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Rapid Eiectrophysiological Changes Leading to Arrhythmias in the Aerobic Rat Heart. Photosensitization Studies With Rose Bengal-Derived Reactive Oxygen Intermediates

The objective of this study was to determine whether reactive oxygen intermediates (e.g., singlet oxygen and the superoxide radical) can rapidly induce eiectrophysiological disturbances leading to the genesis of arrhythmias, even in the absence of ischemia and reperfusion. Rat hearts (n = 6 per group) were perfused aerobically at 37° C for 10 minutes without rose bengal and for 5 minutes with rose bengal (250 nmol/l), during which time no changes in coronary flow or heart rate were observed. Hearts were then uniformly illuminated for 20 minutes with green light (530–590 nm) from 200 fiber optic cables. With light and without rose bengal, or vice versa, all hearts remained stable. However, in the illuminated rose bengal group, eiectrophysiological changes (inversion of the terminal portion of the T wave and an increase in Q-T interval) were observed within 11.8 ± 2.1 seconds (i.e., less than 60 beats). All hearts exhibited ventricular premature beats (within 2.2 ± 0.7 minutes) and ventricular tachycardia (within 2.8 ± 0.7 minutes) before the occurrence of complete atrioventricular block (within 5.5 ± 0.9 minutes). During the illumination period, coronary flow progressively fell in the rose bengat-perfused hearts from 11.6 ± 0.5 ml/min to 2.0 ± 0.4 ml/min (< 0.05 when compared with any control group). When a similar progressive reduction in coronary flow was mimicked (with or without rose bengal), no arrhythmias occurred. Photosensitization of the rose bengal solution in the cannula at a point close to the heart did not induce any eiectrophysiological disturbances or arrhythmias, indicating that it was the short-lived reactive oxygen intermediates rather than the rose bengal product that were responsible for the observed effects. The addition of histidine (100 nmol/l) as a quenching agent to the rose bengal solution significantly delayed the occurrence of the eiectrophysiological changes and arrhythmias. Our results provide evidence that reactive oxygen intermediates can rapidly induce eiectrophysiological changes and arrhythmias even in the absence of ischemia or reperfusion. {Circulation Research 1989;65:146–153)