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Research On Pharmacology Of Novel Calcium Sensitizedcompounds

Posted on:2007-04-11Degree:MasterType:Thesis
Country:ChinaCandidate:Z WangFull Text:PDF
GTID:2144360185488699Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Using some modles of heart and blood vessel in vitro and in vivo to explore whether 16 compounds ramificated from levosimendan, a calcium sensitiser which facilitates the activation of the contractile apparatus by calcium, have the cardioprotective activity on prostrate heart and on improving myocardial contractile function during severe heart failure. In modles of heart-failure guinea pig induced by pentobarbital sodium and isolated ischemia and reperfusion (I/R) rat hearts, we compared the cardioprotective effect of levosimendan and 16 compounds on the failure hearts. And we investigated the possible mechanism for its cardiopdrotective effect on the modles of isolated aorta and atrial myocardium in guinea pig.The results showed that compound 05114, 0416 and 0417 (0.125~1 mg·kg-1, i.v.)had the effect to improve the cardiac contractile function of failure hearts in anaesthetized guinea pigs, and compound 05114(0.5 mg·kg-1) put up the equivalent cardiopreotective activity to cromakalim(0.1 mg·kg-1) , increasing LVDP of failure heart from 51.1% to 105.2% and LVSP*HR up to 43% compared heart failure, on the concentration 1 mg·kg-1. But in isolated I/R hearts, none of them could increase the index of cardiac function.All compounds(10-7~10-4mol·L-1) could concentration-dependently relax the aortic rings contracted with KC1 30mmol·L-1, but the vasodilating activity of compounds was much lower, compared with levosemendan(10-8~3×10-7 mol·L-1) and cromakalim(10-8~3×10-6) mol·L-1. The ratio of compound 0416, 0417 and 05114 to cromakalim is 780,475 and 664 respectively.Compound 05114 couldn't reduce the RVHI and SPAP in the modle of lung of hypoxic pulmaonary hypertension rat, but expressed benefic effect on the atrial myocardium,...
Keywords/Search Tags:ischmia/reperfusion, levosimendan, contractile function, heart failure, compounds
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