Abstract
The biguanide, metformin, is widely used for the treatment of type 2 diabetes mellitus. In the recently published United Kingdom Prospective Diabetes Study (UKPDS), it was shown that the use of metformin was associated with a reduction of macrovascular complications compared to other blood glucose-lowering strategies. The present study was aimed at determining whether metformin has direct beneficial effects on the heart. We tested the effects of metformin on cardiac functional recovery after a mild ischemic incident (stunning) in our isolated, erythrocyte perfused, rat working-heart model. Three groups were tested: vehicle, 50 and 500 µmol/l metformin (total n = 6). In diabetic rats, a concentration of 50 µM has been shown to reduce the blood glucose concentration. Slight metformin-induced increases in coronary blood flow during normoxia (pre-ischemically) and during reperfusion (post-ischemically) were observed and compared to vehicle (p < 0.05). Both metformin concentrations significantly reduced cardiac functional loss induced by the 12-min global ischemic incident compared with vehicle (3.4 ± 1.0 % and 3.5 ± 0.6 % loss during metformin versus 10.7 ± 0.8 % during vehicle, p < 0.001). This study clearly shows that metformin acutely improves cardiac function after a mild ischemic incident (stunning) in rats.
Key words
Myocardial - Biguanides - Type 2 Diabetes - Stunning - Coronary Blood Flow - Isolated Rat Heart
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P. Smits, M.D., Ph.D.
Prof of Pharmacology · Department of Pharmacology-Toxicology 233 · University Medical Center Nijmegen
P.O. Box 9101 · NL-6500 HB Nijmegen · The Netherlands
Phone: + 31 (0) 24-361 88 35
Fax: + 31 (0) 24-361 42 14
Email: P.smits@farm.kun.nl
