In vitro studies of isolated supported human hearts.

We developed methods to revive human hearts, obtained at the time of cardiac transplantation, and study them in the physiology laboratory. The hearts were arrested with cardioplegic solution at the time of explanation and transported to the laboratory at 4 degrees C. The hearts were perfused with a human blood based solution whose flow rate, temperature, and ionic concentration were controlled. Six hearts with various endstage cardiomyopathies were revived in this manner. Once perfusion was started, the hearts maintained a steady contractile state for approximately 30 min during which time data could be collected. Within this time period we could measure end-systolic and end-diastolic pressure-volume relations, the time courses of contraction and relaxation, and the influence of heart rate and premature stimulation on contractile state. The results suggest that evidence of specific cellular abnormalities in human heart disease might be obtained from measurements of global ventricular performance. Furthermore, the type of abnormality identified, namely sarcoplasmic reticulum dysfunction, in several forms of cardiomyopathy was in concordance with results obtained in muscle bath studies of similarly diseased human and animal myocardium.

Influence of ventricular contractility on non-work-related myocardial oxygen consumption.

The relationship between myocardial oxygen consumption (MVO2) and the total pressure-volume area (PVA), which represents the total mechanical work performed during a cardiac cycle, has been shown to be linear and independent of loading conditions: MVO2 = aPVA + b. When inotropic state is enhanced, the MVO2-PVA relation shifts upward (increase in b), and when inotropic state is depressed the relation shifts downward (decrease in b). However, the quantitative relationship between contractility and b (the non-work-related myocardial oxygen consumption) determined over a wide range of contractilities is not known. In seven isolated blood perfused canine hearts, left ventricular (LV) contractility was increased by dobutamine and decreased with nifedipine or reduction of coronary blood flow. At each level of contractility, the end-systolic pressure-volume relationship (ESPVR) and the MVO2-PVA relation were determined. For each heart, the resulting values of b (ml O2/beat) were plotted as a function of Emax (mmHg/ml), an index of contractility defined as the slope of the ESPVR. There was a linear relation between Emax and b over a wide range of contractilities; on average, b (ml O2/beat) = 0.0036 Emax (mmHg/ml) + 0.0101 [r = 0.929-0.978 (95% confidence interval)], when Emax was varied over an average range of 2.8-9.6 mmHg/ml. These results suggest a common underlying determinant of contractility and non-work-related oxygen consumption.

Extracardiac pressure changes do not alter contractile function of the isolated left ventricle.

To determine whether or not extracardiac pressure has an effect on left ventricular contractile function, we analyzed pressure-volume relationships of six isolated, perfused canine hearts in an air-tight chamber. The chamber pressure was set at -60, -30, 0, 30 and 60 mm Hg and left ventricular pressure-volume relationships studied. The slope (Ees) and volume axis intercept (Vo) of the transmural pressure-volume relationship were used to compare the pump functions of an individual heart at the different extracardiac pressures applied. No significant difference in either Ees or Vo was seen with different extracardiac pressures. During isovolumic ventricular contraction, developed left ventricular pressure did not change over the range of extracardiac pressures applied. The same was true during ejecting contraction; when the downstream pressure of the computer simulated afterload circuit and the venous filling pressure of the preload circuit were changed in parallel with the extracardiac pressure, pressure-volume loops remained identical throughout their course for all of the extracardiac pressures applied. We conclude that transmural pressure is the overwhelmingly dominant loading factor governing LV contraction, and myocardial contractile function is unaffected by the absolute value of extracardiac pressure.

Influence of pacing site on canine left ventricular contraction.

We investigated the influence of pacing site on several aspects of left ventricular (LV) performance to test the hypothesis that "effective ventricular muscle mass" is reduced with direct ventricular pacing. All studies were performed on isolated supported canine hearts that were constrained to contract isovolumically. To determine the influence of pacing site on magnitude and time course of isovolumic LV pressure (P) generation, LVP waves were recorded in eight isolated hearts paced at 130 beats/min. Pacing was epicardially from atrium, LV apex, LV free wall, right ventricular free wall (RVF), and endocardially from right ventricular endocardium. In a given heart, peak LVP was greatest with atrial pacing and smallest with RVF pacing, the difference being on average 26 +/- 10% (mean +/- SD) of the former pressure. The other pacing sites produced intermediate peak LVPs. When instantaneous LVP waves, obtained while pacing from each of the five sites, were normalized by their respective amplitudes, they were virtually superimposable up to the time of peak pressure and only slightly different during the remainder of the cardiac cycle. With changes in pacing site there was a linear negative correlation (r = 0.971) between changes in peak pressure and changes in duration of the QRS complex of a bipolar epicardial electrogram with an average slope of -0.51 mmHg/ms. Compared with atrial pacing, the slope of the end-systolic pressure-volume relation, Ees, was decreased with ventricular pacing, but Vo, the volume axis intercept, was relatively constant.(ABSTRACT TRUNCATED AT 250 WORDS)