Abstract 330: Intralipid Rescues Delayed Cooling and Restores Contractions in Ischemia-Stunned Heart Cells
Introduction: Cooling is a promising treatment for cardiac arrest. However, delayed cooling (DC) can result in loss of protection against ischemia/reperfusion (I/R) injury. We sought to develop drugs that mimic or augment cooling protection. Intralipid (ILP), a soy-based fat emulsion that is widely used in different clinical setting for parenteral nutrition, has been recently introduced as an antidote against local anesthetic-induced cardiotoxicity. In this study, we utilized a stunned mouse cardiomyocyte model to study the effect of ILP on improving contractile function and its potential role in rescuing abnormal contractility.
Methods: Cardiomyocytes, isolated from 1-2-day old C57Bl6/J mice were used. Protocols: 1) Stunning: cells were exposed to 30 min simulated ischemia and 90 min reperfusion followed by 10 min isoproterenol (10 μM). 2) ILP treatment: ILP (0.25%) was administered during 90 min reperfusion. 3) Delayed ILP treatment: ILP was given at 20 min of reperfusion. 4) DC: cooling (32оC) was initiated at 20 min of reperfusion and lasted for 40 min, followed by 30 min re-warming. 5) DC + ILP: ILP was given at start of reperfusion for 90 min in DC. The contraction velocity was measured using Matlab software. Akt phosphorylation was analyzed by Western blot.
Results: ILP administration at the onset of reperfusion significantly increased the contraction velocity in stunned cells (66.0 +/- 3.9 % vs. 40.6 +/- 1.7%, P < 0.001) and enhanced the cell response to isoproterenol. The contractile function was not recovered when ILP administration was delayed. Intra-ischemic cooling (IC) improved contractile function that was abolished by DC. Co-treatment of ILP and DC significantly enhanced contractility (43.3 +/- 3.0 % vs. 20.1 +/- 3.9 %, P < 0.01). Akt phosphorylation (p-Akt) was increased by ILP, but decreased when ILP was delayed. Similarly, DC attenuated p-Akt which was increased by ILP+DC. This ILP-induced p-Akt was blocked by API-2, an Akt inhibitor.
Conclusion: Our results suggest that optimal ILP treatment improved contractile function and contractile preservation that was mediated by Akt in stunned mouse cardiomyocytes. ILP may serve as a therapeutic agent or adjunct agent to delayed cooling in patients after cardiac arrest.
- © 2013 by American Heart Association, Inc.