Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin equilibrium and cardiac responses during hypoxemia

Abstract

Intermittent hypoxia (IH) is extensively applied to challenge cardiovascular and respiratory function, and to induce physiological acclimatization. The purpose of this study was to test the hypothesis that oxyhemoglobin equilibrium and tachycardiac responses during hypoxemia were enhanced after 14-day IH exposures. Normobaric-poikilocapnic hypoxia was induced with inhalation of 10% O2 for 5-6 min interspersed with 4 min recovery on eight nonsmokers. Heart rate (HR), arterial O2 saturation (SaO 2), and end-tidal O2 (PetO 2) were continuously monitored during cyclic normoxia and hypoxia. These variables were compared during the first and fifth hypoxic bouts between day 1 and day 14. There was a rightward shift in the oxyhemoglobin equilibrium response following 14-day IH exposures, as indicated by the greater PetO 2 (an index of arterial Po2) at 50% of SaO 2 on day 14 compared with day 1 [33.9 ± 1.5 vs. 28.2 ± 1.3 mmHg (P = 0.005) during the first hypoxic bout and 39.4 ± 2.4 vs. 31.4 ± 1.5 mmHg (P = 0.006) during the fifth hypoxic bout] and by the augmented gains of ΔSaO 2/ΔPetO 2 (i.e., deoxygenation) during PetO 2 from 65 to 40 mmHg in the first (1.12 ± 0.08 vs. 0.80 ± 0.02%/mmHg, P = 0.001) and the fifth (1.76 ± 0.31 vs. 1.05 ± 0.06%/mmHg, P = 0.024) hypoxic bouts. Repetitive IH exposures attenuated (P = 0.049) the tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and high-frequency spectra without changes in arterial blood pressure at rest or during hypoxia. We conclude that 14-day IH exposures enhance arterial O2 delivery and improve vagal control of HR during hypoxic hypoxemia.

Physiological Responses to Two Hypoxic Conditioning Strategies in Healthy Subjects

“…Significant reductions in PetCO 2 during SH and IH sessions indicate however that subjects hyperventilated during both types of hypoxic exposure (Figure 2). The hypoxic hyperventilatory response was nevertheless relatively modest since V E increased by <2 L·min −1 and PetCO 2 decreased by <3 mmHg on average whatever the hypoxic condition, which is consistent with previous observations during SH and IH conditioning sessions [~50-min IH with 5–6 min FiO 2 = 0.10–4 min FiO 2 = 0.21 (Zhang et al, 2014); 1-h SH or IH at SpO 2 = 80–90% (Rodway et al, 2007)]. This modest increase in ventilation probably contributed to the absence of significant discomfort reported by all subjects during both SH and IH sessions.…”

“…Changes in arterial blood pressure during acute hypoxic exposure result from the opposite effect of hypoxia-induced peripheral vasodilation (Crawford et al, 2006) and sympathetic activation (Halliwill et al, 2003). Previous studies reported inconsistent changes in arterial blood pressure during acute SH or IH exposure with no change [~50-min IH with 5–6 min FiO 2 = 0.10–4 min FiO 2 = 0.21 (Zhang et al, 2014)] or slight increase [1-h SH at SpO 2 = 80% (Lusina et al, 2006), 1-h SH or IH at SpO 2 = 80–90% (Rodway et al, 2007), 1-h IH with 5–7 min normocapnic rebreathing–5–7 min FiO 2 = 0.21 (Bernardi et al, 2001b)]. In the present study both SH and IH induced a significant increase in blood pressure (Figure 3) which may be of larger magnitude compared to some previous studies due to the relatively low target SpO 2 (70–80%).…”

“…Changes in hypoxic ventilatory response may require a larger amount of hypoxic conditioning sessions than performed in the present study. Hypoxic heart rate response has been reported to be reduced [~50-min IH with 5–6 min FiO 2 = 0.10–4 min FiO 2 = 0.21, (Zhang et al, 2014)] or unchanged [7 days, 1-h/day SH at 4500 m (Katayama et al, 2001); 10 days, 1-h/day IH with 5 min FiO 2 = 0.12–5 min FiO 2 = 0.21 (Foster et al, 2005)] by repeated exposure to intermittent hypoxia. In the present study, the SH- or IH-induced increases in HR were similar at S1 and S3 (Figure 3), indicating no change in heart rate hypoxic response after three hypoxic conditioning sessions.…”

“…It is now recognized that the consequences of hypoxic exposure depend on a dose–response relationship ranging from normoxia to deleterious severe hypoxia [intermittent inspiratory oxygen fraction (FiO 2 ) < 0.08–0.10 and arterial oxygen saturation (SpO 2 ) <70%, with short cycles <2 min], with intermediate doses (moderate hypoxia, FiO 2 > 0.10 or SpO 2 ≥ 70–80%) and patterns (intermittent hypoxia with >5-min cycles or sustained hypoxia) of hypoxia that can have positive cardiovascular and metabolic effects (Navarrete-Opazo and Mitchell, 2014; Verges et al, 2015). Previous studies on hypoxic conditioning in healthy subjects and patients used two main types of hypoxic exposure, with repetitive sessions of either intermittent [IH, e.g., 3–7 min hypoxia and 3–5 min normoxia, repeated 3–10 times (Bernardi et al, 2001a; Burtscher et al, 2004; Lyamina et al, 2011; Zhang et al, 2014)] or sustained [SH, e.g., 1 h under sustained hypoxia (Rodríguez et al, 1999; Katayama et al, 2001, 2009; Lusina et al, 2006)] hypoxia. Whether these two types of hypoxic conditioning may induce different adaptations needs to be elucidated in order to establish optimal hypoxic conditioning strategies.…”

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity

“…The IHT mediated decline in left ventricular TH content and downward trend in TH positive fibers supports an evolving shift in myocardial autonomic balance in favor of a protective parasympathetic influence. This conclusion is further supported by observations in humans where an enhanced vagal control over the heart, accompanied by decrease tachycardic responses to hypoxia stimulus, following 14 d of intermittent hypoxia exposure was demonstrated [Zhang et al, 2014]. …”