Action Potential Duration and QT Interval During Pinacidil Infusion in Isolated Rabbit Hearts
- 12 April 2005
- journal article
- Published by Wiley in Journal of Cardiovascular Electrophysiology
- Vol. 16 (8), 872-878
- https://doi.org/10.1111/j.1540-8167.2005.40811.x
Abstract
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. 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). 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.Keywords
This publication has 27 references indexed in Scilit:
- Ventricular repolarization components on the electrocardiogramJournal of the American College of Cardiology, 2003
- QT interval and mortality from coronary artery diseaseProgress in Cardiovascular Diseases, 2000
- Assessment of QT Interval and QT Dispersion for Prediction of All-Cause and Cardiovascular Mortality in American IndiansCirculation, 2000
- Electrical Alternans and Vulnerability to Ventricular ArrhythmiasNew England Journal of Medicine, 1994
- Activation of ATP-sensitive K+ channels by cromakalim. Effects on cellular K+ loss and cardiac function in ischemic and reperfused mammalian ventricle.Circulation Research, 1992
- Effects of pinacidil on guinea-pig isolated perfused heart with particular reference to the proarrhythmic effectBritish Journal of Pharmacology, 1992
- Sulfonylureas, ATP-sensitive K+ channels, and cellular K+ loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.Circulation Research, 1991
- Enhancement of potassium-sensitive current in heart cells by pinacidil. Evidence for modulation of the ATP-sensitive potassium channel.Circulation Research, 1989
- Reconstitution and characterization of a calcium-activated channel from heart.Circulation Research, 1988
- Mechanism and time course of S-T and T-Q segment changes during acute regional myocardial ischemia in the pig heart determined by extracellular and intracellular recordings.Circulation Research, 1978