Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes.

Abstract

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 ...

Effects of ischemia on rat myocardial function and metabolism in diabetes.

“…Evidence has been presented which indicates that chronic diabetes in the dog results in decreased diastolic ventricular compliance (Regan, 1975) and that the heart of chronically diabetic animals shows greater reductions of function in response to regional ischemia (Haider et al, 1977). In the present study, diabetic hearts tolerated perfusion under mildly ischemic conditions in vitro just as well as did normal hearts.…”

“…The decreased ability to recover function after anoxic perfusion was associated with the inability to use glucose. Longterm diabetes in dogs has been reported to increase ventricular stiffness (Regan, 1975), and these hearts showed greater reductions in work output in response to regional ischemia (Haider et al, 1977).…”

Arrhythmia susceptibility and myocardial composition in diabetes. Influence of physical conditioning.

“…This canine model is characterized by normal coronary arteries (2) and collateral blood flow response during coronary occlusion (34), as well as preserved ultrastructure of cardiac cells (8).…”

“…This limit was imposed since this diabetic model exhibits a greater degree of left ventricular dysfunction during ischemia over time than do normals (34), which may represent an additional variable affecting outcome. Arrhythmias were recorded at a 25 mm/s paper speed on a recorder (Electronics for Medicine) with automatic devel6per.…”

Isolation and characterization of mitochondria from goat hearts

“…The effect of varying concentrations of oleic and palmitic acid (20,25,40,80, 120 mM) were therefore studied on the complexes and marker enzymes of control mitochondria (26). The final concentration of ethanol used to dissolve fatty acids in each was adjusted to 2%.…”