Left ventricular performance in the isolated dog heart was observed in a preparation in which left ventricular pressure and volume could be monitored continuously while the ventricle contracted isobarically by compressing air into a large chamber. By suddenly reducing the orifice connecting the ventricle to the chamber a constant load was imposed on the ventricle, abruptly forcing it to develop pressure in systole. This pressure increased over the ensuing 3 minutes while both the load and the end-diastolic pressure remained constant, implying that the sudden development of pressure by the ventricle was attended by a positive inotropic effect, otherwise known as homeometric autoregulation. Further studies showed this positive inotropic effect to be a function of the magnitude of the abrupt increase in systolic pressure and the time course of the experiment. /3-adrenergic receptor blockade with propranolol decreased but did not abolish this effect. Infusion of norepinephrine did not enhance it. Increases in ventricular compliance that accompanied loading could not fully account for it. Evidence is presented that this positive inotropic effect may in part be mediated through the release of intrinsic catecholamines when the ventricle is forced to increase its systolic pressure.

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In an isolated dog heart, perfused with blood from an anesthetized donor, left ventricular performance was observed during periods in which the left ventricle either contracted isovolumically or was allowed to eject saline. Heart rate and left ventricular end-diastolic pressure were comparable in both. Ventricular performance, as judged by peak systolic ventricular pressure, declined relatively rapidly during isovolumic loading when initial systolic pressures were higher. The efflux of norepinephrine (NE) from the heart was directly related to the systolic pressure of the left ventricle both when the NE concentration of the perfusing blood was normal and when it was reduced to undetectable levels by dialysis. Changes in heart rate did not affect NE efflux nor was NE efflux increased by isobaric loading when the ventricle was distended in diastole without developing pressure in systole. A pathway is described whereby ventricles developing a high systolic pressure may be depleted of NE.ADDITIONAL KEY WORDS systolic pressure isovolumic loading heart rate coronary flow ventricular performance isobaric loading canine heart • It has been reported that isolated, supported hearts perfused with the blood of an intact animal maintain left ventricular performance, as defined by their ability to maintain their stroke work at a near constant end-diastolic pressure for varying periods of time after isolation (1). Preliminary observations from this laboratory have confirmed these findings in that the left ventricular performance of hearts so perfused did not deteriorate provided the ventricle was allowed to eject a critical stroke volume of saline ( 2 ) . If, on the other hand, the ventricle was forced to contract isovolumically at a constant enddiastolic pressure, its performance as reflected by peak systolic pressure progressively declined. It was decided, then, to reexamine the performance of isovolumically contracting ventricles in comparison with those ejecting fluid and, insofar as possible, to explore causes for any discrepancies observed.Recent reports have indicated that the norepinephrine content is relatively low in ventricles that have been subjected to a high systolic pressure and subsequent failure compared with that of normal hearts (3). These findings imply that there is either a faster depletion of ventricular norepinephrine stores when the ventricle is subjected to the described stress, or that there is a diminution in the rate at which stores are reconstituted either by biosynthesis or uptake. Our studies were undertaken to determine the rate at which norepinephrine was released by the heart under various conditions of ventricular loading, particularly during the decline in ventricular performance which occurred when the ventricle was forced to contract isovolumically and produce a high systolic pressure. 774

Left ventricular performance in the isolated heart of the dog as expressed by the peak systolic intraventricular pressure was observed during control periods when the heart was perfused with blood from a healthy anesthetized donor and after the donor was removed and the heart perfused with blood oxygenated by isolated lungs. Heart rate, coronary perfusion pressure, ventricular end-diastolic pressure, and stroke volume were maintained constant throughout. While the heart was perfused with blood from a donor, ventricular performance showed no tendency to decline, although coronary flow invariably increased. On removing the donor and perfusing the heart with blood oxygenated by isolated lungs, myocardial performance declined in proportion to the decline in the total catecholamine concentration of the perfusing blood. Restoration of catecholamine levels by infusing epinephrine and norepinephrine also restored left ventricular performance.