Cecil E. Cross

Influence of Coronary Artery Pressure Upon Myocardial Elasticity

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.

Acute ischemia of inner layers of ventricular wall

Abstract Regional blood flow in heart muscle was studied by adding a dye to coronary blood. The pericardium was closed. Coronary and aortic pressures varied independently and were controlled. When the left ventricular diastolic pressure (LVDP) was intentionally elevated above 25 mm. Hg, and when the coronary arterial pressure was reduced below 70 mm. Hg at the same time, extensive sheets of heart muscle remained unstained by the marker dye, indicating that the inner layers of the left ventricular wall had been deprived of their supply of blood while the heart was beating. Ischemia of the inner layers must be explained by an excess of local intramyocardial pressure over local coronary pressure, that persists even in diastole. Ischemia of the inner layers may explain the “descending limb” of the systolic pressure-volume diagram, which is regularly observed in beating ventricles but not in heart muscle strips. Ischemia of the inner layers of ventricular wall can initiate vicious cycles that cause sudden death in persons with coronary stenosis. Ischemia of the inner layers is a cause of irreversible cardiac damage that can terminate life suddenly, without leaving obvious traces that can be detected at autopsy.

Comparison of Two Types of Mechanical Assistance in Experimental Heart Failure

In open-chest dog experiments, 7 different types of cardiac failure were produced. In each type of failure, the effect of veno-arterial pumping and of left ventricular bypass (blood pumped from the left atrium to femoral artery) was investigated. Pressures were recorded in the left ventricle, the left atrium, the right ventricle, and the femoral artery. Veno-arterial pumping reversed failure of the right ventricle. It also was beneficial when overtransfusion had aggravated failure of the right or left ventricles, except in pre-existing aortic insufficiency. Veno-arterial pumping markedly increased decompensation of the left heart in the majority of observations, even though it occasionally reduced pressures in the left atrium and the right ventricle. The experiments suggest the use of veno-arterial pumping or of partial bypass with a heart-lung machine in acute cor pulmonale and in pulmonary congestion caused by abnormalities of the mitral valve where the left ventricle remains compensated. Veno-arterial pumping appears contraindicated in true failure of the left ventricle. Left ventricular bypass always restored compensation in all types of heart failure except cor pumonale. The experiments suggest the clinical use of left ventricular bypass in left heart failure.

Reflex Effects of Left Ventricular Distention

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.

Intramyocardial Pressure and Strength of Left Ventricular Contraction

Intramyocardial pressure was followed with the Johnson-DiPalma method in isolated hearts and in hearts in situ. Systolic intramyocardial pressure curves from hearts in situ exhibited two pressure peaks which were believed to coincide with peak contractile tension and with myocardial fiber shortening, respectively. The following factors influenced intramyocardial pressure: ventricular cavity volume, heart rate, coronary perfusion pressure, outflow resistance, and “epicardial” compression. The contractile strength of the left ventricle varied in proportion with the intramyocardial pressure; it did not appear to be regulated primarily by diastolic volume or by metabolic support. Intramyocardial pressure was believed to determine the contractile strength of the heart by controlling the release of a potentiating substance.

Coronary Driving Pressure and Vasomotor Tonus as Determinants of Coronary Blood Flow

A method is described that measures the contribution of coronary vasomotor tonus and extracoronary factors in the regulation of coronary blood flow. Coronary flow was measured from the bypassed right heart when the left ventricle pumped the entire systemic flow (method “A”) and when a heart-lung machine generated systemic pressure (method “B”). In method “B,” the mechanical activity and the oxygen consumption of the heart could be dissociated from systemic pres sure by the use of a balloon in the ventricle. Control measurements were performed in “uninjured” hearts; when a balloon was inflated to a left ventricular diastolic pressure of 15 mm. Hg or more, a state of “cardiac injury” supervened. The arterial oxygen content was kept above 20 to 21 vol. per cent, but the cardiac oxygen consumption varied over a wide range. Whenever hemodynamic factors changed, coronary flow was a highly correlated, straight-line function of the difference between the aortic pressure and the left ventricular pressure, which we call the “coronary driving pressure.” In “injured” hearts this linearity and high correlation persisted, but the slope of the regression line increased. We conclude that coronary flow is determined by the integrated difference between the propulsive force (the fluctuating pressure head at the coronary ostia) and opposing forces (intramyocardial pressure, which is known to oppose local coronary flow whenever and wherever it exceeds intravascular pressures). Cardiac oxygen consumption and coronary blood flow were not significantly related and were, therefore, coordinated by purely mechanical pressure differentials and not by changes of coronary vasomotor tonus. However, coronary vasomotor tonus decreased markedly during arterial anoxia or after various types of cardiac injury; it increased after Pitressin.

Distensibility and Water Content of Heart Muscle Before and After Injury

In open-chest dogs the circulation was carried on a heart-lung machine. The right heart and the left atrium were drained. A balloon was placed in the virtually bloodless left ventricle and filled with a known volume of air at the beginning of an experiment; left ventricular pressure was recorded after a steady state had become established. After this control observation, the preparation was exposed to experimental maneuvers, such as variation of the systemic flow rate or changes of the air volume in the balloon. At one or more later stages of the same experiment, the balloon was emptied, the heart was allowed to beat empty for several minutes, and the standard observation was again repeated. Comparison of left ventricular pressures from the initial and later observations showed that the diastolic pressure in the left ventricle increased in the course of the experiment even though other conditions were comparable. From this we conclude that experimental maneuvers injuring the heart muscle reduce its distensibility. The water content of injured hearts was abnormally elevated; myocardial edema is therefore not excluded as one of the mechanisms explaining the reduced distensibility of injured heart muscle.

FUNCTIONAL SUBAORTIC STENOSIS PRODUCED IN ANIMALS.

Abstract Important systolic pressure gradients between the left ventricle and the arterial system were intentionally reproduced in dogs with closed pericardium, when their cardiac output was diminished and the contractile strength of the heart was maintained or increased. Pressure patterns reverted to normal when the pericardium was widely opened or when the cardiac output was increased while other factors remained constant.

Factors Which Initiate or Influence Edema in the Isolated Dog's Heart

Isolated dog hearts were perfused while time heart weight was electrically recorded. Arterialized blood was pumped into a coronary perfusion reservoir either from the femoral artery of a donor dog or from the arterial outlet of various oxygenators. The right heart was widely open. The presence of myocardial edema and the rate of fluid accumulation in heart muscle were observed from the slopes of tile weight registration and from the difference of the directly measured heart weights before and after an experiment. Blood hold-up was measured in three experiments with tagged red cells: it accounted for 15 per cent or less of the observed weight gain. When the heart was perfused from a donor dog and was not otherwise injured, myocardial edema fluid did not accumulate unless the coronary pressure exceeded 200 mm. Hg. Myocardial edema also formed when blood was diluted with Ringers solution or after cardiac injury; the rate of edema formation was then dependent on the coronary perfusion pressure. Edematous hearts could often be made to lose weight (i.e., edema fluid) when perfused at pressures below 100 mm.Hg. Perfusion with blood from a disposable bag oxygenator initiated inyocardial edema formation almost immediately.

Stretch Reflexes from the Main Pulmonary Artery to the Systemic Circulation

In open-chest dogs, the greater and lesser circulations were perfused by a system of pumps and oxygenator. All blood was drained from the right heart and from the left atrium. in most experiments, there was no dissection around the pulmonary hila, the aorta, or the pulmonary artery. A 30-ml. balloon (Foley catheter) was inserted into the pulmonary artery through a stab wound in the wall of the right ventricle. Pressures were recorded in the pulmonary-artery balloon and in a femoral artery. In other experiments, the main pulmonary artery was distended with blood at known pressures after hydraulic isolation with ligatures and snares. When the main pulmonary artery was distended proximal to its bifurcation, constriction of the systemic arteries occurred. This phenomenon was abolished by local anesthesia of the wall of the main pulmonary artery, by interrupting conduction in the vagi, by a sympatholytic drug, and by reflex systemic hypotension elicited by multiple small pulmonary emboli. The pressor reflex from the pulmonary artery to the systemic circulation was not influenced by changes of pulmonary blood flow or by inflation of other balloons in various chambers of the heart. Limitations inherent in the experimental procedure did not permit us to assign physiological significance to the phenomenon.