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Updated: Aug 18, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Polyadenosine diphosphate-ribose polymerase inhibition modulates skeletal muscle injury following ischemia
Hong T Hua1, Hassan Albadawi, Fateh Entabi
1Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA 20114, USA.
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.
Insights
Polyadenosine diphosphate-ribose polymerase (PARP) inhibition improves skeletal muscle viability during reperfusion. This study shows PARP modulates skeletal muscle injury and cytokine levels, suggesting PARP inhibitors could treat ischemia-reperfusion damage.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Polyadenosine diphosphate-ribose polymerase (PARP) is implicated in inflammation and necrosis.
- PARP's role in skeletal muscle ischemia-reperfusion injury is not fully understood.
Purpose of the Study:
- To determine if PARP inhibition modulates skeletal muscle injury.
- To investigate PARP's effect on cytokine and growth factor levels during ischemia-reperfusion.
Main Methods:
- Prospective controlled animal study using mice.
- Mice received PARP inhibitor PJ34 or were PARP-1 knockout (PARP-/-).
- Hind limb ischemia-reperfusion was induced, followed by assessment of muscle edema, viability, cytokines, and vascular endothelial growth factor (VEGF).
Main Results:
- PJ34 treatment and PARP-/- significantly increased skeletal muscle viability post-reperfusion.
- Edema was not affected by PARP inhibition.
- Cytokine levels were altered at 48 hours, and VEGF levels were reduced by PARP inhibition, especially at 4 hours.
Conclusions:
- PARP plays a significant role in modulating skeletal muscle viability, cytokine, and VEGF synthesis during reperfusion.
- PARP inhibition may offer a novel therapeutic strategy for skeletal muscle ischemia-reperfusion injury.
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