The inotropic effect of isoniazid on isolated atria of guinea - pigs

The incidence of heartfailure is increasing every year, while there is no ideaL inotropic agent yet available. Therefore the searchfor an ideaL inotropic agent is still needed. Isoniazid (INH) has been wideLy used as an anti-tuberculosis agent that htts similar structure to the K+ channel blocker 4-aminopyridine. Considering tlnt K* channel blocker may prolong depolarization leading to a more influx of Ca** into the cell and increase cardiac contractility, the effect of INH on cardiac contractility were investigated. In guinea' pig isoiated atria preparations, INH produced concentration-dependeitt increase contractility. The maximal concentration of INH in 'increasing force of contractility is 100 mM. This is approximately an equieffective concenffation compared to I uM of adrenaline induced cardiac contractility. The difference is that INH has no effect on the rate of contraction. A non-selective beta-adrenoceptor antagonist propranolol (I uM) inhibits the inotopic action of adrenaline (1 uM) but with no effect on INH (100 mM) induced rdiac contractility. It is speculated that INH possesses a positive inotropic effcct. This effect is not associated with the activation of cardiac beta-adrenoceptoi by catecholamine as a consequence of monoamine oxidase inhibition, but may be through the prolongation of depolarization of the myocardial cells by blocking of Kt channels.