Similar endothelium-dependent vascular responses to intermittent hypoxia in young and older adults.

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation caused partly by a decreased nitric oxide bioavailability. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, was reported to either maintain or improve vascular function in young adults. The aim of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Twelve young adults and 11 older adults visited the laboratory on two occasions. Plasma nitrate concentrations and brachial artery flow-mediated dilation were assessed before and after exposure to either intermittent hypoxia or a sham protocol. Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, and the sham protocol consisted of eight 4-min normoxic cycles interspersed with breathing room air. Vascular responses were assessed during intermittent hypoxia and the sham protocol. Intermittent hypoxia elicited a brachial artery vasodilation but did not change brachial artery shear rate in both young and older adults. Plasma nitrate concentrations were not significantly affected by intermittent hypoxia compared with the sham protocol in both groups. Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or the sham protocol in either young or older adults. In conclusion, the brachial artery vasodilatory response to intermittent hypoxia was not influenced by age. Intermittent hypoxia increased brachial artery diameter but did not acutely affect endothelium-dependent vasodilation in young or older adults.NEW & NOTEWORTHY The objective of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Eight 4-min bouts of hypoxia at a targeted oxygen saturation of 80% induced a brachial artery vasodilation in both young and older adults, indicating that age does not influence the vasodilatory response to intermittent hypoxia. Intermittent hypoxia did not acutely affect brachial artery flow-mediated dilation in young or older adults.

Impaired erythropoietin response to hypoxia in type 2 diabetes.

AIMS: Patients with type 2 diabetes have a 20% lower total blood volume than age- and weight-matched healthy adults, suggesting a reduced capacity to transport oxygen in this population. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases erythropoietin levels, the hormone regulating red blood cell production, in young and older adults. The objective of this study was to determine the effect of a single session of intermittent hypoxia on erythropoietin levels and hemoglobin mass, the absolute mass of hemoglobin contained in red blood cells, in patients with type 2 diabetes. METHODS: Ten patients with type 2 diabetes were exposed to an intermittent hypoxia protocol consisting of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Erythropoietin and hemoglobin mass responses to intermittent hypoxia in patients with type 2 diabetes were compared to previously published data from an identical intermittent hypoxia protocol performed in age-matched older adults. RESULTS: Intermittent hypoxia increased erythropoietin levels in older adults but did not induce any change in erythropoietin levels in patients with type 2 diabetes (3.2 ± 2.2 vs. 0.2 ± 2.7 mU/ml, p = 0.01). Hemoglobin mass indexed to body weight was 21% lower in patients with type 2 diabetes than in older adults (8.1 ± 1.7 vs. 10.2 ± 2.1 g/kg, p < 0.01). CONCLUSIONS: These findings suggest an impaired erythropoietin response to decreased oxygen levels in patients with type 2 diabetes, which may contribute to the reduced oxygen transport capacity observed in this population.

Brief exposure to intermittent hypoxia increases erythropoietin levels in older adults.

Eight 4-min cycles of intermittent hypoxia represent the shortest hypoxic exposure to increase erythropoietin (EPO) levels in young adults. The impact of aging on the EPO response to a hypoxic stimulus remains equivocal. Thus, the objective of this study was to determine the effect of the same intermittent hypoxia protocol on EPO levels in older adults. Twenty-two participants (12 women, age: 53 ± 7 yr) were randomly assigned to an intermittent hypoxia group (IH, n = 11) or an intermittent normoxia group (IN, n = 11). Intermittent hypoxia consisted of eight 4-min cycles at a targeted oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into a breathing circuit. Intermittent normoxia consisted of the same protocol, but nitrogen was not added to the breathing circuit. EPO levels were measured before and 4.5 h after the beginning of each protocol. Intermittent hypoxia lowered oxygen saturation to 82 ± 3%, which corresponded to a fraction of inspired oxygen of 10.9 ± 1.0%. There was a greater increase in EPO levels following intermittent hypoxia than intermittent normoxia (IH: 3.2 ± 2.2 vs. IN: 0.7 ± 0.8 mU/mL, P < 0.01). A single session of eight 4-min cycles of hypoxia increased EPO levels, the glycoprotein stimulating red blood cell production, in older adults. Exposure to intermittent hypoxia has therefore the potential to increase oxygen-carrying capacity in a population with reduced red blood cell volume.NEW & NOTEWORTHY We previously identified the shortest intermittent hypoxia protocol necessary to increase erythropoietin levels in young adults. The objective of this study was to determine whether the same intermittent hypoxia protocol increases erythropoietin levels in older adults. Eight 4-min bouts of hypoxia, representing a hypoxic duration of 32 min at a targeted oxygen saturation of 80%, increased erythropoietin levels in older adults, suggesting that exposure to intermittent hypoxia has the potential to increase oxygen-carrying capacity in an aging population.

Hypoxic preconditioning reduces endothelial ischemia-reperfusion injury in older adults.

Sudden blood flow restoration to an ischemic vessel paradoxically damages endothelial cells. Ischemic preconditioning, caused by repeated bouts of brief ischemia using local or remote cuff inflation before reperfusion, attenuates endothelial dysfunction following an ischemia-reperfusion injury in young adults but does not consistently protect endothelial function in older adults prone to ischemic events. Intermittent exposure to systemic hypoxemia, induced via brief bouts of breathing low levels of oxygen, attenuates endothelial dysfunction following an ischemia-reperfusion injury in young adults. The aim of this study was to determine whether systemic hypoxic preconditioning protects against ischemia-reperfusion injury in older adults. Twelve adults (five women, 57 ± 9 yr) participated in this randomized crossover trial. Endothelium-dependent vasodilation was assessed by brachial artery flow-mediated dilation using a semiautomated diagnostic ultrasound system before and after a 20-min blood flow occlusion that was preceded by either intermittent hypoxia, consisting of three 4-min hypoxic cycles at an oxygen saturation of 80% interspersed with 4-min room air cycles, or intermittent normoxia, consisting of three 4-min normoxic cycles separated by 4-min room air cycles. When preceded by intermittent normoxia, ischemia-reperfusion injury reduced flow-mediated dilation by 4.1 ± 2.6% (6.5 ± 1.7 to 2.4 ± 1.7%). In contrast, flow-mediated dilation was reduced by 2.0 ± 1.5% when ischemia-reperfusion injury was preceded by intermittent hypoxia (5.6 ± 1.7 to 3.6 ± 2.3%). In conclusion, hypoxic preconditioning significantly attenuated the reduction in brachial artery flow-mediated dilation induced by an ischemia-reperfusion injury in older adults at greater risk for ischemic events.

Nitric oxide enhancement supplement containing beet nitrite and nitrate benefits high intensity cycle interval training.

This study investigated the effects of a beet nitric oxide enhancing (NOE) supplement comprised of nitrite and nitrate on cycling performance indices in trained cyclists. METHODS: Subjects completed a lactate threshold test and a high-intensity interval (HIIT) protocol at 50% above functional threshold power with or without oral NOE supplement. RESULTS: NOE supplementation enhanced lactate threshold by 7.2% (Placebo = 191.6 ± 37.3 W, NOE = 205.3 ± 39.9; p = 0.01; Effect Size (ES) = 0.40). During the HIIT protocol, NOE supplementation improved time to exhaustion 18% (Placebo = 1251 ± 562s, NOE = 1474 ± 504s; p = 0.02; ES = 0.42) and total energy expended 22.3% (Placebo = 251 ± 48.6 kJ, NOE = 306.6 ± 55.2 kJ; p = 0.01; ES = 1.079). NOE supplementation increased the intervals completed (Placebo = 7.00 ± 2.5, NOE = 8.14 ± 2.4; p = 0.03; ES = 0.42) and distance cycled (Placebo = 10.9 ± 4.0 km, NOE = 13.5 ± 3.9 km; p = 0.01; ES = 0.65). Also, target power was achieved at a higher cadence during the HIIT work and rest periods (p = 0.02), which enhanced muscle oxygen saturation (SmO2) recovery. Time-to-fatigue was negatively correlated with the degree of SmO2, desaturation during the HIIT work interval segment (r = -0.67; p 0.008), while both SmO2 desaturation and the SmO2 starting work segment saturation level correlated with a cyclist's kJ expended (SmO2 desaturation: r = -0.51, p = 0.06; SmO2 starting saturation: r = 0.59, p = 0.03). CONCLUSION: NOE supplementation containing beet nitrite and nitrate enhanced submaximal (lactate threshold) and HIIT maximal effort work. The NOE supplementation resulted in a cyclist riding at higher cadence rates with lower absolute torque values at the same power during both the work and rest periods, which in-turn delayed over-all fatigue and improved total work output.

Short exposure to intermittent hypoxia increases erythropoietin levels in healthy individuals.

Few minutes of hypoxic exposure stabilizes hypoxia-inducible factor-1α, resulting in erythropoietin (EPO) gene transcription and production. The objective of this study was to identify the shortest intermittent hypoxia protocol necessary to increase serum EPO levels in healthy individuals. In a first experiment, spontaneous EPO changes under normoxia (NORM) and the EPO response to five 4-min cycles of intermittent hypoxia (IH5) were determined in six individuals. In a second experiment, the EPO response to eight 4-min cycles of intermittent hypoxia (IH8) and 120 min of continuous hypoxia (CONT) was determined in six individuals. All hypoxic protocols were performed at a targeted arterial oxygen saturation of 80%. There was no significant change in EPO levels in response to normoxia or in response to five cycles of intermittent hypoxia (NORM: 9.5 ± 1.8 to 10.5 ± 1.8, IH5: 11.4 ± 2.3 to 13.4 ± 2.1 mU/mL, main effect for time P = 0.35). There was an increase in EPO levels in response to eight cycles of intermittent hypoxia and 120 min of continuous hypoxia, with peak levels observed 4.5 h after the onset of hypoxia (IH8: 11.2 ± 2.0 to 16.7 ± 2.2, CONT: 11.1 ± 3.8 to 19.4 ± 3.8 mU/mL, main effect for time P < 0.01). Eight cycles of intermittent hypoxia increased EPO levels to a similar extent as 120 min of continuous hypoxia (main effect for condition P = 0.36). Eight 4-min cycles of intermittent hypoxia represent the shortest protocol to increase serum EPO levels in healthy individuals.NEW & NOTEWORTHY The objective of this study was to identify the shortest intermittent hypoxia protocol necessary to increase serum erythropoietin levels in healthy individuals. Eight 4-min bouts of intermittent hypoxia, representing a hypoxic duration of 32 min at an arterial oxygen saturation of 80%, significantly increased erythropoietin levels in healthy individuals. These findings suggest that a short session of intermittent hypoxia has the potential to increase oxygen-carrying capacity.