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Aim: Evaluation of TNF-alpha and ET-1 inhibition on ischemia induced myocardial contracture and quality of functional cardiac recovery after reperfusion in diabetes induced rat heart failure. Material and methods: Diabetes mellitus induced heart failure DHF was reproduced by streptozotocin 5 days, 50 mg/kg. TNF-? and ET-1 inhibition has been realized by i/p administration during this period of TNF-? antagonist 2,0 mg/kg, TNF-McAb; BQ-123 15 mg/kg,a selective antagonist of ETA receptor, and CGS 35066 2,0 mg/kg, aselective ECE-1 inhibitor. At 6-th day isolated heart was perfused by Langendorff method during 20 min, the left ventricle end diastolic pressure LVEDP being adjusted on 14 mm Hg. Thereby LVEDP has been assayed the myocardial contracture level after 30 min of total ischemia as well as the cardiac recovery after 45 min of reperfusion. In a special series BQ-1235mu;g/g/min or CGS 35066 0,75 mu;g/g/min were infused in perfusate before ischemia. Results: The ischemic myocardial contracture was in DHF almost doubly augmented: 56,3 plusmn; 3,6 vs 28,4 plusmn; 1,9 mm Hg control. On the other hand LVEDP remained significantly higher after reperfusion: 39,2 plusmn; 2,5 vs 18,8 plusmn; 1,2 mm Hg. The ET-1 inhibition during DHF developing showed a notable cardioprotection: ischemic LVEDP reduced by 31,97% p = 0,026 in BQ-123 action and 33,57% p = 0,024 due to CGS 35066 action. Postreperfusion recovery was improved also: LVEDP was less by 32,14% and 34,44% respectively. Remarkably, that ET-1 inhibition before ichemia perfusion was conspicuously more effective in case of ETA receptor blocking. BQ-123 action led to a significant postischemic and postreperfusion LVEDP diminution by 28,4% 40,3 plusmn; 3,3 mm Hg and 27,3% 28,5 plusmn; 1,8 mm Hg. CGS 35066 action reduced LVEDP only by a mean range of 14-16% p 0,05. TNF-alpha antagonist produced a similar to ET-1 inhibition beneficial effect: postischemic and postreperfusion LVEDP by 29,3% 39,8 plusmn; 3,1 mm Hg and 26,8% 28,7 plusmn; 2,2 mm Hg. Conclusions: 1. ET-1 and ... |
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