Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Feb 2008
Possible involvement of erythropoietin in remote renal preconditioning-induced cardioprotection in rats.
Remote preconditioning is a unique phenomenon in which brief episodes of ischemia and reperfusion to remote organs protect the target organ against sustained ischemia/reperfusion (I/R)-induced injury. Protective effects of remote renal preconditioning are well established in the heart, but their mechanisms still remain to be elucidated. Hence, the present study was designed to investigate the possible involvement of erythropoietin in remote renal preconditioning (RRPC)-induced cardioprotection in rats. ⋯ However, cardioprotective effects of RRPC were not observed in renal failure rats, indicating the protective role of humoral factor was released from functional kidneys. In renal failure rats, exogenous administration of rhEPO (5,000 IU/kg intraperitoneal) with RRPC restored the cardioprotective effects of later. These results implicate that RRPC-induced cardioprotective effects may be mediated through release of erythropoietin from kidney.
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J. Cardiovasc. Pharmacol. · Jan 2008
Differential effects of inhaled and intravenous sildenafil in the prevention of the pulmonary endothelial dysfunction due to cardiopulmonary bypass.
The objective of the present study was to evaluate the effects of inhaled and intravenous sildenafil on the pulmonary endothelium-dependent relaxations, the hemodynamic profile and oxygenation after cardiopulmonary bypass. Five groups of Landrace swine were compared: 1) control; 2) cardiopulmonary bypass: 90 min of normothermic cardiopulmonary bypass; 3) precardiopulmonary bypass sildenafil nebulization; 4) postcardiopulmonary bypass sildenafil nebulization; 5) intravenous sildenafil administration prior to cardiopulmonary bypass. All groups underwent a 60-min period of pulmonary reperfusion after cardiopulmonary bypass. ⋯ Moreover, intravenous and inhaled sildenafil after cardiopulmonary bypass also prevented the increase in alveoloarterial gradient (P < 0.05). Both sildenafil formulations of administration prevent the occurrence of pulmonary endothelial dysfunction. Depending on the administration moment and the route, the administration of sildenafil improves the hemodynamic profile and post-cardiopulmonary bypass oxygenation.
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J. Cardiovasc. Pharmacol. · Aug 2007
Tetramethylpyrazine-eluting stents prevented in-stent restenosis in a porcine model.
Tetramethylpyrazine, a drug originally isolated from the rhizome of Ligusticum walliichi, is an inhibitor of phosphodiesterase and inhibits platelet aggregation and smooth muscle cell proliferation. The effect of the tetramethylpyrazine-eluting stent (TES) on preventing in-stent restenosis was investigated in comparison with control bare metal stents in a porcine coronary stent restenosis model. ⋯ TES inhibited the neointimal hyperplasia and reduced in-stent restenosis in a porcine coronary artery restenosis model.
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J. Cardiovasc. Pharmacol. · Apr 2007
Cardioprotective properties of humoral factors released from rat hearts subject to ischemic preconditioning.
Myocardial protection can be achieved by transfer of coronary effluent from ischemically preconditioned to non-preconditioned hearts. This study was designed to test the hypothesis that preconditioned effluent from rat hearts purified by Sep-Pak C-18 cartridges could induce remote cardioprotection against ischemia/reperfusion (I/R) injury through the activation of protein kinase C signaling pathway. Buffer-perfused rat hearts were subject to 30 min ischemia and 60 min reperfusion. ⋯ Recovery of the contractile function at reperfusion was higher in preconditioned group (74 +/- 6% versus 17 +/- 7% in control, P < 0.001) and hydrophobic fraction (66 +/- 7% versus 8 +/- 4% in hydrophilic fraction, P < 0.001). Similarly, chelerythrine was able to abrogate the contractile function recovery (12 +/- 6%, P < 0.001 versus preconditioned group and 19 +/- 7%, P < 0.001 versus hydrophobic fraction). In conclusion, the cardioprotective factors released in the coronary effluent by IPC are thermolabile hydrophobic substances with molecular weights higher than 3.5 kDa and acting through PKC activation.
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J. Cardiovasc. Pharmacol. · Mar 2007
Randomized Controlled Trial Comparative StudyDose-dependent inhibition of human platelet aggregation by prasugrel and its interaction with aspirin in healthy subjects.
The aims of this open-label, randomized, dose-escalation pharmacodynamic study of prasugrel, an orally active antiplatelet agent, were to assess its interaction with aspirin (ASA, 325 mg) in healthy subjects after a loading dose (LD) and subsequent 5 days of once-daily maintenance doses (MD) of prasugrel or the active comparator, clopidogrel. We measured platelet aggregation induced by ADP, collagen, and TRAP and compared effects on maximal and residual platelet aggregation responses. On a background of ASA, subjects were randomly assigned to 1 of 4 prasugrel treatment groups (LD/MD in mg: 20/5, 30/7.5, 40/10, or 60/15; n = 8/group) or to clopidogrel 300 mg LD/75 mg MD (n = 11). ⋯ Although inhibition of residual aggregation was greater than inhibition of maximal aggregation, values were highly correlated. The safety and tolerability of prasugrel plus ASA were also monitored. Within the limitations of the study, prasugrel was found to be well tolerated when dosed as LD followed by MD in the presence of ASA and provided greater platelet inhibition than ASA alone.