Attenuation of verapamil-induced myocardial toxicity in an ex-vivo rat model using a verapamil-specific ovine immunoglobin.
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 degrees 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.


CONCLUSIONS
Verapamil-specific IgG attenuated verapamil-induced reduction of developed tension in an ex-vivo rat model.
Hill
R E
RE
Rocky Mountain Poison and Drug Center, Denver Health Authority, Denver, CO 80230-6800, USA.
Heard
K
K
Bogdan
G M
GM
Cairns
C B
CB
Dart
R C
RC
D000818:Animals; D002121:Calcium Channel Blockers / Q000633:toxicity*; D009202:Cardiomyopathies / Q000139:chemically induced*; D004359:Drug Therapy, Combination; D007074:Immunoglobulin G / Q000633:toxicity*; D008297:Male; D008955:Models, Cardiovascular; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D014700:Verapamil / Q000633:toxicity*
D002121:Calcium Channel Blockers; D007074:Immunoglobulin G; D014700:Verapamil