Norepinephrine Release and Left Ventricular Pressure in the Isolated Heart

Abstract

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 Pressure-Volume Relations and Performance as Affected by Sudden Increases in Developed Pressure

“…Later work by Sarnoff et al lent additional support to the second hypothesis (4). A subsequent publication from our laboratory gave evidence implicating the third (5). Recently, Sonnenblick et al called attention to the increase in ventricular compliance observed to accompany an abrupt increase in the pressure developed by the ventricle (6).…”

“…To accomplish this isolated lungs, in lieu of a donor dog, were used to oxygenate the blood perfusing the heart. In addition, the blood was dialyzed on its return from the heart by passing it through a dialysis unit (Travenol U210) as reported in a previous study (5). Catecholamine determinations were likewise made as previously described, using a modification of the trihydroxyindole method (5).…”

The effects of ventricular end‐diastolic and systolic pressures on action potential and duration in anaesthetized dogs.

“…We also perfused the cephalic region of the animals, including the aortic and carotid baroreceptors, at constant pressure to reduce the likelihood of alterations in the levels of circulating catecholamines. A further possibility, suggested from previous studies in isolated dog hearts, is that shortening of action potential following increases in LVPP may have been secondary to release of noradrenaline from endogenous stores at sympathetic nerve endings (Monroe, LaFarge, Gamble, Hammond & Morgan, 1966). This effect has also been demonstrated in vivo (LaFarge, Monroe, Rosenthal & Hammond, 1970).…”

Acute pressure overload cardiac arrhythmias are dependent on the presence of myocardial tissue catecholamines

“…We attribute the great reduction in ectopic frequency in denervated myocardium to myocardial catecholamine depletion rather than loss of sympathetic and parasympathetic afferent or efferent neuronal pathways because pressure load induced arrhythmias occur after acute denervation 12 Acute pressure loading of myocardium induces release of proarrhythmic noradrenaline from the myocardium, presumably from sympathetic neurones 5…”