Cardiac ischemia and reperfusion in spontaneously diabetic rats with and without application of EGb 761: II. Interstitium and microvasculature.

Besides alterations in cardiomyocytes themselves, diabetic cardiopathy is characterized by interstitial and microvascular disorders. On the assumption that a specific heart muscle disease develops due to permanently increased oxidative stress on liberation of oxygen-free radicals, adjuvant application of antioxidative therapeutics appears promising in preventing or delaying long-term diabetic complications and protecting the myocardium against acute ischemia. We have investigated the effects of Ginkgo biloba extract (EGb 761), a radical scavenger, against diabetes-induced myocardial interstitium and microvasculature damage, and against additional ischemia/reperfusion injury in spontaneously diabetic BioBreeding/Ottawa Karlsburg (BB/OK) rats modelling diabetic cardiac infarction. Morphological and morphometric parameters in the heart muscle were evaluated by light and electron microscope. We used immunohistochemistry to investigate collagen protein expression as a marker for tissue remodelling together with endothelial nitric oxide synthase (eNOS) protein expression as a marker for endothelial-dependent vasodilation. We also evaluated inflammation response caused by neuropeptide Substance P and interacting mast cells in the diabetic heart. Our results revealed that A) Diabetic myocardium appears more vulnerable to ischemia/reperfusion injury than normal myocardium with regard to myocardial interstitium and microvessel ultrastructure, as well as eNOS protein expression; B) Inflammation response increases in diabetic animals exposed to ischemia/reperfusion injury compared to controls; C) Pre-treatment of diabetic myocardium with EGb results in an improvement of impaired endothelial-dependent vasodilation in diabetes and additional ischemia/ reperfusion, diminished mast cell and substance P accumulation, and better preserved myocardial ultrastructure compared to unprotected myocardium. In conclusion, EGb may act as a potent therapeutic adjuvant in diabetics with respect to ischemic myocardial injury, and may contribute to preventing late complications in diabetic cardiopathy.