Abstract 30: Therapeutic Hypothermia Suppresses Arrhythmogenic, Calcium-Mediated Delayed Afterdepolarizations
Background: Therapeutic hypothermia (TH) is recommended for patients with return of spontaneous circulation after resuscitation from cardiac arrest. Hypothermia is known to cause derangements in cellular calcium (Ca) cycling, leading to Ca overload; however, the effect of TH on Ca-mediated arrhythmogenic substrates remains unclear. We hypothesized abnormal Ca cycling during TH would promote spontaneous Ca release and delayed afterdepolarizations (DADs).
Methods and Results: Transmural dual optical mapping of Ca transients and action potentials was performed in canine wedge preparations during normothermia (36ºC; N group, n=5) or TH (32ºC; n=6). Multicellular spontaneous Ca release events (mSCR) and resultant DADs were induced by rapid pacing. TH significantly slowed the kinetics of Ca cycling compared to normal controls, significantly prolonging the time to peak (60.4 ± 5.7 vs. 40.1 ± 2.6 ms), duration (401.2 ± 13.8 vs. 305.8 ± 12.4 ms) and rate of decay (247.4 ± 29.2 vs. 146.0 ± 12.6 ms, all p<0.05) of full Ca transients. The maximal mSCR amplitude was not significantly different in TH (21.1 ± 6.0%) compared to normals (28.4 ± 1.9%, p=NS). However, the slope (mSCR amplitude/time to peak) of mSCR activity, an important determinant of triggered activity, was significantly slower in TH (14.3 ± 3.7 %/s) compared to N (29.9 ± 3.9%/s, p<0.05). Importantly, DAD amplitude was also significantly lower in TH (4.1 ± 2.2%) compared to N (11.1 ± 1.5%, p<0.05).
Conclusion: Even though therapeutic hypothermia did not decrease the magnitude of spontaneous calcium release, it did significantly reduce the slope, which was associated with significantly lower DAD amplitude. These results suggest that TH could be antiarrhythmic, in part, by slowing the kinetics of spontaneous calcium release and, thus, decreasing delayed afterdepolarizations, an important cause of triggered activity and arrhythmias.
- © 2012 by American Heart Association, Inc.