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Ischemia and reperfusion—from mechanism to translation

Abstract

Ischemia and reperfusion–elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion–associated tissue inflammation and organ dysfunction.

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Figure 1
Figure 2: Injury and resolution during ischemia and reperfusion.
Figure 3: Therapeutic gases for the treatment of ischemia and reperfusion.
Figure 4: Nucleotide and nucleoside signaling during ischemia and reperfusion.
Figure 5: MiRNA pathways implicated in myocardial ischemia and reperfusion.

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Acknowledgements

We thank S.A. Eltzschig for providing artwork during the manuscript preparation. This work is supported by US National Institutes of Health Grants R01-HL0921, R01-DK083385 and R01-HL098294 and a grant from the Crohn's and Colitis Foundation (H.K.E.) and grant number K08HL102267-01 (T.E.).

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Correspondence to Holger K Eltzschig.

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Eltzschig, H., Eckle, T. Ischemia and reperfusion—from mechanism to translation. Nat Med 17, 1391–1401 (2011). https://doi.org/10.1038/nm.2507

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