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

Abstract

The incidence of heart failure is increasing every year, while there is no ideal inotropic agent yet available. Therefore the search for an ideal inotropic agent is still needed. Isoniazid (INH) has been widely used as an anti-tuberculosis agent that has similar structure to the K+ channel blocker 4-aminopyridine. Considering that 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 isolated atria preparations, INH produced concentration-dependent increase contractility. The maximal concentration of INH in increasing force of contractility is 100 mM. This is approximately an equieffective concentration compared to 1 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 (1 uM) inhibits the inotropic 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 effect. This effect is not associated with the activation of cardiac beta-adrenoceptor by catecholamine as a consequence of monoamine oxidase inhibition, but may be through the prolongation of depolarization of the myocardial cells by blocking of K+ channels.