Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin

OBJECTIVES: This study investigated the effects of acute global ischemia on the vulnerable window, the upper limit of vulnerability and the defibrillation threshold. BACKGROUND: Myocardial ischemia, an important factor for arrhythmogenesis and sudden death, may affect the inducibility of ventricular fibrillation by T wave shocks as well as the defibrillation threshold. However, studies of the effect of ischemia on the defibrillation threshold remain inconclusive, and the effect of ischemia on recently established variables of ventricular fibrillation vulnerability is still unknown. METHODS: Ten isolated, perfused rabbit hearts were immersed in a tissue bath between two shock plate electrodes. Truncated 5-ms biphasic shocks were used to determine the vulnerable window, the upper limit of vulnerability and the defibrillation threshold. Measurements were performed during baseline and at 10 to 15 min of acute ischemia induced by an 80% reduction of coronary flow. The effects of ischemia were monitored by measuring the dispersion of ventricular activation and repolarization using multiple monophasic action potential recordings. RESULTS: Acute ischemia caused an increase in dispersion of activation (baseline vs. ischemia mean +/- SD]: 22 +/- 6 vs. 34 +/- 10 ms, p < 0.001) and dispersion of repolarization (37 +/- 16 vs. 69 +/- 29 ms, p < 0.01). The width of the vulnerable window increased from 25 +/- 22 ms during baseline to 75 +/- 26 ms during ischemia (p = 0.001). The upper limit of vulnerability (baseline vs. ischemia: 294 +/- 44 vs. 274 +/- 53 V, p = 0.21) and the defibrillation threshold (271 +/- 33 vs. 268 +/- 42 V, p = 0.74) remained unchanged during ischemia. CONCLUSIONS: Acute global ischemia caused a threefold increase in the width of the vulnerable window. This increase was associated with increased heterogeneity of ventricular activation and repolarization. Despite these marked changes, the upper limit of vulnerability and the defibrillation threshold were not affected by acute myocardial ischemia. Thus, the previously reported similarity between both measures was maintained under these adverse conditions.