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.
Schneider
Rick
R
Department of Surgery, University of Leipzig, Germany. rick.schneider@medizin.uni-leipzig.de
Welt
Klaus
K
Aust
Wolfram
W
Löster
Heinz
H
Fitzl
Günther
G
D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D020441:Ginkgo biloba; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D011913:Rats, Inbred BB; D013373:Substance P / Q000378:metabolism; D000096983:Ginkgo Extract
D002317:Cardiovascular Agents; D003094:Collagen; D016166:Free Radical Scavengers; D052250:Nitric Oxide Synthase Type III; D010936:Plant Extracts; D013373:Substance P; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C496316:Nos3 protein, rat