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

Abstract

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 x 10(-5)M amitriptyline. An adenosine A(1) receptor antagonist, DPCPX, might shorten amitriptyline-induced QRS prolongation by activating beta adrenergic receptors.

Correlation between Amitriptyline-Induced Cardiotoxic Effects and Cardiac S100b Protein in Isolated Rat Hearts

“…In our previous isolated heart studies, we demonstrated that an amitriptyline infusion (5.5×10 −5 M) caused a significant prolongation of the QRS duration as an indicator of amitriptyline cardiotoxicity (18)(19). In the present study, the same dose of amitriptyline (5.5×10 −5 M) infusion was used to achieve amitriptyline cardiotoxicity.…”

“…In control group (Group 1, n=5), isolated hearts were subjected to an infusion of 5% dextrose for 60 minutes. In our previous isolated rat heart studies, 5.5×10 −5 M amitriptyline infusion prolonged QRS duration by 50-75% (18)(19). In the amitriptyline group (Group 2, n=7), the same dose (5.5×10 −5 M) of amitriptyline was infused for 60 minutes to achieve amitriptyline toxicity.…”

“…After the stabilization period, baseline measurements were obtained; if hearts had LVDP <70 mmHg or were mechanically unstable, they were excluded from the experiment (18)(19). The cardiac parameters (LVDP, dp/dt max , QRS duration and HR) were recorded continuously during the experimental protocol.…”

“…To measure left ventricular developed pressure (LVDP), a balloon catheter filled with distilled water connected to a transducer (MLT844 Physiological Pressure Transducer, Interlab LTD; İstanbul, Turkey) was inserted into the left ventricle cavity. The balloon volume was adjusted so that the left ventricular end-diastolic pressure (LVEDP) was 10 mmHg during the experiment (18)(19).…”

Effects of Adenosine Receptor Antagonists on Survival in Amitriptyline-poisoned Mice

“…In another study, Kalkan et al demonstrated that amitriptyline induced a vasodilation in the isolated rat aorta model via A 2a receptors, which suggests that adenosine A 2a -receptor stimulation seems to be partly responsible for amitriptyline-induced vasodilation and hypotension (Kalkan et al, 2007). Likewise, in an isolated rat-heart model, DPCPX, an adenosine A 1 -receptor antagonist, shortened amitriptyline-induced QRS prolongation (Akgun et al, 2008).…”