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Evaluation of the antifibrillatory drug interactions between propranolol and valsartan in perfused rabbit hearts
The alarming reports of the proarrhythmic effects of several antiarrhythmic agents (Peters et al., 1994) have stimulated our interest to study the antifibrillatory interactions that may occur when antiarrhythmic and antihypertensive drugs from different classes are combined. We used the serial-shock technique of measuring ventricular fibrillation threshold (VFT), a method that proved to be reliable in assessing the antifibrillatory potency of many antiarrhythmic drugs (Almotrefi & Baker, 1981). Recently, we have presented the interactions between lidocaine and propranolol (Almotrefi et al., 1999), propranolol and bretylium (Almotrefi et al., 2003) and that between lidocaine and valsartan (Almotrefi & Arif, 2004). This abstract reports the results with propranolol and valsartan. Studies were carried out on hearts isolated from New Zealand white rabbits of either sex weighing 1.5 to 2 Kg. The method used has been described previously (Almotrefi & Baker, 1981). Perfusion with propranolol produced significant, dose-dependent increase in VFT while perfusion with valsartan did not cause any significant change (Table1 ). In addition, there was no significant difference in VFT with the combined infusion of 0.34 µmol of propranolol and 1µmol of valsartan, in contrast to a synergistic antifibrillatory effect of the combined use of lidocaine and propranolol (Almotrefi et al., 1999). This suggests that valsartan does not have antifibrillatory interactions with propranolol, which may be taken as indicative of its safety in combining with class 2 antiarrhythmic agents. Table 1. Effect of propranolol, valsartan and their combination on (VFT) in isolated-perfused rabbit hearts.
Values are means ± s.e.m * P< 0.05, ** P<0.005,*** p<0.0005.
Almotrefi, AA & Baker, JBE (1981) Br.J.Pharmacol., 73,373-377. | |||||||||||||||||||||||||||||||||||||||||||||||||||||
