Effect of glucagon on amitriptyline-induced cardiovascular toxicity in rats.
The aim of this study was to investigate the effect of glucagon on cardiovascular parameters in anesthetized rat model of tricyclic antidepressant overdose. Toxicity was induced by infusion of amitriptyline 0.94 mg/kg/min until a 40-45% of reduction in mean arterial pressure was observed. Amitriptyline infusion rats were then randomized into three groups. Control group of rats (group 1) received a bolus of 5% dextrose followed by the continuous infusion of dextrose, whereas treatment groups received 1 mg/kg (group 2) or 2 mg/kg (group 3) bolus doses of glucagon followed by continuous infusion (0.1 mg/kg/min) of glucagons for 60 min. Mean arterial pressure, heart rate, and electrocardiogram were recorded. Amitriptyline caused a significant decrease in mean arterial pressure and a prolongation in QRS, yet it did not change the heart rate. High-bolus dose of glucagon (2 mg/kg) followed by glucagon infusion significantly increased mean arterial pressure at 40, 50, and 60 min (P < 0.05) and shortened the prolonged QRS at 50 and 60 min (P < 0.05) when compared with control group. There was also a significant increase in heart rate. In conclusion, bolus doses followed by a continuous infusion of glucagon were found to be effective in reversing the hypotension and QRS prolongation in the rat model of amitriptyline toxicity. Further studies are needed to reveal the exact mechanism of the proposed effect.
Kaplan
Y C
YC
Dokuz Eylul University School of Medicine, Department of Pharmacology, Inciralti, 35340 Izmir, Turkey.
Hocaoglu
N
N
Oransay
K
K
Kalkan
S
S
Tuncok
Y
Y
D000639:Amitriptyline / Q000633:toxicity*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy*; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004562:Electrocardiography; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005934:Glucagon / Q000008:administration & dosage / Q000627:therapeutic use*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000929:Antidepressive Agents, Tricyclic; D005765:Gastrointestinal Agents; D000639:Amitriptyline; D005934:Glucagon