Reversal of diabetes-induced rat graft transplant coronary artery disease by metformin

• Published in: The Journal of heart and lung transplantation Vol. 21; no. 6; pp. 637 - 643
• Main Authors: Cantin, Bernard, Zhu, Dening, Wen, Peizhong, Panchal, Shyam N., Dai, Xiaohong, Gwathmey, Judith K., Reaven, Gerald M., Valantine, Hannah A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2002; Elsevier Science
• Subjects: Aminoglycosides; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anti-Bacterial Agents; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Coronary Disease - drug therapy; Coronary Disease - etiology; Coronary Disease - pathology; Diabetes Mellitus, Experimental - complications; Disease Models, Animal; Heart Transplantation; Hypoglycemic Agents - therapeutic use; Medical sciences; Metformin - therapeutic use; Rats; Time Factors; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Endocrinopathy; Heart; Graft(material); Rat; Homograft; Cardiovascular disease; Transplantation; Daily; Biguanides; Surgery; Lead; Graft; Streptozotocin; Induction; Diabetes mellitus; Rodentia; Method; Coronary heart disease; Section; Abdomen; Vertebrata; Mammalia; Treatment; Animal; Models; Metformin; Severe; Heterotopic transplantation
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/S1053-2498(01)00768-9

Induction of diabetes in rat heterotopic heart transplantation models leads to an accelerated form of severe transplant coronary artery disease (TxCAD). We undertook this study to determine whether treatment of diabetes with metformin would favorably affect TxCAD. Heterotopic abdominal heart transplantation was performed in rat isograft and allograft models. After transplantation, diabetes was induced with streptozotocin. Fifty percent of the animals received metformin at 500 mg/kg twice daily. We quantitatively assessed TxCAD using histologic sections of harvested hearts at 30 and 60 days with computer-assisted morphometry. We compared vessels in the first tertile of the area distribution with vessels in the last tertile. Fasting glucose levels in metformin-treated animals were 161 ± 45 mg/dl compared with 400 ± 120 mg/dl ( p < 0.05) in untreated rats. Treatment with metformin led to decreased diabetes-induced TxCAD in the larger vessels. This effect was sustained during the study course in the isografts but not in the allografts. Treatment with metformin did not prevent progression of TxCAD in the smaller vessels at 60 days. Metformin reduced luminal occlusion and severe TxCAD in the larger vessels but did not alter the course of TxCAD in the smaller vessels. These results may have therapeutic implications for patients.