Isoflurane postconditioning protects against reperfusion injury by preventing mitochondrial permeability transition by an endothelial nitric oxide synthase-dependent mechanism.

This is an interesting study demonstrating that brief administration of isoflurane during the late phase of ischemia and early phase of reperfusion (postconditioning) reduces myocardial damage and improves cardiac function by preventing mitochondrial permeability transition (MPT) pore opening. It is the first study showing that the isoflurane postconditioning effect is endothelial nitric oxide synthase (eNOS)-dependent. Nitric oxide produced by eNOS serves not only as a trigger but also as a mediator of isoflurane postconditioning cardioprotection against ischemia/reperfusion (I/R) injury.

The authors used multiple approaches incorporating both in vivo and ex vivo models of myocardial I/R to confirm the cardioprotection of isoflurane postconditioning. In addition, a myocardial I/R model was induced using eNOS knock-out mice to confirm the mechanism of isoflurane postconditioning. This is a complicated and important study confirming the effectiveness and mechanism of volatile anesthetic isoflurane postconditioning. The study highlights the significance of eNOS in volatile anesthetic postconditioning. In diabetes, especially the diabetic myocardium, eNOS signaling is impaired, in part due to the deficiency of the eNOS cofactor tetrahydrobiopterin (BH4). This may cause eNOS uncoupling and decease nitric oxide availability. This could be why isoflurane preconditioning cardioprotection is compromised or lost in diabetes. Another research group recently showed that isoflurane postconditioning is impaired by hyperglycemia {1}. This later study by Ge et al. is another advancement in understanding the mechanism of isoflurane postconditioning. Further study is needed using chronic animal models of diabetes to help clarify the possible clinical relevance of these findings regarding volatile anesthetic postconditioning.

References: {1} Amour et al. Anesthesiology 2010, 112:576-85 [PMID:20124983].