Free radicals potentiate the negative dromotropic effect of adenosine in guinea pig isolated heart.
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.


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 microM) 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 microM) did not affect the A-H interval (0.7 +/- 0.2 ms prolongation, n = 10). However, concurrent infusion of adenosine (2 microM) and pyrogallol (20 microM) 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 microM), 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 microM), a blocker of the adenosine-induced inward potassium current (I(K,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 I(K,ADO)-independent component. This phenomenon may contribute to the genesis of reperfusion arrhythmias.
Rajasekaran
Surender
S
Department of Anaesthesiology, University of Florida, Gainesville, FL 32610-0254, USA.
Morey
Timothy E
TE
Martynyuk
Anatoly E
AE
Dennis
Donn M
DM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects*; D002036:Bundle of His / Q000187:drug effects; D005260:Female; D005609:Free Radicals / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D030421:Peroxynitrous Acid / Q000502:physiology; D058915:Purinergic P1 Receptor Antagonists; D011748:Pyrogallol / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D005609:Free Radicals; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; D011748:Pyrogallol; D030421:Peroxynitrous Acid; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D000241:Adenosine