Attenuation of Verapamil-induced Myocardial Toxicity in an Ex-vivo Rat Model Using a Verapamil-specific Ovine Immunoglobin

Abstract

Objective: To determine whether an ovine verapamil-specific immunoglobin G (V-IgG) attenuates verapamil toxicity in an ex-vivo rat left ventricular papillary muscle model. Methods: The authors dissected left ventricular papillary muscle strips from male Sprague-Dawley rats (350-410 g) and suspended them in an oxygen-perfused Tyrode buffer bath at 37.5°C. Muscle strips equilibrated for 90 minutes under electrical stimulation of 1 Hz. Resting and developed tension (mg) were monitored continuously. A concentration—response trial was performed with verapamil concentrations ranging from 31 to 1,020 nM; 510 nM produced consistent reduction in developed tension. A trial of V-IgG was then conducted by administering the following treatments to papillary muscle strips in a randomized manner: V-IgG + 510 nM verapamil, nonspecific ovine IgG (N-IgG) + 510 nM verapamil (protein control), and 510 nM verapamil alone. Immunoglobin G was administered in equimolar concentrations to verapamil. Attenuation was expressed as inhibition of the verapamil-induced reduction of developed tension. Results: The V-IgG comparative trial indicated the V-IgG + verapamil treatment had a mean reduction in developed tension of 14.1% (SD ± 12.2) compared with 36.2% (SD ± 14.9) for N-IgG + verapamil and 34.9% (SD ± 8.1) for verapamil alone (p < 0.05). There was no difference between the two control groups. Conclusion: Verapamil-specific IgG attenuated verapamil-induced reduction of developed tension in an ex-vivo rat model.