Abstract 38: Transmural Dispersion of Repolarization as a Mechanism for Arrhythmogenesis in Hypothermia
Ventricular fibrillation (VF) is a major cause of death in patients with hypothermia. With increased use of hypothermic therapy after resuscitation from cardiac arrest, there is an increased need to understand the mechanisms that underlie arrhythmogenesis in hypothermia. Since hypothermia profoundly effects cellular repolarization, we hypothesized that enhanced transmural dispersion of repolarization (DOR) is a mechanism of arrythmogenesis in hypothermia. To test this hypothesis, optical action potentials were recorded with high spatial (1 mm), temporal (.5 ms) and voltage (.5mv) resolution from cells spanning the transmural wall of canine left ventricular wedge preparations (n = 6) at baseline temperature (36° C), during induction of hypothermia (cooling to 26° C) and during rewarming. With cooling, QT interval and mean action potential duration (APD) increased from 223 ± 20 ms to 600 ± 165 ms and 272 ± 10 ms to 638 ± 84 ms, respectively (both p < .001) and conduction velocity (CV) decreased by 49 ± 24% (p < .05). Hypothermia caused a > 4-fold increase in DOR (p < .03), which was attributable to relatively greater prolongation (> 100 ms) of APD in mid-myocardial (M) vs. epicardial myocytes. Increased DOR during hypothermia was associated with conduction block and reentry in response to programmed electrical stimulation (PES) in all preparations, with conduction block frequently observed when impulses propagated into the markedly prolonged M cell region. CV was restored to baseline by rewarming but interestingly, DOR remained prolonged by > 3-fold (p < .03) at temperatures of 34–36° C. The incidence of arrhythmias was greatest during rewarming: in 3 preparations, spontaneous VF was observed and in the remaining 3 preparations, reentrant polymorphic ventricular tachycardia was inducible with 1 or 2 premature stimuli during rewarming.
Conclusions: Hypothermia heterogeneously effects repolarization of ventricular cells, which amplifies DOR and represents a mechanism for arrhythmogenesis. The increased incidence of arrhythmias during rewarming suggests that patients are at high risk for arrhythmogenesis during rewarming from accidental hypothermia and therapeutic hypothermia initated after resuscitation from cardiac arrest.