Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

Abstract

The inhibitory effects of disopyramide on electromechanical responses were investigated in guinea‐pig papillary muscles driven by electrical stimuli. Disopyramide up to 10−5 m did not cause a negative inotropic effect, while the maximum upstroke velocity of the action potential (dV/dtmax) was significantly decreased. At higher concentrations, this drug dose‐dependently inhibited the contraction, and dV/dtmax was further decreased. This inhibition of contraction was accompanied by a depression of the slow action potential in partially depolarized preparations by increasing [K+]o (26 mm). In preparations pretreated with nifedipine (10−6 m) and ryanodine (10−6 m), the contraction was almost completely inhibited. In such preparations, ouabain (2 × 10−6 m) markedly increased the contraction, probably through the Na+‐Ca2+ exchange mechanism. This contraction was inhibited by disopyramide above 10−8 m, and an almost complete inhibition was caused at 3 × 10−5 m. A similar inhibitory effect was observed on the contraction increased by the lowering of [Na+]o (36 mm). These results suggest that disopyramide at high concentrations inhibits Ca influx through slow Ca2+ channels and at low concentrations, it reduces the contraction increased through the Na+‐Ca2+ exchange mechanism. Disopyramide had a greater effect on cardiac contractility mediated by the Na+‐Ca2+ exchange mechanism.

Effects of HNS-32, a Novel Antiarrhythmic Agent, on Guinea-Pig Myocardium

“…2A, 3B, C) and showed negative chronotropic and inotropic effects ( fig. 4), which is similar to the effects of Ca 2+ channel antagonists such as verapamil [3,4,18,19]. Moreover, HNS-32 at higher concentrations inhibited the initial peak of the inactivating inward current on depolarization ( fig.…”

Negative Inotropic Effects of Class I Antiarrhythmics on Guinea Pig Ventricular Myocardium: Correlation with L-Type Ca²⁺ Channel Blockade

“…The myocardial contractile force under elevated extracellular K + concentration, used in the present study, was shown to be highly dependent on Ca 2+ channel function. 9,10) The present observation that the negative inotropic effect of class I antiarrhythmic drugs observed under normal conditions was mostly preserved under elevated extracellular K + conditions implies the involvement of Ca 2+ channel blockade. The negative effects of all drugs tended to converge on a single concentration-response curve when the concentration of each drug was expressed as a ratio against its IC 50 value for Ca 2+ channel blockade (Fig.…”

“…The effects of class I antiarrhythmic drugs were also examined under elevated extracellular K + concentration, under which the function of Na + channels is markedly reduced while the dependence of myocardial contraction on the Ltype Ca 2+ channel is maintained 9,10) ; this was confirmed by the observation that the contractile force was highly sensitive to nifedipine but not to tetrodotoxin. The contractile force under elevated extracellular K + concentration was decreased to 10.7 ± 3.9% (n = 5) with 1 µM nifedipine, but to 89.1 ± 3.0% (n = 5) with 10 µM tetrodotoxin.…”

Management of Symptoms in Hypertrophic Cardiomyopathy

“…Although disopyramide is a weak calcium channel antagonist, its principal native inotropic effect appears to be mediated by sodium-calcium exchange. 69 Pollick and associates 70 administered intravenous disopyramide to 43 patients with HOCM. The LVOT gradient was abolished or reduced; the effect was greater than that seen previously for either propranolol or verapamil.…”