Aortic Ischemia-reperfusion Research Articles

Abstract Introduction: Vascular endothelial growth factor (VEGF) has been implicated as a tissue protective agent following ischemia reperfusion. We have demonstrated that poly-ADP ribose polymerase (PARP) blockade prevented spinal cord dysfunction and improved survival following murine thoracic aortic ischemia reperfusion (TAR). Because renal and cardiac derangements are a significant source of morbidity following TAR, experiments were designed to examine the potential protective effect of PARP inhibition on VEGF expression and renal and cardiac tissue injury. Methods: Mice (n = 23) were subjected to 11 minutes of TAR. Animals were treated 1 hr prior to and 1 hr after surgery with either saline (Control, n = 8, 0.5 mL saline IP) or PARP inhibitor (PJ34, n = 10, PJ34 10 mg/kg IP). MS (n = 5) mice underwent median sternotomy without TAR. At 48 hours, surviving mice (n = 13) were sacrificed. Serum, kidney and cardiac tissues were subjected to VEGF analysis (ELISA) and tissue viability index determined (MTT assay, expressed as % sham). Results: PARP inhibition resulted in increased serum, renal and cardiac VEGF levels and improved renal viability (table, ∗p Table 1 . Serum, renal and cardiac VEGF, renal and cardiac viability index Serum VEGF (pg/mL) Renal VEGF (pg/mg) Renal viability index (%) Cardiac VEGF (pg/mg) Cardiac viability index (%) MS (5) 56.8 ± 5.3 52.8 ± 5.4 83.6 ± 9.5 25.3 ± 2.9 102.7 ± 6.7 Control (5) 152.6 ± 49.9 18.0 ± 3.4 75.8 ± 2.2 17.8 ± 1.4 90.1 ± 4.1 PJ34 (8) 1977.4 ± 571.1 + 36.1 ± 4.0 ∗∗ 116.5 ± 9.5 ∗ 34.1 ± 3.0 ∗ 86.7 ± 2.3 ∗ p ∗∗ p + p Conclusions: In the setting of TAR, PARP inhibition markedly increases serum VEGF and prevents a decrease in renal and cardiac VEGF levels. These higher VEGF levels coincide with an improvement in renal viability index and suggest that PARP inhibition may represent a novel therapeutic approach to the preservation of renal function in the setting of TAR.

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