NIV Congres

Aims Ischemia/reperfusion (I/R) injury is a common clinical problem. Although the pathophysiological mechanisms underlying I/R injury are unclear, oxidative damage is considered a key factor in the initiation of I/R injury. Findings from preclinical studies consistently show that quenching reactive oxygen and nitrogen species (RONS), thus limiting oxidative damage alleviates I/R injury. Results from clinical intervention studies on the other hand are largely inconclusive. In this clinical study, we systematically evaluated release of established biomarkers of oxidative and nitrosative damage during planned I/R of kidney and heart in a wide range of clinical conditions.

Results Sequential arteriovenous concentration differences allowed specific measurements over the reperfused organ in time. None of the biomarkers of oxidative and nitrosative damage (i.e. malondialdehyde, 15(S)-8-iso-prostaglandin F2α, nitrite, nitrate and nitrotyrosine) were released upon reperfusion. Cumulative urinary measurements confirmed plasma findings. As of these negative findings we tested for oxidative stress during I/R and found activation of Nrf2, the master regulator of oxidative stress signaling, but no upregulation of the antioxidant response genes (i.e. Nfr2, HMOX1, NQO1 and GSTA2 expression) was observed upon reperfusion.

Innovation This comprehensive, clinical study evaluates the role of RONS in I/R injury in two different human organs (kidney and heart). Results show oxidative stress but do not provide evidence for oxidative damage during early reperfusion, thereby challenging the prevailing paradigm on RONS-mediated I/R injury.

Conclusion Findings from this study suggest that the contribution of oxidative damage in human I/R may be less than commonly thought and propose a re-evaluation of the mechanism of I/R.