Effects of Coronary Blood Flow and Perfusion Pressure on Left Ventricular Contractility in Dogs

Abstract

The effects of changes in coronary blood flow and coronary artery pressure on left ventricular (LV) contractility were determined in 18 animals. Dogs on cardiopulmonary bypass provided isovolumetric LV contractions during controlled perfusion of the coronary circulation. Coronary venous efflux, myocardial oxygen consumption, peak LV pressure, LV dp/dt, and the forcevelocity relations of the LV were determined at normal and at "supernormal" levels of flow and pressure. Coronary vasodilatation was obtained with nitroglycerine, permitting independent variation of flow and pressure. Augmenting flow by increasing pressure increased LV contractility, as reflected by increases in peak LV pressure, dp/dt max, peak wall tension, and maximal measured contractile element velocity. Increased contractility appeared to be primarily due to increased flow, rather than to pressure, as an increase in flow without an increase in pressure produced similar changes, and decreases in pressure at constant flow did not change maximal measured contractile element velocity or dp/dt max, although some decrease in peak LV pressure and wall tension did occur. These data suggest that coronary flow is an independent determinant of the contractile state of myocardium, and that an increase in flow in excess of that required to supply metabolic demands augments myocardial contractility. ADDITIONAL KEY WORDSmyocardial contractility nitroglycerine coronary vascular resistance myocardial oxygen consumption contractile element velocity force-velocity relations inotropic state ventricular compliance• The relationships between ventricular work, coronary blood flow and myocardial oxygen consumption (MVo 2 ) are well established (1). Ventricular contractility, as assessed by developed wall tension and the rate of contractile element shortening, has been shown to be an important determinant of MVo 2 and coronary vascular resistance (2, 3). The converse causal relationship (viz., coronary blood flow as a determinant of contractility), however, has not been established. Gregg (4, 5) observed that a change in left circumflex artery perfusion pressure caused directional changes in both coronary flow and MV02 without consistent changes in heartFrom the Clinic of Surgery, National Heart and Lung Institute, Bethesda, Maryland 20014.Received April 2, 1970; accepted for publication October 19, 1970. rate, cardiac output, aortic pressure, or left ventricular end-diastolic pressure (LV, EDP). "Gregg's phenomenon" or the suggestion that coronary flow and coronary artery pressure (CAP) were independent determinants of MV02 and ventricular contractility has been investigated in several laboratories by a variety of experimental methods (6-9). The results of these studies have been the subject of controversy possibly related to the variety of preparations utilized, amount of myocardial work generated in these studies and the failure to differentiate between the effects produced by changes in coronary flow versus coronary artery pressure. The present studies we...

Dynamic relation between myocardial contractility and energy metabolism during and following brief coronary occlusion in the pig.

“…The Gregg phenomenon has been demonstrated in experimental models in which coronary flow is increased by pharmacological vasodilation, without an increase in perfusion pressure. 33 The most widely proposed mechanism for the phenomenon is that mechanical distension of myofibrils by adjacent distended intramyocardial vessels34,35 leads to increased contractility, perhaps by a localized Frank-Starling mechanism. An alternative explanation is that a surfeit of myocardial oxygen delivery leads to increased oxygen utilization,36 improved energetics with an increased phosphorylation potential, and augmented ATP utilization for contractile activity.…”

The rate of force generation by the myocardium is not influenced by afterload

“…According to present knowledge, other factors that may alter the dP/dt values after increasing AP are shortening deactivation (21)(22)(23)(24), the Anrep effect (15,18,19) and variations in coronary flow (25) or coronary perfusion pressure (26). Previous studies from our laboratory have shown that large increases of developed force (27) and coronary perfusion (28) do affect left ventricular performance in the intact canine left ventricle.…”

“…It has been described that, in addition to myocardial ischemia, coronary perfusion pressure can affect cardiac mechanics interfering with intracellular calcium concentration (30,31) and sarcomere resting length (26,32). Abel and Reis (25) described an enhancement of cardiac performance following the increase of coronary Table 2 -Isometric contraction data of rats.…”

The Anrep Effect Reconsidered

“…5, panel D). As may be seen from Table I Table II. Sodium nitrite was specifically selected for this study as it reportedly does not induce a positive inotropic effect hlen administered to isolated cat papillary muscle preparations (19,20). Papaverine likewise, if anything, has been shown to depress ventricular contraction in Langendorff perfused frog and turtle hearts (21,22) which, it may be presumed, are in a state of maximal or near maximal vasodilation.…”