Thierry C. Gillebert

Contraction-relaxation coupling and impaired left ventricular performance in coronary surgery patients

BACKGROUND Dependence of left ventricular (LV) relaxation on cardiac systolic load is a function of myocardial contractility. The authors hypothesized that, if a tight coupling would exist between LV contraction and relaxation, the changes in relaxation rate with an increase in cardiac systolic load would be related to the changes in LV contraction. METHODS Coronary surgery patients (n = 120) with preoperative ejection fraction >40% were included. High-fidelity LV pressure tracings (n = 120) and transgastric transesophageal echocardiographic data (n = 40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on contraction were evaluated by analysis of changes in dP/dt(max) and stroke area. Effects on relaxation were assessed by analysis of R (slope of the relation between tau and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearsons coefficient r. RESULTS Baseline LV end-diastolic pressure was 10+/-3 mm Hg (mean +/- SD). During leg raising, systolic LV pressure increased from 93+/-9 to 107+/-11 mm Hg. The change in dP/dt(max) was variable and ranged from -181 to +254 mm Hg/s. A similar variability was observed with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in dP/dt(max) and in stroke area were closely related to individual R values (r = 0.87, P<0.001; and r = 0.81, P<0.001, respectively) and to corresponding changes in LV end-diastolic pressure (r = 0.81, P< 0.001; and r = 0.74, P<0.001, respectively). CONCLUSIONS A tight coupling was observed between contraction and relaxation. Leg raising identified patients who developed a load-dependent impairment of LV performance and increased load dependence of LV relaxation.

Recovery of systolic and diastolic left ventricular function early after cardiopulmonary bypass.

Background Impairment of left ventricular function after cardiopulmonary bypass (CPB) is well recognized, but little is known about the time course of recovery of cardiac function early after separation from CPB. Therefore, recovery of left ventricular function was evaluated early after separation from CPB in patients undergoing coronary artery surgery. The authors tried to determine whether this recovery might be attributed to autoregulation of function by preload. Methods Left ventricular pressure was measured with fluid-filled catheters. Data were digitally recorded during increased pressure induced by elevating the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/ml) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, ml sup -1) of the diastolic pressure-volume relation. Cardiac function was assessed before CPB, after termination of CPB, and 5, 10, and 15 min later. Two different separation procedures from CPB were compared: in protocol 1, left ventricular function was documented during the standard procedure (n = 24); in protocol 2, the heart was optimally filled 10 min before separation from CPB (n = 12). Results In protocol 1, Ees was 2.88 +/- 0.21 mmHg/ml (mean +/- SEM) and Kc was 0.012 +/- 0.001 ml sup -1 before CPB. Within 10 min after separation from CPB, Ees increased from 1.10 +/- 0.32 to 2.92 +/- 0.34 (P = 0.001) and Kc decreased from 0.022 +/- 0.002 to 0.011 +/- 0.001 (P = 0.001). The parameters remained stable thereafter. In protocol 2, Ees was 2.92 +/- 0.51 mmHg/ml and Kc was 0.011 +/- 0.002 ml sup -1 before CPB. Depression of systolic and diastolic function was not observed in these patients. At time 0, Ees was 2.46 +/- 0.16 and Kc was 0.012 +/- 0.002. These values remained stable throughout the entire observation period. Conclusions Significant functional recovery was observed early after separation from CPB, which was suggestive of time-dependent changes in both systolic and diastolic left ventricular function induced by preload restoration.

Alteration of left ventricular endocardial function by intracavitary high-power ultrasound interacts with volume, inotropic state, and alpha 1-adrenergic stimulation.

Background. High‐power intracavitary ultrasound abbreviates left ventricular (LV) ejection duration, thereby decreasing mechanical LV performance, presumably by selective impairment of endocardial endothelial function. Methods and Results. Effects of ultrasound were evaluated in the ejecting LV of anesthetized, open‐chest dogs under different conditions of LV volume and contractile state and after mild selective &agr;1‐adrenergic stimulation. LV pressures, left atrial pressures, and regional segment lengths were measured in anterior and posterior midwall. A cylindrical ultrasound probe (0.9 MHz, 25 W) mounted on a catheter was inserted into the LV cavity through the apex and was activated for 4 minutes in each condition. In protocol A (n=7), LV volume was altered with caval vein occlusion and intravenous dextran infusion. The ultrasound probe was activated at low (4.1±0.9 mm Hg), mid (10.6±1.5 mm Hg), and high (17.9±1.8 mm Hg) LV end‐diastolic pressure (EDP). Effects of ultrasound were less pronounced at higher EDP. For example, the time interval from end‐diastole to peak (−)dP/dt decreased by 7.5±2.3% at low, 4.4±2.2% at mid, and 1.9±1.6% at high LVEDP (p<0.001). In protocol B (n=7), LV inotropic state was altered by slow intravenous infusion of low‐dose calcium. The ultrasound probe was activated before and after calcium. Effects of ultrasound were less pronounced after calcium. Time from end‐diastole to peak (‐)dP/dt decreased by 8.4±3.1% at baseline and by 3.5±2.1% after calcium (p<0.001). In protocol C (n=7), activation of the ultrasound probe was performed at baseline and after mild selective &agr;1‐adrenergic stimulation (propranolol plus phenylephrine). Effects of ultrasound were similar at baseline and after propranolol but increased after phenylephrine. Time from end‐diastole to peak (‐)dP/dt decreased by 5.2±2.4% at baseline, by 5.3±1.9% after propranolol, and by 8.9±3.2% after phenylephrine (p<0.05). Conclusions. Effects of intracavitary ultrasound, which are presumably mediated through modulation of endocardial endothelial function, were more important at low volume, lower calcium, and under mild selective &agr;1‐adrenergic stimulation. (Circulation 1993;87:1275‐1285)

The effects of beta-adrenergic stimulation on the length-dependent regulation of myocardial function in coronary surgery patients.

UNLABELLED Increasing cardiac load by leg elevation identifies patients with load-dependent impairment of left ventricular (LV) function. This impairment is related to a deficient length-dependent regulation of LV function. We investigated the effects of dobutamine on length-dependent regulation of LV function in coronary surgery patients (n = 25). High-fidelity LV pressure tracings were obtained at end-expiration, while hearts were paced at a fixed rate of 90 bpm. Effects of leg elevation on contraction and relaxation were compared before and during dobutamine 5 microg x kg(-1) x min(-1). Effects on contraction were evaluated by analysis of changes in dP/dtmax. Effects on relaxation were assessed by analysis of R (slope of the relation between the time constant of isovolumic relaxation and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearsons coefficient r. The effects of leg elevation on variables of contraction and relaxation were coupled. We found a close relationship between changes in dP/dtmax and individual values of R (r = 0.84; P < 0.001). Dobutamine improved myocardial function and accelerated LV pressure decrease. Under dobutamine, the increase in dP/dtmax with leg elevation was larger (P < 0.001) and load dependence of LV relaxation was reduced (P = 0.001). Dobutamine improved the effects of leg elevation on LV function, reflecting improved length-dependent regulation of LV function. IMPLICATIONS This study demonstrated that beta-adrenoreceptor stimulation with dobutamine improved length-dependent regulation of myocardial function assessed during leg elevation in cardiac surgical patients.

Effects of Calcium on Left Ventricular Function Early After Cardiopulmonary Bypass

OBJECTIVES Evaluation of the effects of intravenous CaCl2 on systolic and diastolic function early after separation from cardiopulmonary bypass (CPB) DESIGN: Prospective study SETTING University hospital PARTICIPANTS Twenty patients scheduled for elective coronary artery surgery INTERVENTIONS Left ventricular (LV) pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the LV were simultaneously recorded on videotape. Measurements were obtained before the start of CPB, 10 minutes after termination of CPB, after intravenous administration of CaCl2, 5 mg/kg, and 10 minutes later. MEASUREMENTS AND MAIN RESULTS Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relation. CaCl2 increased Ees from 2.62 +/- 0.46 to 5.58 +/- 0.61 (mean +/- SD), but induced diastolic dysfunction with an increase in Kc from 0.011 +/- 0.006 to 0.019 +/- 0.007. These changes were transient and had disappeared within 10 minutes after administration of CaCl2. CONCLUSIONS CaCl2 early after CPB transiently improved systolic function at the expense of an increase in ventricular stiffness, suggesting temporary diastolic dysfunction.

Effects of lidoflazine on left ventricular function in patients

OBJECTIVE The present study evaluated the effects of the nucleoside transport inhibitor, lidoflazine, at a dose of 1 mg/kg, on left ventricular function. DESIGN Patients were randomly assigned to receive either lidoflazine or saline in a double-blind manner. SETTING A university hospital. PARTICIPANTS The study was performed in 32 patients scheduled for elective coronary artery bypass surgery. INTERVENTIONS Left ventricular pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the left ventricle were simultaneously recorded on videotape. Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relationship. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relationship. Cardiac function was assessed at baseline and after administration of either lidoflazine (group A [n = 16]) or placebo (group B [n = 16]). Data were compared using two-factor analysis of variance. MEASUREMENTS AND MAIN RESULTS At baseline, diastolic and systolic function were comparable in both groups. Lidoflazine increased Kc from 0.079 +/- 0.015 to 0.125 +/- 0.017 mmHg/mL and decreased Ees from 2.481 +/- 0.213 to 1.217 +/- 0.211 mmHg/mL (p = 0.009 and p = 0.004, respectively). None of these changes occurred when placebo was administered. CONCLUSIONS Administration of lidoflazine before the start of cardiopulmonary bypass impaired left ventricular systolic function but also increased diastolic stiffness.