Preconditioning prevents the negative inotropic action of phenylephrine in rat isolated stunned papillary muscle.
The aim of the present study was to establish a model of ischemic preconditioning of rat isolated papillary muscle and to investigate its effect on the simulated ischemia-induced disturbances in contractility and responsiveness to isoproterenol and phenylephrine. Experiments were performed in rat left ventricle papillary muscle. The following parameters were measured: force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt), time to peak contraction (ttp), and relaxation time at the level of 10% of total amplitude (tt10). After 60 min of simulated ischemia induced by the perfusion of isolated tissues with no-substrate solution aerated by 95% N2/5% CO2, all of the measured parameters were markedly decreased. There was not complete recovery of Fc, +dF/dt and -dF/dt after 60 min of reperfusion. Positive inotropic action of isoproterenol does not differ before and after simulated ischemia. In contrast, phenylephrine induces a positive inotropic action in non-treated, but a significant negative one in simulated ischaemia/reperfusion treated preparations. The latter effect of phenylephrine was reversed by chloroethylclonidine (CEC), a selective blocker of alpha1b-adrenoceptor, but not by WB-4101, a selective blocker of alpha1a-adrenoceptor. Ischemic preconditioning of rat isolated cardiac tissue induced by the 5 min perfusion with no-substrate solution, aerated by 95% N2/ 5% CO2, in the presence of fast electrical pacing (BCL shortened from 2000 ms to 700 ms) and 10 min reperfusion, significantly improves a recovery of the contractility and prevents phenylephrine negative inotropic action.
Kocić
I
I
Department of Pharmacology, Medical University of Gdańsk, Poland.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D019157:Ischemic Preconditioning, Myocardial; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D002316:Cardiotonic Agents; D004146:Dioxanes; D010656:Phenylephrine; D015016:Yohimbine; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D007545:Isoproterenol; D003000:Clonidine