A B S T R A C T Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease.During an afterload test of LV function the pressor response to angiotensin evoked a threefold rise of enddiastolic pressure in the alcoholic group which was substantially greater than the 4 mm Hg rise in control subjects. The stroke volume and stroke work response in the noncardiac alcoholic was significantly less than in controls. Diminished LV function was corroborated in the noncardiac alcoholic at rest, using a contractility index.To evaluate the dose-response relationship of ethanol in the production of cardiac malfunction, two groups of noncardiac alcoholic subjects were studied acutely at low and moderate dose levels. After 6 oz, ventricular function, myocardial blood flow, and metabolism were not significantly affected. After 12 oz, there was a progressive rise of end-diastolic pressure and decrease of stroke output at a mean blood alcohol level of 150 mg/ 100 ml, reverting toward control by 4 hr. The coronary effluent transiently evidenced leakage of cell constituents, despite an increase of coronary blood flow, suggesting a direct but reversible cardiac injury. Myocardial extraction of triglyceride was enhanced, whereas FFA uptake was reduced. A possible role of myocardial triglyceride accumulation in heart muscle was considered in pathogenesis.Chronic ingestion of 16 oz of Scotch daily by an alcoholic subject while on a normal diet-produced, after 12 wk, a progressive increase of heart rate and size,

Although ethyl alcohol has a long medicinal history (1), its precise effects on the cardiovascular system have not been defined. Acute alcohol ingestion is known to result in triglyceride accumulation in the liver, which appears dependent upon an intact sympathetic nervous system (2). Evidence for stimulation of this system after ethanol ingestion has been advanced (3). Since sustained catecholamine infusion has been associated with lipid accumulation in the myocardium (4, 5), a study of the acute effects of ethanol on myocardial metabolism and function has been undertaken in animals considered nutritionally normal. The quantity given produced blood level concentrations usually associated with moderate intoxication. MethodsMongrel male dogs weighing 19 to 22 kg were anesthetized 18 hours postprandially with morphine sulfate, 3 mg per kg, and pentobarbital (Nembutal), 12 mg per kg, and studied without opening the chest. After insertion of an endotracheal tube, respiration was regulated with a Harvard respiratory pump, facilitating the maintenance of arterial oxygen saturation and pH in the normal range. Catheters were placed in the coronary sinus, pulmonary artery, aorta, and left ventricle for blood sampling and pressure determinations. Although initially the catheters were filled with dilute heparin, slow saline infusions or intermittent flushes were used during the experiment to maintain their patency. Since the level of arterial free fatty acids did not rise during the experiment, the earlier limited use of heparin did not appear to affect substrate concentrations.During the evaluation of cardiac performance in the intact animal in experiments of many hours duration, a direct measurement of contractility utilizing the forcevelocity relationship is not feasible, but less direct methods may be employed to characterize myocardial function. Thus, contractility change has been deduced from the relation of stroke output to left ventricular end-diastolic pressure (LVEDP) (6, 7).Sympathetic stimulation of isolated papillary muscle analyzed in terms of the force-velocity relationship has revealed an enhanced velocity of muscle shortening, representing a primary contractility increase (8). Sympathetic stimulation of the intact heart under conditions of controlled heart rate, before and after loading, has evoked an increase of stroke output as well as dp/dt maximum of left ventricular pressure as manifestations of primary contractility increments (9).A rise in LVEDP is normally associated with a corresponding stroke output increment (9), presumably a reflection of the rise in maximal isometric force without a velocity change that attends increased length of papillary muscle (8). The failure of stroke output to rise in this situation would appear to represent impaired muscle function (6,9,10) particularly when the duration of systole is prolonged or unchanged (6). In this present study the ventricular ejection rate was analyzed in terms of ventricular systolic duration and the maximal rate of rise of left ventricular pres...

To examine the influence of preexistent diabetes mellitus on left ventricular performance and coronary blood flow responses to acute ischemia, mild normoglycemic diabetes was induced in nine mongrel dogs after three doses of alloxan, (20 mg/kg, iv), at monthly intervals. Hemodynamic measurements and coronary blood flow (85 Kr clearance) were obtained before and after the onset of ischemia. This was produced by oc-clusion of the proximal left anterior descending coronary artery via a balloon-type catheter in nine intact anesthetized diabetic dogs and 10 nondiabetic dogs. During the 1st hour of ischemia in the diabetic group, the end-diastolic pressure rose from 7 ± 1.1 (mean ± SE) mm Hg to 23.8 ± 2. 3 without a significant increase of end-diastolic volume. In controls end-diastolic pressure rose from 8.6 ± 1.1 mm Hg to 15.3 ± 1.4, and end-diastolic volume was significantly increased, so that the ratio of end-diastolic pressure and volume was significantly higher in the diabetic group (/•< 0.005). Although indices of contractility did not differ, stroke volume and work reductions were significantly greater in diabetics , despite the fact that coronary blood flow was reduced to a similar extent. Size of the ischemic areas appeared comparable as judged by distribution of dye injected distal to the occlusion. Since potassium loss and sodium gain in the inner and outer layers of ischemic tissue did not differ between the two groups, the intensity of ischemia seemed similar. Glycogenolysis was unimpaired in the diabetic ischemic muscle but triglyceride levels remained elevated. Morphologically the diabetic myocardium was characterized by a diffuse accumulation of periodic acid-Schiff-positive glycoprotein in the interstitium, which was thought to limit diastolic filling of the ischemic ventricle and to contribute to the substantial reduction of ventricular performance. ALTHOUGH the influence of acute regional ischemia on left ventricular function has been well defined in the previously normal animal. lt2 the response of the ventricle affected by a chronic metabolic or structural abnormality has not been described. Acute myocardial infarction has been reportedly associated with a greater incidence of pump failure and higher mortality in diabetes mellitus. 3 Although the increased mortality from cardiac disease complicating diabetes mellitus has been traditionally attributed to accelerated atherosclerosis of the coronary arteries. 4 this is a disputed issue since recent evidence in studies using more quantitative methods and age-matched controls has shown that the complicated lesions of atheroscle-rosis may occur to only a slightly greater extent in diabetics. 5 In a previous study from this laboratory. 6 we observed altered myocardial function in chronic diabetes mellitus in dogs, associated with accumulation of periodic acid-Schiff (PAS)-positive glycoprotein in the myocardial interstitium without coronary obstructive lesions; this morphological abnormality also has been observed in man ?• 8 To examine the response of ...

No abstract

No abstract