Left Ventricular Relaxation Rate Research Articles

Effects of direct-current electrical shocks on systolic and diastolic left ventricular function in dogs

Although direct-current (DC) electrical shocks do not significantly alter left ventricular systolic performance, their effects on ventricular diastolic properties and the role of sympathetic stimulation in maintaining postshock contractility are unknown. Accordingly, we studied both diastolic and systolic left ventricular performance in seven open-chest dogs before and after three consecutive 50 joule DC shocks applied directly to the heart. High-fidelity left ventricular pressure and segmental dimensions were recorded as pressure was varied systematically under conditions of beta-adrenergic blockade. The exponential left ventricular end-diastolic pressure-segment length relationship was not significantly altered by electrical shocks. Likewise, pre- and postshock beats matched for loading conditions did not differ in peak positive dP dt , end-systolic segment length, or percentage of segment shortening, although mean normalized shortening rate decreased by approximately 11% ( p < 0.05). However, the time constant (T) for isovolumic pressure fall, an index of the rate of left ventricular relaxation, increased after shocks in all animals (T = 42.2 ± 5.3 and 51.1 ± 7.0 msec before and after shock, respectively; ( p < 0.01). We conclude that high-energy electrical shocks applied directly to the heart cause modest slowing of left ventricular relaxation but do not have important effects on left ventricular compliance or on systolic myocardial performance. These data suggest that DC shocks have only minor functional consequences when applied to normal hearts, even when sympathetic compensation is prevented.

Myocardial relaxation. VI. Effects of beta-adrenergic tone and asynchrony on LV relaxation rate

We studied the effect of left ventricular (LV) asynchrony and alterations in beta-adrenergic tone on the systolic load (pressure) dependency of LV isovolumic relaxation rate in anesthetized dogs. The time constant (T) of isovolumic exponential pressure decline was used as an index of relaxation rate. Variably afterloaded LV contractions resulted in a progressive increase in LV end-systolic pressure from 124 +/- 6 in the control beat to 176 +/- 11 mmHg in the third beat and a progressive lengthening of T from 19 +/- 2 to 30 +/- 4 ms. The direct relation between LV end-systolic pressure and T was nearly linear (r = 0.98), and the slope (k) of this relation was taken to reflect the systolic load dependency of T. Administration of isoproterenol (n = 6) produced a decrease in k from 0.11 +/- 0.02 to 0.08 +/- 0.02 (P less than 0.05); with propranolol (n = 6), k increased from 0.08 +/- 0.02 to 0.27 +/- 0.04 (P less than 0.01). Right ventricular epicardial pacing (n = 6) produced an asynchronous LV contraction and an increase in k from 0.09 +/- 0.02 (atrial pacing) to 0.25 +/- 0.04 (P less than 0.01). These studies confirm the dependency of LV relaxation rate on systolic loads and indicate that this form of load-dependent relaxation can be modified by alterations in beta-adrenergic tone and LV asynchrony. The observed alterations suggest the importance of temporal dispersion of the contraction-relaxation sequence as a mechanism responsible for disturbed relaxation.

Pathophysiology of the hypertrophied heart in man.

Increase in sympathetic drive, the Frank-Starling effect and myocardial hypertrophy represent the three compensatory mechanisms in chronic mechanical overloading of the heart. Chronic pressure overload is associated with concentric and chronic volume overload with eccentric hypertrophy. The changes in ventricular geometry have an important influence on the ejection dynamics of the heart; the magnitude of fiber shortening is the predominant mechanism for systolic reduction of cavity size in eccentric hypertrophy whereas in concentric hypertrophy the contribution of systolic wall thickening to ejection becomes very important. The main abnormality of diastolic function in patients with left ventricular (LV) hypertrophy is the increase of chamber stiffness indicated by the steepened slope of the diastolic pressure-volume relationship. In contrast LV diastolic myocardial stiffness as evaluated from the stress-strain relationship remains relatively unaltered in hypertrophy unless there is massive admixture of fibrosis in the LV wall (congestive cardiomyopathy). Finally LV relaxation (rate of pressure decay) is often impaired in hypertrophied states although the relationship of abnormalities of relaxation to alterations of systolic function remains to be established. There has been considerable debate whether in secondary LV hypertrophy from chronic pressure or volume overload myocardial contractility is normal or depressed. We have recently shown that in patients with myocardial hypertrophy from aortic stenosis ejection phase indexes of contractility are correlated inversely to peak systolic wall stress and that this relationship is modulated according to the actual inotropic state. The patients on the downward shifted curve (depressed contractile state) had a significantly increased LV angiographic mass. Thus advanced LV hypertrophy in chronic pressure overload appears to be associated with compromised contractile state. The structural and metabolic abnormalities which may be ultimately responsible for the depression of contractility of the hypertrophied human myocardium encompass the following findings: reduced intracellular volume fraction of myofibrils; massive increase of the average fiber diameter and increased variability of the thickness of the individual fibers and reduced activity of the myofibrillar ATPase.

Relationship between changes in left ventricular inotropic state and relaxation in normal subjects and in patients with coronary artery disease.

The aim of the study was to examine the changes in left ventricular (LV) relaxation rate induced by variations in inotropic state. Eight normal subjects and 29 patients with coronary artery disease (CAD) were studied. First, we used interventions that increase myocardial calcium influx (atrial pacing or postpacing beat) or decrease it (intracoronary injection of nifedipine). Relaxation rate was estimated from the time constant (T1) of isovolumic LV pressure fall during the fist 40 msec after peak negative dP/dt. Under basal conditions, T1 was impaired in CAD patients (58 vs 43 msec; p less than 0.01), despite similar heart rate, LV pressures and peak positive dP/dt (1620 vs 1787 mm Hg/sec; NS). During atrial pacing at 135 +/- 7 beats/min, peak positive dP/dt increased to 2220 mm Hg/sec in 11 CAD patients and to 2256 mm Hg/sec in eight normal subjects. T1 decreased more in CAD patients than in normal subjects (17 vs 7 msec; p less than 0.01). T1 changes also differed in the postpacing beat between CAD patients and normal subjects (-6 vs 5 msec; p less than 0.01) or when nifedipine was injected during the pacing (4 vs 20 msec; p less than 0.01). Intravenous calcium injection during atrial pacing in another group of 18 CAD patients further improved peak positive dP/dt and T1 (-3 msec; p less than 0.05) and normalized the changes in relaxation during the postpacing heart. Our data indicate that a variable coupling between LV inotropic state and relaxation rate exists in man during changes in calcium influx and that this coupling is abnormal in CAD patients.

Volume loading slows left ventricular isovolumic relaxation rate. Evidence of load-dependent relaxation in the intact dog heart.

Volume loading slows left ventricular isovolumic relaxation rate. Evidence of load-dependent relaxation in the intact dog heart.

Impaired cardiac contractile response to isoproterenol in the spontaneously hypertensive rat.

To test the ability of the hypertrophied ventricle to increase its contractility in response to sympathetic stimulation, we compared the chronotropic, inotropic, and relaxation responses to graded in fusions of isoproterenol in spontaneously hypertensive rats (SHR) with responses of matched Wistar-Kyoto (WKY) controls. A closed-chested, direct ventricle puncture was used for the study. The SHR required a higher threshold dose (0.04 vs 0.01 micrograms/kg/min) for a significant chronotropic response, and their maximal response of heart rate was smaller than in WKY (delta HR = +12.5 +/- 5.4 vs +22.8 +/- 10.7 beats/min, p less than 0.01). Contractility indices did not increase in the SHR after isoproterenol infusion: (delta dP/dt +2224.3 +/- 1304.7 mm Hg/sec; delta dP/dt/P = +5.1 +/- 9.3 sec-1, p greater than 0.05) in sharp contrast with the marked increases observed in WKY (delta dP/dt = +4682.1 +/- 435.0 mm Hg/sec, p less than 0.01; delta dP/dt/P +78.6 +/- 8.0 sec-1, p less than 0.001). Left ventricular relaxation rate was marked diminished by isoproterenol in SHR (delta neg dP/dt = -2598.6 +/- 855.0 mm Hg/sec) whereas it was not altered significantly in normotensive rats. Thus, cardiac contractile and chronotropic responses were markedly diminished in SHR, possibly as a result of diminished beta adrenoreceptor mediation; further, the impairment of the relaxation rate induced by isoproterenol in SHR might also interfere with contractile cardiac performance during stress.

Cardiac contractile reserve in spontaneously hypertensive rats.

1. In response to graded infusions of isoprenaline, adult spontaneously hypertensive rats (20-24 weeks old) showed diminished responses of left ventricular contractile indices, diminished chronotropic responses and impairment of left ventricular relaxation rate as compared with matched Kyoto-Wistar rats. 2. These findings suggest reduced capacity to increase contractility in response to stress.

Impaired early left ventricular relaxation in coronary artery disease: effects of intracornary nifedipine.

It has been shown that the maximal rate of left ventricular (LV) relaxation is impaired in patients with coronary artery disease (CAD) under basal conditions. To test the hypothesis that this impaired LV relaxation could be related to viable but metabolically abnormal myocardium, we studied the time course of isovolumic LV pressure fall in 21 patients with CAD and in 13 control subjects under basal conditions. This study was repeated after intracoronary injection of the calcium antagonist nifedipine (N) in 11 patients with CAD and in eight controls. Our data showed that isovolumic pressure fall was biexponential in 20 of 21 CAD patients and in six of 13 controls. Moreover, the time constant of isovolumic pressure fall during the first 40 msec after peak (negative) dP/dt (T1) was significantly greater in CAD patients than in controls (62 +/- 3 vs 44 +/- 1 msec, p < 0.002); the time constant of pressure fall during the 40-80 msec after peak (negative) dP/dt (T2) was similar in both groups ( 42 +/- 2 vs 39 +/- 2 msec, NS). Thirty seconds after injection of nifedipine, T1 and T2, were significantly prolonged in patients with CAD (14 msec and 16 msec, respectively, p < 0.005) and in controls 12 msec and 14 msec, respectively, p < 0.05), and a negative inotropic effect was observed in both groups (peak (positive) dP/dt - 16% in controls and -23% in CAD patients, p < 0.01). At rest, impairment of isovolumic relaxation in CAD patients is mainly limited to the first 40 msec after peak (negative) dP/dt, suggesting a dyssynchronous wall motion. This impairment of LV relaxation is better identified by T1 than by peak (negative) dP/dt in individual patients, and cannot be improved by administration of a calcium antagonist.

Alterations in left ventricular relaxation and diastolic compliance in congestive cardiomyopathy.

Elevated ventricular diastolic pressures are characteristic of congestive heart failure, and are generally thought to result from reduced ventricular emptying in systole. To determine whether other factors might contribute to the increased diastolic pressures within the left ventricle in con- gestive heart failure, we examined parameters of both left ventricular relaxation rate and diastolic compliance in eight patients with chronic congestive heart failure due to cardiomyopathy, and compared them with similar observations in a control population. Combined recordings of simultaneous left ventricular pressure and echocardiogram were obtained in each case. Left ventricular relaxation rate was assessed by measurement of the maximum rate of left ventricular pressure decline (peak negative dP/dt) and the mean velocity of circumferential fibre lengthening (VCFL) in early diastole. Both of these parameters were significantly decreased in congestive cardiomyopathy patients compared with controls (peak negative dP/dt: 138 ± 15 kPa·s−1 (1037 ± 115 mmHg·s1) versus 347 ± 22 kPa·s−1 (2607 ± 120 mmHg·s−1) for controls, P<0.0005; VCFL; 0.9 ± 0.1 s−l in congestive cardiomyopathy versus 1.3 ± 0.1 s−1 in controls, P<0.01). Left ventricular diastolic distensibility, ΔD/ΔP, and normalised distensibility, (ΔD/ΔP)/D, were significantly decreased in cardiomyopathy subjects as compared with controls (ΔD/ΔP=0.165 ± 0.03 cm (dimension) kPa−1 [0.02 ± 0.004 cm (dimension)·mmHg−1) compared with 1.28 ± 0.23cm (dimension)·kPa−1 [0.17 ± 0.03 cm (dimension)·mmHg−1] for controls, P<0.0005; (ΔD/ΔP)/D=25.6 ± 3.8 kPa−1 × 10 −3 (3.4 ± 0.5 mmHg−1 × 10−3) versus 301 ± 75 kPa−1 × 10 −3 (40 ± 10 mmHg−1 × 10 −3) for controls, P <0.0005). Linear regression analysis showed a strong correlation between peak negative dP/dt and both diastolic distensibility (r=0.89, P<0.0005) and normalised distensibility (r=0.88, P<0.0125). These data suggest that early diastolic left ventricular relaxation is impaired in congestive cardiomyopathy and that this defect occurs in association with a decrease in left ventricular diastolic compliance.

Impaired maximal rate of left ventricular relaxation in patients with coronary artery disease and left ventricular dysfunction.

It has been suggested that the rate of left ventricular (LV) relaxation is related to the inotropic state, end-systolic fiber length and peak LV pressure, but little information is available regarding the rate of LV relaxation in patients with coronary artery disease (CAD) and LV dysfunction. To assess the rate of LV relaxation we obtained high-fidelity LV pressure measurements with manometer-tip catheters in 39 patients. The signal was analyzed by a digital computer to yield the maximal rate of pressure rise (pos dP/dt) and the maximal rate of pressure fall (neg dP/dt). Selective coronary arteriography and biplane LV angiography with determination of LV volumes, ejection fraction (EF) and percent abnormally contracting segments (ACS) when present, were performed in all patients. In 10 patients with normal LV function (EF greater than 0.50, no asynergy) mean neg dP/dt (2074 +/- 121 mm Hg/sec) was significantly (p less than 0.01) greater than in 29 patients with CAD and LV dysfunction (1695 +/- 66 mm Hg/sec). In nine patients with LV dysfunction and EF less than 0.35, mean neg dP/dt was reduced to 1405 +/- 107 mm Hg/sec, significantly (p less than 0.01) lower than in patients with normal LV function. Neg dP/dt correlated well with pos dP/dt (r = 0.75), with EF (r = 0.74), and with ACS (r = -0.74), and less well with LV end-systolic volume (r = 0.67). There was very poor correlation between neg dP/dt and peak LV pressure (r = 0.30). These data suggest that the rate of LV relaxation, as assessed by neg dP/dt, is impaired in patients with CAD and LV dysfunction, and the extent of impairment is related to the severity of the dysfunction as determined hemodynamically by pos dP/dt, and angiographically by EF and ACS. In these patients the maximal rate of LV relaxation is inversely related to LV end-systolic volume, and is not related to peak LV pressure.

The influence of left ventricular filling on postextrasystolic potentiation in the dog heart.

SUMMARY We studied the role of left ventricular filling on postextrasystolic potentiation (PESP) in the intact dog heart by calculating changes in end-systolic and end-diastolic volumes on a beat-to-beat basis from electromagnetic measurements of phasic mitral inflow and aortic outflow. In all, 161 extrasystolic sequences with compensatory pauses in 13 dogs were analyzed. The first postextrasystolic cycle showed an increased end-diastolic volume (EDV) in 94%, a decreased end-systolic volume (ESV) in 50%, and an estimated increased ejection fraction in 85% of the sequences. In the 91 sequences with a coupling index £0.7, despite a 76% increase in filling time, there was during the compensatory pause only a 6% increase in filling volume when compared to control. The net filling volume, stroke volume, and diastolic filling period for the sum of the extra- and postextrasystolic cycles were, respectively, 78%, 80%, and 116% of the sum of two control cycles. This retarded filling rate is attributed to a lower left atrial pressure, a reduced left ventricular relaxation rate, and a relaxation to a higher pressure minimum, all of which decrease the amplitude of the atrioventricular pressure gradient. Nevertheless, in 98% of the postextrasystolic cycles, stroke volume was augmented when compared to control (ratio, 1.49 ± 0.26; mean ± SD), due in part to intrinsic mechanisms, to increased preload (EDV), and to decreased afterload. As a first approximation, the effects of increases in preload were separated from intrinsic increases in contractility following an extrasystole by defining potentiation in terms of decreased ESV and/or increased ejection fraction. With the former criterion, 50% of the sequences showed PESP; with the latter, PESP occurred in 85% of the sequences. Circ Res 44: 712-722, 1979

Impaired rate of left ventricular relaxation in patients with coronary artery disease and left ventricular dysfunction

Impaired rate of left ventricular relaxation in patients with coronary artery disease and left ventricular dysfunction

Pharmacologic and hemodynamic influences on the rate of isovolumic left ventricular relaxation in the normal conscious dog.

We studied the effects of acute pharmacologic and hemodynamic interventions on isovolumic left ventricular relaxation in 19 conscious dogs using micromanometer tip catheters. Isoproterenol (11 studies) augmented peak rate of rise of left ventricular pressure [(+) dP/dt] by 1,275+/-227 (SE) mm Hg/s (P < 0.001) and dP/dt at an isopressure point of 35 mm Hg during isovolumic relaxation [(-) dP/dt(35)] by 435+/-80 mm Hg/s (P < 0.001). Peak (-) dP/dt decreased by 467+/-89 mm Hg/s (P < 0.002). The time constant, T, derived from the logarithmic fall of pressure during isovolumic relaxation, shortened from 20+/-2.8 to 14.9+/-1.8 ms (P < 0.003). Calcium (11 studies) increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.0001); peak (-) dP/dt was unchanged. T shortened from 20.4+/-1.8 to 17.3+/-1.5 ms (P < 0.002). Volume (13 studies) did not affect either dP/dt or T. Phenylephrine (13 studies) augmented peak (-) dP/dt, but reduced (-) dP/dt(35) (both P < 0.01); T lengthened from 22.1+/-1.5 to 32.5+/-1.5 ms (P < 0.01). In 15 studies, rapid atrial pacing increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.01). In the first post-pacing beat, peak (-) dP/dt and (-) dP/dt(35) decreased (both P < 0.01), although peak (+) dP/dt increased further. T paralleled values of (-) dP/dt(35). In five dogs, beta adrenergic blockade had no significant effect on any variable after calcium, volume, or phenylephrine infusion or during or after atrial pacing when the pre-and post-propranolol states were compared. We conclude that positive inotropic interventions augment both left ventricular contraction and relaxation. The changes in isovolumic relaxation are independent of alterations in sympathetic tone produced by beta-adrenergic blockade. Peak (-) dP/dt may not be a valid measure of left ventricular relaxation rate during acute alterations in inotropic state or afterload.

Effects of Ouabain on Early Ventricular Relaxation in Patients with Acute Myocardial Infarction

The effects of the administration of ouabain on the peak negative left ventricular (LV) dP/dt were studied in 14 patients with acute myocardial infarction. Prior to administration of ouabain, negative LV dP/dt was lower than previously reported for patients without coronary arterial disease. One hour after administration of ouabain, significant (P < 0.05) increases in peak positive LV dP/dt and maximal velocity of contractile-element shortening and decreases in LV diastolic pressure were present. These changes were associated with small and insignificant increases in negative LV dP/dt. Early LV relaxation rate is impaired in patients with acute myocardial infarction; however, the reduction in LV diastolic pressures which occurs after administration of ouabain does not appear to be due to an increase in the rate of early LV relaxation but rather is probably related to improved contractility.

Alterations in myocardial function during bacterial infective cardiomyopathy

The status of myocardial function in rabbits subjected to cardiac catheterization and infection with Streptococcus viridans was assessed at 3 and 6 days. Sham-operated control animals as well as uninfected catheterized animals were used for comparison. Although left heart hypertrophy and interstitial edema were evident in both uninfected and infected animals, the infected animals exhibited in addition mononuclear cell infiltration and muscle degeneration as well as lung congestion and accumulation of pleural fluid. Both uninfected and infected animals had elevated levels of serum creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase as well as electrocardiographic abnormalities such as increased amplitude of the QRS complex and flattening or inversion of the T wave. Unlike findings in the uninfected animals, the serum calcium, magnesium and sodium levels were slightly but significantly decreased and serum potassium levels were increased in the infected rabbits. Both heart rate and pulse pressure were higher in 6 day uninfected and 3 day infected animals whereas 6 day infected animals showed a decrease in heart rate. In comparison to the sham-operated control rabbits and the uninfected animals, the infected animals exhibited depression in the rates of left ventricular pressure development and relaxation as well as prolongation in time for half relaxation in situ. Relative maximal contractile element velocity extrapolated from intraventricular pressure-velocity curves was decreased by 24, 52 and 76 percent, respectively, of control values in the uninfected hearts and those with 3 and 6 days of infection. The isolated perfused hearts from infected animals also generated less contractile force and showed a decrease in the rates of contraction and relaxation, but half-relaxation time was increased. These results demonstrate myocardial dysfunction during experimental bacterial endocarditis and provide evidence that infective cardiomyopathy is associated with heart failure.

Impaired left ventricular relaxation during pacing-induced ischemia

Rapid atrial pacing was performed in 15 patients at the time of cardiac catheterization. The results indicate that tachycardia may produce incomplete left ventricular relaxation in patients with disorders characterized by ischemia, but not in those with a normal left ventricle. This phenomenon was characterized by (1) a decrease in the peak negative value for first derivative of left ventricular pressure (dP/dt), which was used in the study as an index of left ventricular relaxation rate, (2) an increase in left ventricular diastolic pressure, and (3) a decrease in left ventricular internal diameter. These findings suggest that ventricular relaxation is an important determinant of left ventricular diastolic pressure-volume relations and that an impairment of ventricular relaxation may be partly responsible for the apparent decrease in left ventricular diastolic compliance observed during pacing-induced angina pectoris.

Infected Urine

AIM--To assess whether left ventricular function shows circadian variation in healthy people. SUBJECTS AND METHODS--10 healthy men (7) and women (3) aged 35-50 underwent M mode echocardiography of the left ventricle and Doppler velocimetry of transmitral flow at 4 h intervals over 24 h. The participants were in hospital over the study period and their diet, meal times, and sleeping hours were standardised as far as possible. MEASUREMENTS--Heart rate, blood pressure, left ventricular and atrial diameters, fractional shortening, peak early and late transmitral velocities, time from the second heart sound to the early diastolic velocity peak (relaxation time), isovolumic relaxation period, acceleration and deceleration of the early transmitral flow, atrial filling fraction. RESULTS--A circadian rhythm was observed in heart rate and blood pressure, but neither the left ventricular diameters and systolic function nor the left atrial size showed statistically significant diurnal trends. The relaxation time (mean (SD)) measured 144 (16) ms at 2 pm, 144 (21) ms at 6 pm, 149 (22) ms at 10 pm, 168 (23) ms at 2 am, 174 (28) ms at 6 am, and 151 (21) ms at 10 am (P = 0.009). Diurnal rhythms were seen also in the isovolumic relaxation period (P = 0.003) and in the acceleration of the early diastolic transmitral flow (P = 0.037); the lowest and highest values of flow acceleration were observed during the nocturnal and daytime hours, respectively. CONCLUSIONS--The Doppler indices of left ventricular filling in healthy people show diurnal changes suggestive of a circadian rhythm in the rate of left ventricular relaxation. The most likely underlying mechanism is the day-night cycle in sympathoadrenal activity.