This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (4)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in this journal  Topic Collections  • Neurology  • Cerebrovascular Disease  • Stroke  • Surgical Physiology, Other  • Cardiovascular Disease/ Myocardial Infarction  • Alert me on articles by topic  Social Bookmarking   What's this?

Hong T. Hua, MD; Hassan Albadawi, MD; Fateh Entabi, MD; Mark Conrad, MD; Michael C. Stoner, MD; Bryan T. Meriam, AB; Ramses Sroufe, AB; Stuart Houser, MD; Glenn M. LaMuraglia, MD; Michael T. Watkins, MD

Arch Surg. 2005;140:344-351.

Hypothesis  Polyadenosine diphosphate–ribose polymerase (PARP) has been implicated as a mediator of inflammation and tissue necrosis in murine models of human stroke and myocardial infarction. This study was designed to determine whether PARP modulates skeletal muscle injury and cytokine-growth factor levels during ischemia-reperfusion.

Design  Prospective controlled animal study.

Setting  Medical school–affiliated university hospital.

Interventions  Mice were divided into 2 groups—treated (PJ) and untreated; all mice were subjected to unilateral hind limb tourniquet ischemia followed by 4 or 48 hours of reperfusion. In treated mice, PJ34, an ultrapotent-specific PARP inhibitor was given immediately before ischemia and prior to reperfusion. A group of PARP-1 knockout mice (PARP^–/–) were also subjected to hind limb ischemia followed by 48 hours of reperfusion.

Main Outcome Measures  After ischemia-reperfusion, muscle was harvested for measurement of edema, viability, cytokine, and vascular endothelial growth factor content.

Results  The PJ34-treated mice had increased skeletal muscle viability when compared with the untreated mice after 4 and 48 hours of reperfusion (P<.01). Viability between PARP^–/– and PJ34-treated mice were similar at 48 hours of reperfusion (P>.05), and it exceeded that of untreated mice (P<.01). Tissue edema was unaltered by PARP inhibition. Tissue levels of cytokine were only different (P<.05) in PJ34-treated vs untreated mice at 48 hours of reperfusion. Vascular endothelial growth factor levels in PJ34-treated mice were markedly reduced when compared with untreated mice only after 4 hours of reperfusion (P<.01), and in PARP^–/– mice (P<.01) at 48 hours of reperfusion.

Conclusions  Polyadenosine diphosphate–ribose polymerase modulates skeletal muscle viability, cytokine and vascular endothelial growth factor synthesis during reperfusion. Polyadenosine diphosphate–ribose polymerase inhibition may represent a novel method to modulate skeletal muscle ischemia-reperfusion injury.

Author Affiliations: Division of Vascular and Endovascular Surgery (Drs Hua, Albadawi, Entabi, Conrad, Stoner, LaMuraglia, and Watkins and Messrs Meriam and Sroufe) and the Department of Pathology (Dr Houser), Massachusetts General Hospital, Harvard Medical School, and the Veterans Administration Boston Healthcare System (Dr Watkins), Boston.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLE

Polyadenosine Diphosphate–Ribose Polymerase Inhibition Modulates Skeletal Muscle Injury Following Ischemia Reperfusion—Invited Critique
Alden H. Harken
Arch Surg. 2005;140(4):352.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Basic Control of Reperfusion Effectively Protects Against Reperfusion Injury in a Realistic Rodent Model of Acute Limb Ischemia
Dick et al.
Circulation 2008;118:1920-1928.
ABSTRACT | FULL TEXT  

Activation of hypoxia-inducible factor-1 via prolyl-4 hydoxylase-2 gene silencing attenuates acute inflammatory responses in postischemic myocardium
Natarajan et al.
Am. J. Physiol. Heart Circ. Physiol. 2007;293:H1571-H1580.
ABSTRACT | FULL TEXT