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Xenon preconditioning: the role of prosurvival signaling, mitochondrial permeability transition and bioenergetics in rats.
Anesth Analg. 2009 Mar; 108(3):858-66.A&A

Abstract

BACKGROUND

Similar to volatile anesthetics, the anesthetic noble gas xenon protects the heart from ischemia/reperfusion injury, but the mechanisms responsible for this phenomenon are not fully understood. We tested the hypothesis that xenon-induced cardioprotection is mediated by prosurvival signaling kinases that target mitochondria.

METHODS

Male Wistar rats instrumented for hemodynamic measurements were subjected to a 30 min left anterior descending coronary artery occlusion and 2 h reperfusion. Rats were randomly assigned to receive 70% nitrogen/30% oxygen (control) or three 5-min cycles of 70% xenon/30% oxygen interspersed with the oxygen/nitrogen mixture administered for 5 min followed by a 15 min memory period. Myocardial infarct size was measured using triphenyltetrazolium staining. Additional hearts from control and xenon-pretreated rats were excised for Western blotting of Akt and glycogen synthase kinase 3 beta (GSK-3beta) phosphorylation and isolation of mitochondria. Mitochondrial oxygen consumption before and after hypoxia/reoxygenation and mitochondrial permeability transition pore opening were determined.

RESULTS

Xenon significantly (P < 0.05) reduced myocardial infarct size compared with control (32 +/- 4 and 59% +/- 4% of the left ventricular area at risk; mean +/- sd) and enhanced phosphorylation of Akt and GSK-3beta. Xenon pretreatment preserved state 3 respiration of isolated mitochondria compared with the results obtained in the absence of the gas. The Ca(2+) concentration required to induce mitochondrial membrane depolarization was larger in the presence compared with the absence of xenon pretreatment (78 +/- 17 and 56 +/- 17 microM, respectively). The phosphoinositol-3-kinase-kinase inhibitor wortmannin blocked the effect of xenon on infarct size and respiration.

CONCLUSIONS

These results indicate that xenon preconditioning reduces myocardial infarct size, phosphorylates Akt, and GSK-3beta, preserves mitochondrial function, and inhibits Ca(2+)-induced mitochondrial permeability transition pore opening. These data suggest that xenon-induced cardioprotection occurs because of activation of prosurvival signaling that targets mitochondria and renders them less vulnerable to ischemia-reperfusion injury.

Authors+Show Affiliations

Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19224794

Citation

Mio, Yasushi, et al. "Xenon Preconditioning: the Role of Prosurvival Signaling, Mitochondrial Permeability Transition and Bioenergetics in Rats." Anesthesia and Analgesia, vol. 108, no. 3, 2009, pp. 858-66.
Mio Y, Shim YH, Richards E, et al. Xenon preconditioning: the role of prosurvival signaling, mitochondrial permeability transition and bioenergetics in rats. Anesth Analg. 2009;108(3):858-66.
Mio, Y., Shim, Y. H., Richards, E., Bosnjak, Z. J., Pagel, P. S., & Bienengraeber, M. (2009). Xenon preconditioning: the role of prosurvival signaling, mitochondrial permeability transition and bioenergetics in rats. Anesthesia and Analgesia, 108(3), 858-66. https://doi.org/10.1213/ane.0b013e318192a520
Mio Y, et al. Xenon Preconditioning: the Role of Prosurvival Signaling, Mitochondrial Permeability Transition and Bioenergetics in Rats. Anesth Analg. 2009;108(3):858-66. PubMed PMID: 19224794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Xenon preconditioning: the role of prosurvival signaling, mitochondrial permeability transition and bioenergetics in rats. AU - Mio,Yasushi, AU - Shim,Yon Hee, AU - Richards,Ebony, AU - Bosnjak,Zeljko J, AU - Pagel,Paul S, AU - Bienengraeber,Martin, PY - 2009/2/20/entrez PY - 2009/2/20/pubmed PY - 2009/3/13/medline SP - 858 EP - 66 JF - Anesthesia and analgesia JO - Anesth Analg VL - 108 IS - 3 N2 - BACKGROUND: Similar to volatile anesthetics, the anesthetic noble gas xenon protects the heart from ischemia/reperfusion injury, but the mechanisms responsible for this phenomenon are not fully understood. We tested the hypothesis that xenon-induced cardioprotection is mediated by prosurvival signaling kinases that target mitochondria. METHODS: Male Wistar rats instrumented for hemodynamic measurements were subjected to a 30 min left anterior descending coronary artery occlusion and 2 h reperfusion. Rats were randomly assigned to receive 70% nitrogen/30% oxygen (control) or three 5-min cycles of 70% xenon/30% oxygen interspersed with the oxygen/nitrogen mixture administered for 5 min followed by a 15 min memory period. Myocardial infarct size was measured using triphenyltetrazolium staining. Additional hearts from control and xenon-pretreated rats were excised for Western blotting of Akt and glycogen synthase kinase 3 beta (GSK-3beta) phosphorylation and isolation of mitochondria. Mitochondrial oxygen consumption before and after hypoxia/reoxygenation and mitochondrial permeability transition pore opening were determined. RESULTS: Xenon significantly (P < 0.05) reduced myocardial infarct size compared with control (32 +/- 4 and 59% +/- 4% of the left ventricular area at risk; mean +/- sd) and enhanced phosphorylation of Akt and GSK-3beta. Xenon pretreatment preserved state 3 respiration of isolated mitochondria compared with the results obtained in the absence of the gas. The Ca(2+) concentration required to induce mitochondrial membrane depolarization was larger in the presence compared with the absence of xenon pretreatment (78 +/- 17 and 56 +/- 17 microM, respectively). The phosphoinositol-3-kinase-kinase inhibitor wortmannin blocked the effect of xenon on infarct size and respiration. CONCLUSIONS: These results indicate that xenon preconditioning reduces myocardial infarct size, phosphorylates Akt, and GSK-3beta, preserves mitochondrial function, and inhibits Ca(2+)-induced mitochondrial permeability transition pore opening. These data suggest that xenon-induced cardioprotection occurs because of activation of prosurvival signaling that targets mitochondria and renders them less vulnerable to ischemia-reperfusion injury. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/19224794/Xenon_preconditioning:_the_role_of_prosurvival_signaling_mitochondrial_permeability_transition_and_bioenergetics_in_rats_ L2 - https://doi.org/10.1213/ane.0b013e318192a520 DB - PRIME DP - Unbound Medicine ER -