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.

References

1.
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
2.
Li
J
,
Iorga
A
,
Sharma
S
,
Youn
JY
,
Partow-Navid
R
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S
,
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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
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,
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M
:
Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.
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2011
;
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8
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G
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M
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Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.
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