Preconditioning prevents the negative inotropic action of phenylephrine inrat isolated stunned papillary muscle

The aim of the present study was to establish a model of ischemic precondit ioning of rat isolated papillary muscle and to investigate its effect on th e simulated ischemia-induced disturbances in contractility and responsivene ss to isoproterenol and phenylephrine. Experiments were performed in rat le ft ventricle papillary muscle. The following parameters were measured: forc e of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxa tion (-dF/dt), time to peak contraction (ttp), and relaxation time at the l evel of 10% of total amplitude (tt(10)). After 60 min of simulated ischemia induced by the perfusion of isolated tissues with no-substrate solution ae rated by 95% N-2/5% CO2, all of the measured parameters were markedly decre ased. There was not complete recovery of Pc, +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 bloc ker of alpha(1b)-adrenoceptor, but not by WB-4101, a selective blocker of a lpha(1a)-adrenoceptor. Ischemic preconditioning of rat isolated cardiac tis sue induced by the 5 min perfusion with no-substrate solution, aerated by 9 5% 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 recove ry of the contractility and prevents phenylephrine negative inotropic actio n. (C) 1999 Elsevier Science Inc. All rights reserved.