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E L Yellin

Publications and source records attributed to E L Yellin.

At least 19 recordsLinked to original sources
PubMed2000

Physiology of diastolic function and transmitral pressure-flow relations.

The study of diastolic function, in particular, the creative application of noninvasive modalities, such as echocardiography and MR imaging, requires an understanding and appreciation of the basic physiology of left ventricular filling dynamics. The physics and physiology of diastolic function and dysfunction is examined by relating the phasic patterns of transmitral flow to the properties of the cardiac chambers. Particular attention is paid to the equations governing the transmitral pressure-flow relations and the active and passive chamber properties that determine the flow patterns: Active relaxation, passive compliance, viscoelasticity, and elastic deformation. The physiologic role of diastolic suction is discussed within this context.

Animals↗
PubMed2000

Modeling of diastole.

Modeling methods have been employed to further characterize the physical and physiologic processes of filling and diastolic function. They have led to more detailed understanding of the effect of alteration of physiologic parameters on the Doppler E-wave contour as well as pulmonary vein flow. Depending on the modeling approach, different aspects of the filling process have been considered from AV gradient and net compliance to atrial appendage function to the mechanical suction pump attribute of the heart. The models have been applied for further characterization of diastolic function and elucidation of novel basic physiologic relations. We trust that readers recognize that this article could not serve as a comprehensive and global review of the state-of-the-art in physiologic modeling, but rather as a selective overview, with emphasis on the main modeling principles and options currently in use. Modeling of systems physiology, especially as it relates to the function of the four-chamber heart, remains a fertile area of investigation. Future progress is likely to have profound influence on (noninvasive) diagnosis and quantitation of the effect of therapy and lead to continued discovery of "new" (macroscopic, cellular, and molecular biologic) physiology.

Animals↗
PubMed1999

Contraction-relaxation coupling: determination of the onset of diastole.

Left ventricular relaxation is dependent on afterload conditions during systole. An abrupt increase in afterload while the ventricle is actively contracting prolongs the duration of systole. An increase in afterload during ventricular relaxation shortens the duration of systole. Therefore, we hypothesized that the point during systole when an abrupt increase in afterload had no effect on the duration of systole represented the onset of ventricular relaxation. To determine when this point occurs, we performed aortic occlusions progressively throughout the duration of systole in six dogs. We determined the change in systolic time (t(sys)) after an intervention normalized to t(sys) of a control beat (t(sys,i)/t(sys, c)) as a function of systolic occlusion time as a percentage of total systolic time (t(occ)/t(sys,c)), where t(sys) is the duration from time of left ventricular end-diastolic pressure to the time of minimum first derivative of left ventricular pressure. Our results show the onset of left ventricular relaxation during normal ejection occurs at 34 +/- 3% of systolic time and approximately 16% after the onset of ejection. Thus the beginning of relaxation occurs soon after the beginning of ejection, suggesting that relaxation is modulated by variable loading conditions during ejection, significantly before what has been conventionally been assumed to be the beginning of ventricular relaxation.

Animals↗
PubMed1999

Concepts related to the study of diastolic function: a personal commentary.

The phasic character of the transmitral flow wave is determined by the AV pressure difference and the impedance of the mitral valve complex. The measured LV pressure is determined by the complex contributions from 4 sources: rate and extent of deactivation, passive myocardial properties, deformation due to shape change, and viscoelasticity. An understanding of the functional value of diastolic indices is helped by an understanding of the basic physiology. Many questions remain unanswered at both the macro level, which has been the focus of this commentary, and the micro level where the ultimate source of function arises. New modalities for the study of diastolic function at the macro level are constantly under development, and progress is being made at the micro level. It is unfortunate that the role of left atrial properties has not received the attention required, considering that it is more than 10 years since Ishida et al. demonstrated the importance of LA pressure in creating the early filling wave. I trust that the reader understands that this paper is not meant to be a comprehensive review, but rather a discussion of basic principles from the very personal, albeit limited, point of view of my years of collaboration with colleagues from Japan. I dedicate this paper to all my former Fellows included among the authors in References 1-14, whose contributions to the study of diastolic function deserve the highest praise.

Animals↗
PubMed1998

UL-FS 49 (zatebradine) does not affect arterial baroreflex in conscious normal or aortic-constricted rats.

Heart-rate reduction is an important element of patient management during cardiac bypass surgery and in therapeutic measures for combating ischemia and relieving pain in patients with angina. UL-FS 49 is a novel bradycardic agent that purportedly acts solely on the sinoatrial node without potentially deleterious effects on arterial pressure and cardiac inotropism. However, little is known about influences of this agent on neuronal tissue and cardiovascular reflexes. Moreover, left ventricular hypertrophy, which often accompanies cardiovascular disease, is known to attenuate the arterial baroreflex and could have effects interactive with those of UL-FS 49. In this study, the effects of UL-FS 49 on the arterial baroreflex were tested in normal rats (N), rats with left ventricular hypertrophy 14 days after abdominal aortic constriction (AC), and sham-operated controls (SH). Arterial baroreflex sensitivity (BRS) was estimated as the slope of the relation between mean arterial pressure (independent variable) and the RR interval (dependent variable). At the time of study, the AC group had significantly greater mean arterial pressure than either SH or N (159 +/- 2, 122 +/- 3, and 124 +/- 3 mm Hg, respectively; mean +/- SEM, p < 0.01) and significantly greater left ventricular mass to body mass ratio than did SH (3.73 +/- 0.11, 2.33 +/- 0.11 mg/g; p < 0.01). As expected, BRS was significantly depressed in AC, compared with either SH or N (0.52 +/- 0.16, 1.48 +/- 0.12, 1.69 +/- 0.25 ms/mm Hg, respectively; p < 0.01). Despite its potent dose-dependent bradycardic effects in all three groups, UL-FS 49 did not affect BRS significantly in any group. These results show that the arterial baroreflex is largely unaffected by UL-FS 49 in both normal rats and rats with systemic hypertension and left ventricular hypertrophy.

Animals↗
PubMed1998

Left ventricular diastolic function of remodeled myocardium in dogs with pacing-induced heart failure.

In patients with heart failure, decreased contractility resulting in high end-diastolic pressures and a restrictive pattern of left ventricular filling produces a decrease in early diastolic filling, suggesting a stiff ventricle. This study investigated the elastic properties of the myocardium and left ventricular chamber and the ability of the heart to utilize elastic recoil to facilitate filling during pacing-induced heart failure in the anesthetized dog. Elastic properties of the myocardium were determined by analyzing the myocardial stress-strain relation. Left ventricular chamber properties were determined by analyzing the pressure-volume relation using a logarithmic approach. Elastic recoil was characterized using a computer-controlled mitral valve occluder to prevent transmittral flow during diastole. We conclude that, during heart failure, the high end-diastolic pressures suggestive of a stiff ventricle are due not to stiffer myocardium but to a ventricle whose chamber compliance characteristics are changed due to geometric remodeling of the myocardium. The restrictive filling pattern is a result of the ventricle being forced to operate on the stiff portion of the diastolic pressure-volume relation to maintain cardiac output. Slowed relaxation and decreased contractility result in an inability of the heart to contract to an end-systolic volume below its diastolic equilibrium volume. Thus the left ventricle cannot utilize elastic recoil to facilitate filling during heart failure.

Animals↗
PubMed1996

Time to dP/dtmax reflects both inotropic and chronotropic properties of cardiac contraction: a conscious dog study.

This study supports a mathematical model and previous findings indicating that td, the time from onset of contraction to dP/dtmax, reflects the time-dependent aspects of contraction and hence decreases with increasing contractility. Combined data from 20 conscious instrumented dogs create a highly significant inverse and linear td-HR (heart rate) relation. Both norepinephrine and isoproterenol decreased td values, but norepinephrine, in contrast to isoproterenol, decreased the heart rate by a reflex response. Despite the remarkable decline in heart rate (25.8%) td was decreased (16.5%). During wide spontaneous R-R variations longer preceding intervals gave shorter td values. The latter two facts indicate the dependence of td on the contractile state rather than it being merely interval dependent.

Adrenergic alpha-Agonists↗
PubMed1996

Left ventricular diastolic suction with zero left atrial pressure in open-chest dogs.

We investigated left ventricular (LV) diastolic volume changes (suction inflows) with left atrial pressure (LAP) clamped to ambient pressure in six open-chest, anesthetized dogs. The left atrium was cannulated and connected to a servo pump, and LAP was clamped to a set point near 0 mmHg for four beats by withdrawing blood. LAP averaged 5.88 +/- 1.44 mmHg before the clamp and fell to 0.74 +/- 0.61 mmHg (P < 0.0001) after the clamp. During the first clamped beat a transmitral pressure gradient of 1.0 +/- 0.6 mmHg was observed, resulting in LV filling of 2.6 +/- 1.8 ml. Subsequent beats developed suction-driven (mean negative LV pressure: -1.5 +/- 1.3 mmHg; P < 0.005 vs. zero) LV filling of 4.5 +/- 2.8 ml/beat with a peak transmitral pressure gradient of 1.7 +/- 0.6 mmHg. These data are consistent with the hypothesis that LV suction can be an important filling mechanism under condition in which LV end-systolic volume is reduced, e.g., reduced filling pressures, high heart rates, exercise, or increased inotropic drive.

Animals↗
PubMed1996

Viscoelastic behavior of the isolated guinea pig left ventricle in diastole.

To determine left ventricular (LV) viscoelastic properties during acute volume changes, the relaxation of LV pressure (2-Fr, Millar) at steady LV volume after a known volume change was measured in 14 isolated guinea pig left ventricles arrested in diastole. The left ventricle was loaded and unloaded by manual injection and withdrawal of saline in 10 x 0.1-ml steps, controlling the steadiness of LV volume by measuring LV major and minor diameters (ultrasonic crystals). Cyclic stepwise volume loading and unloading resulted in a hysteresis loop, the complexity of which was caused by stress relaxation at each steady volume. With the use of linear regression analysis, the gross elastic effect of the pressure signal was separated from the viscoelastic part, decomposed into the fast and the slow component with time constants of relaxation equal to 1 and 20 s, respectively. The amplitudes of the fast and the slow component showed that 1) stress relaxation is more expressed at higher LV volume and 2) it is asymmetric, i.e., it is well expressed during volume loading and almost absent during volume unloading. Both suggest that viscoelasticity of passive myocardium is not quasilinear, when the left ventricle is subjected to aperiodic volume loading to a high LV volume. The asymmetric viscoelastic behavior is consistent with the hypothesis of extracellular fluid filtration.

Animals↗
PubMed1995

Origin of regional pressure gradients in the left ventricle during early diastole.

Left ventricular (LV) pressure (P)-diameter, LVP-area, or LVP-volume relationships used to evaluate LV diastolic function assume uniform LV wall motion and constant LVP. Contrary to these assumptions, there are significant differences in ventricular dynamic geometry and in LV pressures measured simultaneously in different parts of the LV, particularly during early diastole. We instrumented six anesthetized open-chest dogs with three pairs of orthogonal ultrasonic crystals (anterior-posterior and septal-free wall minor axes, and base-apex major axis) and two micromanometers (in the apex and in the LV base). The mitral valve occluder was implanted during standard cardiopulmonary bypass in the mitral annulus. Data were recorded during 11 transient vena caval occlusions. The mitral valve was occluded for 1 beat every 6-8 beats during each vena caval occlusion to produce nonfilling diastole. With the decrease of the LV end-systolic volume (Ves) below the equilibrium volume Veq (volume of the completely relaxed LV at LVP = 0); the minimum negative LVP in nonfilling beats increases, the shape of the ventricle is more ellipsoidal in both filling and nonfilling beats, and the base-to-apex pressure gradient at the time of LVP minimum increases regardless of the presence or absence of filling. Thus heterogeneous myocardial stresses during isovolumic relaxation and early diastole result in ventricular shape changes, intraventricular redistribution of chamber volume, local accelerations of blood, and associated intraventricular LVP gradients. The role of elastic recoil assumes greater importance at Ves smaller than Veq, when the left ventricle becomes more ellipsoidal in shape during isovolumic relaxation, leading, in turn, to greater shape changes and greater LVP gradient.

Animals↗
PubMed1995

Determination of vascular impedance in the peripheral circulation by transcutaneous pulsed Doppler ultrasound.

Instantaneous blood flow velocity characteristics and vascular impedance spectra derived noninvasively by pulsed Doppler ultrasound and invasively by electromagnetic flow probe were compared in the canine common femoral artery to validate the pulsed Doppler technique for determination of vascular impedance in the peripheral circulation. Although Doppler ultrasonography is routinely performed to evaluate blood flow velocity patterns in the human peripheral circulation; the validity of this technique to derive peripheral vascular impedance has yet to be investigated. Simultaneous measurements of blood flow velocity were determined by both noninvasive pulsed Doppler ultrasound and surgically implanted electromagnetic flow probe in the common femoral artery of eight dogs and compared in both time and frequency domains. Vascular impedance spectra derived from measurements of blood flow velocity determined by Doppler ultrasound and electromagnetic flow probe and simultaneous measurement of arterial pressure by a micromanometer-tipped catheter were obtained at baseline and after intra-arterial injection of acetylcholine in five additional dogs. During the first 10 to 20% of the cardiac cycle, Doppler ultrasound blood flow velocity was transiently greater than the simultaneously recorded electromagnetic blood flow velocity. During the remainder of the cardiac cycle, the two blood flow velocity waveforms were nearly superimposable. The frequency spectra of the blood flow velocity waveforms derived from Doppler ultrasound and electromagnetic flow probes were similar for harmonies less than 10 Hz. Vascular impedance spectra derived from measurements of blood flow velocity determined by Doppler ultrasound and electromagnetic flow probe with simultaneous measurement of arterial pressure by a micromanometer-tipped catheter were similar at baseline and after regional administration of acetylcholine. Mean vascular resistance (impedance at 0 Hz), characteristic impedance, and the first minima of the impedance modulus derived from Doppler ultrasound and electromagnetic flow probe blood flow velocity measurements were closely correlated at baseline and after dilation with acetylcholine (r > or = 0.89, p < 0.05 for all correlations). Doppler ultrasonography is a convenient and accurate technique for determination of vascular impedance in the peripheral circulation.

Animals↗
PubMed1994

Modeling the transient response to volume perturbations in the beating heart by the difference equation method.

Discrete theoretical methods, compatible with the discrete features of the beating heart, are used together with experimental study to attain a quantitative understanding of the transient response to a volume perturbation and of sustained mechanical alternans (SMA) in the beating heart. This is done in three stages. In stage A, a first-order difference equation describes the stroke volume (SV) response due to the Frank-Starling mechanism. It is shown that the value of gamma, the slope of the SV-end-diastolic volume curve, determines the type of response obtained because of a perturbation: 1) nonoscillatory decay for gamma < 1,2) oscillatory decay for 1 < gamma < 2, 3) SMA for gamma = 2, and 4) chaotic response for gamma > 2. In stage B, when the effect of each SV change on the successive end-diastolic aortic pressure (P) is considered, SV response to a perturbation is determined by a second-order difference equation. The solution of this equation shows that the response is determined by gamma and by the afterload factor lambda 1 = alpha 1.delta, where alpha 1 = delta Pj + 1/delta SVj and delta = delta SVj + 1/delta Pj + 1. The responses are a nonoscillatory decay for lambda 1 < 1 - gamma (type 1), oscillatory decay for 1 - (gamma/2) > lambda 1 > 1 - gamma (type 2), SMA for lambda 1 = 1 - gamma/2 (type 3), and 2:1 electrical-mechanical response for lambda 1 > 1 - gamma/2 (type 4). In stage C, a single volume perturbation, delta SVj, will directly affect not only Pj + 1 but also the subsequent values of P. Filling volume perturbations performed with a mitral valve occluder in eight anesthetized dogs led only to type 1 and 2 responses. The responses predicted by the model (using the experimental values of gamma and lambda 1) in each of the eight open-chest dogs are compatible with the experimental responses, suggesting that it is unlikely that SMA is initiated and maintained by variations in preload and afterload.

Animals↗
PubMed1994

Left atrial pressure-clamp servomechanism demonstrates LV suction in canine hearts with normal mitral valves.

A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular pressure (LVP) and left atrial pressure (LAP) were measured, the left atrium was cannulated and connected to a servo pump, and LAP was controlled to a setpoint near 0 mmHg by withdrawing blood from the left atrium. Heart rate [103 +/- 17 (SD) min-1], peak pressure (100 +/- 13 mmHg), minimum pressure (1.4 +/- 0.8 mmHg), and maximum rate of change of pressure with respect to time during isovolumic contraction and relaxation (2,506 +/- 775 and -1,761 +/- 855 mmHg/s, respectively) were normal. Servo control of LAP was possible to +/- 1 mmHg. LV suction was demonstrated in each heart (mean negative LVP -2.3 +/- 1.1 mmHg; P < 0.0001). This new technique demonstrates that the left ventricle can generate negative diastolic suction pressures when examined in vivo and in situ with an undisturbed mitral valve and physiologically normal preload and afterload. This adds to a growing body of evidence that, under appropriate circumstances, the heart can suck blood into itself and thereby aid in its own filling.

Animals↗
PubMed1993

Studies on the safety of intrasplenic hepatocyte transplantation: relevance to ex vivo gene therapy and liver repopulation in acute hepatic failure.

Hepatocytes transplanted into the host liver engraft promptly, retain normal function, and survive indefinitely. Although intrasplenic transplantation is effective in delivering hepatocytes to the liver, to define potentially limiting complications, we studied its safety in normal, cirrhotic, and partial portal vein-ligated rats. In normal rats, portal pressures increased severalfold after hepatocyte transplantation but returned to normal within 3 weeks. In contrast, in portal hypertensive rats with partial portal vein ligation or cirrhosis, portal pressures were either unchanged or increased less after hepatocyte transplantation. However, more transplanted cells migrated to the lungs along with a rise in right atrial pressures in portal hypertensive rats. Further quantitative studies using 111Indium-labeled hepatocytes showed that intrasplenic retention of transplanted hepatocytes was similar in all animal groups. Intrahepatic cell translocation was comparable in normal and cirrhotic rats, whereas fewer cells migrated to the liver in partial portal vein-ligated rats. The most remarkable difference, however, was significantly greater intrapulmonary translocation of hepatocytes in portal hypertensive rats, which was presumably related to portosystemic shunting. These results indicate that because intrasplenic hepatocyte transplantation induces only temporary portal hypertension in normal subjects, potential strategies to augment liver repopulation could include repeated cell transplantation. This should be useful for optimizing the results of ex vivo gene therapy, or other hepatocyte-based therapies. However, the hepatic and portal hemodynamic status requires careful evaluation in portal hypertensive or cirrhotic subjects if serious complications are to be avoided.

Animals↗
PubMed1992

Diphenylhydantoin inhibits calcification of bovine pericardial implants and myocardium: a preliminary study.

Calcification is a major cause of glutaraldehyde-fixed bioprosthetic valve failure. Recent studies have shown that dystrophic calcification shares basic features with normal bone mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. In this study, we observed that calcification of the myocardium of DBA/2J mice was inhibited or reversed by diets supplemented with 100 mg/kg diet diphenylhydantoin (dilantin) for 70 days, with a calcification incidence of 25% in the dilantin group versus 58% in control. We further studied the effects of dilantin on bioprosthetic valve calcification. Three groups of young male Sprague-Dawley rats (100 g, 9/group) were implanted subcutaneously with 1-cm2 pieces of glutaraldehyde-fixed bovine pericardium. Controls were fed a ground chow for 45 or 90 days postimplantation; experimentals received the same chow for the first 45 days postimplantation and then were fed the same diet supplemented with 1000 mg dilantin/kg for the succeeding 45 days. Calcium content (microgram/mg dry weight) of the implants in the dilantin group was 137 +/- 18.6 versus 214 +/- 34.3 in 90 days control and 79.9 +/- 41.5 in 45 days control (mean +/- SD, P < 0.01 and P < 0.05 respectively, t test). The tibia calcium content of the dilantin group was not significantly different from 90 days control. We conclude that orally administered dilantin inhibits calcification of glutaraldehyde-fixed bovine pericardial implants preferentially. It does not cause decalcification either of implants that have already calcified or of the bones. The anti-calcification effect of dilantin may be associated with its anti-vitamin D effect.

Animals↗
PubMed1992

Improved postfixation treatment of glutaraldehyde fixed porcine aortic valves by monosodium glutamate.

The use of bioprosthetic valves remains limited due to poor long-term durability primarily because of tissue calcification-associated degeneration. Release of locally cytotoxic residual aldehyde after glutaraldehyde fixation is one of the major causes of this degeneration. In this study, monosodium glutamate was used as postfixation treatment to bind residual aldehyde in order to block its toxic effects. Thirty-six pieces of fresh porcine aortic valves were fixed by 0.625% glutaraldehyde for 14 days, and then 18 of them were treated with 1% monosodium glutamate for another 3 days before they were implanted subcutaneously into the backs of two groups of rats (n = 9 in each group) for 45 and 90 days, respectively. Retrieved specimens were examined grossly, and calcium analysis and measurements of tissue collagen and water content were carried out. The results showed that, compared with glutaraldehyde fixed specimens, monosodium glutamate postfixation treated specimens had less calcification (calcium 104.93 + 50.94 versus 141.58 +/- 58.10 at 45 days and 103.07 +/- 76.48 versus 199.33 +/- 53.44 at 90 days, micrograms/mg dry weight, p < 0.01), higher collagen content (hydroxyproline 5.50 +/- 1.29 versus 3.58 +/- 1.48 at 45 days and 5.64 +/- 0.87 versus 4.25 +/- 0.65 at 90 days, micrograms/mg wet weight, p < 0.01), and higher water content (68.00 +/- 6.95% versus 61.33 +/- 8.83% at 90 days, p < 0.05) (mean +/- SD, paired t test). We conclude that monosodium glutamate couples with residual aldehyde, which significantly reduces calcification of glutaraldehyde fixed porcine aortic valves while preserving a higher tissue collagen and water content after implantation. The preserved tissue collagen and water content of the implants is closer to that of unimplanted native valves.

Animals↗