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

• Published in: Academic emergency medicine 2001-10, Vol.8 (10), p.950-955
• Main Authors: Hill, Robert E., Heard, Kennon, Bogdan, Gregory M., Cairns, Charles B., Dart, Richard C.
• Format: Article
• Language: English
• Subjects: Animals; antibodies; calcium channel blockers; Calcium Channel Blockers - toxicity; Cardiomyopathies - chemically induced; Drug Therapy, Combination; IgG; immunoglobins; Immunoglobulin G - toxicity; Male; Models, Cardiovascular; papillary muscles; Papillary Muscles - drug effects; Rats; Rats, Sprague-Dawley; Sensitivity and Specificity; verapamil; Verapamil - toxicity
• ISSN: 1069-6563; 1553-2712
• DOI: 10.1111/j.1553-2712.2001.tb01092.x

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.