range for the flow simulations was varied between 105 and 106 to simulate a variety of flow conditions. Each flow Re number is studied with three open positions for the valve, i.e., fully open, two-thirds open, and one-third open. The simulation was used to calculate two important parameters used in characterizing the flow properties in a typical valve namely the loss coefficient, K, and the flow coefficient, Cv. An attempt was also made to compare some of the simulation results with experimental data and available American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) data on valves. The simulations agree reasonably well with recently published experimental results and indicate that in most cases the K factor is independent of Re. The ASHRAE data for K factor values showed similar trends to the simulation but with lower values as it was only reported for gates valves. The Cv values show strong increases with the degree of valve opening and lesser influence by the Re number variations in the range studied     

Regression of left ventricular hypertrophy after aortic valve replacement for aortic stenosis with different valve substitutes

OBJECTIVE: Stentless biologic aortic valves are less obstructive than stented biologic or mechanical valves. Their superior hemodynamic performances are expected to reflect in better regression of left ventricular hypertrophy. We compared the regression of left ventricular hypertrophy in 3 groups of patients undergoing aortic valve replacement for severe aortic stenosis. Group I (10 patients) received stentless biologic aortic valves, group II (10 patients) received stented biologic aortic valves, and group III (10 patients) received bileaflet mechanical aortic valves. METHODS: Echocardiographic evaluations were performed before the operation and after 1 year, and the results were compared with those of a control group. Left ventricular diameters and function, left ventricular wall thickness, and left ventricular mass were assessed by echocardiography. RESULTS: Group I patients had a significantly lower maximum and mean transprosthetic gradient than the other valve groups (P = .001). One year after operation there was a significant reduction in left ventricular mass for all patient groups (P < .01), but mass did not reach normal values (P = .05). Although the rate of regression in the interventricular septum and posterior wall thickness differed slightly among groups, their values at follow-up were comparable and still higher than control values (P = .002). The ratio between interventricular septum and posterior wall and the ratio between wall thickness and chamber radius did not change significantly at follow-up. CONCLUSIONS: Because the number of patients was relatively small, we could not use left ventricular mass regression after I year to distinguish among patients undergoing aortic valve replacement for aortic stenosis by means of valve prostheses with different hemodynamic performances.     

Echocardiographic and phonocardiographic confirmation of suspected caged mitral valve malfunction

Seven patients studied by echocardiography with and without simultaneous phonocardiography for suspected malfunction of a caged mitral valve prosthesis are presented. In case 1, with inaudible prosthetic clicks, thrombosis of the cage and immobility of the ball were suggested by echocardiographic studies and confirmed at surgery. In case 2, simultaneous echocardiographic and phonocardiographic studies demonstrated wide and variable intervals between the aortic second sound the the opening click and also "sticking" of the ball. In case 3 a thrombus prevented full motion of the ball to the apex of the cage, which was seen on the echocardiogram, while in case 4, with a thrombus within the ventricle and prosthesis, the prosthetic opening click was present intermittently and was associated with only subtle echocardiographic changes. In case 5, echocardiographic studies demonstrated abnormal rocking of the cage secondary to severe prosthetic dehiscence. In case 6, dul prosthetic clicks were to be secondary to a low cardiac-output state. In case 7, with multiple valve prostheses, simultaneous echocardiographic and phonocardiographic studies allowed identification of individual valve sounds and abnormal timing of valve opening. Based on these studies, we believe that echocardiography and simultaneous phonocardiography can yield very useful information in the evaluation of patients with suspected malfunction of a caged mitral valve prosthesis.     

The use of enzyme activated milk for in vitro simulation of prosthetic valve thrombosis

BACKGROUND AND AIM OF THE STUDY: Thrombosis remains a serious risk for patients with artificial heart valves and may be attributed in part to adverse blood flow patterns. Although the final assessment of a valve must follow years of clinical experience, in vitro flow analyses give valuable information prior to implantation. Laser Doppler velocimetry and computational fluid dynamics enable quantitative flow analyses to be made in vitro. Whilst these techniques highlight features such as areas of stasis, turbulence and high shear which may predispose to thrombus formation, the complex and time varying nature of the flow through valves makes it difficult to predict accurately potential sites of thrombus deposition and accumulation. METHODS: A technique is described which uses enzyme activated milk as a coagulable blood analogue to indicate flow related clotting. Milk flowing past a test valve or object was activated to clot downstream of the test piece after a certain time period. Milk clot was deposited clot at sites determined by the local flow disturbances. Milk clotting patterns produced on and around standard objects were compared with the transient flow patterns predicted around identical configurations to test the validity of computational flow analyses for predicting flow disturbances leading to clotting. Milk clots on valves were compared with examples of thrombus found on explanted valves of the same design. RESULTS: The sites of deposition were consistent with the predicted flow patterns around the two configurations of flow obstruction studied. Milk clotting patterns on valves corresponded with the early stages of thrombus on explanted valves of the same design. CONCLUSIONS: Whilst a coagulable milk mixture may be used to evaluate the risk of flow induced clot adherence, care must be taken when extrapolating to the clinical situation as other factors such as material properties, blood chemistry and concomitant disease must also be considered.     

Particle image velocimetry in the investigation of flow past artificial heart valves

Full-field measurement of instantaneous velocities in the flow field of artificial heart valves is vital as the flow is unsteady and turbulent. Particle image velocimetry (PIV) provides us the ability to do this as compared to other point measurement devices where the velocity is measured at a single point in space over time. In the development of a PIV system to investigate the flow field of artificial heart valves, many problems associated with the project arose and were subsequently resolved. Experience gained in the setting up of an environment conducive for PIV studies of artificial heart valves; from seed particle selection to refractive index matching, and the evolution of computer algorithms to satisfy the varied flow conditions in artificial heart valves are presented here. Velocity profiles and distributions are computed and drawn for a porcine tissue heart valve based on measurements with the PIV system developed.     

Hydrodynamics of shunt valves

A study of differential pressure valves (DPV) used in the treatment of hydrocephalus was undertaken to determine their pressure-flow characteristics and compatability with the antisiphon valve (ASV). DPV could be classified into two groups: low resistance valves (LRV) and high resistance valves (HRV). The LRV maintains intraventricular pressure (IVP) near the closing pressure (CP) of the valve by permitting a high flow whenever CP is exceeded. The HRV regulates IVP by attempting to match inflow with some point on the pressure-flow curve of the valve. These characteristics were lost unless valve outlet pressure was maintained at atmospheric pressure. This could be accomplished by using a proximal DPV with an ASV at the DPV outlet, thus converting the DPV into a gauge pressure valve and preventing the 'siphon effect' seen with the use of a DPV alone.     

The human capsaicin model of allodynia and hyperalgesia: sources of variability and methods for reduction

The paper deals with the hydrodynamics of artificial heart valves (AHVs) used in clinical practice. It reviews and analyzes the studies of AHV hydrodynamics, as well as the hydrodynamic beds which stimulate physiological flow through the valve. Photochronic imaging (PCI) is proposed for examination of AHV hydrodynamic characteristics under model physiological flow. The hydrodynamics of different AHVs was tested on the beds simulating blood flow through AHVs by employing PCI. PCI involved preparation of model photochronic solution that simulates blood, colour labels by using laser radiation. In the model photochronic solution, 10(-6)-10(-9)-sec laser radiation gave rise to linear colour labels whose movement was recorded by a speed camera in the flow behind the valve. The profiles of speed behind the valves, the dimensions of congestive areas, the positions of flow detachment and regurgitation flow were calculated by a speed shooting in different periods of valvular performance. PCI defined congestive areas behind the valves, the areas of closed circulations, the sizes of reversing flow areas and examined the time course of flow behind the valves as a whole. The paper is of interest for AHV designers and cardiac surgeons who apply various AHVs.     

Sustained-release naltrexone for alcoholism treatment: a preliminary study

OBJECTIVES: To evaluate midterm results of mechanical valves in pulmonary position in patients with pulmonary regurgitation and right ventricular dysfunction as an alternative to bioprostheses. PATIENTS: Mechanical valves (six tilting disc valves and two bileaflet valves) were implanted in eight patients previously operated on for tetralogy of Fallot (n = 7) and truncus arteriosus (n = 1), with severe right ventricular dysfunction caused by massive pulmonary regurgitation. RESULTS: All patients survived prosthesis implantation and are currently well. At follow-up (3 months to 9 years), they do not show signs of valve failure, and right ventricular function has dramatically improved in all but one, who still shows moderate ventricular hypokinesia. CONCLUSION: After operative correction of congenital heart defects in selected patients who show severe dysfunction of the right ventricle caused by pulmonary regurgitation/stenosis, mechanical valves may represent an alternative to bioprosthetic valves. The selection of the valve type is still a matter of debate. However, according to literature data, complications seem to have occurred only in patients with bileaflet mechanical valves in the pulmonary position, whereas no thromboembolic episodes or valve failure is reported in subjects with tilting disc valves in the right ventricular outflow. Tilting disc valves might perform better in the right ventricular outflow than bileaflet valves.     

Usefulness of magnetic resonance imaging for managing patients with prosthetic carbon valve in the mitral position

The safety, findings and clinical usefulness of magnetic resonance (MR) imaging were assessed in patients with a prosthetic carbon valve in the mitral position. In vitro deflection, heating and image distortion due to the magnetic field of a 1.5 tesla MR machine were examined in three carbon valves (CarboMedics, St. Jude Medical and Bj?rk-Shiley valves). In vivo MR imaging of the left ventricular horizontal long-axis, vertical long-axis and short-axis views was performed by electrocardiographically synchronized spin echo and field (gradient) echo techniques in eight patients with prosthetic mitral carbon valves, consisting of six CarboMedics valves, one St. Jude Medical valve and one Bj?rk-Shiley valve. No deflection and significant heating was seen in all three valves in vitro. Although little image distortion was shown in the CarboMedics and St. Jude Medical valves, a small distortion toward the frequency encoded direction was seen in the Bj?rk-Shiley valve but caused no difficulty in assessing the surrounding images. Four of the eight patients had normal sinus rhythm and the other four had atrial fibrillation. The prosthetic valves were depicted as signal voids in the images taken by both spin echo and field echo techniques in vivo. Clear structural information with little image distortion of the adjacent tissues of the prosthetic valves were obtained in all patients, although the image of the Bj?rk-Shiley valve which contained stainless steel in the frame had a slightly stronger distortion than those of the CarboMedics and St. Jude Medical valves which contained titanium. The stainless wire suture material used to close the sternal incision was depicted as a signal void, and the areas of the signal loss were larger in the images taken by the field echo technique than those by the spin echo technique. The images taken by the spin echo technique in patients with atrial fibrillation had reduced quality due to the irregularity of repetition time. Cine MR imaging by the field echo technique showed physiological mitral regurgitant jets as signal loss within the flowing blood, which appeared as high signal intensity, bidirectionally in the bileaflet mechanical valve and unidirectionally in the monoleaflet mechanical valve. An abnormal cavity was seen behind the basal left ventricular myocardium in one patient with a CarboMedics valve. The wall of the abnormal cavity was disrupted abruptly and the rest of the wall consisted of pericardium and adjacent tissue in the image taken by the spin echo technique. The image taken by the field echo technique showed an abnormal jet flow from the basal part of the left ventricular cavity into the abnormal cavity, which was compatible with left ventricular pseudoaneurysm. Two-dimensional echocardiography and Doppler color flow mapping disclosed the abnormal cavity and the abnormal flow inside, but failed to show the connection between the left ventricle and the cavity due to reverberation of the ultrasound signal by the prosthetic valve. These findings suggest that MR imaging is a safe and promising method to assess the complications and valvular function in patients with a prosthetic carbon valve in the mitral position.     

Technetium-99m MIBI to assess coronary collateral flow during acute myocardial infarction in two closed-chest animal models

Collateral flow is an independent determinant of infarct size in both animal and clinical studies of myocardial infarction. The purpose of this study was to quantitatively evaluate, in a closed-chest animal model, a noninvasive method of measuring coronary collateral flow over a wide spectrum of collateral flow rates from a tracer that can be injected during occlusion but measured after reperfusion. METHODS: Fourteen animals underwent 40 min of coronary occlusion using a closed-chest technique. Two closed-chest models representing different rates of collateral flow were used: canine and porcine. Coronary blood flow was measured by radiolabeled microspheres. Collateral blood within the risk zone was estimated from the severity of 99mTc-sestamibi tomographic perfusion defect. RESULTS: Collateral blood flow was significantly higher in the canine model than it was in the porcine model. There was close agreement (r = 0.90) between absolute collateral flow by microspheres and the severity of the tomographic perfusion defect. CONCLUSION: These results suggest that an accurate noninvasive estimate of collateral blood flow can be provided by an intravenous injection of 99mTc-sestamibi.     

Expression of microfibrillar proteins by bovine bladder urothelium

OBJECTIVE: To compare hydrodynamic characteristics of a new bileaflet heart valve, the CarboMedics kinetic cardiac valve prosthesis, with those of a St. Jude Medical (SJM) heart valve. METHODS: Hydrodynamic characteristics were determined in the mitral and aortic positions of a Vivitro Systems pulse duplicator for size 23 Kinetic aortic values, size 23 SJM aortic valves, size 29 Kinetic mitral valves and size 29 SJM mitral valves. Test conditions were 72 beats per min with cardiac outputs of 2, 5 and 7 l/min. Values of forward flow pressure drop (delta P), regurgitant and energy loss were determined for each valve. The test results for the two valve designs were compared by valve size. RESULTS: The test results show that both the size 23 and size 29 Kinetic valves have 8-14% lower delta P values and 5-10% greater effective orifice area (EOA) values. The size 29 Kinetic mitral valve has a 1-2 ml lower regurgitant volume, while the size 23 Kinetic aortic valve has a 0.5 ml greater regurgitant volume than the corresponding SJM values. These factors combine to provide a 5-10% lower energy loss for size 23 Kinetic aortic valves and a 15-25% lower energy loss for size 29 Kinetic mitral valves over the cardiac cycle than for corresponding sizes of SJM valves. CONCLUSIONS: The Kinetic valve's fluid dynamics are superior to equivalent sizes of SJM valves. This is especially impressive considering that the tissue annulus diameters for Kinetic valves are approximately 0.5 mm less than equivalent size SJM valves. The primary reasons for the superior hydrodynamic performance of Kinetic valves are (1) the larger orifices which result in lower forward flow delta P values and (2) the opening angles, which have been customized for each valve size to minimize energy loss.     

A new in vitro test method for calcification of bioprosthetic heart valves

To investigate the calcification behavior of different bioprosthetic heart valves and verify possible hypotheses of the etiology of valve calcification, an accelerated pulse tester for bioprostheses was developed, whereby up to ten valves can be tested under identical test conditions. Each valve was mounted in a separate compartment on a piston and cyclically moved through a calcifying solution at frequencies of up to 800/min at 37 degrees C: An appropriate calcifying solution was evaluated by incubation tests of bovine and porcine tissue. Calcification was confirmed by measuring Ca and phosphate depletion by atomic absorption spectroscopy, von Kossa staining, EDAX, and microradiography. The first tests were successfully carried out on porcine valves that had been nondestructively assessed for tissue/stress anomalies by holographic interferometry prior to the calcification test. The tests showed that 75% of irregular fringe pattern areas corresponded to the calcification areas.     

Frame-mounted porcine valve bioprostheses: preparation during aortic-root dilation. Biomechanics and design considerations

The leaflet geometry and function of frame-mounted porcine bioprostheses prepared with dilation of the aortic root during frame mounting was investigated. The diameter of the porcine aortic root increased by 47% when dilated with a pressure of 120 mm Hg. In the absence of pressure dilation, the ratio of circumferential leaflet length to the radius of the aortic root (S/RA) was 2.7 +/- 0.1, and the angle of inclination of the leaflet to the base of the valve was 17 +/- 4.3 degrees. In this condition, the leaflet geometry was similar to that of some second-generation porcine bioprostheses, which demonstrated high open-leaflet bending strains at the commissures. Dilation of the porcine root with 120 mm Hg reduced the value of S/RA to 1.84 and produced a triangular open-leaflet configuration with minimum open-leaflet bending strains. Open-leaflet bending strains were also reduced in two prototype frame-mounted valves prepared with partial dilation of the aortic root, which had an S/RA ratio of less than 2.3 and a leaflet angle greater than 27 degrees. The study indicates that the next generation of porcine bioprostheses should be prepared with at least 17% dilation of the aortic root during frame mounting and with zero pressure difference across the leaflets during fixation. This can be achieved by applying an equal hydrostatic pressure to both sides of the valve leaflets during fixation and frame mounting.     

Porcine aortic wall flexibility. Fresh vs Denacol fixed vs glutaraldehyde fixed

It has been postulated that, in theory, stentless bioprosthetic heart valves provide improved hemodynamics and durability over their stented counterparts. A number of glutaraldehyde modified porcine stentless valves are currently either on the market or in clinical trials. Polyepoxy compound as an alternative cross-linking reagent to glutaraldehyde for bioprostheses has been reported to mitigate calcification. The present study was to investigate the effect of the fixation methods on porcine aortic wall flexibility. Ring specimens were selected from three groups of porcine roots: fresh, low pressure glutaraldehyde fixed, and low pressure Denacol (polyepoxy compound) fixed. Pulled between two rods on a tensile tester, a ring specimen's load-deformation relationship was recorded and analyzed to numerically compute the tissue modulus at low strains. The results showed that the Young's moduli were 0.113 +/- 0.036, 0.494 +/- 0.113, and 1.320 +/- 0.292 MPa (mean +/- SD, n = 10) for the fresh, Denacol fixed, and glutaraldehyde fixed aortic walls, respectively. The Denacol fixed aortic wall was more flexible than the glutaraldehyde fixed one. It was also found that the Denacol fixed aortic wall maintained most of the natural residual strains, while the glutaraldehyde fixed aortic wall did not.     

Temperature of the sclera during diathermocoagulation carried out in patients with retinal detachment

Regional coronary blood flow was measured by injecting radioactive microspheres (15 mum +/- 5 in diameter) into the left atrium of anesthetized ponies with surgically prepared open thorax before and during occlusion of the coronary arteries. The normal blood flow to the myocardium of the interventricular septum and the left ventricular wall were highest, followed in decreasing order by the right ventricular wall, the interatrial septum, the atrial walls, and the valves. Measurement of transmural blood flow in the normal left ventricle yielded a mean endocardial/epicardial flow ratio of 1.36 in the free wall. The left ventricular flow ratio was 1.33 in the septal wall. The percentage of the left ventricular myocardium made ischemic during occlusion of the right coronary artery or of the left coronary artery (cranial descending and circumflex arteries) was approximately equal. Blood flow to the ischemic areas of the left ventricle after occlusion of coronary arteries ranged from 3.8 to 20.6% of the normal flow. A disproportionate decrease in flow to the endocardial regions of the left ventricle was also observed in ischemic areas (mean inner/outer left ventricular wall flow ratio was 68.89% of the normal flow ratio).