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The British Journal of Diabetes & Vascular Disease
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Effects of chronic treatment with glibenclamide and/or metformin on the resistance to ischaemia of isolated hearts from Zucker Diabetic Fatty rats (ZDF/GMI-fa/fa)

Nicole Lavanchy

Laboratoire de Bioénergétique Fondamentale et Appliquée (EMI 02-21) BP 53X, F-38041 Grenoble Cedex 9, France, Nicole.Lavanchy{at}ujf-grenoble.fr

Georges Christe

Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothélium (EMI 02-19), BP 53X, F-38041 Grenoble Cedex 9, France

Francine Cand

Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothélium (EMI 02-19), BP 53X, F-38041 Grenoble Cedex 9, France

Nicolas Wiernsperger

Merck-Lipha S.A., 37 Rue Saint Romain, F-69379 Lyon Cedex 08, France

Jean Verdetti

Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothélium (EMI 02-19), BP 53X, F-38041 Grenoble Cedex 9, France

The study was carried out to determine whether metformin (M) had any deleterious effect on the tolerance to ischaemia of the isolated diabetic rat when administered chronically in combination with glibenclamide (G). The male Zucker Diabetic Fatty (ZDF) rat served as a model of type 2 diabetes that resembles the human syndrome. Three groups of rats were treated for one month with M (100 mg/kg) or G (2 mg/kg) or G + M in their daily food. One group was untreated (C). Aortically perfused hearts were subjected to a 25-minute global low-flow ischaemia and a 30-minute reperfusion. Heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP) and coronary flow (CF) were monitored.

When compared to C hearts, the hearts from G + M rats showed improvements in HR, LVDP and RPP at the end of reperfusion. Hearts from G and M rats exhibited no difference. Myocardial glycogen stores at the end of in the three other groups.

The study did not reveal any deleterious effect of the chronic G + M therapy on the functional recovery of the isolated diabetic heart submitted to ischaemia and reperfusion: indeed, an increase in residual contractile capacity was found.

Key Words: diabetes type 2 • ZDF rats • isolated heart • glibenclamide • metformin • chronic treatment.

The British Journal of Diabetes & Vascular Disease, Vol. 3, No. 5, 375-380 (2003)
DOI: 10.1177/14746514030030051301
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