The relationship of external work to exogenous substrate supply and whole heart lipid content was studied in hearts isolated from 27 normal and 24 alloxan-diabetic rabbits. In addition, we evaluated hearts from seven rabbits after 4 days of untreated diabetes followed by 10 days of insulin therapy. Hearts were retrogradely perfused with erythrocyte-enriched modified Krebs-Henseleit media in which glucose, palmitate, and insulin were present in concentrations simulating diabetic plasma (13 mM, 0.4 mM, and 15 microU/ml, respectively). Diabetes was associated with a greater than 40% reduction in peak left ventricular systolic pressure, dP/dtmax, and left ventricular pressure-time index (P less than 0.01 for each). Perfusion of hearts from six diabetic animals with low concentrations of exogenous fatty acid (0.06 mM) normalized left ventricular (LV) performance. Insulin therapy also completely normalized LV performance. This improvement was associated with lower heart fatty acid and triacylglycerol content. These studies suggest that the myocardial dysfunction in hearts from rabbits with alloxan-induced diabetes of 2-wk duration may be, in part, due to enhanced sensitivity to deleterious effects of high exogenous levels of fatty acid.
- Copyright © 1986 the American Physiological Society