Abstract 19830: Reduced Electromechanical Activity Related to the Functional Modification of Ion Channels in Hibernating Myocardium of Porcine Heart
Introduction: Chronic ischemia can lead to the development of hibernating myocardium, which is associated with an increased risk for cardiac sudden death. However, little is known of the changes in individual ionic channels during hibernation. In the present study, we characterize the features of electromechanical abnormalities in the hibernating myocardium in vivo and in vitro.
Methods: Porcine models of chronic ischemia were created by implantation of an ameroid constrictor in the proximal left circumflex coronary artery (LCX) for 4 weeks. In vivo, the ischemic areas were examined by ECG, echocardiography, angiography and electromechanical (NOGA and Ensite) mapping systems. In vitro, action potential duration (APD), potassium currents (Ik-total), sodium current (INa) and L-type calcium current (ICaL) were recorded by whole cell patch-clamp techniques on myocytes.
Results: In 6 chronic ischemic hearts, the LCX showed 99% narrowing with TIMI 0∼I blood flow, and ECG in lead I and avL showed depressed ST segments and inverted T waves. The hibernating myocardium was defined as viable myocardium with decreased systolic thickening in the lateral wall segments examined by resting echocardiographs and biphasic responses during dobutamine stress tests. Results from both contact and non-contact mapping indicated significant decreases in unipolar voltages and reduced relative amplitudes in hibernating areas. Patch-clamp results revealed that APD shortened significantly in cardiomyocytes isolated from hibernating regions (APD90: 438.48 ± 74.83 ms vs. 651.49 ± 64.41 ms, p<0.05). In hibernating myocytes, the Ik-total was increased in comparison to that in non-ischemic myocytes (4.71± 0.88 pA/pF vs. 2.14 ± 0.47 pA/pF, p<0.05), but ICaL was decreased (4.95± 0.96 pA/pF vs. 9.47 ± 0.92 pA/pF, p=0.01), indicating contributes to the shortening of ADP as well as the decreases in contractility. In addition, INa was decreased (21.64 ± 1.42 pA/pF vs. 24.74 ± 1.12 pA/pF, p<0.05) and that could contribute to conduction slowing.
Conclusion: The reduced electromechanical activity of hibernating myocardium reflects the changes in ionic currents due to cellular electrophysiology remodeling, which may contribute to increased arrhythmogeneity during chronic ischemia.
- © 2010 by American Heart Association, Inc.