Left Ventricular Isovolumic Pressure Decay Research Articles

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.

Pyridoxamine protects against mechanical defects in cardiac ageing in rats: studies on load dependence of myocardial relaxation.

New FindingsWhat is the central question of this study?This study aimed to investigate the hypothesis that pyridoxamine, one of the three natural forms of vitamin B6, can protect against myocardial relaxation of senescent animals by targeting arterial stiffening and contractile dysfunction of the left ventricle.What is the main finding and its importance?We found that treating the senescent rats with pyridoxamine for 5 months might improve myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor.Our team demonstrated in the past that pyridoxamine attenuated arterial stiffening by targeting the pathogenic formation of glycated collagen cross-links in aged rats. Herein, we examined whether pyridoxamine therapy can protect against mechanical defects in myocardial relaxation by improving arterial wave properties and cardiac contractile performance in senescent animals. Fifteen-month-old male Fisher 344 rats were treated daily with pyridoxamine (1 g l−1 in drinking water) for 5 months and compared with age-matched untreated control animals (20 months old). Arterial wave properties were characterized by wave transit time (τw) and wave reflection factor (Rf). We measured the contractile status of the myocardium in an intact heart as the left ventricular (LV) end-systolic elastance (Ees). Myocardial relaxation was described according to the time constant of the LV isovolumic pressure decay (τe). Pyridoxamine therapy prevented the age-associated prolongation in LV τe and the diminished Ees in senescent rats. The drug also attenuated the age-related augmentation in afterload imposed on the heart, as evidenced by the increased τw and decreased Rf. We found that the LV τe was significantly influenced by both the arterial τw and Rf (τe = 16.3902 + 8.3123 × Rf − 0.4739 × τw; r = 0.7048, P < 0.005). In the meantime, the LV τe and the LV Ees showed a significant inverse linear correlation (τe = 13.9807 − 0.0068 × Ees; r = 0.6451, P < 0.0005). All these findings suggested that long-term treatment with pyridoxamine might ameliorate myocardial relaxation rate, at least partly through its ability to enhance myocardial contractile performance, increase wave transit time and decrease wave reflection factor in aged rats.

Myocardial Relaxation, Restoring Forces, and Early-Diastolic Load Are Independent Determinants of Left Ventricular Untwisting Rate

Peak left ventricular (LV) untwisting rate (UTR) has been introduced as a clinical marker of diastolic function. This study investigates if early-diastolic load and restoring forces are determinants of UTR in addition to the rate of LV relaxation. In 10 anesthetized dogs we measured UTR by sonomicrometry and speckle tracking echocardiography at varying LV preloads, increased contractility, and myocardial ischemia. UTR was calculated as the time derivative of LV twist. Because preload modified end-diastolic twist, LV systolic twist was calculated in absolute terms with reference to the end-diastolic twist configuration at baseline. Relaxation rate was measured as the time constant (τ) of LV isovolumic pressure decay. Early-diastolic load was measured as LV pressure at the time of mitral valve opening. Circumferential-longitudinal shear strain was used as an index of restoring forces. In a multivariable mixed model analysis a strong association was observed between UTR and LV pressure at the time of mitral valve opening (parameter estimate [β]=6.9; P<0.0001), indicating an independent effect of early-diastolic load. Furthermore, the associations between UTR and circumferential-longitudinal shear strain (β=-11.3; P<0.0001) and τ (β=-1.6, P<0.003) were consistent with independent contributions from restoring forces and rate of relaxation. Maximal UTR before mitral valve opening, however, was determined only by relaxation rate and restoring forces. The present study indicates that early-diastolic load, restoring forces, and relaxation rate are independent determinants of peak UTR. However, only relaxation rate and restoring forces contributed to UTR during isovolumic relaxation.

Index-Beat Assessment of Left Ventricular Systolic and Diastolic Function during Atrial Fibrillation Using Myocardial Strain and Strain Rate

Accurate assessment of left ventricular (LV) function in patients with atrial fibrillation (AF) remains difficult, mainly because of the beat-to-beat variability of many echocardiographic parameters. The aim of this study was to assess the hypothesis that LV function can be estimated from an index-beat echocardiographic assessment in patients with AF using myocardial strain and strain rate. A prospective study was conducted to assess 25 patients with AF (mean age, 66 ± 10 years). Peak systolic longitudinal strain (LS) and peak diastolic longitudinal strain rate (dSR) were measured using two different methods: (1) mean LS and dSR, the averages of instantaneous LS and dSR over 10 sec, and (2) index-beat LS and dSR, calculated when the ratio of the preceding (RR1) to the pre-preceding (RR2) interval was 1 (range, 0.96-1.04). These variables were compared with simultaneously measured LV pressure parameters using Millar catheters. There was a positive linear relationship between mean LS and index-beat LS at RR1/RR2 = 1 (r = 0.94, P < .001) and a positive linear relationship between mean dSR and index-beat dSR (r = 0.69, P < .001). Index-beat LS was correlated with the maximal positive derivative of LV pressure (peak +dP/dt) (r = -0.73, P < .001). Index-beat dSR was correlated with the time constant of isovolumic LV pressure decay (τ) (r = -0.63, P < .001). To investigate the independent predictors of τ, a stepwise multilinear regression analysis showed that index-beat dSR was the best predictor of τ. Index-beat parameters accurately reflect the mean values of parameters in patients with AF. These noninvasively obtained index-beat parameters are useful to assess surrogate LV function even in patients with AF.

Early return of augmented wave reflection impairs left ventricular relaxation in aged Fisher 344 rats

Left ventricular (LV) relaxation is influenced by vascular loads imposed on the heart. The current study investigated the influence of the timing and magnitude of arterial wave reflection on LV isovolumic pressure relaxation, with a specific focus on the aging process. Fisher 344 rats aged 6, 18, and 24months were anesthetized and thoracotomized. Arterial wave reflection was characterized by wave transit time (τw) and wave reflection factor (Rf) using the impulse response of the filtered aortic input impedance spectra. Indices of LV pressure relaxation included peak –dPLV/dt and the isovolumic relaxation time constant (τe). The vascular dynamic condition in the rats was characterized by (1) a progressive increase in Rf and decrease in τw associated with age, especially at 24months; and (2) a decline in aortic compliance (Cm). Changes in LV relaxation consisted of a fall in peak –dPLV/dt and a rise in LV τe with age. Taking LV τe as the dependent variable and arterial Rf and τw as the two independent variables, multiple linear regression was employed to fit the data. The correlation among the three parameters reached significance (τe =11.885+5.350×Rf−0.213×τw; r=0.5823, p<0.05). This finding indicated that as arterial τw shortened and arterial Rf was augmented with age, LV τe became more prolonged and late pressure relaxation slowed. Thus, the heavy reflection intensity with early return of the pulse wave reflection might account for the age-related deterioration in LV isovolumic pressure decay.

Non-invasive assessment of left ventricular relaxation during atrial fibrillation using mitral flow propagation velocity

To elucidate the usefulness of the early diastolic mitral flow propagation velocity (V(p)) obtained from colour M-mode Doppler for non-invasively assessing left-ventricular (LV) relaxation during atrial fibrillation (AF). Ten healthy adult dogs were studied to correlate V(p) with the invasive minimum value of the first derivative of LV pressure decay (dP/dt(min)) and the time constant of isovolumic LV pressure decay (tau) at baseline, during rapid and slow AF, and during AF after inducing myocardial infarction. There were significant positive and negative curvilinear relationships between V(p) and dP/dt(min) and tau, respectively, during rapid AF. After slowing the ventricular rate, the average value of V(p) increased, while dP/dt(min) increased and tau decreased. After inducing myocardial infarction, the average value of V(p) decreased, while dP/dt(min) decreased and tau increased. The non-invasively obtained V(p) evaluates LV relaxation even during AF regardless of ventricular rhythm or the presence of pathological changes.

Estimation of the left ventricular relaxation time constant τ requires consideration of the pressure asymptote.

The left ventricular isovolumic pressure decay, obtained by cardiac catheterization, is widely characterized by the time constant τ (tau) of the exponential regression p(t)= P¥+(P0–P¥)exp(–t/τ). However, several authors prefer to prefix P¥=0 instead of coestimating the pressure asymptote empirically; others present τ values estimated by both methods that often lead to discordant results and interpretation of lusitropic changes. The present study aims to clarify the relations between the τ estimates from both methods and to decide for the more reliable estimate. The effect of presetting a zero asymptote on the τ estimate was investigated mathematically and empirically, based on left ventricular pressure decay data from isolated ejecting rat and guinea pig hearts at different preload and during spontaneous decrease of cardiac function. Estimating τ with preset P¥=0 always yields smaller values than the regression with empirically estimated asymptote if the latter is negative and vice versa. The sequences of τ estimates from both methods can therefore proceed in reverse direction if τ and P¥ change in opposite directions between the measurements. This is exemplified by data obtained during an increasing preload in spontaneously depressed isolated hearts. The estimation of the time constant of isovolumic pressure fall with a preset zero asymptote is heavily biased and cannot be used for comparing the lusitropic state of the heart in hemodynamic conditions with considerably altered pressure asymptotes.

Tissue Doppler-derived myocardial acceleration for evaluation of left ventricular diastolic function

Our purpose was to evaluate a tissue Doppler-based index-peak myocardial acceleration (pACC)-during isovolumic relaxation and in evaluating left ventricular (LV) diastolic function. Simple, practical indexes for diastolic function evaluation are lacking, but are much desired for clinical evaluation. We examined eight sheep by using tissue Doppler ultrasound images obtained in the apical four-chamber views to evaluate mitral valve annular velocity at the septum and LV wall. The pACC thus derived was analyzed during isovolumic relaxation (IVRT) and during the LV filling period (LVFP). We then changed the hemodynamic status of each animal by blood administration, dobutamine, and metoprolol infusion. We compared the pACC values during IVRT and LVFP over the four different hemodynamic conditions with a peak rate of drop in LV pressure (-dP/dt(min)) and the time constant of LV isovolumic pressure decay (tau), as measured with a high-frequency manometer-tipped catheter. The pACC of the septal side of the mitral valve annulus during IVRT showed a good correlation with -dP/dt(min) (r = -0.80, p < 0.0001) and tau (r = -0.87, p < 0.0001). The mean left atrial pressure (LAP) correlated well with the septal side pACC during LVFP (r = 0.81, p < 0.0001). There was a weak correlation between the mitral valve annulus pACC at the LV lateral wall and mean LAP. The pACC during IVRT is a sensitive, preload-independent marker for evaluation of LV diastolic function. In addition, pACC during LVFP correlated well with mean LAP.

Ransacking the Curve of Cardiac Isovolumic Pressure Decay by Logistic-and-Oscillation Regression

The decelerative part of the left ventricular isovolumic pressure decay is an important phase to make the heart ready for diastolic refill (lusitropy). Its widely used characterization by an exponential regression with zero pressure asymptote or coestimated asymptote provides empirically biased time constant estimates because of significant deviations of the pressure decay from exponentiality. We systematically analyzed the regression residua of these pressure decays in isolated ejecting rat, guinea pig, and ferret hearts. A four-parametric logistic (tangens hyperbolicus) function, together with a superimposed acustomechanic oscillation, yields normally distributed residua with standard regression error typically less than one per cent of the initial pressure; this is the first model with proved unbiased and statistically complete regressive extraction of the information provided by the time course of pressure decay. Equal values of the lusitropic parameters (logistic time constant and pressure asymptote) were estimated even after the oscillatory component was removed from the regression model. Reliable estimates of the frequency, but not of the amplitude, can be obtained by fitting the oscillation model to the residua provided by the logistic; this two-step method is statistically weaker than the full one-step model, but it reduces computational effort. In conclusion, the four-parametric logistic, but not a three-parametric exponential or logistic model, suffices to obtain unbiased lusitropic parameters characterizing the left ventricular isovolumic pressure decay of small animal hearts.

Compensatory responses of left atrial conduit flow to atrial fibrillation with acute myocardial infarction in a canine model

The aim of this study was to examine the interaction of acute atrial fibrillation (Af) and acute myocardial infarction (AMI) on left atrial (LA) and left ventricular (LV) filling in atrioventricular (A-V) sequential paced, open chest, anesthetized dogs. Left atrial conduit function was determined from pulmonary venous flow (PVF) and detailed analysis of early diastolic flow with the use of micromanometers and transmitral Doppler echocardiography. We studied 8 dogs with regular ventricular rates to avoid the confounding effect of ventricular arrhythmia in Af. In the control stage, Af increased the diastolic PVF volume to the left atrium compared with that during regular A-V pacing (from 0.58 +/- 0.11 mL/beat to 0.70 +/- 0.13 mL/beat, P <.05), as a compensatory response to the impaired systolic PVF volume (from 0.56 +/- 0.12 mL/beat to 0.41 +/- 0.11 mL/beat, P <.05). As a result, cardiac output was maintained. However, in the AMI stage, Af decreased cardiac output (from 0.95 +/- 0.32 L/min to 0.80 +/- 0.23 L/min, P <.05 versus AMI with A-V pacing), and decreased diastolic PVF volume (from 0.46 +/- 0.13 mL/beat to 0.33 +/- 0.14 mL/beat, P <.05 versus AMI with A-V pacing). These changes were associated with a prolonged LV isovolumic pressure decay rate. Our study demonstrates that Af does not affect cardiac output in the setting of normal LV function at a controlled ventricular rate because enhanced LA conduit flow compensates for impaired LA reservoir function. In contrast, in the setting of AMI, the compensatory response to Af is attenuated because of abnormal LV relaxation, resulting in a decrease in cardiac output.

Usefulness of early diastolic flow propagation velocity measured by color M-mode doppler technique for the assessment of left ventricular diastolic function in patients with hypertrophic cardiomyopathy

Flow propagation velocity (FPV) of left ventricular (LV) filling flow has been shown to be a useful index for the evaluation of LV diastolic function, which is relatively independent of preload in myocardial infarction and dilated cardiomyopathy, but the usefulness of FPV for hypertrophic cardiomyopathy (HCM) has not yet been determined. In 23 HCM patients and 26 control subjects, peak transmitral flow velocities in early diastole (E) and during atrial contraction (A), E/A ratio, deceleration time of E velocity, and isovolumic relaxation time were measured with the conventional Doppler technique, and FPV was measured from color M-mode Doppler images of LV filling flow. The time constant of LV isovolumic pressure decay (tau) was measured by a micro-manometer-tipped catheter in all HCM patients and 13 control subjects. Flow propagation velocity was significantly lower and deceleration time was significantly greater in HCM patients than in the control subjects, though no significant differences were observed in the other noninvasive indexes. Tau was significantly prolonged in HCM patients compared with that of control subjects (54 ± 12 cm/s and 32 ± 7 cm/s, respectively; P <.0001). While the conventional indexes did not correlate with tau among the 36 patients in whom invasive studies were performed, FPV correlated well with tau (r = −0.76, P <.0001). Flow propagation velocity is a useful noninvasive index for the assessment of LV diastolic function in patients with HCM. (J Am Soc Echocardiogr 2000;13:801-8.)

Postextrasystolic left ventricular isovolumic pressure decay is not monoexponential.

The relationship between the left ventricular (LV) relaxation time constant and early diastolic filling is not fully defined. This study provides additional evidence that LV isovolumic pressure fall in the normal intact heart in response to certain interventions is not adequately described by a model of monoexponential decay and that its relationship to filling is complex. To gain further insight into the relationship between LV relaxation and early rapid filling we measured LV isovolumic relaxation rate, peak early filling velocity (E), LV volumes, and transmitral pressures at baseline and in the first postextrasystolic beat after a short-coupled extrasystole in 9 anesthetized dogs. Postextrasystolic isovolumic relaxation rate was slowed as measured by 3 commonly used time constants, while E was increased 32%. LV contractility and peak pressure were also increased, while LV end-systolic volume was decreased. LV minimum pressure was deceased, while the early diastolic transmitral pressure gradient was increased. Although all relaxation time constants measured over the entire isovolumic relaxation phase indicated slowed relaxation, direct measurement of isovolumic relaxation time indicated no change in relaxation rate. Calculation of the time constants and direct measurement of isovolumic relaxation time during early isovolumic pressure decay indicated slowed postextrasystolic pressure decay rate compared with baseline, while calculation of time constants and direct measurement of isovolumic relaxation time during late isovolumic relaxation indicated augmented postextrasystolic pressure decay rate versus baseline. This non-exponential behavior of LV isovolumic pressure decay in postextrasystolic beats after short-coupled extrasystoles provides further evidence that the relationship that exists between ventricular relaxation and early filling is not simple. The results are interpreted in terms of current theoretical formulations that attribute control of myocardial relaxation to the interaction between inactivation-dependent and load-dependent mechanisms.

Correlation between left ventricular contractility and relaxation in patients with idiopathic dilated cardiomyopathy.

It is not fully understood whether alterations in left ventricular (LV) relaxation in patients with idiopathic dilated cardiomyopathy (DCM) precede or follow alterations in LV systolic function. Accordingly, we investigated the relationship between LV systole and diastolic relaxation in patients with DCM using LV pressure-volume analysis. Hemodynamic data were collected for 38 consecutive patients with DCM in normal sinus rhythm and in the resting steady state (New York Heart Association functional class II to III). Continuous simultaneous pressure-volume relationships were obtained by conductance catheter. Left ventricular end-systolic elastance (Ees) was determined during transient occlusion of the inferior vena cava. Left ventricular ejection fraction, peak negative dP/dt, and peak positive dP/dt were depressed (31 +/- 11%, -1242 +/- 351 mmHg/s, and 1118 +/- 253 mmHg/s, respectively). The LV end-diastolic volume index, the time constants of isovolumic LV pressure decay TL and TD were increased (141 +/- 38 ml/m2, 54 +/- 14 ms, and 69 +/- 17 ms, respectively). Ees was markedly depressed (0.9 +/- 0.5 mmHg/ml) and was not correlated with established systolic or diastolic indices except for peak positive dP/dt. Our results showed that abnormalities of relaxation were not correlated with contractile dysfunction in patients with DCM in the resting steady state; however, most patients (79%) had both prolonged relaxation and extremely depressed contractility. Abnormal relaxation may have been transient or compensated in some patients (21%) with DCM who had preserved relaxation despite severely depressed contractility.

Blood cardioplegia in the senescent heart

As an increasingly aged population undergoes cardiac surgery, myocardial protective strategies must address the fundamental differences between adult and senescent myocardium. In a test of the hypothesis that senescent myocardium is less tolerant of cardioplegic arrest, adult (0.5 to 1.0 years) and senescent (6 to 9 years) sheep underwent 55 minutes of hypothermic blood cardioplegic arrest. A 5-minute dose of terminal warm blood cardioplegic solution was administered followed by 30 minutes of vented reperfusion. Left ventricular volume was monitored by means of sonomicrometric crystals in three orthogonal planes. Myocardial function was assessed with the preload recruitable stroke work relationship. Diastolic function was assessed with two techniques: the “stiffness” coefficient ( β ), derived from the exponential end-diastolic pressure-volume relationship, and the time constant of isovolumic left ventricular pressure decay (tau). Data were acquired before arrest and after the reperfusion period. Contractility in the adult hearts was well preserved (preload recruitable stroke work: 63.7 ± 6.1 versus 56.8 ± 4.1 mJ/beat per milliliter per 100 gm, prearrest versus postarrest, p = not significant). In contrast, senescent heart contractility was poorly preserved (56.8 ± 4.1 versus 35.4 ± 4.2 mJ/beat per milliliter per 100 gm, p < 0.025). Early diastolic relaxation (tau) was prolonged in the adult hearts (42.5 ± 3.3 versus 48.8 ± 3.5 msec prearrest versus postarrest, p < 0.05), whereas the senescent hearts were essentially unchanged (49.3 ± 3.1 versus 52.3 ± 4.5 msec, p = 0.35). Myocardial stiffness ( β ) was unchanged in both groups. When compared with adult hearts, contractility in senescent hearts is poorly preserved after cold blood cardioplegic arrest. Active diastolic relaxation, however, is more prolonged in adult hearts. Passive diastolic properties are unchanged in both groups. Because there are specific age-related differences in tolerance to cardioplegic arrest, extrapolation of myocardial protective strategies from studies in adult hearts to elderly patients may not be appropriate. (J T HORAC C ARDIOVASC S URG 1995; 109: 269-74)

Heart rate and force-frequency effects on diastolic function of the left ventricle in exercising dogs.

Previous studies from our laboratory have shown pronounced augmentation of the force-frequency relation on myocardial contraction during exercise, but the influence of this effect on diastole has not been investigated. Accordingly, the effect of changing heart rate on left ventricular (LV) relaxation, filling dynamics, and pressure-volume relations during exercise was studied in eight conscious dogs. The exercise heart rate was slowed from 208 +/- 21 (SD) to 163 +/- 11 beats per minute by injection of a specific sinus node inhibitor (UL-FS 49, or zatebradine, 0.6 mg/kg) during continuous exercise. Heart rate was then abruptly restored to the predrug level by atrial pacing during continued exercise. LV volume was calculated by use of implanted ultrasonic crystals, and LV pressure was determine with an implanted micromanometer. Comparing conditions after pacing back to a heart rate of 210 beats per minute with those obtained when the heart rate was slowed by atrial pacing, LV dP/dtmax was increased by 27% at the higher rate (P < .01), despite a marked decrease in LV end-diastolic pressure (24 +/- 4 versus 10 +/- 5 mm Hg, P < .01) and the time constant of isovolumic LV pressure decay (tau) was significantly shortened (19 +/- 5 versus 14 +/- 4 milliseconds, P < .01). The peak rapid filling rate in early diastole (PFR) was not significantly changed by increasing the heart rate, since it was maintained at the slower rate. During exercise, at the slowed heart rate the early portion of the diastolic pressure-volume curve was significantly shifted upward and to the right compared with that at the physiological heart rate, but the late portion of the curve was unchanged. These data indicate that the negative inotropic effect of the force-frequency relation when heart rate was slowed during exercise caused pronounced impairment of LV relaxation and early filling dynamics. Conversely, an important component of the pronounced improvement of diastolic ventricular function during normal exercise was shown to result from exercise-induced enhancement of the positive inotropic effects of the force-frequency relation on myocardial contraction and relaxation.

Left ventricular filling measured by Doppler echocar diography during dynamic exercise in patients with myocardial infarction

To assess left ventricular diastolic properties in response to dynamic exercise, mitral inflow velocity integrals were measured by pulsed-wave Doppler echocardiography in ten patients with myocardial infarction and in ten normal subjects, and simultaneous left ventricular pressure was obtained with micromanometry in the patients. Early filling velocity integrals were maintained in the patients during exercise. Late filling velocity integrals were not augmented during exercise in the patients, but were increased in the normal subjects. In the patients, there was an increase in mitral valve opening pressure, left ventricular end-diastolic pressure, and the time constant of left ventricular isovolumic pressure decay. The lowest diastolic pressure and the number of time constants that had elapsed before the lowest diastolic pressure remained unchanged. These results show that in patients with myocardial infarction, early filling is maintained by an increase in driving pressure during exercise, despite incomplete relaxation. Augmentation of late filling, seen in normal subjects, is impaired in patients with myocardial infarction, probably due to an increase in left ventricular stiffness.

Early left ventricular filling: An approach to its multifactorial nature using a combined hemodynamic-Doppler technique

It has recently been shown that early left ventricular filling is a multifactorially determined phenomenon, the characteristics of which are highly dependent on relative changes in any of its determinants (left ventricular end-systolic volume, the constant of isovolumic left ventricular pressure decay, left atrial pressure at the onset of mitral valve flow, and left ventricular and left atrial compliance). Thus changes in the pattern of filling do not necessarily reflect changes in diastolic properties; they might instead simply reflect changes in loading conditions. To define a clinically implemented approach where the contribution of each of the covariates of early filling to the filling process and their modification by load manipulation could be assessed, nine patients with ischemic heart disease underwent simultaneous assessment of micromanometer left ventricular pressure and two-dimensional echo-guided Doppler mitral flow velocity before and after administration of nitroglycerin (0.2 mg intravenously). Nitroglycerin induced a significant reduction in the early-filling E wave (from 41 ± 5 cm/sec to 32 ± 7 cm/sec; p < 0.002), whereas the late-filling A wave did not change (from 51 ± 12 cm/sec to 55 ± 9 cm/sec; p = 0.15), so that the E/A ratio decreased 27 ± 16% ( p = 0.016). End-systolic volume, the constant of isovolumic left ventricular pressure decay, and left atrioventricular pressure crossover at the onset of mitral flow decreased (from 49 ± 37 to 43 ± 38 ml [ p = 0.016], from 52 ± 14 to 47 ± 13 msec [ p = 0.016], and from 19 ± 10 to 12 ± 7 mm Hg [ p = 0.08], respectively), whereas left atrial compliance (defined as stroke volume/atrioventricular pressure crossover) and left ventricular compliance (computed as change in volume/change in pressure at early and late diastole) did not change ( p = 0.15 and p = 0.38, respectively); the diastolic pressure-volume relationship, however, was displaced slightly leftward and markedly downward, suggesting relief of pericardial constraint. A multilinear regression analysis, performed with pooled data at baseline and during infusion of nitroglycerin in each patient, identified left atrioventricular pressure crossover at the onset of mitral flow as the only significant predictor ( p < 0.02) of peak E wave velocity in the circumstances considered. Thus the interaction among covariates of early left ventricular filling and the relationship between filling and diastolic left ventricular and left atrial properties can be addressed with relative ease by means of this clinically implemented approach, in an effort to sort out the contribution of each cofactor to such a complex event.

Myocardial Contractile Behavior of a New Sotalol Derivative

The effects of E4031, a new class III antiarrhythmic agent similar to sotalol, were tested in isometrically contracting rabbit papillary muscles and in anesthetized, open-chest dogs. In papillary muscles, E4031 caused a modest dose-dependent increase of 26 +/- 8% in developed tension and 38 +/- 8% in its maximal rate of rise. Since there was no significant change in the maximal rate of relaxation, the ratio between both maximal velocities increased from 0.92 +/- 0.03 to 1.19 +/- 0.10. Time to peak tension did not change significantly, whereas time to half relaxation increased from 72 +/- 3 to 85 +/- 4 ms. The effective refractory period in the rabbit papillary muscles increased from 179 +/- 10 to 414 +/- 45 ms. In the open-chest dog, the i.v. administration of E4031 did not induce significant changes in heart rate, mean arterial pressure, or left ventricular end diastolic pressure. +dP/dt increased from 1,839 +/- 162 to 2,470 +/- 247 mm Hg/s with no significant change in -dP/dt after 100 micrograms/kg of E4031. Consequently, (+dP/dt)/(-dP/dt) increased from 0.97 +/- 0.07 to 1.18 +/- 0.08. To further evaluate the effects of E4031 on myocardial relaxation, the time constant of isovolumic left ventricular pressure decay was measured by two different methods (tau 1 and tau 2) before and after administering 10 micrograms/kg E4031. Tau 1 increased from 27 +/- 1.8 to 33 +/- 1.6 ms and tau 2 increased from 30 +/- 2.3 to 41 +/- 3.3 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Negative lusitropic effect of DPI 201-106 and E4031. Possible role of prolonging action potential duration

In open-chest anesthetized dogs, the time constant of isovolumic left ventricular pressure decay increased following the intravenous administration of either E4031, a class III antiarrhythmic agent which acts by K+ channel blockade, or DPI 201-106 (DPI), a cardiotonic agent which acts by delaying Na+ channel inactivation. In addition to prolonging cardiac refractoriness, both E4031 and DPI increased left ventricular +dP/dt but without significantly altering -dP/dt. Consequently, the value of the ratio (+dP/dt)/(-dP/dt) increased. There were no significant changes in heart rate, mean arterial pressure, or left ventricular end diastolic pressure. Since both E4031 and DPI prolonged the action potential duration (APD) and the refractory period, and slowed relaxation in vivo, the possibility of a causal link between these effects was further investigated under in vitro conditions. In isometrically contracting rabbit papillary muscles, E4031 and DPI increased peak developed tension (DT) and its maximal rate of rise (+T). Since the maximal rate of fall of DT (-T) did not increase by the same factor that +T increased, the value of the ratio +T/-T increased. Time to half relaxation increased, whereas time to peak tension was not significantly changed by either E4031 or DPI. These negative lusitropic effects produced by E4031 or DPI were not observed when equivalent increases in contractility were produced by increasing the extracellular Ca2+ concentration. The effective refractory period measured in the papillary muscles increased following superfusion with either of the two drugs, consistent with their known ability to increase APD. A causal link between the prolongation of APD and the negative lusitropic effects of E4031 and DPI is postulated as the possible mechanism.

Diastolic function after cardiac and heart-lung transplantation.

The mechanical efficiency of left ventricular contraction and relaxation, the asynchrony of the onset of left ventricular relaxation, the time constant of left ventricular isovolumic pressure decay, and left ventricular chamber and myocardial stiffness were analysed in 32 patients after cardiac (24) and heart-lung transplantation (8). After cardiac transplantation left ventricular myocardial stiffness was increased and a mild degree of incoordinate contraction and relaxation was seen. In contrast, after heart-lung transplantation diastolic function was almost normal. Impairment of passive diastolic properties was significantly related to the ischaemic time of the donor heart and the donor's age. The index of left ventricular asynchrony was related to the ischaemic time and the recipient's age. The interval between transplantation and study did not influence the number of rejection episodes. This study confirms the presence of diastolic dysfunction after cardiac transplantation. Impairment of diastolic function seems to be related to the ischaemic time of the donor heart and to a mismatch between the size of the donor heart and the recipient's needs.