• Jing Wu, Joanna Stefaniak, Christina Hafner, Johannes Peter Schramel, Christoph Kaun, Johann Wojta, Roman Ullrich, Verena Eva Tretter, Klaus Markstaller, and Klaus Ulrich Klein.
• From the *Department of Anesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria; †Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; ‡Unit of Anesthesiology and Perioperative Intensive Care, University of Veterinary Medicine, Vienna, Austria; §Department of Internal Medicine II and ‖Core Facilities, Medical University of Vienna, Vienna, Austria; and ¶Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.
• Anesth. Analg. 2016 Feb 1; 122 (2): 373-80.

BackgroundIntermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia.MethodsHACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression.ResultsIn comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways.ConclusionsIntermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia exposure may produce rapid and substantial damage to the human heart.

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