INTRODUCTION: Extracellular signal-related kinases 1 and 2 (Erk1/2) are mitogen-activated protein kinases that have been implicated in anesthetic preconditioning; but whether Erk1/2 triggers or mediates this beneficial effect and the mechanisms by which Erk1/2 produces cardioprotection are unknown. We tested the hypothesis that isoflurane preconditioning is triggered by Erk1/2 concomitant with upregulation of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression in rats instrumented for hemodynamic measurement and subjected to a 30-min coronary artery occlusion and 2-h reperfusion. METHODS: Rats randomly received IV 0.9% saline (control) or isoflurane (1.0 minimum alveolar concentration administered for 30 min and discontinued 15 min [memory period] before coronary occlusion) in the absence or presence of the selective Erk1/2 inhibitor PD 098059 (1 mg/kg in dimethylsulfoxide administered IV either 3 min before exposure to isoflurane [trigger] or 3 min after discontinuation of the drug [mediator]). Additional rabbits were pretreated with dimethylsulfoxide alone. Left ventricular tissue samples were obtained at selected intervals from additional groups of rats for Western immunoblot analysis of phospho-Erk1/2, HIF-1alpha, and VEGF protein expression. RESULTS: Isoflurane significantly (P < 0.05) reduced infarct size (41% +/- 8% of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (59% +/- 4%). PD 098059 administered before, but not after, isoflurane abolished this cardioprotection (61% +/- 5% and 42% +/- 9%, respectively). Isoflurane-induced increases in phospho-Erk1/2, HIF-1alpha, and VEGF expression were also inhibited by PD 098059 pretreatment. CONCLUSIONS: The results indicate that Erk1/2 triggers isoflurane preconditioning concomitant with HIF-1alpha and VEGF upregulation in vivo.
INTRODUCTION: Extracellular signal-related kinases 1 and 2 (Erk1/2) are mitogen-activated protein kinases that have been implicated in anesthetic preconditioning; but whether Erk1/2 triggers or mediates this beneficial effect and the mechanisms by which Erk1/2 produces cardioprotection are unknown. We tested the hypothesis that isoflurane preconditioning is triggered by Erk1/2 concomitant with upregulation of hypoxia-inducible factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) expression in rats instrumented for hemodynamic measurement and subjected to a 30-min coronary artery occlusion and 2-h reperfusion. METHODS:Rats randomly received IV 0.9% saline (control) or isoflurane (1.0 minimum alveolar concentration administered for 30 min and discontinued 15 min [memory period] before coronary occlusion) in the absence or presence of the selective Erk1/2 inhibitor PD 098059 (1 mg/kg in dimethylsulfoxide administered IV either 3 min before exposure to isoflurane [trigger] or 3 min after discontinuation of the drug [mediator]). Additional rabbits were pretreated with dimethylsulfoxide alone. Left ventricular tissue samples were obtained at selected intervals from additional groups of rats for Western immunoblot analysis of phospho-Erk1/2, HIF-1alpha, and VEGF protein expression. RESULTS:Isoflurane significantly (P < 0.05) reduced infarct size (41% +/- 8% of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (59% +/- 4%). PD 098059 administered before, but not after, isoflurane abolished this cardioprotection (61% +/- 5% and 42% +/- 9%, respectively). Isoflurane-induced increases in phospho-Erk1/2, HIF-1alpha, and VEGF expression were also inhibited by PD 098059 pretreatment. CONCLUSIONS: The results indicate that Erk1/2 triggers isoflurane preconditioning concomitant with HIF-1alpha and VEGF upregulation in vivo.
Authors: Andreas Goetzenich; Nima Hatam; Stephanie Preuss; Ajay Moza; Christian Bleilevens; Anna B Roehl; Rüdiger Autschbach; Jürgen Bernhagen; Christian Stoppe Journal: Interact Cardiovasc Thorac Surg Date: 2013-12-18
Authors: Naoyuki Hirata; Yon Hee Shim; Danijel Pravdic; Nicole L Lohr; Philip F Pratt; Dorothee Weihrauch; Judy R Kersten; David C Warltier; Zeljko J Bosnjak; Martin Bienengraeber Journal: Anesthesiology Date: 2011-09 Impact factor: 7.892
Authors: Casper Hempel; Valery Combes; Nicholas Henry Hunt; Jørgen Anders Lindholm Kurtzhals; Georges Emile Raymond Grau Journal: Am J Pathol Date: 2011-08-18 Impact factor: 4.307
Authors: Thorsten M Leucker; Martin Bienengraeber; Maria Muravyeva; Ines Baotic; Dorothee Weihrauch; Anna K Brzezinska; David C Warltier; Judy R Kersten; Phillip F Pratt Journal: J Mol Cell Cardiol Date: 2011-07-21 Impact factor: 5.000