Free
Correspondence  |   May 2013
Intralipid: The New Magic Bullet in Cardioprotection?
Author Affiliations & Notes
  • Matthias L. Riess, M.D., Ph.D.
    Veterans Affairs Medical Center, and Medical College of Wisconsin, Milwaukee, Wisconsin. mriess@mcw.edu
  • (Accepted for publication January 29, 2013.)
    (Accepted for publication January 29, 2013.)×
  • Research funding provided in part by the Department of Veterans Affairs, Washington, D.C. (CARA-026-10F to M.L.R.), the National Institutes of Health, Bethesda, Maryland (5R01 HL098490-03 to M.L.R. and NIH R01 HL092071 to M.V.P.), and institutional funds.
    Research funding provided in part by the Department of Veterans Affairs, Washington, D.C. (CARA-026-10F to M.L.R.), the National Institutes of Health, Bethesda, Maryland (5R01 HL098490-03 to M.L.R. and NIH R01 HL092071 to M.V.P.), and institutional funds.×
Article Information
Correspondence
Correspondence   |   May 2013
Intralipid: The New Magic Bullet in Cardioprotection?
Anesthesiology 05 2013, Vol.118, 1237-1238. doi:10.1097/ALN.0b013e31828bac35
Anesthesiology 05 2013, Vol.118, 1237-1238. doi:10.1097/ALN.0b013e31828bac35
To the Editor:
In two recent publications in Anesthesiology, Dr. Eghbali’s group reports the attenuation of myocardial reperfusion injury in rodents by intralipid administered on reperfusion.1,2  Taken together with another study by the same group in which intralipid prevents and even rescues pulmonary hypertension,3  and the serendipitous landmark discoveries of lipid rescue therapy against bupivacaine-induced cardiotoxicity first in dogs4  and then humans,5  intralipid appears to have become a new magic bullet for cardioprotection. Nevertheless, many questions remain. Li et al.2  state that intralipid acts through the phosphorylation of Akt/extracellular signal-regulated kinase-1/glycogen synthase kinase-3β and ultimately leads to delayed opening of the mitochondrial permeability transition pore (mPTP). In contrast to the mPTP inhibitor cyclosporine-A or other proven postconditioning agents,6,7  however, intralipid is a mixture of various different compounds: fractionated soybean oil, fractionated egg phospholipids, and glycerol.8,9  Which of these compounds is ultimately responsible for the cardioprotective effect? Is this truly a receptor-mediated effect, or could it simply be a metabolic switch from glucose to fatty acid metabolism that paradoxically protects the heart as suggested in another of Dr. Eghbali’s publications10  and by us?11,12  Since intralipid is metabolized in vivo and its contents may reach the heart in a very different form8  than in the isolated heart preparation, both models are difficult to compare directly in this context. Lastly, as much as delayed mPTP opening appears to be a common end-effector in many different animal models of protection against myocardial reperfusion injury,13  Li et al.2  show once more that inhibition of the mPTP may be necessary but by far not sufficient for cardioprotection: although not formally done in their study, the extent of delayed mPTP opening in control, cyclosporine-A-, and intralipid-treated animals does not correlate with the observed degree of functional and tissue protection in the three groups. Therefore, despite these interesting findings, it may still be a long way to a potential clinical usage of intralipid in preventing myocardial reperfusion injury.
Matthias L. Riess, M.D., Ph.D.,* Mihai V. Podgoreanu, M.D. *Veterans Affairs Medical Center, and Medical College of Wisconsin, Milwaukee, Wisconsin. mriess@mcw.edu
References
Rahman, S, Li, J, Bopassa, JC, Umar, S, Iorga, A, Partownavid, P, Eghbali, M Phosphorylation of GSK-3β mediates intralipid-induced cardioprotection against ischemia/reperfusion injury.. Anesthesiology. (2011). 115 242–53 [Article] [PubMed]
Li, J, Iorga, A, Sharma, S, Youn, JY, Partow-Navid, R, Umar, S, Cai, H, Rahman, S, Eghbali, M Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A.. Anesthesiology. (2012). 117 836–46 [Article] [PubMed]
Umar, S, Nadadur, RD, Li, J, Maltese, F, Partownavid, P, van der Laarse, A, Eghbali, M Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.. Hypertension. (2011). 58 512–8 [Article] [PubMed]
Weinberg, G, Ripper, R, Feinstein, DL, Hoffman, W Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity.. Reg Anesth Pain Med. (2003). 28 198–202 [Article] [PubMed]
Rosenblatt, MA, Abel, M, Fischer, GW, Itzkovich, CJ, Eisenkraft, JB Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest.. Anesthesiology. (2006). 105 217–8 [Article] [PubMed]
Feng, J, Lucchinetti, E, Ahuja, P, Pasch, T, Perriard, JC, Zaugg, M Isoflurane postconditioning prevents opening of the mitochondrial permeability transition pore through inhibition of glycogen synthase kinase 3beta.. Anesthesiology. (2005). 103 987–95 [Article] [PubMed]
Huhn, R, Heinen, A, Weber, NC, Kerindongo, RP, Oei, GT, Hollmann, MW, Schlack, W, Preckel, B Helium-induced early preconditioning and postconditioning are abolished in obese Zucker rats in vivo.. J Pharmacol Exp Ther. (2009). 329 600–7 [Article] [PubMed]
Nordenström, J, Thörne, A Comparative studies on a new concentrated fat emulsion: Intralipid 30% vs. 20%.. Clin Nutr. (1993). 12 160–7 [Article] [PubMed]
Morris, S, Simmer, K, Gibson, R Characterization of fatty acid clearance in premature neonates during intralipid infusion.. Pediatr Res. (1998). 43 245–9 [Article] [PubMed]
Partownavid, P, Umar, S, Li, J, Rahman, S, Eghbali, M Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.. Crit Care Med. (2012). 40 2431–7 [Article] [PubMed]
Podgoreanu, MV, Ma, Q, Mackensen, GB, Zhang, Z, Kohl, F, Smith, M, Bain, J, Newgard, C, Drew, K, Barnes, BMetabolic correlates of cardioprotection following deep hypothermic circulatory arrest in hibernating arctic ground squirrels.. Presented at: Annual Meeting of American Society of Anesthesiologists. Chicago Illinois A0008October 15, 2011
Podgoreanu, M, Ma, Q, Zhang, Z, Bain, J, Newgard, C, Riess, M, Barnes, B The cardioprotective phenotype in mammalian hibernators is associated with attenuation of reperfusion-induced nuclear factor-kappa B regulated myocardial inflammation.. Circulation. (2012). 126 A1952
Hausenloy, DJ, Boston-Griffiths, EA, Yellon, DM Cyclosporin A and cardioprotection: From investigative tool to therapeutic agent.. Br J Pharmacol. (2012). 165 1235–45 [Article] [PubMed]