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Document Details : Title: Free radicals potentiate the negative dromotropic effect of adenosine in guinea pig isolated heart Author(s): RAJASEKARAN, Surender , MOREY, Timothy E. , MARTYNYUK, Anatoly E. , DENNIS, Donn M. Journal: Acta Cardiologica Volume: 58 Issue: 3 Date: June 2003 Pages: 191-197 DOI: 10.2143/AC.58.3.2005278 Abstract : Objective— Adenosine is released during myocardial ischaemia and delays atrioventricular nodal (AV) conduction. We hypothesized that free radicals present during reperfusion potentiate the negative dromotropic effect of adenosine on the AV node. Methods and results— Guinea pig hearts were prepared using the Langendorff technique,paced (200 beats/min), and instrumented to measure the atrium-to-His bundle (A-H) interval, an index of AV nodal conduction time. Adenosine (2 μM) prolonged the A-H interval by 5.7±0.5 ms from a control value of 35.7±1.3 ms. (n = 10, P<0.05). In the absence of adenosine, the superoxide (O2-) generator pyrogallol (20 μM) did not affect the A-H interval (0.7±0.2 ms prolongation, n = 10). However, concurrent infusion of adenosine (2 μM) and pyrogallol (20 μM) lengthened the A-H interval by 11.0±0.8 ms from control (n = 10, P<0.001).This A-H interval prolongation was reversed by cyclopentyl-1,3-dipropylxanthine (100 nM), a selective A1-adenosine receptor antagonist (P<0.001, n = 5). Similarly, A-H interval prolongation was decreased to 4.3±0.4 ms when NG-methyl-L-arginine (100 μM), a nitric oxide (NO) synthase inhibitor, was infused (n = 4). The superoxide scavenger superoxide dismutase (200 U/ml) also diminished the A-H interval prolongation to 7.1±0.6 ms (n = 4, P<0.001). Ba2+ (100 μM), a blocker of the adenosine-induced inward potassium current (IK,ADO), did not significantly affect this potentiation (13.0±0.8 and 10.8±0.7 ms greater than control A-H interval in the absence and presence of Ba2+, respectively, n = 4). Conclusions— Superoxides and adenosine delay AV nodal conduction in a synergistic manner via a NO-dependent mechanism involving an IK,ADO-independent component. This phenomenon may contribute to the genesis of reperfusion arrhythmias. |
