More on sulfinpyrazone after myocardial infarction.
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Biomedical subjects
Publications and source records attributed to W B Hood.
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In this double-blind randomized study, 19 patients with acute transmural myocardial infarction were treated with methylprednisolone administered 4.4 +/- 0.7 hours (+/- SEM) after the onset of chest pain, and were compared with 21 patients who received placebo 4.5 +/- 0.4 hours after the start of clinical symptoms. The two groups were comparable in reference to sex, prevalence of risk factors, clinical status on admission, location of myocardial infarction and magnitude of ischemic injury as assessed by standard ECGs and precordial ST-segment and QRS maps. The treated patients, however, were older than the patients who received placebo. Methylprednisolone in an i.v. dose of 2.0 g was administered on admission and a similar dose was infused 3 hours later. Placebo administration followed an identical schedule. Mortality, cardiac rupture, incidence of ventricular arrhythmias, blocks, extension of myocardial infarction, pericarditis, postinfarction chest pain, persistent ST-segment elevation at discharge, and change in Killip class during hospitalization were the same in both groups. Peak enzyme values, and changes in ECG variables pertaining to resolution of ST-segment elevation or development of QRS evolutionary alterations were similar in both groups. Follow-up for 6 months did not reveal any differences in the clinical course of the two groups. Methylprednisolone infused in a total dose of 4.0 g within 12 hours after the onset of chest pain in patients with acute transmural myocardial infarction does not result in any demonstrable beneficial or harmful effects.
Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 micrograms/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p less than 0.05) decreased peripheral vascular resistance (from 3804 +/- 1158 to 2876 +/- 816 dy-sec-cm-5) (+/- SD) and mean aortic pressure (from 117 +/- 12 to 107 +/- 15 mm Hg), and increased cardiac output (from 2.63 +/- 0.67 to 3.12 +/- 0.74 l/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.
Cardiovascular actions of insulin were studied by intravenous infusions of insulin (4 and 8 mU/kg per min) in normal conscious dogs. This resulted in increases in cardiac output, heart rate, and left ventricular derivative of pressure with respect to time (dP/dt) and dP/dt/P, as blood glucose was reduced. The inotropic and chronotropic effects of insulin were not related to hypoglycemia, as they persisted even when blood glucose was restored to control values or when it was prevented from falling by a simultaneous infusion of glucose. These cardiac effects were accompanied by increases in plasma catecholamines, and were abolished by propranolol pretreatment. Both plasma epinephrine and norepinephrine increased during insulin hypoglycemia, but only norepinephrine increased during insulin infusion when euglycemia was maintained. Mean arterial blood pressure did not change significantly during insulin hypoglycemia, but rose if euglycemia was maintained, probably due to the selective increase in norepinephrine in the latter condition. A pressor response also occurred in propranolol-pretreated dogs during insulin hypoglycemia, but was abolished when the animals also had been pretreated with phentolamine, indicating that the vasoconstrictor action of insulin was mediated via alpha adrenergic receptors. Insulin infusion increased left ventricular work and myocardial blood flow in dogs with and without hypoglycemia. Myocardial blood flow, however, did not change significantly during insulin infusion in dogs pretreated with propranolol. As propranolol also diminished the inotropic response, it appears that the increase in myocardial blood flow caused by insulin in the normal dog is causally related to the increased myocardial metabolic demand. Insulin also produced vasomotor effects on other vascular beds. In skeletal muscle, blood flow was increased under all study conditions, except during insulin hypoglycemia after propranolol-pretreatment when unopposed alpha-mediated vasoconstriction was present. The persistent increase in flow during both alpha and beta adrenergic blockade suggests that insulin has a direct dilator effect on skeletal muscle vasculature. In the adrenal gland, flow was increased except during euglycemia, when no rise in plasma epinephrine was observed, suggesting coupling between adrenal flow and catecholamine release. In the splanchnic bed, flow was decreased during euglycemia, when plasma norepinephrine rose, and during beta adrenergic blockade with propranolol, when unopposed alpha-mediated vasoconstriction also predominated. A similar pattern was found in the kidney, except that renal blood flow also fell after combined alpha and beta adrenergic blockade. The results show that the vasomotor effects on regional flows are mediated both via adrenergic mechanisms, and in the case of skeletal muscle and kidney, via mechanisms unrelated to sympathetic stimulation.
Sickle cell anemia is a lifelong debilitating disease often required multiple, frequent hospital admissions. Multiple organ systems become damaged, but the heart, although demonstrating abnormalities, is relatively spared. With increasing life span of these patients, cardiac dysfunction may become more prominent. Recent noninvasive and pathologic studies have given new information on the effect of this disease on the heart. This article reviews the current knowledge of cardiac involvement in sickle cell anemia.
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.
The effect of verapamil, an inhibitor of transmembrane calcium flux, was studied in intact conscious dogs with myocardial ischemia produced by inflating a balloon cuff implanted on the left anterior descending coronary artery. Six dogs received a continuous infusion of verapamil (10 microgram/kg per min) beginning prior to coronary occlusion, and six received normal saline infusions. Systolic ejection shortening (SES) was measured from subendocardial ultrasonic crystals implanted in the central ischemic zone (IZ) and border zone (BZ), and in a nonischemic control zone (CZ). Hearts were paced at a constant heart rate with periodic introduction of closely coupled extrasystoles. SES was measured both for normally paced beats and during postextrasystolic potentiation (PESP). Regional myocardial blood flow was measured by injecting radioactive microspheres before, during, and after coronary occlusion. There were no significant differences between verapamil-treated dogs and saline control dogs in mean aortic pressure, heart rate, left ventricular end-diastolic pressure or dP/dt, cardiac output, or regional myocardial blood flow in IZ, BZ, or CZ. Differences in mechanical performance between two groups were noted, however. In the IZ, SES was abolished completely for normally paced beats in both groups but was significantly preserved for PESP beats in the verapamil-treated animals. In the BZ, SES was significantly reduced for normally paced beats only in the saline controls, and PESP responses were preserved to a significantly greater degree in the verapamil-treated animals. These results indicate that verapamil pretreatment exerts beneficial effects upon mechanical performance of ischemic myocardium. Since no changes in systemic hemodynamics or regional myocardial blood flow were observed, the effect may be due to the calcium-antagonistic properties of the agent.
We infused dobutamine (20 microgram/kg per min) intravenously, once before and once after coronary artery occlusion, in 10 chronically instrumented dogs. Both infusions increased cardiac output and left ventricular dP/dt and dP/dt/P, but divergent effects on heart rate and aortic blood pressure were observed. Dobutamine decreased heart rate and increased mean aortic blood pressure before coronary artery occlusion, whereas after occlusion it increased heart rate while mean aortic blood pressure remained unchanged. A greater decrease in total peripheral vascular resistance occurred during dobutamine infusion after coronary artery occlusion than before. These differences may relate to withdrawal of enhanced sympathetic tone after coronary occlusion. Similar infusions of normal saline (n = 9) produced no systemic hemodynamic changes either before or after coronary artery occlusion. Myocardial blood flow increased to both non-ischemic and ischemic regions of the heart during dobutamine infusion, but the endocardial:epicardial blood flow ratio did not change significantly. In addition, infarct size, measured by nitroblue tetrazolium stain, was smaller in the dobutamine group (10 +/- 1 g) than in the normal saline group (15 +/- 2 g). Neither left ventricular weight nor risk zone differed between the two groups. These results indicate that dobutamine may be a useful inotropic agent during acute myocardial infarction.
An increase in QRS amplitude with S-T elevation occurs during the acute phase of myocardial infarction, coronary ligation and variant angina. Ischemic conduction delay, postulated as the cause, has not been well characterized. Six patients with transient chest pain, S-T elevation and increase in R-wave voltage also displayed concomitant shift of the frontal QRS axis toward the locus of injury. Electrocardiographic considerations suggest that regional ischemic block, not true hemiblock as has been suggested, offers the most inclusive explanation, providing previously neglected clinical confirmation of experimental observations.
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A mathematical instrument was developed to supplement the diagnostic information available to physicians in the emergency room to improve physicians' diagnostic accuracy in managing patients with acute ischemic heart disease and thereby reduce inappropriate coronary care unit admissions. The instrument was empirically derived and is based on nine clinical, historical, and electrocardiographic predictive variables. Probabilities of acute ischemic heart disease generated by the instrument were given to the house staff in an emergency room during alternate months. Comparison of the control months (455 patients) with the experimental months (401 patients) showed the following: The overall diagnostic accuracy increased from 83% to 91% (P less than 0.005), the overdiagnostic accuracy increased from 51% to 33% (P less than 0.01), and the admission rate to the coronary care unit fell from 26% to 14% (P less than 0.001), while the inappropriate discharge rate from the emergency room did not change, 3% versus 3% (not significant).
The apexcardiogram (ACG) and cardiokymogram (CKG) (displacement cardiogram) tracings were compared in 45 patients with a variety of cardiac diseases and in 16 normal subjects. The ACG and CKG were generally comparable in waveform and timing of standard tracing intervals; however, on a case by case comparison frequent discrepancies between the ACG and CKG were observed. In 13 patients where no ACG could be recorded, an interpretable CKG tracing was obtained. However, the CKG produced frequent artifacts, mirror images, was very sensitive to probe position, and was judged to be of limited advantage over the ACG.
The effects of nitroglycerin on regional left ventricular performance, assessed by echocardiographic techniques, were investigated in anesthetized, open-chest dogs during acute myocardial ischemia. During transient occlusion of the left anterior descending coronary artery, there was end-diastolic thinning and marked reduction in systolic thickening in the central ischemic zone. Similar changes of lesser degree were noted in the border zone. The normal zone was unaffected. Infusion of nitroglycerin during ischemia in dosages of 2.5--50 microgram/kg/min reduced left ventricular end-diastolic pressure without changing the abnormalities of systolic wall thickening. Effects of bolus injections of 20 and 50 microgram/kg of nitroglycerin were similar, although this also lowered aortic pressure. In a subgroup of animals in which nitroglycerin infusion was unaccompanied by tachycardia, there was also no evidence that ischemic dysfunction was altered. We conclude that nitroglycerin does not improve regional myocardial performance in acutely ischemic canine myocardium. The decrease in preload is probably entirely due to the peripheral effects of the agent.
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We studied the conditioning effects of chronic infusion of dobutamine and exercise training in three groups of chronically instrumented dogs. One group was infused with normal saline, a second group was infused with dobutamine (40 mug/kg per min), and the third group was exercised on a treadmill at 4 mph, up a 10 degrees incline. Each group was either infused or exercised for 2 h a day, 5 d a week for 5 consecutive wk. Resting heart rate and arterial blood lactate concentration, measured at weekly intervals, decreased progressively in the dobutamine and exercise groups, but not in the group that received normal saline infusion. Cardiovascular responses to submaximal treadmill exercise were not changed by 5 wk of normal saline infusion. However, the increases in heart rate, cardiac output, mean aortic blood pressure, arterial blood lactate, plasma renin activity, and norepinephrine concentration during exercise were significantly smaller after 5 wk of conditioning with either dobutamine or exercise training. After conditioning, the increases in arteriovenous oxygen difference during exercise were larger in the latter two groups, but the increases in total body oxygen consumption did not differ before and after conditioning. To assess ventricular function, we intravenously infused methoxamine both before and after conditioning. The slope of the line that related systolic aortic blood pressure and mean left atrial pressure increased in the animals conditioned with either dobutamine or exercise, indicating enhanced myocardial contractility. Left ventricular blood flow was lower in these two groups of animals than it was in the normal saline group. Left ventricular weight did not differ among the three groups. Our results show that chronic infusion of dobutamine produced cardiovascular and metabolic conditioning effects like those produced by exercise training, and further suggest that sympathetic stimulation during exercise plays a role in physical conditioning.
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The periodic influx of large numbers of people into resort areas substantially increases the use of emergency medical services. This investigation assesses the effects of such a threefold increase in the summer population of the Cape Cod area upon the accuracy of emergency medical technicians' diagnoses and treatments. The technicians' diagnoses for ambulance patients were evaluated against those given by the emergency room physicians during the months of August 1975 and February 1976. The distribution of conditions was similar for both months and the observed frequency of correct diagnoses for common conditions was more than 90% in both months. The overdiagnosis rate of 25% to 50% for common conditions and the correct treatment rate for suspected myocardial infarction of 65% did not vary significantly between summer and winter. Thus, a large influx in population does not seem to affect adversely EMT diagnosis rates. Although misdiagnoses were uncommon, a failure to follow through with a correct treatment for patients with suspected myocardial infarctions, thus indicating the need for better quality control on EMT performance.