Effects of adenosine receptor antagonists onamitriptyline-induced QRS prolongation in isolated rat hearts

Abstract

Objective. We investigated the effects of adenosine receptor antagonists on amitriptyline-induced cardiotoxicity in isolated rat hearts. Methods. The amitriptyline concentrations that prolonged the QRS duration more than 150% (10⁻⁴ M) and 50–75% (5.5 × 10⁻⁵ M) were accepted as the control groups for two experimental protocols, respectively. In the first protocol, amitriptyline (10⁻⁴ M) was 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 A_2a receptor antagonist, CSC (8-3-chlorostyryl-caffeine,10⁻⁴ to 10⁻⁶ M). In the second protocol, amitriptyline (5.5 × 10⁻⁵ M) was infused following pretreatment with DPCPX (10⁻⁴ M) or CSC (10⁻⁵ M). Left ventricular developed pressure (LVDP), dp/dt_max, QRS duration and heart rate (HR) were measured. Results. In the first protocol, 10⁻⁴ M DPCPX pretreatment shortened QRS duration at 50 minutes when compared to the control group (p < 0.05). In 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 the control group (p < 0.05, p < 0.01 and p < 0.05, respectively). Pretreatment with 10⁻⁵ M CSC prolonged QRS duration at 20, 30, and 60 minutes (p < 0.05). Amitriptyline infusion following pretreatment with DPCPX or CSC did not change LVDP, dp/dt_max, or HR when compared to control in both protocols (p > 0.05). Conclusion. While 10⁻⁴ M DPCPX shortened QRS prolongation, 10⁻⁵ M CSC prolonged QRS duration in the isolated rat hearts with prolonged QRS duration induced by 5.5 × 10⁻⁵M amitriptyline. An adenosine A₁ receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.

Keywords: :

• Amitriptyline
• Adenosine
• Adenosine receptor antagonists
• Isolated rat heart

Acknowledgement

This study was supported by Dokuz Eylul University Research Foundation, Grant No. 03.KB.SAG.003.