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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.

1. 1. Experiments using radioactive spherules demonstrate that the coronary interarterial collateral circulation is not functional in the normal dog's heart. Hypoxemia can activate some coronary interarterial anastomosis. 2. 2. Three weeks after coronary occlusion the interarterial anastomosis is at least 35 μ in diameter, and at 12 weeks is even more extensive.

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.

Sixty per cent of a control series of the dogs died from a standard toxic dose of digitalis. In a series rendered toxic by a similar dose of digitalis, only 10 per cent died when they were treated with the combination of sodium-potassium citrate salts. A combination of sodium and potassium citrate salts administered intravenously is effective for the treatment of digitalis-induced arrhythmias.

The effect of glyceryl trinitrate (nitroglycerin) on systemic and coronary hemodynamics was studied in normal dogs by means of electromagnetic flowmeters and integrator computers. When given intravenously, glyceryl trinitrate produced changes in the hemodynamics which can be of benefit to the patient with angina pectoris. The drug first increased the coronary blood flow and cardiac index and reduced peripheral vascular resistance for about 20 seconds. This was followed by normal coronary flow with reduced peripheral and coronary vascular resistance, for about 60 seconds; at the same time cardiac work was markedly reduced. These results confirm that the beneficial effects of nitroglycerine are due to its action on the coronary as well as the systemic circulation.

The effects of venoarterial pulsatile partial bypass upon the coronary, mesenteric and renal circulations were studied in cardiogenic shock. Circulatory assist corrected the shock state in 9 of the 10 animals as exhibited by return of systemic pressure to normotensive levels. The most uniform effect was the increase in coronary flow with lowering of coronary resistance associated with other objective signs of improved myocardial nutrition—that is, less cardiac irritability and correction of S-T elevations. Mesenteric flow was irregularly improved by pumping. Renal flow was not corrected; it remained at the same low levels that occurred during shock because of an increased renal vascular resistance.

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.

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.

Because of the controversy concerning techniques of cardiac resuscitation, it was decided to return to the laboratory to evaluate the hemodynamic benefits of these techniques under more controlled conditions. The experimental design revealed closed-chest massage to be an effective technique when compared to open-chest resuscitation. Closed-chest massage is proposed as a scientifically valid interim resuscitative measure which, if applied within the crucial four-minute limit, will maintain life until definitive diagnostic and therapeutic procedures can be instituted.

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.

Ninety-six percent successful resuscitation was achieved after circulatory support in 25 dogs with resistant ventricular fibrillation; in 17 of these the fibrillation was induced by coronary occlusion. When arterial-coronary sinus lactate differences were studied, a negative balance of lactate was found during ventricular fibrillation. Circulatory assist was able to provide a positive lactate balance, suggesting improvement of altered metabolic pathways in the myocardium. Since cardiac arrest secondary to myocardial infarction induces hemodynamic and metabolic disturbances similar to those presented in this experimental model, this study provides evidence of the value of circulatory assist to enhance defibrillation when refractory cardiac arrest is present.

Ajmalin is an effective drug for the treatment of serious digitalis-toxic cardiac arrhythmias. The mortality rate in the ajmalin-treated animals was 10 per cent. The mortality rate in a control series was 50 per cent.

When given early vasopressor drugs can be an effective from of therapy for cardiogenic shock because they increase coronary blood flow, cardiac output and blood pressure. They vasodilate the coronary vascular bed and in 40 percent of the experiments, reduce total peripheral vascular resistance. The use of 3-hydroxytyramine and the vasopressor-vasodilator combination provide most effective coronary and regional perfusion to other vital organs. New mechanical circulatory assistance techniques applied to the treatment of irreversible cardiogenic shock promise that the high mortality rate associated with this dreaded complication will be reduced.

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.

Phantom arrhythmias and evanescent cardiac abnormalities may cause distressing symptoms, but unless the electrocardiogram is recorded during the event, the diagnosis will escape the clinician. The recent introduction of the Holter monitor for electrocardiographic monitoring for periods up to ten hours in the patient's native environment allows the clinician to detect these pathological states. Instances of neurological symptoms due to cerebrovascular insufficiency and chest pain due to coronary insufficiency detected by this monitoring system suggests that many episodes of hemodynamic crises escape detection by the clinician.

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

Digitalis toxicity must be considered a serious cardiac emergency when it causes ectopic arrhythmias, conduction defects, and suppression of sinus pacemaking function. It has been estimated that 6% to 20% of patients receiving the glycosides develop digitalis toxicity1,2because of the narrow range that exists between the therapeutic and toxic dose. The therapeutic dose is approximately 60% of the toxic dose.3 There are a number of factors which precipitate digitalis toxicity: (1) overdose, (2) individual idiosyncracy, (3) electrolyte imbalance following potassium loss due to diarrhea or gastric intubation, etc, and (4) calcium administration to the digitalized patient causing a sudden potassium exodus from cardiac muscle.4,5At present, a common precipitating cause of digitalis toxicity is hypokalemia resulting from the use of saluretic drugs in conjunction with digitalis.3,6-9 There is no specific arrhythmia due to digitalis toxicity. When the glycosides are used in excess, or if there is an associated loss

Sixty symptomatic patients, with recurrent cardiac arrhythmias resistant to conventional antiarrhythmic therapy, were treated with orally administered sodium diphenylhydantoin to assess the antiarrhythmic efficacy of the drug. The arrhythmias seen were (1) premature ventricular contractions, (2) paroxysmal atrial tachycardia, (3) paroxysmal atrial fibrillation, (4) premature atrial systoles, (5) premature nodal systoles, and (6) chronic atrial flutter. On an initial regimen of 100 mg three times daily, 37 of the 60 patients had an excellent response in that they have maintained regular sinus rhythm over an average of 16.8 months to date. A moderate response was obtained in six additional patients in whom there was a marked reduction in the frequency of the arrhythmia and the severity of symptoms. Six other patients failed to respond to the medication, and 11 were forced to discontinue taking the drug because of the development of side effects. No blood dyscrasias were seen.