Tissue Oxygenation and Mitochondrial Respiration under Different Modes of Intermittent Hypoxia

Abstract

We compared the results of five modes of intermittent hypoxia training (IHT) on gastrocnemius muscle Po2 and heart and liver mitochondrial respiration in rats. Minutes of hypoxia, %O2, and recovery minutes on air in each mode were: 1) 5, 12%, 5; 2) 15, 12%, 15; 3) 5, 12%, 15; 4) 5, 7%, 5; and 5) 5, 7%, 15. Mode 1 proved best in that Pmo2 dropped minimally at the end of every hypoxic bout and recovered quickly after each bout. One, 2, and 3 week IHT in mode 1 each increased tissue PO2 in both normoxic and 30 min severe hypoxic (7% O2) tests. Adaptation to IHT in Mode 1 caused the substrate-dependent reorganization of liver and heart mitochondrial energy metabolism favoring NADH-dependent oxidation and improving the efficiency of oxidative phosphorylation. Mitochondrial adaptation occurred after 14 days of IHT in liver tissue, but after 21 days in myocardium, and was preserved during the 3 months following IHT termination. When using Mode 2, positive changes were also registered, but were less pronounced. Other IHT modes provoked negative effects on Pmo2 levels, both during hypoxic periods and reoxygenation. In conclusion, the most effective IHT regimen is 5 min 12% O2 with 5 min breaks, five cycles per day during 2 or 3 weeks depending on the task of IHT.

Fitness and therapeutic potential of intermittent hypoxia training: a matter of dose

“…Experiments on animals also confirm that short cycles of hypoxic exposures alternating with normoxic periods are more effective than longer bouts or continuous daily hypoxic exposures [13,[60][61]. Powerful hypoxic-induced gene transcription factors (HIF-1/HIF-2 alpha) are activated very early upon hypoxic exposure, guaranteeing time-dependent up-regulation of cardiorespiratory and hematological responses aimed at limiting deficits in O 2 transport [62].…”

“…Some characteristics of different regimes are described in recent reviews [4,5,7,8,12,13]. Historically, first methodical recommendations for IHT implementation in human practice were published by the Russian Health Ministry in 1988 which recommended the inhalation of 10-12% O 2 during 5-min periods with 5 min rest, 1 h per session, 1-4 weeks per course for the treatment of various diseases.…”

Remote ischemic preconditioning versus intermittent hypoxia training: a comparative analysis for cardioprotection

“…In practice, normobaric hypoxic regimens vary broadly from 3-12 short hypoxic sessions (2-10 min) with 2-20 min normoxic breaks during 7-30 days to hypoxic influences lasting from 1 -12 hours during 2-90 days [83]. As Navarrete-Opazo et al [84] describe, modest hypoxia (9-16% inspired O 2 ) and low cycle numbers (3-15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2-8% inspired O 2 ) and more episodes per day (48-2,400 episodes/day) elicit progressively greater pathology.…”

“…As Navarrete-Opazo et al [84] describe, modest hypoxia (9-16% inspired O 2 ) and low cycle numbers (3-15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2-8% inspired O 2 ) and more episodes per day (48-2,400 episodes/day) elicit progressively greater pathology. Serebrovskaya et al [83] investigating 5 modes of IHT on gastrocnemius muscle PO2, heart and liver mitochondrial respiration in rats, concluded that the most effective IHT regimen is 5 min 12% O 2 with 5 min breaks, five cycles per day during two or three weeks depending on the task of IHT. Accumulating evidence suggests that "low dose" IHT (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders.…”

“…In practice, hypoxic regimens that are used for the study of hypoxic adaptations vary broadly from 3-12 short hypoxic sessions (2-10 min) with 2-20 min normoxic breaks during 7-30 days to hypoxic influences lasting from 1 -12 hours during 2-90 days [ 83].…”