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Myocardial disease in diabetes mellitus is usually attributed to coronary atherosclerosis. To examine the influence of uncomplicated diabetes on the left ventricle, a mild noninsulin-requiring diabetes was produced in male mongrel dogs after three intravenous doses of alloxan were administered at monthly intervals. There was a persistent decline in glucose tolerance and a reduced insulin content in the pancreas of each alloxan-diabetic dog at the termination of the experiment. The dogs were anesthetized for hemodynamic and metabolic studies after approximately 11 months. Left ventricular end-diastolic volume and cardiac output were measured by the indicator-dilution method. An increase in afterload with moderate aortic pressure elevations elicited a significant rise in end-diastolic volume and stroke volume in normal control dogs. In diabetes, despite a similar end-diastolic pressure response, the end-diastolic volume and the stroke volume responses were significantly less than those in control dogs. During acute volume expansion of the ventricle with saline, the end-diastolic pressure increment in diabetic dogs was twice that in control dogs. These responses were attributed to an increased stiffness of the left ventricle that was apparently due to accumulation of glycoprotein (measured by periodic acid-Schiff staining) in the interstitium. Since similar abnormalities were observed in dogs with diabetes occurring spontaneously and were absent when the pancreatic effects of alloxan were inhibited in a separate group of dogs, the pathogenetic role of alloxan via a direct action on myocardium was excluded. Analysis of lipids in the left ventricle revealed elevated triglyceride and cholesterol concentrations despite normal plasma levels. During infusion of 14 C-1-oleic acid, cardiac oxidation appeared to be normal, but fatty acid incorporation, which was predominantly into phospholipid in the control dogs, was diverted to triglyceride in the diabetic dogs. Since an aberration of de novo synthesis was not found during studies with 14 C-acetate, triglyceride accumulation was attributed to altered intracellular metabolism, perhaps related to glycerol phosphate acyl transferase activity. The basis for cholesterol accumulation was less clear, since neither 14 C-acetate nor 14 C-oleate incorporation into sterol was enhanced. Myocardial ischemia was excluded on the basis of patency of coronary arteries and normal coronary blood flow, myocardial cation content, and mitochondrial morphology. Thus, it was concluded that chronic diabetes mellitus can alter myocardial composition and function independent of vascular effects.

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SUMMARYPrevious studies relating systolic time intervals and measures of cardiac performance have suggested that the time intervals may be useful indices of myocardial contractility. To explore this possibility, systolic times and left ventricular (LV) performance and contractility were measured nearly simultaneously in 14 normal subjects and 56 patients with cardiac disease. Preejection period (PEP) and the ratio of PEP to LV ejection time (LVET) changed significantly with acute inotropic influences (exercise and isoproterenol), were normal in patients with right or left ventricular overloads in whom cardiac index and ejection fraction were depressed but contractile element velocity at peak dP/dt and the Frank-Levinson contractility index were normal, and were significantly abnormal in patients with either clinically evident or occult LV decompensation in whom the measures of contractility were reduced. Correlations of PEP and PEP/LVET with measures of both performance and contractility were insignificant for patients with valvular disease, shunts, or cor pulmonale and significant but weak for the entire series. However, in subjects with either normal left ventricles or cardiac disease confined to the left ventricle, PEP and PEP/LVET exhibited good correlations with measures of pump function and excellent correlations with measures of contractility. These results indicate that the systolic times are a valid measure of contractility which should prove useful in comparing patients with cardiac pathology confined to the LV myocardium and in following patients with extramyocardial hemodynamic lesions of constant severity.