The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats.
The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/ kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group (P < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP. Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group (P < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates (P < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.
Tuncok
Y
Y
Dokuz Eylul University Medical Faculty, Department of Pharmacology, Balcova Izmir, Turkey.
Apaydin
S
S
Kalkan
S
S
Ates
M
M
Guven
H
H
D000676:Amrinone / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy; D002121:Calcium Channel Blockers / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy*; D004338:Drug Combinations; D005934:Glucagon / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000633:toxicity*
D002121:Calcium Channel Blockers; D004338:Drug Combinations; D010726:Phosphodiesterase Inhibitors; D005934:Glucagon; D014700:Verapamil; D000676:Amrinone