The role of the adenosine receptor antagonists on amitriptyline-induced cardiotoxicity

Objective We investigated the effects of adenosine receptor antagonists on amitriptyline-induced cardiotoxicity in isolated rat hearts. Methods The amitriptyline concentration that prolongated the QRS duration more than 150 % (10-4 M) and 50-75 % (5.5x10-5 M) were accepted as the control groups for two experimental protocols, respectively. In the first protocol, 10-4 M amitriptyline were infused following pretreatment with a selective adenosine A1 receptor antagonist, DPCPX (8-cyclopentyl-1,3- Dipropylxanthine,10-4 to 10-6 M) or a selective adenosine A2a receptor antagonist, CSC (8-3- chlorostyryl -caffeine,10-4 and 10-5 M). At the second protocol, 5.5x10-5 M amitriptyline were infused following pretreatment with DPCPX (10-4 M) or CSC (10-5 M). Left Ventricular Developed Pressure (LVDP), maximum rates of LVP development (dp/dtmax), QRS duration and Heart Rate (HR) were measured. Results At the first protocol, 10-4 M DPCPX pretreatment shortened QRS duration at 50 minute significantly when compared to control group (p<0.05). At the second protocol, pretreatment with 10-4 M DPCPX shortened the QRS duration at 40., 50. and 60. minutes after amitriptyline infusion when compared to control group (p<0.05, p<0.01 and p<0.05 respectively). Pretreatment with 10-5 M CSC prolongated QRS duration at 20, 30 and 60 minutes (p<0.05). Amitriptyline infusion following pretreatment with DPCPX or CSC did not change LVDP, dp/dtmax and HR when compared to control in both protocols (p>0.05). Conclusion While 10-4 M DPCPX shortened QRS prolongation, 10-5 M CSC prolongated QRS duration in the isolated rat hearts with QRS prolongation induced by 5.5x10-5 M amitriptyline. An adenosine A1 receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.