MEANDERING AND UNSTABLE REENTRANT WAVE-FRONTS INDUCED BY ACETYLCHOLINE IN ISOLATED CANINE RIGHT ATRIUM

The mechanism(s) by which acetylcholine (ACh) increases atrial vulnera bility to reentry and maintains its activity for longer durations rema ins poorly defined. In the present study we used high-resolution activ ation maps to test the hypothesis that ACh promotes meandering of atri al reentrant wave fronts, resulting in breakup and the generation of n ew wave fronts that sustain the activity. Reentry was induced in II is olated canine right atrial tissues (3.8 x 3.2 cm) by a premature point stimulus (S-2) before and after superfusion with ACh (15 x 10(-6) M). Endocardial isochronal activation maps were constructed with the use of 509 bipolar electrodes (1.6-mm spatial resolution), and the dynamic s of the activation wave fronts were visualized with animation. A vuln erable period was found during which an Sa current strength >4.4 +/- 2 .5 mA [lower Limit of vulnerability (LLV)] and <26 +/- 13 mA [upper li mit of vulnerability (ULV)] induced a single stationary reentrant wave front that lasted 3 +/- 2.5 s with a period of 159 +/- 17 ms (16 epis odes). ACh shortened the refractory period from 100 +/- 12 to 59 +/- 9 ms (P < 0.001) and increased vulnerability to reentry induction by si multaneous decrease in the LLV (0.7 +/- 0.2 mA, P < 0.001) and an incr ease in the ULV (82 +/- 24 mA, P < 0.01). ACh accelerated the rate (pe riod of 110 +/- 16 ms, P < 0.001) and converted the stationary reentra nt wave front to a nonstationary (meandering) reentrant wave front sho wing polymorphic electrograms, i,e., ''fibrillation-like'' activity (2 2 episodes). Rapid meandering of the reentry tip led to wave front bre akup (18 episodes) and the generation of new wave fronts (19 episodes) . These wave front dynamics also led to sustained (76 +/- 224 s, P < 0 .001) fibrillation-like electrograms. We conclude that ACh increases t he ULV and promotes meandering of a single reentrant wave front, leadi ng to breakup and the generation of new wave fronts. Single meandering and complex wave front dynamics cause fibrillation-like activity and sustain the activity for longer duration.