William B. Hood

Reduction of Coronary Atherosclerosis by Moderate Conditioning Exercise in Monkeys on an Atherogenic Diet

All available evidence that exercise may protect against coronary heart disease is circumstantial, and direct evidence is difficult to obtain in human beings. Therefore, we studied the effect of moderate conditioning with treadmill exercise on developing coronary-artery disease in monkeys on an atherogenic diet. Physical training was demonstrated by slow heart rates. Serum total cholesterol was the same (approximately 600 mg per deciliter or 15.5 mmol per liter) in exercising and non-exercising monkeys, with significantly higher high-density-lipoprotein (HDL) cholesterol and much lower triglyceride and low-density-lipoprotein (LDL) plus very-low-density-lipoprotein (VLDL) triglyceride in the exercise group. Ischemic electrocardiographic changes, angiographic signs of coronary-artery narrowing, and sudden death were observed only in non-conditioned monkeys, in which post-mortem examination revealed marked coronary atherosclerosis and stenoses. Exercise was associated with substantially reduced overall atherosclerotic involvement, lesion size, and collagen accumulation; it also produced much larger hearts and wider coronary arteries, further reducing the degree of luminal narrowing. Our data suggest that moderate exercise may prevent or retard coronary heart disease in primates.

Unresolved problems in coronary care

Abstract Recently the focus of the coronary care unit has shifted from resuscitation to prevention of cardiac arrest. From the data presented in this paper it appears that careful application of this policy will result in a one-third reduction in mortality among hospitalized patients with acute myocardial infarction. This result is achieved mainly by reducing the number of deaths due to unexpected catastrophic cardiac arrhythmias, e.g., primary electrical failure of the heart. Premonitory arrhythmias which herald the onset of such a catastrophe are defined as “arrhythmias of electrical instability” (multiple ventricular premature beats and ventricular tachycardia), and “arrhythmias of potential electrical instability” (bradycardia and heart block). Evidence is presented to show that aggressive treatment of these disorders should be employed. In this series of 300 hospitalized patients, death from myocardial infarction usually was due to overwhelming myocardial injury resulting in shock or pulmonary edema. Patients with this syndrome who do not respond immediately to catecholamines, digitalis and other routine measures carry an extremely poor prognosis; presently available methods have not significantly altered mortality in this group. Definitive treatment of intractable pump failure awaits the development of new technics such as circulatory assist devices. Immediate further reduction in mortality from acute myocardial infarction requires intelligent application of what has thus far been learned in the coronary care unit. Since sudden death prior to hospitalization, possibly due to arrhythmia, is still the chief cause of death from coronary occlusion, it follows that institution of coronary care unit technics closer in time to the onset of infarction may result in further salvage of life. The concept of “precoronary care” encompasses those measures required to effect this salvage. These include immediate hospitalization on mere suspicion of myocardial infarction, early electrocardiographic monitoring in emergency wards and in ambulances, and ultimately continuous telemetric monitoring of high-risk patients as they go about their daily tasks. Finally, it is clear that improved methods are needed for diagnosing myocardial infarction and for grading the severity of an attack. Standardized criteria should be established which will allow the vast accummulation of information currently pouring forth from coronary care units to be utilized in improving treatment of the disease.

Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine.

Fifteen patients with congestive cardiomyopathy (six idiopathic and nine alcoholic) manifested by heart failure (New York Heart Association class III or IV) were randomly assigned to a protocol in which dobutamine (n = 8) or 5% dextrose in water (n = 7) was infused continuously for 72 hr. The dose of dobutamine was titrated to increase cardiac output to twice the baseline values. The patients were evaluated before infusion, shortly after infusion, and 1, 2, and 4 weeks thereafter. Functional class improved in six of eight dobutamine-treated patients but in only two of seven control patients during the 4 week observation period. Maximal exercise time and left ventricular ejection fraction increased significantly above baseline only in the dobutamine group. However, neither dobutamine nor placebo infusion produced significant changes shortly after infusion in heart rate, cardiac index, or total peripheral vascular resistance at rest or during exercise at similar workloads. The group receiving dobutamine did show a reduction in systemic systolic and pulmonary arterial mean and diastolic pressure at rest (123 +/- 5 to 108 +/- 6, 32 +/- 5, to 24 +/- 3, and 26 +/- 4 to 20 +/- 2 mm Hg, respectively). In addition, total body oxygen consumption during similar workloads was lower after dobutamine infusion than before.(ABSTRACT TRUNCATED AT 250 WORDS)

Symptomatic myocardial infarction without chest pain: prevalence and clinical course.

Symptomatic myocardial infarction without chest pain was identified in 26 of 102 patients (25.5%) admitted to the hospital with acute myocardial infarction. As a group, these patients had a significantly lesser prevalence of a history of angina (P less than 0.05) and cigarette smoking (P less than 0.01). Their mean age was 69.1 years compared with 58.7 years for patients with chest pain (P less than 0.001). The group had a significantly greater median delay between the onset of symptoms and (1) arrival at the hospital (P less than 0.05), (2) examination by a physician in the emergency room (P less than 0.05), (3) diagnosis of possible myocardial infarction (P less than 0.001), and (4) transfer from the emergency room to the intensive care unit (P less than 0.001). They had significantly higher admission values for mean heart rate, respiratory rate, temperature and white blood cell count and more frequent in-hospital complications of pneumonia (P less than 0.001) and cardiogenic shock (P less than 0.05). Mortality in the group was 50% compared with 18% in the group with chest pain (P less than 0.05). Discriminant function analysis identified an at-risk population with 80% reliability.

Myocardial Infarction Following Coronary Ligation in Dogs: Hemodynamic Effects of Isoproterenol And Acetylstrophanthidin

In the subacute phase of myocardial infarction following coronary ligation in dogs, a relationship was noted between the extent of infarction and the degree of elevation of left ventricular end-diastolic pressure. Left ventricular filling pressure was consistently increased when 25% or more of the left ventricle was infarcted. Isoproterenol infusion resulted in enhanced left ventricular function in both control and infarcted dogs, but the response was clearly weakened in those animals in which more than 20% of the left ventricle was infarcted. Acetylstrophanthidin caused no improvement in left ventricular function in infarcted dogs as judged by the relationship between filling pressure and cardiac output. The peak rate of rise of left ventricular pressure did increase in animals with infarcts, but was less than that in controls. Animals with infarcts had a lowered threshold for production of ventricular tachycardia by acetylstrophanthidin. These results in dogs suggest the need for further assessment of the role of digitalis in the treatment of heart failure following acute myocardial infarction.

Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis

To determine the value of technetium-99m-pyrophosphate myocardial scintigraphy in the diagnosis of amyloid heart disease this procedure was prospectively performed in 20 consecutive patients with biopsy-proven primary amyloidosis. Eleven patients had echocardiographic abnormalities compatible with amyloid cardiomyopathy, 9 of whom had congestive heart failure. Diffuse myocardial pyrophosphate uptake was of equal or greater intensity than that of the ribs in 9 of the 11 patients with echocardiograms suggestive of amyloidosis, but in only 2 of the 9 with normal echocardiograms, despite abnormal electrocardiograms (p less than 0.01). Increased wall thickness measured by M-mode echocardiography correlated with myocardial pyrophosphate uptake (r = 0.68, p less than 0.01). None of 10 control patients with nonamyloid, nonischemic heart disease had a strongly positive myocardial pyrophosphate uptake. Thus, myocardial technetium-99m-pyrophosphate scanning is a sensitive and specific test for the diagnosis of cardiac amyloidosis in patients with congestive heart failure of obscure origin. It does not appear to be of value for the early detection of cardiac involvement in patients with known primary amyloidosis without echocardiographic abnormalities.

Correlation of serum magnesium levels and cardiac digitalis intoxication

Abstract A prospective study was undertaken to compare the prevalence of hypomagnesemia and hypermagnesemia in patients with cardiac digitalis toxicity and in digitalized patients without toxicity. During an 8 month period on a general medical service, there were 38 patients with “definite” or “possible” digitalis toxicity, by serial electrocardiographic studies, among 120 digitalized patients whose serum magnesium levels were obtained. Serum magnesium concentrations were measured by atomic absorption spectrometry. Hypomagnesemia was present in 21 percent of patients with and 10 percent of those without digitalis toxicity. Hypomagnesemia was not more prevalent in patients with toxicity but relatively lower serum levels of digoxin or digitoxin. The presence of hypermagnesemia was significantly greater in patients with toxicity (18 percent) than in those without toxicity (5 percent), and appeared to be related to a significantly greater prevalence of abnormal renal function in the former group. The potential value of magnesium administration in hypomagnesemic patients with cardiac digitalis toxicity warrants investigation. Caution should be exercised in the administration of magnesium sulfate to digitalis-toxic, azotemic patients who may already be hypermagnesemic.

Reversible obstruction of the ventricular outflow tract.

Abstract Obstruction of the left ventricular outflow tract with characteristics of subaortic muscular hypertrophy has been produced in a human subject and 2 of 8 dogs by infusion of isoproterenol. In 2 other dogs with outflow tract gradients in the “control” state, infusion of blood relieved the obstruction. The possible role of adrenergic stress in producing the clinical disease and the relationship of both to the hyperkinetic heart syndrome are discussed.

Graded global ischemia and reperfusion. Cardiac function and lactate metabolism.

The effect of global ischemia of different degrees of severity and reperfusion was studied in the isolated working rat heart. Four degrees of ischemia were induced by reducing the control total coronary flow of 8 ml/min to 0, 0.04, 0.4, or 0.8 ml/min for 30 minutes, after which the coronary flow was returned to the control level. After severe ischemia (0 and 0.04 ml/min ischemic coronary flow groups), recovery of contractility was to less than 30% of the control, pre-ischemic value of ventricular developed pressure and dP/dt, and irreversible cardiac contracture and an increised pacing threshold occurred. After moderate ischemia (0.4 and 0.8 ml/min ischemic coronary flow groups), contractile function recovered com- pletely, ischemic contracture was rapidly reversible and the pacing threshold did not increase. The moderately ischemic groups were able to function at a stable, low level of contractility for the 30 minute ischemic period, whereas the severely ischemic groups had no contractile activity. The amount of calculated tissue lactate accumulation correlated with the occurrence of irreversible ischemic injury; the severely ischemic groups which failed to recover with reperfusion accumulated 3-5 times as much lactate as the moderately ischemic groups which recovered completely. The results suggest that relatively small differences in the severity of the ischemic condition can markedly affect the degree of tissue injury.

The predictive value of anginal chest pain as an indicator of coronary disease during exercise testing

To determine the significance of anginal chest pain during exercise testing, a series of 302 patients undergoing coronary arteriography with exercise testing was reviewed. Of the 302 patients, 85 had ischemic ECG changes and chest pain (Group I); 87 patients had ischemic ECG changes but no chest pain (Group II); 25 patients had chest pain but no ischemic ECG changes (Group III); 105 patients had neither chest pain nor ischemic ECG changes (Group IV). Coronary artery disease was present in 95% of Group I, 75% of Group II, 72% of Group III, and 28% of Group IV. Of those patients with coronary disease, multiple vessels were involved in 94% of Group I, 51% of Group II, 67% of Group III, and 21% of Group IV. The predictive value for presence and extent of coronary disease showed Group I greater than Groups II and III greater than Group IV (p less than 0.025). We conclude that (1) anginal chest pain during exercise testing predicts the presence and extent of coronary disease more accurately than its absence; (2) the presence of chest pain even without an ischemic ECG response during exercise testing appears to be as predictive of coronary disease as an ischemic ECG response alone; and (3) the combination of anginal chest pain during exercise testing and an ischemic ECG response is highly predictive of multivessel coronary artery disease.