Suhua Wu1, Hideki Hayashi, Shien-Fong Lin, Peng-Sheng Chen. 1. Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.
Abstract
INTRODUCTION: Acute myocardial ischemia, which opens K(ATP) channel, is associated with shortened action potential duration (APD) but prolonged QT interval. This discrepancy has not been adequately explained. We hypothesize that the duration of intracellular calcium (Ca(i)) transient (DCaT) may play a role in determining QT interval. METHODS AND RESULTS: We performed simultaneous optical mapping of voltage and Ca(i) in 15 isolated rabbit hearts during a K(ATP) channel opener (pinacidil) infusion. Anterior epicardial mapping (n = 7) showed no difference of APD(90), QT interval, and the DCaT(90) at baseline. When perfused with 80 microM pinacidil, the APD(90), the QT interval, and the DCaT(90) were 105 +/- 10 msec, 199 +/- 14 msec, and 189 +/- 13 msec, respectively, during right ventricular (RV) pacing (P < 0.05). Posterior epicardial mapping (n = 4) showed that the APD(90) was significantly (P < 0.05) shorter than QT interval and DCaT(90) during pinacidil infusion. The results of the transmural mapping studies (n = 4) showed that the QT interval during RV pacing was not different than the DCaT(90) in the epicardium, midmyocardium, and endocardium, but was significantly (P < 0.01) longer than the APD(90) in epicardium, midmyocardium, and endocardium, respectively. There was a good correlation between the DCaT(90) and QT interval at baseline (r = 0.92, P < 0.0001) and during pinacidil infusion (r = 0.74, P < 0.0001). CONCLUSION: We conclude that K(ATP) channel opening shortened APD but not the QT interval. Because Ca(i) did not return to diastolic level at the end of action potential, it may have created a heterogeneous membrane potential distribution that determined the QT interval.
INTRODUCTION: Acute myocardial ischemia, which opens K(ATP) channel, is associated with shortened action potential duration (APD) but prolonged QT interval. This discrepancy has not been adequately explained. We hypothesize that the duration of intracellular calcium (Ca(i)) transient (DCaT) may play a role in determining QT interval. METHODS AND RESULTS: We performed simultaneous optical mapping of voltage and Ca(i) in 15 isolated rabbit hearts during a K(ATP) channel opener (pinacidil) infusion. Anterior epicardial mapping (n = 7) showed no difference of APD(90), QT interval, and the DCaT(90) at baseline. When perfused with 80 microM pinacidil, the APD(90), the QT interval, and the DCaT(90) were 105 +/- 10 msec, 199 +/- 14 msec, and 189 +/- 13 msec, respectively, during right ventricular (RV) pacing (P < 0.05). Posterior epicardial mapping (n = 4) showed that the APD(90) was significantly (P < 0.05) shorter than QT interval and DCaT(90) during pinacidil infusion. The results of the transmural mapping studies (n = 4) showed that the QT interval during RV pacing was not different than the DCaT(90) in the epicardium, midmyocardium, and endocardium, but was significantly (P < 0.01) longer than the APD(90) in epicardium, midmyocardium, and endocardium, respectively. There was a good correlation between the DCaT(90) and QT interval at baseline (r = 0.92, P < 0.0001) and during pinacidil infusion (r = 0.74, P < 0.0001). CONCLUSION: We conclude that K(ATP) channel opening shortened APD but not the QT interval. Because Ca(i) did not return to diastolic level at the end of action potential, it may have created a heterogeneous membrane potential distribution that determined the QT interval.