Cardioprotection by intermittent hypoxia conditioning

Evidence, mechanisms, and therapeutic potential

Robert T. Mallet, Eugenia B. Manukhina, Steven Shea Ruelas, James L. Caffrey, H. Fred Downey

Research output: Contribution to journalReview articleResearchpeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)H216-H232
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume315
Issue number2
DOIs
StatePublished - 1 Aug 2018

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Ischemia
Myocardial Reperfusion
Coronary Occlusion
Sleep Apnea Syndromes
Tachycardia
Adrenergic Agents
Protein Kinases
Antihypertensive Agents
Lung Diseases
Reperfusion
Cardiac Arrhythmias
Coronary Artery Disease
Coronary Vessels
Myocardium
Transcription Factors
Nitrogen
Myocardial Infarction
Exercise
Oxygen
Therapeutics

Keywords

  • Enkephalin
  • Glycolysis
  • Mitochondrial permeability transition
  • Myocardial ischemia
  • Nitric oxide
  • Protein kinase
  • Reactive oxygen species
  • Sarcoplasmic reticulum

Cite this

Mallet, Robert T. ; Manukhina, Eugenia B. ; Ruelas, Steven Shea ; Caffrey, James L. ; Downey, H. Fred. / Cardioprotection by intermittent hypoxia conditioning : Evidence, mechanisms, and therapeutic potential. In: American Journal of Physiology - Heart and Circulatory Physiology. 2018 ; Vol. 315, No. 2. pp. H216-H232.
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Cardioprotection by intermittent hypoxia conditioning : Evidence, mechanisms, and therapeutic potential. / Mallet, Robert T.; Manukhina, Eugenia B.; Ruelas, Steven Shea; Caffrey, James L.; Downey, H. Fred.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 315, No. 2, 01.08.2018, p. H216-H232.

Research output: Contribution to journalReview articleResearchpeer-review

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AU - Downey, H. Fred

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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.

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