John C. Norman

Experimental myocardial infarction: II. Acute depression and subsequent recovery of left ventricular function: serial measurements in intact conscious dogs

Acute myocardial infarction causes depression of left ventricular function, but the capacity of the ventricle to recover from such an injury remains unknown. This problem was explored by measuring left ventricular function in eight intact conscious dogs before, 1 hr after, and again 6-8 days after myocardial infarction. Acute myocardial infarction was produced using a technique which entails gradual inflation over an average period of 1 hr of a balloon cuff previously implanted around the left anterior descending coronary artery. Occurrence of anterior wall infarction was detected electrocardiographically and later confirmed by postmortem examination. Left ventricular function was evaluated from the relationship between left ventricular developed pressure (left ventricular peak systolic pressure minus left ventricular end-diastolic pressure) and left ventricular end-diastolic pressure during transient aortic occlusion with a balloon catheter. Left ventricular function curves were obtained by plotting left ventricular-developed pressure at increasing left ventricular end-diastolic pressures up to 50 mm Hg. Acute myocardial infarction caused marked depression of left ventricular function measured 1 hr after onset of infarction, but 1 wk later all eight animals showed improvement with return of function toward the control levels. A small but significant descending limb was noted at left ventricular end-diastolic pressures above 35 mm Hg. Quantitatively, the descending limb was similar before, 1 hr after, and 1 wk after myocardial infarction. Hemodynamic data revealed evidence of left ventricular failure in all animals, but variability in individual hemodynamic parameters was noted. The data indicate that the marked depression of left ventricular function observed immediately after experimental acute myocardial infarction undergoes considerable resolution within 1 wk, but that functional recovery remains incomplete.

Experimental myocardial infarction: VI. Efficacy and toxicity of digitalis in acute and healing phase in intact conscious dogs

Use of digitalis in myocardial infarction is controversial. To determine the efficacy and toxic threshold, serial infusions of 3 mug/kg per min of acetyl-strophanthidin were given to six intact conscious dogs 24 hr before and 1 hr, 2 days, and 7 days after myocardial infarction induced by inflation of a balloon cuff implanted on the left anterior descending coronary artery. Within 1 hr after myocardial infarction, heart rate increased by 28%. Left ventricular end-diastolic pressure increased from 7 to 20 mm Hg, and stroke volume decreased by 25%. At this time acetylstrophanthidin caused no beneficial hemodynamic change, 1 wk later, the heart rate and left ventricular end-diastolic pressure had declined toward normal but remained elevated. At this time, acetylstrophanthidin lowered left ventricular end-diastolic pressure by 25%, and increased the stroke volume and cardiac output by 25% and 21% respectively, without any change in heart rate or aortic pressure. Tolerance to acetylstrophanthidin, defined as appearance of ventricular tachycardia, declined the 1st hr after myocardial infarction by 24% (P<0.05) from the control level of 43 +/-4 mug/kg (SEM), but subsequently returned to control.Thus, immediately after myocardial infarction, tolerance to acetylstrophanthidin was reduced, and left ventricular failure was not ameliorated. 1 wk later in the healing phase of myocardial infarction, tolerance to acetylstrophanthidin returned to normal and left ventricular performance was improved by this drug. The study suggests a limited therapeutic role for digitalis in the treatment of left ventricular failure in the acute phase immediately after myocardial infarction, but beneficial effects may occur in the healing phase 1 wk later.

Antihemophilic factor release by perfused liver and spleen: relationship to hemophilia.

As judged by perfusion of isolated organs an antihemophilic factor is produced in the liver and the spleen. Perfusates (from hemophiliacs) that are deficient in the human anti-hemophilic factor stimulate production of the factor during perfusion. Apparently there is an antihemophilic-factor-stimulating substance in the plasma of hemophiliacs. The data suggest that splenic homotransplantation might alleviate the symptoms of hemophilia.

Experimental Myocardial Infarction X. Efficacy of Glucagon in Acute and Healing Phase in Intact Conscious Dogs: Effects on Hemodynamics and Myocardial Oxygen Consumption

This study was designed to test the efficacy of glucagon in the treatment of hemodynamic abnormalities of acute and healing experimental canine myocardial infarction. Myocardial infarction was produced in intact, conscious dogs by gradual inflation of a balloon cuff device implanted around the left anterior descending coronary artery 1 to 2 weeks prior to the study. Hemodynamic and metabolic effects of 50 &mgr;g/kg of glucagon were assessed serially in the control state, 1 hour after myocardial infarction and again 1 week later. In the control state glucagon improved cardiac performance and increased myocardial oxygen consumption. One hour after acute myocardial infarction glucagon improved cardiac performance and reduced the degree of left ventricular failure, without any increase in myocardial oxygen consumption. Similar effects of glucagon were noted in the healing phase of myocardial infarction. It is postulated that in this animal model in the presence of heart failure due to myocardial infarction there are reciprocal changes in the factors that increase myocardial oxygen consumption (glucagon-induced inotropy) and decrease oxygen consumption (fall in ventricular end-diastolic volume and wall stress), resulting in no net change in oxygen requirement.

Clinical trials of an abdominal left ventricular assist device (ALVAD): progress report.

Abstract An abdominal left ventricular assist device (ALVAD) is undergoing controlled clinical trials in our institution. The ALVAD is pneumatically-actuated, synchronously or asynchronously with an external console and is interposed between the apex of the left ventricle and the infrarenal abdominal aorta. It is an order of magnitude more effective than conventional intraaortic balloon pumping. Thus far, we have implanted this pump in 21 patients (15 males and six females). The average age has been 50. The duration of cardiopulmonary bypass with intensive pharmacologic support and IABP until ALVAD implantation has been nearly 4 hours. The plasma hemoglobins prior to ALVAD implantation have averaged 168 mg%. The platelet counts at implantation have averaged 68,000 mm3. The average duration of ALVAD support has been in excess of one day and the longest trial extended for one week. We have been able to remove the pump after ventricular recovery in two instances and effected cardiac allografting in one instance of ALVAD dependency. We have found that (1) the profoundly depressed left (and right) ventricles can recover if totally supported with this device; (2) the device can function in the presence of ventricular fibrillation and/or standstill; (3) the device can effectively replace both left and right ventricular function in the presence of normal pulmonary vascular resistance and microcirculatory hemodynamics; and (4) in the presence of impending multiple organ failure, procrastination in use is to be avoided.

Constancy of Myocardial Digoxin Concentration During Experimental Cardiopulmonary Bypass

Abstract Controversy persists regarding the status of myocardial and blood levels of digitalis during cardiopulmonary bypass. Eight dogs were given 1 mg. of tritiated digoxin IV (144 μCi per milligram specific activity) 170 minutes prior to bypass. Normothermic total cardiopulmonary bypass with partial hemodilution was instituted and maintained for 120 minutes. Serial serum or plasma and perfusate samples and right ventricle biopsies were obtained prior to and during bypass for digoxin concentrations determined by liquid scintillation counting. Right ventricular myocardial digoxin levels did not show significant changes. Significant decreases were noted in plasma digoxin levels during bypass, and there were concomitant increases in pump oxygenator perfusate digoxin concentrations. These findings can be accounted for by hemodilution. These observations indicate that myocardium-bound digoxin is not significantly influenced during cardiopulmonary bypass.