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(Circulation Research. 2006;99:e86.)
© 2006 American Heart Association, Inc.

Letter to the Editor

Is 15-min Ischemia too Lethal to Be an Ischemic Preconditioning Stimulus?

Zheqing Cai, Gregg L. Semenza

Vascular Biology Program, Institute for Cell Engineering;, Departments of Pediatrics,, Medicine, Oncology, and Radiation Oncology;, and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Md

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

We would like to take this opportunity to respond to comments by Hausenloy et al¹ regarding our recent study.² In our study, we demonstrated that PTEN activity is modulated during cardiac ischemia/reperfusion, suggesting critical involvement of PTEN in both the induction and decay of ischemic preconditioning (IPC).² Hausenloy et al appear more intent on promulgating a "standard accepted IPC protocol" than on understanding mechanisms of protection against ischemia/reperfusion injury. Without providing any supporting data, they characterize 15 minutes of ischemia as a "prolonged episode of lethal ischemia."¹ In contrast, Kloner and Jennings wrote in the first sentence of their highly cited review of IPC that "total proximal coronary artery occlusions of up to 15 minutes result in reversible injury, meaning that the myocytes survive this insult."³

Our data² show that 15 minutes of ischemia followed by 5 minutes of reperfusion induces higher levels of phosphorylated (activated) Akt in the heart, as compared with hearts subjected to 5 or 10 minutes of ischemia followed by 5 minutes of reperfusion. This ischemic stimulus protects the heart against subsequent prolonged ischemia (30 minutes) and reperfusion (thus fulfilling the criteria for IPC), as demonstrated by significantly improved recovery of left ventricular developed pressure, reduced caspase-3 activation, and reduced PARP cleavage. Finally, we demonstrated that reactive oxygen species (ROS), which are generated after hearts are subjected to 15 minutes of ischemia and then reperfused, oxidize and inactivate PTEN, thus leading to increased Akt activity. Our data provide for the first time a . . . [Full Text of this Article]