Abstract 217: Effect of Amiodarone with Therapeutic Hypothermia on Arrhythmia Substrates During Global Myocardial Ischemia
Background: The effect of therapeutic hypothermia (TH) after cardiac arrest on susceptibility to arrhythmias is not well understood. We have shown that TH has a beneficial effect on reentrant substrates for ischemia-induced arrhythmias by limiting decreases in conduction velocity (CV) and attenuating increases in transmural dispersion of repolarization (DOR). As amiodarone is utilized during TH, it is important to understand the effect of TH and amiodarone on arrhythmia substrates during ischemia. Our hypothesis is that amiodarone worsens the antiarrhythmic effect of TH during global ischemia. To test this hypothesis, a model of no flow global ischemia in the canine wedge preparation was used to study the effects of ischemia on all cell types spanning the transmural wall.
Methods: Optical action potentials were recorded transmurally with high spatial (1 mm), temporal (.5 ms) and voltage (.5mv) resolution. Amiodarone (5microM) was used at both 36oC (control, CTAmio n=4) and 32oC (THAmio, n=4) during 15 min of no flow global ischemia and compared to controls (CT=7, TH=6). Action potential duration (APD), DOR, and CV were measured for all conditions. Programmed electrical stimulation (PES) was performed to assess for ischemia-induced arrhythmias and compared to prior controls (CT, n=5, TH, n=4).
Results: At baseline, TH prolonged APD in both THAmio and TH, but there was no difference between DOR and CV. At 15 minutes of ischemia, DOR increased in the THAmio group compared to TH (34±3 ms to 79±9 ms vs. 25±3 to 37±7 ms, p=.04). There was a trend towards worsening ischemia-induced conduction slowing in the THAmio group vs TH, but not significant (39±4 to 24±3 cm/s vs 44±2 to 35±3 cm/s, p=.06). There was no difference under control temperature of CTAmio vs CT for CV, DOR, or APD. PES induced arrhythmias in 2/4 in the CTAmio group vs. 0/4 in THAmio group (compared to 3/5 in CT group, 1/4 in TH group).
Conclusions: Amiodarone worsens the beneficial effect of TH on ischemia-induced DOR, but does not worsen susceptibility to arrhythmias. Further study in translatable models of ischemia-induced cardiac arrest is warranted to assess the effect of ACLS pharmacology on arrhythmias with the increased use of TH.
- © 2013 by American Heart Association, Inc.