Time Constant Of Ventricular Relaxation Research Articles

Therapeutic evaluation and metabolic reprograming of isosteviol sodium in a rat model of ischemic cardiomyopathy

Ischemia heart disease, one of the lethal cardiovascular diseases, irreversibly impairs cardiac function and is recognized as the primary risk factor for mortality in industrialized countries. The myocardial ischemia treatment still faces a considerable degree of increasing unmet needs. Isosteviol sodium (STVNa) and its derivatives have been proven to effectively alleviate metabolic diseases, hypertension, and heart hypertrophy. Little is known about how STVNa confers the cardioprotective effect during acute myocardial ischemia (AMI). In the present study, a rat model of acute ST-segment–elevation myocardial ischemia by left anterior descending (LAD) ligation was established. Compared to the AMI model group, STVNa administration (4 mg/kg, twice a day) well preserved left ventricle function by ejection fraction (45.10 ± 10.39 vs. 73.64 ± 13.15, p = 0.0013) and fractional shortening (22.94 ± 6.28 vs. 44.00 ± 11.05, p = 0.0017). Further analysis shows that high-dose STVNa (4 mg/kg) significantly improved the hemodynamics in AMI rats, with LVSP (88.25 ± 12.78 vs 99.75 ± 5.10, p = 0.018), max dP/dt (2978.45 ± 832.46 vs 4048.56 ± 827.23, p = 0.096), LVEDP (19.88 ± 2.00 vs 22.26 ± 3.21, p = 0.04) and left ventricular relaxation time constant (Tau) (0.030 ± 0.006 vs 0.021 ± 0.004, p = 0.021). Mechanically, STVNa administration retained the myocardial levels of phosphorylated AMPK, and CPT1b. Moreover, STVNa significantly increased the total energy expenditure, and reduced fatty acid accumulation through mitochondrial oxidative phosphorylation, which was supported by the indirect calorimetry and cellular energy analysis. Taken together, these findings suggest that STVNa is a potential cardioprotection agent for ischemic cardiomyopathy, likely through improving energy homeostasis, left ventricular hemodynamics, and heart function.

Pharmacodynamics and Pharmacokinetics of Injectable Pimobendan and Its Metabolite, O-Desmethyl-Pimobendan, in Healthy Dogs.

Objectives: This study was designed to thoroughly evaluate the effects of bolus pimobendan at a dose of 0.15 mg/kg on cardiac functions, hemodynamics, and electrocardiographic parameters together with the pharmacokinetic profile of pimobendan and its active metabolite, o-desmethyl-pimobendan (ODMP), in anesthetized dogs.Methods: Nine beagle dogs were anesthetized and instrumented to obtain left ventricular pressures, aortic pressures, cardiac outputs, right atrial pressures, pulmonary arterial pressures, pulmonary capillary wedge pressures, electrocardiograms. After baseline data were collected, dogs were given a single bolus of pimobendan, and the pharmacodynamic parameters were obtained at 10, 20, 30, 60, and 120 min. Meanwhile, the venous blood was collected at baseline and 2, 5, 10, 20, 30, 60, 120, 180, 360, and 1,440 min after administration for the determination of pharmacokinetic parameters.Results: Compared with baseline measurements, the left ventricular inotropic indices significantly increased in response to intravenous pimobendan, as inferred from the maximum rate of rise in the left ventricular pressure and the contractility index. Conversely, the left ventricular lusitropic parameters significantly decreased, as inferred from the maximum rate of fall in the left ventricular pressure and the left ventricular relaxation time constant. Significant increases were also noted in cardiac output and systolic blood pressure. Decreases were observed in the systemic vascular resistance, pulmonary vascular resistance, left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, right atrial pressure, and pulmonary arterial pressure. The heart rate increased, but the PQ interval decreased. There was no arrhythmia during the observed period (2 h). The mean maximum plasma concentration (in μg/L) for ODMP was 30.0 ± 8.8. Pimobendan exerted large volume of distribution ~9 L/kg.Conclusions: Intravenous pimobendan at the recommended dose for dogs increased cardiac contraction and cardiac output, accelerated cardiac relaxation but decreased both vascular resistances. These mechanisms support the use of injectable pimobendan in acute heart failure.

Abstract 244: Post- But Not Pre-menopausal Female Smoothelin-like 1 Deficient Mice Develop Diastolic Dysfunction Unlike Their Male Counterparts

Diastolic dysfunction is a core characteristic of heart failure with preserved ejection fraction (HFpEF), which accounts for half of all HF cases. Our group revealed a novel impact of the smoothelin-like 1 (SMTNL1) protein which when subjected to genetic deletion drives alterations in endothelial and cardiovascular performances. Of note, previous cardiac hemodynamic profiling showed that young male SMTNL1 knockout (KO) mice developed diastolic dysfunction as evidenced by increased end diastolic pressure (EDP), left ventricular relaxation time constant (Tau) and steeper end diastolic pressure-volume relationship (EDPVR). A majority of HFpEF patients are post-menopausal women, so this study examined the impact of SMTNL1 silencing on endothelial and cardiac function with increasing age in a novel female murine model. The cardiac function of SMTNL1 global KO mice (3-, 12- and 18-month old, male and female) was assessed by echocardiography and pressure-volume loop. Unlike young males, 3-month old female KO mice did not develop diastolic dysfunction. However, ageing provided progressive impairment of diastolic function in female KO mice with increased EDP (8.4±1.1 vs 12.2±0.8 mmHg, p<0.02) and EDPVR (0.22±0.05 vs 0.51±0.05, p=0.02) at 18 months; an elevated E/E′ (20.8±1.6 vs 28.3±2.2, p=0.02) and decreased E′/A′ (1.49±0.19 vs 0.97±0.14, p<0.05) at 12 months in comparison to their WT counterparts, along with a normal ejection fraction (>60%) for all age groups. Furthermore, while flow-mediated dilation was continuously impaired in male KO cohorts from 3-month age, female KO showed impairment only at 12-months. Aging was also associated with altered cardiac morphology and fibrotic levels in the aged female KO cohort. Taken together, we have identified pathophysiologic effects of SMTNL1 silencing on vascular and cardiac function with ageing in female mice. The SMTNL1 KO model for the first time recapitulates the sex dimorphic onset of diastolic dysfunction that is central to HFpEF clinical phenotypes and represents a novel preclinical model to study the etiology of the HFpEF condition. Furthermore, the absence of diastolic dysfunction in KO female mice until post-menopausal age reveals a protective role of female sex hormones and warrants further study.

P1510 Assessment of left ventricular relaxation time constant by noninvasive left ventricular pressure-strain loop: invasive validation

Abstract Introduction Left ventricular (LV) relaxation time constant, Tau (τ), is one of the best indexes to evaluate left ventricular diastolic function and is usually assessed invasively. Tau is the time constant of the exponential regression Pt =(P0-P∞)e-t/τ+P∞ that expresses left ventricular isovolumic pressure decay, where Pt is LV pressure (LVP) at time t, P0 is LVP at dP/dtmin and P∞ is the asymptotic pressure, to which relaxation would lead if completed without LV filling. Several noninvasive methods were developed to calculate Tau, however, they are time-consuming and complicated. Recently, a simple method regional left ventricular pressure–strain loops and myocardial work was introduced and validated. We hypothesize that left ventricular relaxation time constant can be derived and calculated from the LV pressure–strain loops. Objective To calculate noninvasively Tau using LV pressure–strain loops and compare it to invasive Tau assessment. Methods The study includes patients with preserved LV systolic function without significant valvular disease that were scheduled to elective coronary catheterization. During catheterization, a fluid-filled catheter was placed in the LV to measure pressure. Echocardiography was performed simultaneously with LV pressure recording. Three standard apical views were acquired and subsequently 2D strain analysis was performed using commercially available GE software and LV pressure–strain loops were calculated. Doppler signal was used for timing of valvular events. Tau was calculated by the equation τ =P/(-dP/dt) that is a derivative of the ventricular pressure decline P = P0e-t/τ+PB with respect to time. The pressure between peak negative dP/dt and the lowest LV pressure shortly after mitral valve opening was used for this calculation. The study was approved by the institutional ethics committee. Results Forty patients, (mean age 65.1 ± 10.9 years, 27 male, BSA1.93 ± 0.18 m2) were included in the study. Heart rate and the mean blood pressure at the time of catheterization were 69.9 ± 11.8 min-1 and 85.2 ± 18.8 mmHg, respectively. The mean LV end diastolic diameter was 44 ± 4 mm, the LV mass was 86.7 ± 25.2 g/m2, LVEF 58.4 ± 6.6% and GLS 21.0 ± 3.2%. Tau, calculated noninvasively using derivative method was significantly lower than invasively derived measurement (40.1 ± 13.4 vs 49.8 ± 7.7 msec, p = 0.002). However, a significant positive correlation was observed between the two methods (r =0.67, p <0.001, Figure). Conclusions This preliminary study demonstrates that Tau estimated by a noninvasive method using LV pressure–strain loops has a good correlation with Tau measured invasively. Therefore, Tau can be estimated noninvasively using novel left ventricular pressure–strain loop method. Abstract P1510 Figure.

Role of autophagy in a model of obesity: A long‑term high fat diet induces cardiac dysfunction.

Obesity may induce end-organ damage through metabolic syndrome, and autophagy serves a vital role in the pathogenesis of metabolic syndrome. The purpose of the present study was to define the roles of autophagy and mitophagy in high fat diet (HFD)-induced cardiomyopathy. Male, 8 week-old C57BL/6 mice were fed either a HFD (60% kcal) or a diet of normal chow (NC; 10% kcal) for 42 weeks. Glucose tolerance tests were performed during the feeding regimes. Blood samples were collected for assaying serum triglyceride with the glycerol-3-phosphate oxidase phenol and aminophenazone (PAP) method and total cholesterol was tested with the cholesterol oxidase-PAP method. Myocardial function was assessed using echocardiography and hemodynamic analyses. Western blot analysis was employed to evaluate endoplasmic reticulum stress (ERS), autophagy and mitochondrial function. Electron microscopy was used to assess the number of lipid droplets and the degree of autophagy within the myocardium. The body weight and adipose tissue weight of mice fed the HFD were increased compared with the NC mice. The serum levels of blood glucose, total cholesterol and triglyceride were significantly increased following 42 weeks of HFD feeding. The results of the glucose tolerance tests additionally demonstrated metabolic dysregulation in HFD mice. In addition, HFD mice exhibited hemodynamic and echocardiographic evidence of impaired diastolic and systolic function, including alterations in the cardiac output, end-diastolic pressure, end-diastolic volume and left ventricular relaxation time constant (tau) following HFD intake. Furthermore, a HFD resulted in increased ERS, and a downregulation of the autophagy and mitophagy level. The present study investigated cardiac function in obese HFD-fed mice. These results aid the pursuit of novel therapeutic targets to combat obesity-associated cardiomyopathy.

Assessing the impacts of total liquid ventilation on left ventricular diastolic function in a model of neonatal respiratory distress syndrome.

BackgroundFilling the lung with dense liquid perfluorocarbons during total liquid ventilation (TLV) might compress the myocardium, a plausible explanation for the instability occasionally reported with this technique. Our objective is to assess the impacts of TLV on the cardiovascular system, particularly left ventricular diastolic function, in an ovine model of neonatal respiratory distress syndrome.MethodEight newborns lambs, 3.0 ± 0.4 days (3.2 ± 0.3kg) were used in this crossover experimental study. Animals were intubated, anesthetized and paralyzed. Catheters were inserted in the femoral and pulmonary arteries. A high-fidelity pressure catheter was inserted into the left ventricle. Surfactant deficiency was induced by repeated lung lavages with normal saline. TLV was then conducted for 2 hours using a liquid ventilator prototype. Thoracic echocardiography and cardiac output assessment by thermodilution were performed before and during TLV.ResultsLeft ventricular end diastolic pressure (LVEDP) (9.3 ± 2.1 vs. 9.2 ± 2.4mmHg, p = 0.89) and dimension (1.90 ± 0.09 vs. 1.86 ± 0.12cm, p = 0.72), negative dP/dt (-2589 ± 691 vs. -3115 ± 866mmHg/s, p = 0.50) and cardiac output (436 ± 28 vs. 481 ± 59ml/kg/min, p = 0.26) were not affected by TLV initiation. Left ventricular relaxation time constant (tau) slightly increased from 21.5 ± 3.3 to 24.9 ± 3.7ms (p = 0.03). Mean arterial systemic (48 ± 6 vs. 53 ± 7mmHg, p = 0.38) and pulmonary pressures (31.3 ± 2.5 vs. 30.4 ± 2.3mmHg, p = 0.61) were stable. As expected, the inspiratory phase of liquid cycling exhibited a small but significant effect on most variables (i.e. central venous pressure +2.6 ± 0.5mmHg, p = 0.001; LVEDP +1.18 ± 0.12mmHg, p<0.001).ConclusionsTLV was well tolerated in our neonatal lamb model of severe respiratory distress syndrome and had limited impact on left ventricle diastolic function when compared to conventional mechanical ventilation.

Effect of ventricular relaxation performance on blood flow profiles in fontan circulation.

Flow profiles in the pulmonary veins (PVs) and arteries (PAs), Fontan conduit (conduit), and superior vena cava (SVC) were examined using phase-contrast magnetic resonance imaging. The relationship of the ratio of systolic forward flow volume and diastolic forward flow volume (FV-S/D) with ventricular relaxation time constant (tau) was then investigated. According to the flow profiles in the PVs, the forward flow volumes in diastole were dominant over those in systole. The FV-S/D was significantly negatively correlated with tau, not only in the PVs but also in the PAs and conduit. Moreover, tau was positively correlated with pulmonary wedge pressures, while pulmonary wedge pressures were significantly negatively correlated with FV-S/D in the PVs. In contrast, the FV-S/D in the SVC was also negatively correlated with tau, but the correlation coefficient of this relationship was lower than that of the other relationships. Lastly, the FV-S/D in the SVC correlated more significantly with the ejection fraction of the ventricle rather than with tau. On the basis of our findings, we believe that the flow profiles in the PVs are influenced by the ventricular relaxation performance. Moreover, the ventricular relaxation performance influences the flow profiles in the PAs and conduit, both of which are located upstream of pulmonary circulation. On the contrary, the flow profiles in the SVC seem to be influenced by ventricular contraction rather than ventricular relaxation.

Abstract 16998: Ventricular Systolic and Diastolic Dyssynchrony and Their Relationship with Ventricular Function in Patients with Single Ventricular Circulation

BACKGROUND: Recent studies highlighted importance of ventricular diastolic dyssynchrony as well as systolic dyssynchrony in the pathophysiology of adult heart failure. However, little is known about interaction between diastolic and systolic dyssynchrony and their impacts on ventricular function in pediatric patients with single ventricular circulation. METHODS: We studied 24 pediatric patients (mean age; 2.1±1.3 years) with single ventricular circulation and 12 age-matched control subjects. Transthoracic two-demensional speckle tracking echocardiography (Vivid 7, GE) was performed to assess ventricular dyssynchrony (EchoPac workstation, GE). Systolic and diastolic dyssynchrony was measured as a maximal time delay in peak systolic and early diastolic velocities of longitudinal strain at four segments. Comprehensive ventricular systolic and diastolic function was assessed by employing pressure-area relationships during preload varied by transient inferior vena caval balloon obstruction. RESULTS: Systolic and diastolic time delay were 31.8±14.5 ms and 29.2±14.6 ms respectively in single ventricular patients, and were significantly larger than in the controls (16.2±11.9 ms for systolic and 15.8±11.2 ms for diastolic, both p&lt;0.01). There was no significant correlation between systolic and diastolic dyssynchrony in the patient group. Systolic dyssynchrony was negatively correlated with ventricular contractility indexes of end-systolic elastance (r=0.34, p&lt;0.05) and maximum rate of pressure rise (r=0.585, p&lt;0.05). Diastolic dyssynchrony was positively correlated with end-diastolic pressure (r=0.719, p&lt;0.05), but not with time constant of ventricular relaxation. CONCLUSIONS: Not only systolic but also diastolic dyssynchrony has important impacts on ventricular function in patients with single ventricular circulation. These data suggest important notion that diastolic as well as systolic dyssynchrony is an important therapeutic target when considering cardiac resynchronization therapy for patients with single ventricular circulation.

Calculation of Left Ventricular Relaxation Time Constant-Tau in Humans by Continuous-Wave Doppler

Left ventricular relaxation time constant, Tau, is the best index to evaluate left ventricular diastolic function, but the measurement is only available traditionally in catheter lab. In Echo lab, several methods of non-invasive measurement of Tau have been tried since 1992, however almost all the methods are still utilizing the same formula to calculate Tau as in catheter lab, which makes them inconvenient, time-consuming and sometimes not very accurate. Based on Weiss’ formula and simplified Bernoulli’s equation, a simple method is developed by pure mathematical derivative to calculate Tau by continuous-wave Doppler in patients with mitral regurgitation.

Calculation of Left Ventricular Relaxation Time Constant-Tau in Patients With Aortic Regurgitation by Continuous-Wave Doppler

Left ventricular relaxation time constant, Tau, is the best index to evaluate left ventricular diastolic function. The measurement is only available traditionally in catheter lab. In Echo lab, several methods of non-invasive measurement of Tau have been tried since 1992, however almost all the methods are still utilizing the same formula to calculate Tau as in catheter lab, which makes them inconvenient, time-consuming and sometimes not very accurate. A simple method to calculate Tau in patients with mitral regurgitation has been developed just based on Weiss’ formula and simplified Bernoulli’s equation. Similarly, formulas are developed here by pure mathematical derivative to calculate Tau by continuous-wave Doppler in patients with aortic regurgitation.

Pancreatitis in Fontan patients is related to impaired ventricular relaxation

BackgroundPancreatitis following cardiopulmonary bypass is a well-known complication in adults undergoing cardiac surgery. However, the occurrence of pancreatitis in pediatric patients undergoing repair of congenital heart disease is under-appreciated. Post-Fontan patients are particularly prone to postoperative pancreatitis. In an effort to identify specific perioperative factors predictive of postoperative pancreatitis, we retrospectively reviewed a group of Fontan patients. MethodsFrom June 1996 to June 2001, 40 patients underwent a modified Fontan operation. Four patients developed acute pancreatitis postoperatively. The preoperative, intraoperative, and postoperative hemodynamics and ventricular function parameters were retrospectively analyzed and compared to 10 randomly selected Fontan patients who did not have pancreatitis. Preoperative echocardiographic and angiographic data, including digitized ventricular pressure tracings, were reviewed to obtain ventricular relaxation time constant (tau), pulmonary vascular resistance (PVR), ventricular end diastolic pressure (VEDP), positive dp/dt and negative dp/dt values. ResultsPatients developing acute pancreatitis had very high mortality (50%) compared to no mortality in the control group. The mean preoperative tau was significantly prolonged (41 ms vs 26 ms in control group, p < 0.001), and pre operative systemic output (Qs) lower in the pancreatitis group (mean 2.75 L/min/m2) compared with controls (Qs of 5.09 L/min/m2, p < 0.03). ConclusionsImpaired ventricular relaxation and decreased preoperative cardiac output are predictive of increased risk of postoperative pancreatitis in Fontan patients. Evaluation of preoperative diastolic function in these patients may provide additional insights in to clinical outcome following the Fontan procedure.

Noninvasive assessment of the ventricular relaxation time constant (tau) in humans by Doppler echocardiography.

The time constant of ventricular relaxation (tau) is a quantitative measure of diastolic performance requiring intraventricular pressure recording. This study validates in humans an equation relating tau to left ventricular pressure at peak -dP/dt (P0), pressure at mitral valve opening (PMV), and isovolumic relaxation time (IVRTinv). The clinically obtainable parameters peak systolic blood pressure (Ps), mean left atrial pressure (PLA), and Doppler-derived IVRT (IVRTDopp) are then substituted into this equation to obtain tau Dopp noninvasively. High-fidelity left atrial and left ventricular pressure recordings with simultaneous Doppler by transesophageal echocardiography were obtained from 11 patients during cardiac surgery. Direct curve fitting to the left ventricular pressure trace by Levenberg-Marquardt regression assuming a zero asymptote generated tau LM, the "gold standard" against which tau calc (IVRT inv/[ln(P0)-ln(PMV)]) and tau Dopp [IVRTDopp/[ln(Ps)-ln(PLA)]] were compared. For 123 cycles analyzed in 18 hemodynamic states, mean tau LM was 53.8 +/- 12.9 ms. tau calc (51.5 +/- 11 ms) correlated closely with this standard (r = .87, SEE = 5.5 ms). Noninvasive tau Dopp (43.8 +/- 11 ms) underestimated tau LM but exhibited close linear correlation (n = 88, r = .75, SEE = 7.5 ms). Substituting PLA = 10 mm Hg into the equation yielded tau 10 (48.7 +/- 15 ms), which also closely correlated with the standard (r = .62, SEE = 11.6 ms). The previously obtained analytical expression relating IVRT, invasive pressures, and tau is valid in humans. Furthermore, a more clinically obtainable, noninvasive method of obtaining tau also closely predicts this important measure of diastolic function.

Determinants of Decreased Early Ventricular Filling in Man: A Role for External Forces

The determinants of reduced early left ventricular filling and their relative importance were examined in 14 subjects with an ejection fraction > 40%. Simultaneous high-fidelity left ventricular pressure, mitral annular Doppler velocity recordings, and two-dimensional echocardiographic data were used. Pressure-volume curves were created from pressure/echocardiographic/Doppler data and the chamber stiffness constant calculated. The influence of changing filling pressure was examined by studying subjects before and after ventriculography. The ventricular relaxation time constant, chamber stiffness constant, mean right atrial pressure (an index of pericardial restraint and/or ventricular interaction), pulmonary wedge pressure, and heart rate were analyzed for their influence on Doppler filling parameters: isovolumic relaxation time, peak early (E) and atrial (A) filling velocities, and the E/A ratio. The relaxation time constant was the primary determinant of isovolumic relaxation time (r = 0.82, P<0.001). Prolonged relaxation also caused a decrease in the E/A ratio (r=0.73, P<0.001) and early filling. Peak atrial filling velocity and its integral decreased as chamber stiffness rose (P<0.005). Pulmonary wedge pressure had only a modest influence on early filling (r=0.46, P<0.05). Ventriculography did not eliminate the influence of stiffness and relaxation on filling, although it caused early filling and the E/A ratio to rise and isovolumic relaxation time to shorten. Filling became earlier with increasing right atrial pressure and upward pressure-volume curve shifts. In multivariate regression the E/A ratio was influenced independently by relaxation, filling pressure, right atrial pressure, and chamber stiffness. We conclude that isovolumic relaxation time is a useful measure of ventricular relaxation. However, the E/A ratio is too complex to allow characterization of diastolic function when used alone. Finally, pericardial restraint and/or ventricular interaction during a volume load may confound the relationship between filling pattern and intrinsic ventricular diastolic properties.

The Scientific Basis for the Relations Between Pulsed‐Doppler Transmitral Velocity Patterns and Left Heart Chamber Properties

This article presents a didactic approach toward understanding the complex relations between transmitral flow patterns and cardiac properties. We start with some observations, obtained noninvasively, from normal and diseased human hearts, and supplement them with noninvasive and invasive observations from the dog laboratory. We then formulate a conceptual approach that is consistent with a physical interpretation of the data, and that enables us to clarify the roles of the active and passive properties of the left atrium and left ventricle. These basic concepts are incorporated into a computational model wherein the properties of the cardiovascular system can be varied to simulate physiological and pathological states of diastolic function to produce normal and abnormal ventricular flow patterns. We present examples of normal hearts, pressure overload hypertrophy, dilated failing hearts, and ventricles with poor compliance but apparently normal flow patterns. Various isolated perturbations of interest were performed in each of these conditions; and finally, we studied the effects on diastolic indices of a systematic variation of the time constant of ventricular relaxation, and of cardiac output. Among the interesting findings are: flow patterns that mimic mitral stenosis can be created by the properties of the ventricle as well as by the properties of the mitral apparatus; the A/E ratio is greater than normal in the dilated ventricle and in the hypertrophied ventricle with slowed relaxation; and in both conditions, the A/E ratio also increases with decreased cardiac output. Thus, changes in stroke volume, whether due to diastolic or to systolic function, will change indices of diastolic function. Finally, in concentric hypertrophy: large increases in atrial contractility are a necessary condition for large A/E ratios; and slowed ventricular relaxation by itself is incapable of producing a slowed deceleration of early filling; incomplete relaxation and myocardial viscoelasticity are also required.

Ventricular relaxation and myocardial ischemia: a comparison of different models of tau during coronary angioplasty.

This study compares the sensitivity and variability of four models of tau, the time constant of ventricular relaxation, to detect the presence of myocardial ischemia. High fidelity left ventricular pressure recordings were obtained in ten patients undergoing coronary angioplasty at baseline, during balloon inflation, and at recovery. Four models of tau were considered: 1) a semilogarithmic, zero asymptote model (TL), 2) a semilogarithmic model using data from the first 40 ms of isovolumic relaxation (T40), 3) an exponential non-zero asymptote model (TE), and 4) a derivative non-zero asymptote model (TD). TL, T40, and TE increased significantly during inflation and returned to near baseline values at recovery. TD showed no change during inflation. Comparisons of TL, T40, and TE using the derived relaxation half-time (T1/2), failed to reveal significant differences between the models at baseline, during inflation, or at recovery. The non-zero asymptote models were associated with a greater beat-to-beat variability than the semilogarithmic models. Thus, T1/2 using the semilogarithmic zero asymptote models (TL and T40) may be more useful and consistent when measuring the rate of isovolumic relaxation during myocardial ischemia.

The early response of the systemic ventricle during transition to the Fontan circulation—an acute hypertrophic cardiomyopathy?

SummaryUsing combined epicardial echocardiography and high-fidelity intraventricular pressure recordings, the acute effects of transition to a Fontan circulation were studied in 10 patients. Measurements were made before and after cardiopulmonary bypass. The Fontan operation had no significant effect on load-dependent indices, or on a load independent index (Vmax) of ventricular systolic function. Large changes were observed in ventricular geometry. Maximum and minimum cavity dimensions were reduced, while maximum and minimum thicknesses of the posterior wall were increased.While simultaneous Doppler/intraventricular pressure measurements suggested that the compliance of the ventricle was unchanged, the pattern of atrioventricular flow changed from predominantly early diastolic (E wave) to predominantly atrial systolic (A wave) as a result of surgery in four patients. The time constant of ventricular relaxation was prolonged in all patients and five developed Doppler echocardiographic evidence of incoordinate relaxation of the ventricle, with intraventricular flow occurring during isovolumic relaxation. Thus, the Fontan operation causes acute hypertrophy of the systemic ventricle due to a sudden reduction in ventricular preload in the presence of a maintained shortening fraction. While global ventricular diastolic compliance may be unchanged by the operative procedure, filling of the ventricle during early diastole is altered as a result of incoordinate relaxation and a prolonged time constant of ventricular relaxation.

Systolic direct ventricular interaction affects left ventricular contraction and relaxation in the intact dog circulation.

Changes in right ventricular systolic function directly influence left ventricular systolic function. Most of our knowledge of this systolic direct ventricular interaction comes from studies of isolated hearts, which suggest that changes in right ventricular size only affect left ventricular systolic function at low pressures and volumes. However, almost nothing is known about systolic direct ventricular interaction in a heart functioning in situ as a part of the intact circulation. We used sudden constriction of the pulmonary artery to assess the immediate effect of a change in right ventricular pressure and contraction pattern on left ventricular contraction and relaxation on the beat following the pulmonary artery constriction in anesthetized open-chest dogs. By focusing on this first beat, we were able to avoid the confounding effect of series ventricular interaction, which changes left ventricular filling and, thus, indirectly influences left ventricular function. At baseline left ventricular end-diastolic pressure of 9.6 +/- 2.1 mm Hg (mean +/- SD), sudden pulmonary artery constriction increased left ventricular peak systolic pressure by 3 +/- 2 mm Hg (2% change), left ventricular stroke volume by 2 +/- 2 ml (8% change), and monoexponential time constant of left ventricular pressure fall during relaxation by 9 +/- 6 msec (22% change). This increased left ventricular relaxation time constant was associated with altered regional segment length changes in the posterior and anterior left ventricular free walls during relaxation. We conclude that systolic direct ventricular interaction affects left ventricular systolic function and relaxation under normal conditions in the intact circulation.

Effects of nifedipine on left ventricular distensibility, relaxation and filling dynamics during pacing-induced myocardial ischemia

Diastolic left ventricular properties were assessed in 8 patients with coronary artery disease at rest and during postpacing states before and after nifedipine (10 mg sublingually). Typical anginal pain developed in all patients during pacing tachycardia before but not after nifedipine. Postpacing increases in end-diastolic pressure (10 ± 5 [mean ± standard deviation]to 23 ± 9 mm Hg) and volume (99 ± 29 to 113 ± 27 ml) were greatly attenuated with nifedipine (13 ± 7 and 97 ± 22 ml, respectively). These responses were associated with normalization of postpacing shifts of the ventricular diastolic pressure-volume curve upward or more to the right. The time constant of ventricular relaxation was prolonged by pacing tachycardia (44 ± 10 to 62 ± 5 ms) and was reduced to the control level in postpacing beats after nifedipine. The peak rate of early ventricular filling was affected neither by pacing stress nor by nifedipine. When regional myocardial function was expressed by a radial coordinate system, the nonischemic segment responded to the control pacing with an increase in end-diastolic length and comparable augmentation of the stroke excursion, while the ischemic segment showed a marked reduction in stroke excursion with end-diastolic length unchanged. Thus, the diastolic pressure-length relation moved up to the higher portion of the single curve in the nonischemic segment, while it shifted directly upward in the ischemic segment. These responses were markedly attenuated with nifedipine. The peak rate of segmental lengthening increased in postpacing beats before and after nifedipine in the normal segment, while it decreased by pacing stress with significant improvement with nifedipine in the ischemic segment. Thus, the net global changes in left ventricular diastolic function are determined by the complex interaction of changes in the regional myocardium, and favorable effects of nifedipine on global responses to transient ischemia are largely mediated by selective improvement of the ischemic segment.

The efficacy and safety of chronic oral administration of xamoterol to patients with severe heart failure treated with ACE inhibitors.

Xamoterol 200 mg twice daily was given for 2 months to nine patients with severe heart failure already being treated with angiotensin converting enzyme (ACE) inhibitors. Left ventricular end-diastolic pressure fell from 28 to 13 mmHg and end-systolic volume fell from 115 to 106 ml m-2; indices of contractility improved and ejection fraction rose from 33 to 38%. The time constant of ventricular relaxation, T1, improved from 62 to 44 ms. Exercise tolerance improved. Thus, in this group of patients with severe heart failure, xamoterol produced benefits in systolic and diastolic function. There were no adverse effects.

Influence of acute hemodynamic changes on the normalized negative peak of the first derivative of the apex cardiogram and time constant of ventricular relaxation in dogs.

The effect of various alterations in preload, afterload and inotropic state of the left ventricle on two non-invasive indices of myocardial relaxation was studied in anesthetized dogs, in an attempt to clarify some of the determinants of myocardial relaxation. The first derivative of the displacement left apex cardiogram (dA/dt), the apex cardiogram, left ventricular pressure, the first derivative of left ventricular pressure, electrocardiogram and phonocardiogram were recorded simultaneously. The following mechanocardiographic parameters of myocardial relaxation were investigated: (1) normalized negative peak of dA/dt for simultaneous isovolumic apex cardiographic amplitude (min dA/dt/Ar). and (2) time constant of myocardial relaxation T. The non-invasive time constant was derived from a logarithmic isovolumic calibrated apex cardiographic amplitude v. time plot subsequent to min dA/dt. The indices min dA/dt/Ar and T compared with analogue parameters of left ventricular catheterization (min dP/dt/Pr and T) showed similarity in magnitude and standard deviation during various acute hemodynamic interventions. The min dA/dt/Ar was related to the level of afterload; furthermore isoprenaline accelerated relaxation as determined by the two investigated indices. During the various hemodynamic changes a high correlation existed between invasive and non-invasive indices. The results presented indicate that the apexcardiographic time constant of myocardial relaxation may be a reliable index for ventricular relaxation since it is independent of pre- and afterload, whereas min dA/dt/Ar are load-dependent.