Abstract: 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. Hideo Hashiguchi, MD Hiroaki Morooka, MD Koji Sumikawa, MD Department of Anesthesiology Nagasaki University School of Medicine Nagasaki, Japan [email protected]