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Hypertriglyceridemia in experimental diabetes: relationship to cardiac dysfunction
B Rodrigues1, P F Grassby, M L Battell
1Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Insights
Diabetic rats show impaired cardiac function linked to hypertriglyceridemia. However, improving myocardial glucose utilization, not just lowering triglycerides, appears more critical for preventing heart dysfunction in diabetic conditions.
Area of Science:
- Cardiology
- Endocrinology
- Metabolic Diseases
Background:
- Cardiovascular disease mortality is elevated in diabetic patients.
- Diabetes can lead to cardiac dysfunction, potentially linked to metabolic changes like hypertriglyceridemia.
Purpose of the Study:
- To investigate if hypertriglyceridemia contributes to diabetes-induced cardiac dysfunction.
- To evaluate the efficacy of various treatments in preventing cardiac dysfunction in diabetic rats.
Main Methods:
- Streptozotocin-induced diabetes model in rats.
- Isolated heart preparations to assess cardiac function (left ventricular pressure, +/- dP/dt).
- Administration of hydralazine, clofibrate, verapamil, prazosin, enalapril, benazepril, and dichloroacetate.
Main Results:
- Diabetes induced hyperlipidemia and depressed cardiac function.
- Hydralazine treatment prevented cardiac dysfunction and lowered triglycerides.
- Most other treatments reduced triglycerides but failed to prevent heart dysfunction.
- Dichloroacetate improved cardiac function in early-stage diabetic rats.
Conclusions:
- While hypertriglyceridemia may play a role, it might not be the primary driver of cardiac dysfunction in chronic diabetes.
- Improving myocardial glucose utilization appears more critical than triglyceride lowering for preventing cardiac dysfunction in diabetic rats.
Abstract:
The incidence of mortality from cardiovascular disease is higher in diabetic patients. The objective of the present investigation was to test the hypothesis that the diabetes-induced depression in cardiac function may be due to hypertriglyceridemia. Hyperlipidemia and a depressed left ventricular developed pressure and rate of increase and decrease of ventricular pressure (+/- dP/dt) were produced in isolated hearts from rats made diabetic with streptozotocin compared with hearts from control animals. This depressed cardiac performance was successfully prevented by hydralazine treatment (for 3 weeks), which also lowered plasma triglyceride levels and suggested that hyperlipidemia may be important in altering cardiac function in experimental diabetic rats. The beneficial effects of clofibrate, verapamil, prazosin, enalapril, and benazepril administration were then studied in diabetic rats. The treatments (with the exception of enalapril) significantly reduced plasma triglyceride levels but did not prevent the onset of heart dysfunction in chronically diabetic rats. These studies suggest that in the chronically diabetic rat, hypertriglyceridemia may not be as important as previously suggested, in the development of cardiac dysfunction. Since acute dichloroacetate perfusion improves cardiac function in 6 week (but not 24 week) diabetic rats, it appears more likely that improving myocardial glycose utilization is more critical than triglyceride lowering, in preventing cardiac dysfunction in the diabetic rat at this time point.