TY - JOUR
T1 - Cardioprotection by intermittent hypoxia conditioning
T2 - Evidence, mechanisms, and therapeutic potential
AU - Mallet, Robert T.
AU - Manukhina, Eugenia B.
AU - Ruelas, Steven Shea
AU - Caffrey, James L.
AU - Downey, H. Fred
N1 - Funding Information:
Work by the authors summarized in this manuscript was funded by research grants from the Netherlands Organization for Scientific Research (047-014-016), the Russian Foundation for Basic Research (03-04-49065, 07-04-00650, 10-04-00980), the Russian Science Foundation (17-15-013418), and the US National Center for Complementary and Alternative Medicine (R21 AT-003598), National Heart, Lung and Blood Institute (R01 HL-064785, R01 HL-071684), and National Institute for Neurological Disorders and Stroke (R01 NS-076975).
Publisher Copyright:
© 2018 American Physiological Society. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - The calibrated application of limited-duration, cyclic, moderately intense hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion stress. These intermittent hypoxic conditioning (IHC) programs consistently produce striking reductions in myocardial infarction and ventricular tachyarrhythmias after coronary artery occlusion and reperfusion and, in many cases, improve contractile function and coronary blood flow. These IHC protocols are fundamentally different from those used to simulate sleep apnea, a recognized cardiovascular risk factor. In clinical studies, IHC improved exercise capacity and decreased arrhythmias in patients with coronary artery or pulmonary disease and produced robust, persistent, antihypertensive effects in patients with essential hypertension. The protection afforded by IHC develops gradually and depends on β-adrenergic, δ-opioidergic, and reactive oxygen-nitrogen signaling pathways that use protein kinases and adaptive transcription factors. In summary, adaptation to intermittent hypoxia offers a practical, largely unrecognized means of protecting myocardium from impending ischemia. The myocardial and perhaps broader systemic protection provided by IHC clearly merits further evaluation as a discrete intervention and as a potential complement to conventional pharmaceutical and surgical interventions.
AB - The calibrated application of limited-duration, cyclic, moderately intense hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion stress. These intermittent hypoxic conditioning (IHC) programs consistently produce striking reductions in myocardial infarction and ventricular tachyarrhythmias after coronary artery occlusion and reperfusion and, in many cases, improve contractile function and coronary blood flow. These IHC protocols are fundamentally different from those used to simulate sleep apnea, a recognized cardiovascular risk factor. In clinical studies, IHC improved exercise capacity and decreased arrhythmias in patients with coronary artery or pulmonary disease and produced robust, persistent, antihypertensive effects in patients with essential hypertension. The protection afforded by IHC develops gradually and depends on β-adrenergic, δ-opioidergic, and reactive oxygen-nitrogen signaling pathways that use protein kinases and adaptive transcription factors. In summary, adaptation to intermittent hypoxia offers a practical, largely unrecognized means of protecting myocardium from impending ischemia. The myocardial and perhaps broader systemic protection provided by IHC clearly merits further evaluation as a discrete intervention and as a potential complement to conventional pharmaceutical and surgical interventions.
KW - Enkephalin
KW - Glycolysis
KW - Mitochondrial permeability transition
KW - Myocardial ischemia
KW - Nitric oxide
KW - Protein kinase
KW - Reactive oxygen species
KW - Sarcoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=85051298282&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.00060.2018
DO - 10.1152/ajpheart.00060.2018
M3 - Review article
C2 - 29652543
AN - SCOPUS:85051298282
SN - 0363-6135
VL - 315
SP - H216-H232
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 2
ER -