| pA2 online © Copyright 2004 The British Pharmacological Society |
098P
University of Bath Summer Meeting July 2004 |
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Investigation of the antifibrillatory drug interactions between lidocaine and valsartan in perfused rabbit hearts AA. Almotrefi & M.Arif , Dept. of Pharmacology, King Saud University, Riyadh, Saudi Arabia |
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Print abstractIn view of the reliability of the serial-shock method of measuring ventricular fibrillation threshold (VFT) in assessing antifibrillatory potency of many antiarrhythmic drugs (Almotrefi & Baker, 1981) and the alarming reports of the proarrhythmic effects of several antiarrhythmic agents (Peters et al., 1994) we decided to use the above technique to study interactions that may occur when antiarrhythmic and antihypertensive drugs from different classes are combined. Recently, we have presented the antifibrillatory interactions between lidocaine and propranolol (Almotrefi et al., 1999), lidocaine and bretylium (Almotrefi et al., 2001) and that between propranolol and bretylium (Almotrefi et al., 2003). In this abstract we report the antifibrillatory interactions between lidocaine 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 given previously (Almotrefi & Baker, 1981). Perfusion with lidocaine 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 3.46µmol of lidocaine 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 lidocaine, indicating safety of their combined use in treating hypertensive patients with cardiac arrhythmias.
Drug |
%change in VFT after exposure for |
%change in VFT after washout for |
||||
( µmol) |
15min |
30min |
60min |
15min |
30min |
60min |
Control |
0.37 ± 5.96 |
-3.00 ± 5.45 |
-7.49 ± 6.30 |
-4.83 ± 7.51 |
2.07 ± 9.69 |
1.86 ± 10.50 |
| Lidocaine | ||||||
(3.46) |
28.80 ± 5.24 *** |
37.29 ± 7.31 *** |
53.92 ± 8.49 *** |
-1.28 ± 4.67 |
-5.16 ± 5.04 |
-2.20 ± 4.60 |
(6.92) |
51.31 ± 3.70 * |
97.91 ± 12.11 ** |
145.09 ± 9.35 * |
25.16 ± 8.26 |
3.32 ± 6.97 |
-1.07 ± 3.27 |
(13.85) |
112.51 ± 10.80 *** |
191.17 ± 10.65 *** |
218.22 ± 10.30 *** |
-1.86 ± 4.61 |
-4.96 ± 3.67 |
-9.40 ± 2.86 |
| Valsartan | ||||||
( 1 ) |
10.21 ± 7.23 |
14.36 ± 11.17 |
21.21 ± 16.06 |
14.99 ± 20.42 |
12.52 ± 19.33 |
15.91 ± 22.25 |
( 2 ) |
-11.53 ± 22.81 |
-20.54 ± 13.97 |
10.56 ± 30.38 |
27.71 ± 34.77 |
15.80 ± 24.30 |
14.97 ± 33.22 |
( 4 ) |
-6.76 ± 4.95 |
-10.84 ± 9.18 |
-3.46 ± 8.48 |
-2.61 ± 11.20 |
-7.85 ± 15.32 |
4.09 ± 15.07 |
| Lidocaine | ||||||
+ |
25.84 ± 9.23 * |
16.91 ± 3.62 * |
36.25 ± 12.82 * |
11.35 ± 7.64 |
9.30 ± 7.56 |
6.23 ± 13.05 |
Table 1. Effect of lidocaine, valsartan and their combination on (VFT) in isolated- perfused rabbit hearts.
Almotrefi,AA & Baker, JBE (1981) Br.J.Pharmacol., 73, 373-377
Almotrefi, AA et al., (1999) Br.J.Pharmacol., 128, 55
Almotrefi, AA et al., (2001) Proceedings of the joint meeting of the Australisian, British, Canadian and Western Pharmacology Societies ,Vancouver , PO-324
Almotrefi, AA et al., (2003) Br.J.Pharmacol., 138, 143P
Peters, RW et al., (1994) J.Am.Coll.Cardiol., 23, 283-289