Effect of glucagon on amitriptyline induced cardiovascular toxicity in rats

Kaplan Y. C., Hocaoğlu Aksay N., Oransay K., Kalkan Ş., Tunçok Y.

2007 North American Congress of Clinical Toxicology Annual Meeting, Louisiana, Amerika Birleşik Devletleri, 19 - 24 Ekim 2007, cilt.45, sa.1, ss.605

  • Yayın Türü: Bildiri / Özet Bildiri
  • Cilt numarası: 45
  • Doi Numarası: 10.1080/15563650701610056
  • Basıldığı Şehir: Louisiana
  • Basıldığı Ülke: Amerika Birleşik Devletleri
  • Sayfa Sayıları: ss.605
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Background: The aim of this study was to investigate the effect of glucagon on cardiovascular parameters in anaesthetized rat model of tricyclic antidepressant overdose. Methods: Toxicity was induced by an infusion of amitriptyline 0.94 mg/kg/min until a 40– 45% of reduction in mean arterial pressure (MAP). After amitriptyline infusion rats were randomized into three groups (n = 7, each group). While control group of rats (Group 1) received a bolus of 5 % dextrose followed by the continuous infusion of dextrose, treatment groups received 1 mg/kg (Group 2) or 2 mg/kg (Group 3) bolus doses of glucagon followed by continuous infusions (0.1 mg/kg/min) of glucagon for 60 minutes. MAP, heart rate (HR), electrocardiogram and survival rate were recorded. Results: Amitriptyline caused a significant decrease in MAP and a prolongation in QRS yet it did not change HR. When compared to control, high dose glucagon (2 mg/kg bolus followed by 0.1 mg/kg/min) significantly increased MAP at 40, 50 and 60 minutes (76.5 ± 3.6 %, 54.5 ± 10.6 % at 40 min; 75.9 ± 4.7 %, 52.4 ± 7.3 % at 50 min; 77.5 ± 5.5 %, 45.7 ± 12.2 % at 60 min, p < 0.05, respectively) and shortened the prolonged QRS at 50 and 60 minutes (151.8 ± 15.6 %, 199.7 ± 7.8 % at 50 min; 150.7 ± 14.4 %, 201.6 ± 8.1 % at 60 min, p < 0.05, respectively). Glucagon (1mg/kg bolus followed by 0.1 mg/kg/min) significantly changed HRs at 60 minutes when compared to control group (95.8 ± 3.5 %, 70.7 ± 11.5 %, p < 0.05). High dose glucagon changed HRs at 40, 50 and 60 minutes significantly when compared to control group (105.2 ± 3.5 %, 81.6 ± 11.3 %, p < 0.05 at 40 min; 104.8 ± 2.5 %, 75.2 ± 14.6 %, p < 0.05 at 50 min; 105.7 ± 3.8 %, 70.7 ± 11.5, p < 0.01, at 60 min). Survival rate remained unchanged. Discussion: Glucagon caused an increase in MAP and HR which may be explained by its well-known positive inotropic and positive chronotropic effect. Further studies are needed to reveal the exact mechanism of the improvement in prolongation of QRS. Conclusion: Use of glucagon may be considered for reversing amitriptyline-induced hypotension and QRS prolongation.