Pressure-volume diagrams of paced, isolated hearts were derived from isovolumic contractions and auxotonic contractions (simultaneous changes of pressure and volume). Coronary perfusion, fluid accumulation in heart muscle, and left ventricular volume and pressure were measured and controlled. Pressure-volume diagrams from isovolumic and auxotonic contractions were virtually identical in the same heart and were influenced by the same factors to a similar degree. At equal diastolic volumes the magnitude of systolic, as well as of diastolic pressures, and the occurrence of a systolic descending limb were directly related to coronary perfusion pressure. At equal diastolic volumes, other factors being constant, myocardial edema did not influence the contractile strength (i.e., maximum contractile tension development) of a ventricle, but did decrease its distensibility (i.e., increase diastolic pressure) in proportion to fluid accumulation. Myocardial water content and coronary factors (coronary arterial and venous pressures, coronary blood volume and flow) therefore constitute intrinsic mechanisms which can regulate the performance of a ventricle by changing its contractile strength, its distensibility, or both. The effects of coronary factors and of myocardial edema on the distensibility of a ventricle are sufficient in magnitude to explain hemodynamic abnormalities which characterize certain types of congestive heart failure.

The marked intensification of experimental left ventricular failure by veno-arterial pumping which was seen in earlier experiments suggested changes of myocardial elasticity as a mechanism. Two experimental procedures were therefore applied here, in which the pressure in the coronary arteries and veins could be varied at will, where the left ventricle was distended by an air-filled balloon, and where the coronary tree did not communicate with the left ventricle. Changes of the coronary arterial or venous pressures were accompanied by homodirectional changes of the left ventricular diastolic pressure which were of large magnitude and which could not be explained by unobserved blood flow into the left ventricle or by other factors. The inverse relationship between coronary vascular pressures and myocardial distensibility was probably caused by the increasing volume of blood which was retained in the coronary arteries and veins when the coronary arterial or venous pressures were increased. This passive increase in coronary blood volume (turgor) must have changed the resiliency of the coronary tree. The changed elastic properties of the coronary tree then resulted in a change of the elastic properties of the heart.

In open-chest dogs, the peripheral circulation was carried on a heart-lung machine. The pulmonary artery was obstructed and the left atrium and the right ventricle were drained into the venous reservoir of the machine. A balloon in the bloodless left ventricle permitted its distention. Pressures were recorded in the left ventricle and the aortic arch or a femoral artery. After distention of the left ventricle, the left ventricular diastolic pressure rose, the systemic arterial pressure fell, and bradycardia occurred. Distention of the left ventricle also caused reflex dilation of systemic veins. These effects were reversible and were abolished by section of the vagi. They are attributed to receptors in the myocardium of the left ventricle. It is considered likely that these reflex effects of left ventricular distention contribute to the mechanism of cardiogenic shock.

Evidence is presented that reflex systemic vasodilatation occurs after stretching dog's lungs by either mechanical traction or positive pressure ventilation under conditions of separate pulmonary and systemic perfusion. This reflex is mediated by the vagus.

Tension along chordae tendineae (CTT) was measured in absolute terms in situ and recorded throughout cardiac cycles. The transducers were installed without damage to the LV myocardium or its blood supply. CTT contours paralleled LV pressure traces only during isovolumic pressure development; CTT and LVP were sharply distinct or divergent during other periods of the cardiac cycle. The shape or magnitude of CTT could not be predicted from LVP traces. Hemodynamic and other factors influencing the various phases of CTT contours were investigated. Stroke volume, elastic storage capacity of the arterial tree, presence of a pericardial restraint, and coronary artery pressure influenced the magnitude and shape of CTT traces. Two types of heart failure were differentiated by specific CTT contours.

No abstract

• Earlier experiments 1>2 suggested that the contractile strength of the cardiac ventricles might be determined by the pressure in the coronaiy arteries and not by the quantity of metabolites supplied to the heart muscle or by presystolic factors. In further investigations (reported here in section II), we confirmed this hypothesis: coronary perfusion pressure influenced ventricular contractile strength even under conditions which excluded variation of metabolic support. Coronary pressure might have exerted its inotropic effect, either directly, or else through a corresponding change of intramyocardial pressure. Since the literature did not contain information concerning factors which control intramyocardial pressure, it was necessary to investigate this entity. Data which identify determinants of intramyocardial pressure are reported here in section I; the} were a prerequisite for further experimental analysis of factors Avhich influence contractile strength. Each parameter which had influenced intramyocardial pressure was examined with a view to uncovering its role, if any, in the regulation of contractile strength.The data presented here indicate that: (1) all factors which are known to regulate the contractile strength of isolated hearts (diastolic volume, diastolic pressure, outflow resistance, coronary pressure, heart rate) also have the ability to cause variations of pressure within the heart muscle; (2) it is this variation of "intramyocardial pressure" which brings about changes of contractile strength; and (3) the intrinsic factors which regulate From the Intensive Treatment Center and the

Experiments show that the right ventricle is weakened to the point of irreversible failure by decreased coronary artery pressure and also demonstrate that augmented coronary artery pressure can cause a remarkable increment of the right ventricular strength. Both ventricles, even when in otherwise irreversible decompensation, can be restored to full functional competence by various maneuvers which augment coronary blood flow. The studies reported appear to have important clinical applications in the treatment of circulatory disturbances of the right ventricle.