Abstract 14978: Nitrated Fatty Acids Suppress Ventricular Arrhythmias During Acute Myocardial Ischemia
Background: Nitrated fatty acids (NO2-FA) are termination products of radical chain reactions and have been identified as potent anti-inflammatory signaling mediators. Previously we demonstrated that these compounds are generated during myocardial ischemia-reperfusion, where they diminish infarct size and preserve left ventricular function. We therefore investigated whether NO2-FA - besides their cardioprotective properties - exert anti-arrhythmic effects in the acute phase of myocardial ischemia.
Methods: Myocardial ischemia was induced by left coronary artery ligation after lateral thoracotomy in male FVB wild-type mice. Two minutes after LAD ligation mice underwent electrophysiological investigation via an octapolar catheter positioned in the right ventricle and ventricular burst stimulation (S1:8x50ms, S2:4x30ms at 1mA, 2 mA, respectively) was performed. 20 minutes prior to the ligation mice were treated with an intraperitoneal injection of either 20 nmol/g body weight nitro-oleate (OA-NO2) or vehicle. Additionally, action potentials as well as Ca2+-transients were derived from intact isolated ventricular cardiomyocytes under normoxic and hypoxic conditions after pretreatment with OA-NO2.
Results: Whereas 80% of vehicle-treated mice were inducible for ventricular tachycardia (VT), OA-NO2 pretreated mice developed VT in 20%. Total number of episodes was 23 in the vehicle-treated group compared to 2 in the OA-NO2 pretreated group. Probability of VT induction, defined as inducible episodes divided by total stimulation maneuvers, was 31% for vehicle-treated animals vs 3 % for OA-NO2 pretreated mice (p=0.009) and total time of VT in vehicle-treated animals was 19,5 s compared to 0,38 s in OA-NO2 treated mice. Pretreatment with OA-NO2 in normoxic isolated cardiomyocytes resulted in no signficant changes of action potentials. OA-NO2 lead to a more rapid Ca2+-release as well as higher systolic Ca2+-amplitudes and reversed the hypoxia-induced deceleration of Ca2+-release.
Conclusion: Our data indicate that NO2-FA exhibit anti-arrhythmic effects during the acute phase of myocardial ischemia. NO2-FA may thus evolve as a novel class of protective lipid signaling mediator during the acute phase of myocardial ischemia.
- © 2011 by American Heart Association, Inc.