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Sequential Limb Ischemia Demonstrates Remote Postconditioning Protection of Murine Skeletal Muscle

Eberlin, Kyle R. M.D.; McCormack, Michael C. B.S.; Nguyen, John T. M.D.; Tatlidede, H Soner M.D.; Randolph, Mark A. M.A.S.; Austen, William G. Jr M.D.

Plastic & Reconstructive Surgery: February 2009 - Volume 123 - Issue 2S - pp 8S-16S
doi: 10.1097/PRS.0b013e318191bcd6
Experimental: Transplantation: Original Articles

Background: Ischemic postconditioning, the process of exposing tissues to brief cycles of ischemia-reperfusion after critical ischemia, can mitigate local ischemia-reperfusion injury. Remote protection of skeletal muscle has never been demonstrated in postconditioning models of ischemia-reperfusion injury.

Methods: Mice were subjected to 2 hours of ipsilateral hind limb ischemia followed by reperfusion. Contralateral limb ischemia was subsequently induced for 2 hours after either 0 (n = 6), 20 (n = 6), or 120 (n = 5) minutes of ipsilateral limb reperfusion. These groups were compared with animals subjected to bilateral simultaneous injury (n = 8) and sham animals that did not undergo ischemia (n = 6). The gastrocnemius muscles were harvested for histologic evaluation, and injury was recorded as the percentage of injured fibers.

Results: The first limbs undergoing injury in the 20-minute interval group had a 59 percent injury reduction compared with contralateral limbs (16.0 ± 2.4 percent versus 39.5 ± 6.5 percent) after 24 hours of reperfusion and 62 percent reduction after 48 hours (24.4 ± 3.0 percent versus 63.6 ± 5.5 percent). In animals with no interval or a 120-minute interval between the onset of limb ischemia, there was no significant difference in injury between hind limbs. The injury in these groups was similar to that in hind limbs subjected to simultaneous bilateral ischemia.

Conclusions: A 20-minute reperfusion interval between hind limb ischemia significantly protects against injury in the initially ischemic limb, while similar injury is observed with simultaneous ischemia or an interval of 120 minutes. This study demonstrates remote postconditioning of skeletal muscle and may lead to the development of post hoc therapies.

Boston, Mass.

From the Plastic Surgery Research Laboratory, Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School.

Received for publication December 6, 2007; accepted April 16, 2008.

Presented at the 52nd Annual Meeting of the Plastic Surgery Research Council, in Stanford, California, June 20 through 23, 2007; the Association of Academic Surgery/Society of University Surgeons Conference, in Phoenix, Arizona, February 6 through 9, 2007; and the 23rd Annual Meeting of the Northeastern Society of Plastic and Reconstructive Surgeons, in Boston, Massachusetts, November 30 through December 2, 2006.

Disclosure: None of the authors has a financial interest in the subject matter presented in this article.

William G. Austen, Jr., M.D.; Massachusetts General Hospital; Wang Building, 435; 55 Fruit Street; Boston, Mass. 02114; wausten@partners.org

©2009American Society of Plastic Surgeons