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LETTER TO THE EDITOR

Renal Protection with Isoflurane

Department of Anesthesiology; Nagasaki University School of Medicine; Nagasaki, Japan; cds93710{at}syd.odn.ne.jp

In Response:

We appreciate the concerns of Drs. Lee and Emala (1) regarding our article (2). We previously reported that isoflurane protected against renal ischemia and reperfusion injury when it was administered 20 min before ischemia, and continued until 20 min after reperfusion (3). The dose we used was within the clinical range. Therefore, isoflurane might reduce the risk of renal ischemia/reperfusion. We also examined whether the time of isoflurane administration altered its renal protection.

Our model of renal injury is different from that of Lee et al. (4) We followed Pombo et al.'s (5) study of mitogen-activated protein kinases (MAPKs), in which they used unilateral renal ischemia. Several studies suggested that members of the MAPKs family, such as JNK, p38, and ERK, are activated in the kidney after ischemia and reperfusion (6). In our study, we noted that isoflurane blunts the activation of JNK and ERK (2). This reduction, especially in ERK phosphorylation, may be an epi-phenomenon, as the molecular mechanisms, including MAPKs, by which ischemia and reperfusion lead to cell death and tissue damage are not clear (7,8).

We are examining whether the JNK inhibitor affects renal ischemia and reperfusion (9), although we do not suggest that this is the only mechanism of isoflurane protection.

REFERENCES

1. Thomas Lee H, Emala CW. Renal protection with isoflurane. Anesth Analg 2006;103:1053.[Free Full Text]
2. Hashiguchi H, Morooka H, Miyoshi H, et al. Isoflurane protects renal function against ischemia and reperfusion through inhibition of protein kinases, JNK and ERK. Anesth Analg 2005;101:1584–9.[Abstract/Free Full Text]
3. Miyoshi H, Morooka H, Tsujita T, et al. The protective effect of isoflurane against renal ischemia/reperfusion injury in rats. Anesthesiology 2002;96:A-78.
4. Lee HT, Ota-Setlik A, Fu Y, et al. Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo. Anesthesiology 2004;101:1313–24.[Web of Science][Medline]
5. Pombo CM, Boventre JV, Avruch J, et al. The stress-activated protein kinases are major c-jun amino-terrminal kinases activated by ischemia and reperfusion. J Bio Chem 1994;269:26546–51.[Abstract/Free Full Text]
6. Park KM, Chen A, Boventre JV, et al. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Bio Chem 2001; 276:11870–6.[Abstract/Free Full Text]
7. Armstrong SC. Protein kinase activation and myocardial ischemia/reperfusion injury. Cardiovasc Rec 2004;61:427–36.
8. Bonventre JV, Weinberg JM. Recent advances in the pathophysiology of ischemic acute renal failure. J Am Soc Nephrol 2003; 14:2199–210.[Free Full Text]
9. Hashiguchi H, Morooka H, Miyoshi H, et al. Isoflurane protects renal function against ischemia and reperfusion via inhibition of JNK. Anesthesiology 2005;103:A-689.

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