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ORIGINAL ARTICLE

Chronic and Intermittent Hypoxia Induce Different Degrees of Myocardial Tolerance to Hypoxia-Induced Dysfunction

Giuseppina Milano^*, Antonio F. Corno^*, Silvio Lippa, Ludwig K. von Segesser^* and Michele Samaja^,1

^* Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
Institute of Biochemistry and Clinical Biochemistry, Universita' Cattolica del S .Cuore, Rome, Italy; and
Department of Medicine, Surgery, and Dentistry, University of Milan, San Paolo Hospital, Milan, Italy

Chronic hypoxia (CH) is believed to induce myocardial protection, but this is in contrast with clinical evidence. Here, we test the hypothesis that repeated brief reoxygenation episodes during prolonged CH improve myocardial tolerance to hypoxia-induced dysfunction. Male 5-week-old Sprague-Dawley rats (n = 7–9/group) were exposed for 2 weeks to CH (F_IO₂ = 0.10), intermittent hypoxia (IH, same as CH, but 1 hr/day exposure to room air), or normoxia (N, F_IO₂ = 0.21). Hearts were isolated, Langendorff perfused for 30 min with hypoxic medium (Krebs-Henseleit, PO₂ = 67 mmHg), and exposed to hyperoxia (PO₂ = 670 mmHg). CH hearts displayed higher end-diastolic pressure, lower rate•pressure product, and higher vascular resistance than IH. During hypoxic perfusion, anaerobic mechanisms recruitment was similar in CH and IH hearts, but less than in N. Thus, despite differing only for 1 hr daily exposure to room air, CH and IH induced different responses in animal homeostasis, markers of oxidative stress, and myocardial tolerance to reoxygenation. We conclude that the protection in animals exposed to CH appears conferred by the hypoxic preconditioning due to the reoxygenation rather than by hypoxia per se.

Key Words: chronic hypoxia • intermittent hypoxia • hypoxic preconditioning • isolated perfused heart • reoxygenation

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