Abstract 14395: Adverse Impact of Heart Failure on the Electrophysiological Response to Ischemia-Reperfusion in Humans
Introduction: Acute ischemia and reperfusion (I-R) are associated with pro-arrhythmic electrophysiological changes such as action potential duration (APD) shortening and conduction velocity (CV) slowing, though data from human myocardium are sparse. We studied electrophysiological changes during I-R in intact human ventricular myocardium with optical mapping, and compared differences between failing and non-failing hearts.
Methods: We optically mapped coronary-perfused left ventricular free wall wedge preparations from 6 human hearts with end-stage heart failure (HF) and 6 non-failing hearts from donors rejected for transplant (NF). At baseline, the preparations were subjected to steady-state pacing across a range of cycle lengths (CL). They were then subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Restitution pacing protocols were repeated following reperfusion.
Results: At baseline, HF hearts had longer APD80 and slower transmural CV compared to NF hearts across a range of CLs (both ANOVA P<0.001). APD80 and CV reduced with ischemia (At CL of 1000ms, Baseline vs. 10 mins ischemia: HF APD: 375 ± 23 vs. 324 ± 5 ms, P<0.01; NF APD: 308 ± 14 vs. 271 ± 28 ms, P<0.05; HF CV: 29 ± 4 vs. 16 ± 6 cm/s, P<0.05; NF CV: 40 ± 2 vs. 23 ± 2 cm/s, P<0.001), and were restored with reperfusion. APD shortening was greater in HF hearts during ischemia (ΔAPD80 at 8 mins ischemia: HF 75 ± 11, NF 25 ± 5 ms, P<0.01). Recovery of electrical excitability following reperfusion was delayed in HF (4.8 ± 1.8 vs. NF 1.0 ± 0 mins, P<0.05). APD was restored to pre-ischemic levels within the first minute of reperfusion in NF hearts, but restoration of APD was incomplete in HF early after reperfusion.
Conclusions: In human myocardium, acute ischemia was associated with APD shortening and CV slowing, which were reversed with reperfusion. In end-stage HF, these changes were accelerated during ischemia, and recovery was slower following reperfusion. This may enhance the spatial gradients of repolarization between ischemic and non-ischemic regions during acute I-R in failing hearts, and thus increase arrhythmia susceptibility. Further work is needed to elucidate the metabolic mechanisms underlying the adverse electrophysiological response to I-R in human heart failure.
- © 2012 by American Heart Association, Inc.