| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2601177 | Toxicology Letters | 2009 | 9 Pages |
AimsTo investigate the role of beta receptor blockade via adenosine A1 receptor stimulation on amitriptyline-induced QRS prolongation.MethodsIsolated 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 × 10−5 M).ResultsAmitriptyline (5.5 × 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.ConclusionDPCPX pretreatment shortened amitriptyline-induced QRS prolongation. Beta adrenergic receptor blockade enhanced QRS prolongation shortened by DPCPX pretreatment. Adenosine A1 receptor stimulation related to beta adrenergic receptor blockade may play a role in amitriptyline-induced QRS prolongation in isolated rat hearts.
