4-Aminopyridine induces positive lusitropic effects and prevents the negative inotropic action of phenylephrine in the rat cardiac tissue subjected to ischaemia

The effects of 4-aminopyridine (4-AP) at concentration of 1 mM on the contr actility of rat isolated papillary muscle subjected to simulated ischaemia has been evaluated. Additionally, the effects of 4-AP on the phenylephrine inotropic action (a selective agonist of alpha(1)-adrenergic receptor) on r at isolated cardiac tissue underwent simulated ischaemia and reperfusion wa s studied. Experiments were performed on rat isolated papillary muscles obt ained from left ventricle. The following parameters have been measured: for ce of contraction (Fc), velocity of contraction (+dF/dt), velocity of relax ation (-dF/dt) and the ratio between time to peak contraction (ttp) and rel axation time at the level of 10% of total contraction amplitude (tt(10)) as an index of lusitropic effects. Simulated ischaemia lasting 45 min was ind uced by replacement of standard normoxic solution by no-substrat one gassin g with 95% N-2/5%CO2. Although 4-AP exerted a slight, but significant posit ive inotropic action itself, pretreatment with 1 mM of this compound signif icantly depressed a recovery of Fc and + dF/dt, but improves recovery of -d F/dt in the rat papillary muscle during reperfusion as compared with contro l group of preparations. Moreover, the paradoxical negative inotropic actio n of phenylephrine observed in rat stunned papillary muscle was prevented i n preparations previously treated by 4-AP. These findings suggest that an i nhibition of outward K+ current (probably transient outward and rapid compo nent of delayed rectifying currents at 1 mM of 4-AP) aggravates ischaemia-i nduced failure in contractility but prevents changes in alpha(1)-adrenergic receptor signaling pathway occuring during ischaemia.