Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

Aims: To investigate the role of beta receptor blockade via adenosine A, receptor stimulation on amitriptyline-induced QRS prolongation. Methods: Isolated rat hearts were randomized into three groups (n = 8 for each group). After pretreatment with 5% dextrose (control) or DPCPX (8-cyclopentyl-1,3-dipropylxanthine), or propranolol + DPCPX, amitriptyline infusion was given to all groups. Intact beta adrenergic receptor response was verified with a bolus dose of isoproteranol (3 x 10(-5) M). Results: Amitriptyline (5.5 x 10(-5) M) infusion following pretreatment with 5% dextrose or 10(-4) M DPCPX prolonged QRS by 40-110% and 30-75%, respectively. After the beta receptor blockade with 10(-2) M propranolol bolus, amitriptyline infusion following pretreatment with DPCPX prolonged QRS by 40-130%. Amitriptyline infusion following pretreatment with DPCPX (10(-4) M) shortened the QRS at 40, 50 and 60 min significantly when compared to propranolol + DPCPX group (168.8 +/- 4.9%, p < 0.05; 170.8 +/- 6.9%, P < 0.01; 174.0 +/- 6.9%, p < 0.01, respectively). Amitriptyline infusion following pretreatment with 5% dextrose prolonged QRS duration significantly at 50th minutes (209.5 +/- 6.1%, p < 0.05) compared to DPCPX pretreatment group. Conclusion: DPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A, receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts. (C) 2009 Elsevier Ireland Ltd. All rights reserved.