Effects of adenosine receptor antagonists on amitriptyline-induced QRS prolongation in isolated rat hearts.
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 x 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 A(1) 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 x 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).


CONCLUSIONS
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.
Akgun
Aylin
A
Department of Pharmacology, Dokuz Eylul University, Health Sciences Institute, Izmir, Turkey.
Kalkan
Sule
S
Hocaoglu
Nil
N
Gidener
Sedef
S
Tuncok
Yesim
Y
D000639:Amitriptyline / Q000633:toxicity*; D000818:Animals; D002110:Caffeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D066298:In Vitro Techniques; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C081320:8-(3-chlorostyryl)caffeine; D000639:Amitriptyline; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine