Transient increase in the contractile force induced by antiarrhythmic drugs in guinea pig cardiac muscles

Abstract

During clinical treatment of arrhythmia in patients with chronic heart failure, cardiac function sometimes worsens due to the use of class I antiarrhythmic drugs. Morganroth and Horowitz 1 reviewed the risk of chronic heart failure induced by antiarrhythmic drugs. The class I drugs are classified as local anesthetics because of their sodium channel-inhibiting property. Suppression of the fast sodium current causes a decrease in intracellular calcium concentration and, therefore, a decrease in contractile force of muscles. 2–4 Dennis and Vaughan Williams 5 discussed the role of a reduction in the slow inward current in the negative inotropic effect of antiarrhythmic drugs. Recently, Honerjaeger et al 6 compared several class I antiarrhythmic drugs and tetrodotoxin. They concluded that class I antiarrhythmic drugs have negative inotropic effects due to the sum of sodium channel block and variable additional inotropic properties. They 6 examined calcium channel inhibition as a major additional mechanism underlying the negative inotropic effects, and suggested that several effects result from the sodium, potassium-adenosine triphosphatase inhibition. Concerning the inotropic properties of class I antiarrhythmic drugs, we now report that eibenzoline and aprindine (but not quinidine or disopyramide) transiently increase force by enhancing the effects of intrinsic adrenergic nerves in ventricular muscle at concentrations comparable to those used clinically.