Therapeutic hypothermia (30 degrees C) enhances arrhythmogenic substrates, including spatially discordant alternans, and facilitates pacing-induced ventricular fibrillation in isolated rabbit hearts.

BACKGROUND

Therapeutic hypothermia (TH, 30 degrees C) protects the brain from hypoxic injury. However, TH may potentiate the occurrence of lethal ventricular fibrillation (VF), although the mechanism remains unclear. The present study explored the hypothesis that TH enhances wavebreaks during VF and S(1) pacing, facilitates pacing-induced spatially discordant alternans (SDA), and increases the vulnerability of pacing-induced VF.

METHODS AND RESULTS

Using an optical mapping system, epicardial activations of VF were studied in 7 Langendorff-perfused isolated rabbit hearts at baseline (37 degrees C), TH (30 degrees C), and rewarming (37 degrees C). Action potential duration (APD)/conduction velocity (CV) restitution and APD alternans (n=6 hearts) were determined by S(1) pacing at these 3 stages. During TH, there was a higher percentage of VF duration containing epicardial repetitive activities (spatiotemporal periodicity) (P<0.001). However, TH increased phase singularity number (wavebreaks) during VF (P<0.05) and S(1) pacing (P<0.05). TH resulted in earlier onset of APD alternans (P<0.001), which was predominantly SDA (P<0.05), and increased pacing-induced VF episodes (P<0.05). TH also decreased CV, shortened wavelength, and enhanced APD dispersion and the spatial heterogeneity of CV restitution.

CONCLUSIONS

TH (30 degrees C) increased the vulnerability of pacing-induced VF by (1)facilitating wavebreaks during VF and S(1) pacing, and (2)enhancing proarrhythmic electrophysiological parameters, including promoting earlier onset of APD alternans (predominantly SDA) during S(1) pacing.