To the Editor:
In two recent publications in Anesthesiology, Dr. Eghbali’s group reports the attenuation of myocardial reperfusion injury (RI) 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/ERK1/glycogen synthase kinase-3β and ultimately leads to delayed opening of the mitochondrial permeability transition pore (mPTP). In contrast to the mPTP pore 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 RI13 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 RI.
Acknowledgments
Disclosure: Research funding provided in part by Department of Veterans Affairs (CARA-026-10F to MLR), the National Institutes of Health (5R01 HL098490-03 to MLR and NIH R01 HL092071 to MVP), and institutional funds.
Footnotes
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References
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