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l -dopa was administered to 20 dogs in cardiogenic shock. Beneficial effects were noted three to five minutes after infusion began, but more significant effects were observed within 15 minutes, reaching a maximum 45 to 60 minutes after infusion. The principal changes observed were: (1) a significant increase in coronary flow, (2) a significant rise in left ventricular dp dt max , and (3) a decrease in total peripheral vascular resistance. Aortic and mesenteric flows increased significantly. Renal flow did not improve throughout the l -dopa infusion. l -dopa benefits were probably due to a stimulation of the beta-receptors.

Hemodynamic and regional metabolic measurements were obtained in seven closed chest dogs during a control period, 3 hours of coronary occlusion and 5 hours of reperfusion. Reperfusion resulted in intermittent ectopic arrhythmias in five dogs and severe shock in two. It usually caused increases in heart rate, coronary sinus flow and maximal isovolumetric rate of rise in left ventricular pressure (dP/dt), which were associated with a decrease in systemic pressure, left ventricular end-diastolic pressure, systemic vascular resistance and stroke work. A transitory increase in cardiac output occurred. Global myocardial oxygen consumption, which was reduced during occlusion, increased with reperfusion. Reperfusion induced abnormal lactate metabolism and myocardial potassium loss in the previously occluded area and often in the nonoccluded segment as well. Histopathologic changes of accelerated necrosis, reactive hyperemia and hemorrhage were often noted after reperfusion. These studies indicate that reperfusion after 3 hours of occlusion caused serious abnormalities in hemodynamic states, metabolic function and morphologic features of the heart.

A new closed chest animal technique permits selective intracoronary balloon occlusion and measurement of hemodynamic and regional metabolic function before and during occlusion and reperfusion. The distal end of the double lumen balloon catheter provides information about the nature and extent of flow distal to the occlusion and permits blood sampling or administration of pharmacologic agents directly into the ischemic zone. Independent blood sampling from the great cardiac vein by means of a specially designed balloon catheter and from the coronary sinus by cannula allows simultaneous biochemical and regional blood flow measurements from the occluded and nonoccluded segments of the heart. Simultaneous intracoronary epicardial electrocardiograms permit electrophysiologic correlation with regional hemodynamic and metabolic events. The administration of oxygen by tracheal airway can increase partial oxygen tension in the circulation distal to coronary occlusion. When intracoronary pressures distal to occlusion are markedly reduced, the frequency of ventricular fibrillation is much greater.

Venoarterial pulsatile partial bypass and intraaortic balloon counterpulse techniques produce (1) diastolic augmentation of aortic pressure which improves perfusion of the myocardium, and (2) a sink in presystolic and systolic pressures which lowers the workload of the left ventricle. Both techniques are effective in reversing the shock state in dogs and in man. Regional hemodynamic studies performed before, during and after counterpulsation explain benefits and drawbacks of each technique.

Two experimental series of closed chest dogs were compared: Group A (five dogs with 7 days of continuous occlusion of the proximal left anterior descending coronary artery); and Group B (six dogs with 7 days of reperfusion after 3 hours of acute occlusion of the same artery). Hemodynamic measurements, ventricular wall motion, coronary sinus blood flow and regional metabolism in both coronary occluded and nonoccluded segments of the left ventricle were measured sequentially. The infarct size was characterized by detailed histopathologic analysis. In the control dogs (Group A), mechanical and metabolic function remained severely depressed after 7 days of occlusion, and mean infarct size was 31.6 percent. In Group B, significant mechanical and metabolic dysfunction developed during 3 hours of occlusion and did not improve during the 1st hour of reperfusion. However, after 7 days of reperfusion, function returned to near preocclusion level. Mean infarct size was 14.2 percent, but in two of the six dogs infarct size was 43 percent and 23 percent, respectively. The study confirmed the unstable character of the early phase of reperfusion, attributed to cell swelling, edema and hemorrhages that resulted in inadequate coronary reflow, arrhythmias and functional derangements. Prolonged reperfusion for 7 days reduced mean infarct size and improved cardiac function.

Focal necrosis (microinfarcts) and regional lactate derangements were observed in closed chest dogs in the nonoccluded (remote) posterior segments of the left and right ventricles after acute occlusion of the proximal left anterior descending coronary artery. Focal infarcts in the remote areas were observed in five of the six dogs with 7 days of occlusion of the left anterior descending artery and in six of seven dogs with 7 days of reperfusion after 3 hours of occlusion. There was a good correlation between the finding of microinfarcts and myocardial lactate derangements in the corresponding remote myocardium. No significant lactate derangements or microinfarcts were found in sham experiments. These findings suggest that ischemia of the remote myocardium frequently accompanies an acute coronary occlusion and may result in irreversible focal lesions.

Hemodynamic and regional metabolic function was assessed simultaneously in 34 closed chest dogs during a preocclusion control period and 3 hours of intracoronary balloon occlusion of the proximal left anterior descending artery. The data indicate immediate alteration in hemodynamic measurements with many fluctuations in the 3 hour occlusion period. No specific hemodynamic pattern was evident. When the mean data were analyzed, occlusion was found to cause early increases in left ventricular end-diastolic pressure (43 percent) and systemic vascular resistance (21 percent), and decreases in peak systolic pressure (5 percent), maximal rate of rise of left ventricular pressure (dP/dt) (20 percent), cardiac output (19 percent), stroke work (26 percent) and coronary sinus blood flow (19 percent). Regional metabolic measurements showed significantly different metabolic function in the occluded and nonoccluded zones of the left ventricle. Lactate balance decreased to near production levels, and a substantial potassium loss occurred in the occluded zone shortly after occlusion; lactate and potassium balances later fluctuated, but usually remained depressed. Abnormal lactate metabolism and potassium efflux were often observed in the nonoccluded zone. A 6 to 8 percent increase in oxygen extraction was noted in both segments. Progressive alterations in hemodynamic and metabolic function of the heart after coronary occlusion are not uniform and exhibit dynamic fluctuations. Although a direct relation was noted between the degree of metabolic dysfunction and hemodynamic change, individual experiments often revealed a distinct metabolic-mechanical dissociation.

A considerable net myocardial potassium loss was demonstrated in the dog during rapid ventricular tachycardias. This net potassium loss was associated with some serious arrhythmias which invariably induced resistant ventricular fibrillation. The myocardial potassium loss was associated with an increased myocardial oxygen consumption and lactic acid production. These studies suggest that restoration of the myocardial potassium balance may provide a more proper rationale for the treatment of cardiac arrhythmias.

Ascending aorta synchronized pulsation (AASP) was found to be simple and effective method of counterpulsation directed at the root of the aorta. It provided excellent mechanical assistance for the treatment of severe cardiogenic shock following coronary artery ligation. Because the proximal site of counterpulsation requires low stroke pump volumes, only minimal hemolysis resulted. The AASP counterpulsation was performed for periods up to 90 minutes in ten dogs. After two minutes a significant increase in coronary flow and reduction in systolic pressures were observed, and after 90 minutes of continued AASP counterpulsation, pressures and flows increased from shock levels toward normotensive control levels and hemodynamic indices improved. These improvements persisted after AASP pumping was stopped in nine dogs, which proved AASP reversed the cardiogenic shock state.

After almost 25 years of extensive experimentation there appears to be confusion about the actual clinical performance of available mechanical systems for treatment of cardiogenic shock. Because shock continues to have an 80 to 90 percent mortality rate, we consider it urgent that a multidisciplinary assessment be made of clinical benefits and drawbacks of circulatory assist techniques. The most attractive assist technique is counterpulsation, which provides,, in each cardiac cycle, left ventricular unloading and augmentation of the myocardial perfusion potentia1.l Such a dual assist concept represents an idea:l approach to the treatment of cardiac pump failure because it may reverse the vicious cycle that tends to perpetuate the shock state. Among the growing number of counterpulsation systems developed to date are: (1) femoral arterialarterial counterpulsationl; (2) venoarterial pulsatile phased bypassz; (3) intraaortic balloon pumping3T4; (4) ascending aorta synchronized pulsation5; (5) aortic root balloon pum!ping6; (6) unidirectional intraaortic balloon pumping7; (7) external pressure cardiac assists; (8) body acceleration synchronized with the heartg; and (9) implanted dynamic aortic patch for extended ae.sistance.lO Partial effects of counterpulsation, particularly unloading of the left ventricle, may be achieved with (10) transarterial closed chest left ventricular bypass,ll and (11) left atrium-to-aorta bypass.12 Although most of the physiologic data on the effectiveness of these systems were derived from animal experimentation, the ultimate test of effectiveness is its application to man. Results of 2 techniqu.es that have recently been popularized, intraaortic balloon and external pressure counterpulsation, are now available for evaluation. Clinical results of balloon counterpulsation: Recent reports of 2 major studies13y14 provided statistical data on this technique in patients with