Abstract 388: Postconditioning Beyond The Heart: Postconditioning The Ischemic Kidney Attenuates Renal Reperfusion Injury
Objective: Postconditioning (Poc), defined as brief cycles of arterial occlusion and reflow applied at the onset of reperfusion (R), has proven to reduce multiple consequences of myocardial ischemia-reperfusion injury (I/R). The protective effects of Poc in the kidney I/R are not known. Therefore, we tested the hypothesis that Poc attenuates renal I/R injury via adenosine receptor (AR) activation and protein kinase C (PKC) signaling.
Methods: The in vivo single kidney rat model was used. Rats underwent right nephrectomy and were randomized to 5 groups.
A sham group (n=8) underwent the surgical and perfusion protocol without other interventions. In all remaining groups, the left renal artery is occluded for 45min and the left kidney was reperfused for 24 hours.
Control group (n=8) received no intervention at R;
Poc (n=8) underwent 4 cycles of 45 seconds R and 45 seconds of reocclusion at the onset of R.
PC + ARi (n=6): the AR inhibitor 8-SPT (10mg/kg) was administered i.v. 5 minutes before Poc;
Poc + PKCi: the PKC inhibitor, chelerytherine (5mg/kg), was administered i.v. 5 min before R.
After 24 hours, renal function was assessed by plasma blood urea nitrogen (BUN) and creatinine (Cr), and the kidneys were harvested; apoptotic cells were quantified by TUNEL stain and morphological injury by H&E staining.
Results: Compared to sham, BUN and Cr were greater in control I/R group, which was significantly reduced in Poc (table⇓). Inhibition of AR or PKC stimulation reversed the reductions in BUN and Cr achieved by Poc. In addition, renal I/R increased the percentage of TUNEL positive cells in ten high powered fields vs Sham, which was reduced by Poc. Blockade of AR and PKC reversed the apoptosis reduction achieved by Poc.
Conclusion: Postconditioning attenuates renal dysfunction and apoptosis induced by R injury and involves AR and PKC signaling. Poc suggests that R injury is triggered in early moments of reflow.