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Adaptation to Ischemia by in vivo Exposure to Hyperoxia—Signalling through Mitogen Activated Protein Kinases and Nuclear Factor Kappa B

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Signal Transduction and Cardiac Hypertrophy

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

Summary

We have established a model of adaptation to ischemia by breathing a hyperoxic gas mixture, which may be directly employed in clinical practice. Hyperoxia improves postischemic function and reduces myocardial necrosis in globally and regionally ischemic rat and mouse hearts, protects hearts of animals with severe atherosclerosis, and modulates in vitro reactivity of isolated aortic rings. Hyperoxic preconditioning is most efficient when the inspired oxygen fraction is >80% oxygen, with different exposure times in rats and mice. In rats the protection is both immediate and delayed, while in mice only immediate protection can be evoked. Exposure to hyperoxia causes an oxidative stress evident as increased serum lipid peroxidation products and reduced antioxidant defence. When breathing hyperoxic gas a rapid nuclear translocation of nuclear factor kappa B (NFκB) in the lungs is followed by a cardiac NFκB activation. In conjunction with hyperoxia the mitogen activated protein kinases (MAPK) p38, ERK1/2, and JNK are phosphorylated in the heart. Pharmacological inhibition of NFκB activation abolished the beneficial effects of hyperoxia. During Langendorff-perfusion with induced global ischemia, phosphorylation of MAPK as well as translocation of NFκB is reduced in animals subjected to hyperoxia prior to the experiments, the latter perhaps due to increased formation of the NFκB inhibitor IkBα. A posssible role for the NFκB-regulated gene inducible nitric oxide synthase (iNOS) in the hyperoxia response was investigated in knock out mice, who had no functional or antiinfarct protection of preconditioning by either hyperoxia or classic ischemic preconditioning. However, neither cardiac iNOS nor contents of antioxidants, heat shock protein 70, or endothelial NOS in the heart increased after hyperoxia. Thus, the signal transduction pathways and organ effectors of hyperoxic protection are not fully determined, but appear to involve MAPK and NFκB. Hyperoxia may have a large potential in the pretreatment of patients undergoing not only open heart procedures, but also in front of any major surgery.

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Authors and Affiliations

  1. Crafoord Laboratory of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden

    Guro Valen MD, PhD., Peeter Tähepôld & Arno Ruusalepp

  2. Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden

    Guro Valen MD, PhD. & Jarle Vaage

  3. Clinic of Anesthesiology and Intensive Care, University of Tartu, Tartu, Estonia

    Joel Starkopf

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  1. Guro Valen MD, PhD.
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  2. Peeter Tähepôld
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Correspondence to Guro Valen MD, PhD. .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

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Valen, G., Tähepôld, P., Starkopf, J., Ruusalepp, A., Vaage, J. (2003). Adaptation to Ischemia by in vivo Exposure to Hyperoxia—Signalling through Mitogen Activated Protein Kinases and Nuclear Factor Kappa B. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_34

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  • DOI: https://doi.org/10.1007/978-1-4615-0347-7_34

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