Hypoxia stimulates glucose uptake independently from the action of insulin. The purpose of this study was to determine the effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and room air, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Nine adults with type 2 diabetes (two women, HbA1c: 7.3±1.5%, age: 52±13 years) and nine adults with normal glycemic control (four women, HbA1c: 5.4±0.1%, age: 24±4 years) performed a 2-hour oral glucose tolerance test on two separate visits to the laboratory. Following ingestion of the glucose drink, participants were exposed to either an intermittent hypoxia protocol, consisting of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, or a sham protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. Intermittent hypoxia did not attenuate the increase in glucose concentration but attenuated the increase in insulin concentration in response to an oral glucose tolerance test in comparison with the sham protocol in adults with type 2 diabetes. Insulin sensitivity was greater during intermittent hypoxia in comparison with the sham protocol in adults with type 2 diabetes (0.043±0.036 vs. 0.032±0.046 μmol/kg/min/pmol, p=0.01), but did not change in the control group (0.122±0.015 vs. 0.128±0.008 μmol/kg/min/pmol, p=0.12). In conclusion, intermittent hypoxia improved insulin sensitivity in adults with type 2 diabetes.

Hypoxia stimulates glucose uptake in isolated skeletal muscle through an insulin-independent pathway. Intermittent hypoxia can lower glucose concentration in adults with type 2 diabetes, but its application remains limited by the use of gas tanks to induce hypoxia. The aim of this study was to examine the effect of rebreathing-induced hypoxia on glucose and insulin responses to an oral glucose tolerance test in adults with type 2 diabetes. Ten adults with type 2 diabetes performed an oral glucose tolerance test during either rebreathing-induced hypoxia or spontaneous breathing. The glucose and insulin responses to the oral glucose tolerance test did not differ between rebreathing-induced hypoxia and spontaneous breathing. However, participants who achieved hypoxemia, defined as an oxygen saturation nadir below 90%, during rebreathing-induced hypoxia (n = 5) showed lower glucose concentrations and glucose area under the curve (AUC) (20,376 ± 553 vs. 24,346 ± 639, p < 0.01) than participants who achieved an oxygen saturation nadir above 90% (n = 5). Interestingly, body weight was strongly correlated with oxygen desaturation (r = -0.87, p < 0.01) and glucose AUC (r = -0.81, p < 0.01) during rebreathing-induced hypoxia. Rebreathing-induced hypoxia may represent a promising strategy to improve glycemic control in adults with type 2 diabetes and coexisting obesity.

Current wearable blood pressure monitors using photoplethysmography (PPG) in wrist watches or rings face accuracy issues with darker skin tones, leading to biased AI algorithms and inequitable health monitoring. We propose a smartwatch-integrable, low-power wearable antenna biosensor measuring bioimpedance (BioZ) changes from radial artery blood flow using radio frequencies (RF) for continuous blood pressure estimation. This non-contact RF BioZ-based approach offers a more equitable solution across diverse demographics. Our device has shown good performance with mean absolute errors (MAE) of 5.67 +/- 6.05 mmHg for RF BioZ. It meets British Hypertension Society (BHS) and Association for the Advancement of Medical Instrumentation (AAMI) error threshold requirements for grade A/ passing score for non-cuff-based BP measuring technology, respectively.

Hypoxia stimulates glucose uptake through an insulin-independent pathway. The purpose of this single-blind randomized study was to determine the acute effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, on glucose and insulin concentrations during an oral glucose tolerance test in adults with type 2 diabetes. It was hypothesized that intermittent hypoxia would attenuate the increase in glucose and insulin concentrations during an oral glucose tolerance test. Six adults with type 2 diabetes (5 men, age: 51±15 years, HbA1c: 7.3±1.5%) visited the laboratory on two occasions. On both visits, a 2-hour oral glucose tolerance test was performed, with venous blood samples collected 0, 30, 60, 90, and 120 min after ingestion of a high-glucose drink. Following ingestion of the drink, participants were exposed to either an intermittent hypoxia (IH) protocol, consisting of eight 4-min hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, or an intermittent normoxia (IN) protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. By design, oxygen saturation was lower during intermittent hypoxia than intermittent normoxia (81±3 vs. 97±1%, p<0.01). Relative changes in plasma glucose concentrations in response to the oral glucose tolerance tests were not different between conditions (IH vs. IN: 30: 42±15 vs. 35±15; 60: 57±26 vs. 65±30; 90: 73±32 vs. 88±30; and 120: 78±26 vs. 83±29 mg/dl, interaction effect: p=0.13). Similarly, the relative changes in insulin concentrations in response to the oral glucose tolerance tests were not different between conditions (IH vs. IN: 30: 14±17 vs. 25±17; 60: 42±36 vs. 48±35; 90: 70±58 vs. 86±60; and 120: 103±72 vs. 125±94 ulU/ml, main effect for condition: p=0.12). While these preliminary results did not reach statistical significance, the observed trends for reduced glucose concentrations in combination with lower insulin concentrations during intermittent hypoxia suggest that short bouts of hypoxia improve glucose tolerance by stimulating glucose uptake independently from the action of insulin. Data from a larger sample size of adults with type 2 diabetes are needed to confirm these preliminary findings. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Calisthenics is a form of bodyweight exercise that involves dynamic and rhythmic exercises. The physiological responses during and after calisthenics remain unclear. This study examined whether a bout of full-body calisthenics, a form of circuit resistance exercise that involves bodyweight movements, yields greater excess post-exercise oxygen consumption (EPOC) than steady-state exercise (SSE) at matched oxygen consumption. Twenty-two young adults (age = 22.1 +/- 2.4 years; four females) participated in two separate, oxygen consumption (VO2) matched exercise sessions: full-body calisthenics (nine body weight exercises, 15 reps x 4 sets) and SSE (running on a treadmill at 60-90% of VO(2)max). Energy expenditure, substrate utilization, and EPOC were measured during exercise and 60 min of recovery. SSE showed higher peak VO2 and heart rate during exercise than those during calisthenics. However, the post-exercise VO2 and energy expenditure above baseline level during the first 10 min of recovery were significantly higher with calisthenics than with SSE (0-5 min: 1.7 +/- 0.5 vs. 1.0 +/- 0.6; 6-10 min: 0.5 +/- 0.4 vs. 0.1 +/- 0.2 kcal/min; 31-60 min recovery: -0.1 +/- 0.3 vs. -0.2 +/- 0.2; all p < .05). During calisthenics, participants utilized a significantly higher proportion of energy from carbohydrates (85 vs. 73%; p < .01) but after exercise, they used a greater proportion of fat as the energy source (71 vs. 50%; p < .01) compared to SSE. Full-body calisthenics, a circuit-style bodyweight exercise, may be more effective than VO2 matched SSE in triggering greater EPOC and fat metabolism. Further efforts are warranted to demonstrate whether different amounts of skeletal muscle mass groups indeed lead to varying EPOC responses and energy use.

Patients with type 2 diabetes (T2D) exhibit, on average, a 20% decline in maximal oxygen consumption when compared to healthy adults. Hemoglobin mass strongly correlates to maximal oxygen consumption. A reduced total blood volume has been observed in patients with T2D, suggesting that a reduced hemoglobin mass contributes to the decreased maximal oxygen consumption in this population. Hypoxia stimulates the release of erythropoietin (EPO), the hormone regulating red blood cell production. We previously showed that intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, increases EPO levels. Thus, the objective of this study was to determine the effect of a single session of intermittent hypoxia on serum EPO levels and hemoglobin mass in patients with T2D. We hypothesized that a single session of intermittent hypoxia would raise serum EPO levels and lead to an increase in hemoglobin mass in patients with T2D. Ten patients with T2D (4 women, age: 53 ± 10 years, body mass index: 36.2 ± 8.5 kg/m2, HbA1c: 7.2 ± 1.2%) 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. Air was made hypoxic by titrating nitrogen into a breathing circuit. Pulmonary gas exchange, oxygen saturation, and hemodynamics were continuously measured throughout the protocol. EPO levels were measured before and 4.5 hours after the beginning of the protocol. Hemoglobin mass was assessed via carbon monoxide rebreathing before and seven days following intermittent hypoxia. Intermittent hypoxia lowered oxygen saturation (­­97 ±­ 2 to 81 ± 2%, p<0.01), which resulted in a lower fraction of inspired oxygen (20.8 ±­ 0.1 to 11.1 ± 1.0%, p<0.01). There was no significant change in EPO levels following exposure to intermittent hypoxia (11.9 ± 5.3­ to 12.1 ± 4.3 mU/ml, p=0.83). There was also no change in hemoglobin mass in response to intermittent hypoxia (864 ± 152­ to 850 ± 150 g, p=0.64). Intermittent hypoxia did not affect mean arterial pressure (94 ± 5 to 97 ± 7 mmHg, p=0.18) but increased cardiac output (9.1 ± 2.7 to 9.8 ± 2.8 L/min, p=0.03) due to an increase in heart rate (78 ± 9 to 84 ± 10 bpm, p<0.01). In conclusion, a single session of intermittent hypoxia did not increase serum EPO levels or hemoglobin mass in patients with T2D. These findings suggest an impaired EPO response to decreased oxygen levels in patients with T2D, which may contribute to the reduced hemoglobin mass and total blood volume observed in this population. College of Education Small Grants Program This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Squatting, a traditional resistance exercise classified as strength training, relies on anaerobic pathways, but its aerobic aspects remain unclear. We examined heart rate and oxygen demand during squats, exploring variations across different strength statuses. It fills gaps in understanding the cardiorespiratory effects of squatting, especially during multiple sets. Twenty-two young healthy resistance trained men (age: 28±4 years) participated. Maximal oxygen consumption (V̇O 2 max) and 1 repetition maximum (RM) of squat were measured. Participants performed 5 sets of squat exercises at 65% of 1RM for 10 repetitions with 3-min rest intervals. Heart rate and pulmonary gas exchange were measured during the squat exercise. Participants were divided into high strength (HS) and low strength (LS) groups based on a median split of their 1 RM squat values. During 5 sets of squat exercise, oxygen consumption (V̇O 2 ) increased up to 47.8 ± 8.9 ml/kg/min, corresponding to 100.6% of predetermined V̇O 2 max. The HS group achieved a greater highest point of V̇O 2 in relation to V̇O 2 max than the LS group (108.0 vs. 93.7%). During the exercise intervals, V̇O 2 exceeded V̇CO 2 , while during the rest intervals, V̇CO 2 surpassed V̇O 2 . Our findings suggest that the oxygen demand during squatting is notably substantial, which may vary according to the training status.

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation, which is partly caused by a decreased nitric oxide bioavailability. Continuous exposure to hypoxia, achieved by breathing low levels of oxygen, stimulates nitric oxide production and induces peripheral vasodilation. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, triggers similar physiological responses to chronic hypoxia, but without the detrimental effects often associated with longer hypoxic exposure. The aim of this randomized crossover trial was to determine whether intermittent hypoxia induces brachial artery vasodilation and acutely improves flow-mediated dilation in older adults. Eleven apparently healthy older adults (six women, age: 57±7 years, body mass index: 24.5±3.5 kg/m2) visited the laboratory on two separate occasions. Endothelium-dependent vasodilation was assessed by brachial artery flow-mediated dilation using a semiautomated diagnostic ultrasound system before and 15 minutes after exposure to either intermittent hypoxia (IH) or intermittent normoxia (IN). Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation. Air was made hypoxic by titrating nitrogen into a breathing circuit. Intermittent normoxia consisted of eight 4-min normoxic cycles separated by one minute of breathing room air. Hemodynamics, oxygen saturation, and pulmonary gas exchange were continuously assessed during both conditions. By design, intermittent hypoxia resulted in an oxygen saturation of 81±1%, corresponding to an oxygen concentration of 11.4±0.6%. Exposure to intermittent hypoxia, but not intermittent normoxia, elicited a brachial artery vasodilation (IH: 3.61±0.49 to 3.73±0.48 vs. IN: 3.60±0.51 to 3.55±0.50 mm, p=0.01). Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or intermittent normoxia (IH: 5.4±2.0 to 5.5±2.4% vs. IN: 4.8±1.3 to 4.7±2.3%, p=0.17). Intermittent hypoxia did not affect mean arterial pressure (91±6 vs. 92±7 mmHg, p=0.56) but increased heart rate when compared to intermittent normoxia (61±9 vs. 55±9 bpm, p<0.01). In conclusion, exposure to intermittent hypoxia triggered a brachial artery vasodilation but did not immediately affect endothelium-dependent vasodilation in older adults. Repeated exposure to intermittent hypoxia may be necessary to improve endothelial function in this population. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure.

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.

Hypoxia triggers glucose uptake independently from the action of insulin. The purpose of this study was to determine the acute effect of intermittent hypoxia, defined as alternating short bouts of breathing hypoxic and room air, on plasma glucose levels during an oral glucose tolerance test in healthy individuals. We hypothesized that exposure to intermittent hypoxia would attenuate the increase in glucose levels in response to an oral glucose tolerance test. Nine individuals (5 men, age: 24 ± 4 years, height: 175 ± 9 cm, weight: 71.0 ± 13.5 kg, HbA1c: 5.4 ± 0.1%) participated in the study. Participants visited the laboratory on two occasions. On both visits, a 2-hour oral glucose tolerance test was performed, with venous blood samples collected 0, 30, 60, 90 and 120 minutes following the ingestion of a 75 g glucose drink. On visit 1, an intermittent hypoxia (IH) protocol, consisting of eight 4-minute hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, was performed following ingestion of the glucose drink. On visit 2, an intermittent normoxia protocol consisting of eight 4-minute normoxic cycles interspersed with breathing room air was performed following ingestion of the glucose drink. Visit order was randomized and participants were blinded to the condition. As expected, intermittent hypoxia resulted in a lower arterial oxygen saturation than intermittent normoxia (IH: 83 ± 3, IN: 98 ± 1%, p < 0.01) which corresponded to lower levels of inspired oxygen (IH: 10.9 ± 0.7, IN: 20.9 ± 0.3%, p < 0.01). Plasma glucose responses to the oral glucose tolerance test were not different between conditions (IH vs. IN: 0: 90 ± 7 vs. 89 ± 6; 30: 135 ± 21 vs. 137 ± 24; 60: 110 ± 28 vs. 108 ± 25; 90: 96 ± 18 vs. 88 ± 14; and 120: 101 ± 19 vs. 83 ± 14 mg/dl, p = 0.29). Intermittent hypoxia triggered an increase in cardiac output (6.1 ± 0.9 to 6.8 ± 1.3 L/min, p < 0.01) caused by an increase in heart rate (67 ± 10 to 79 ± 12 bpm, p < 0.01). Contrary to our hypothesis, intermittent exposure to hypoxia did not attenuate the increase in plasma glucose levels during an oral glucose tolerance test in individuals with normal glycemic control. It remains to be determined whether intermittent hypoxia can attenuate the increase in plasma glucose levels in response to an oral glucose tolerance test in individuals with impaired glucose tolerance.

Sudden restoration of blood flow to an ischemic vessel paradoxically damages endothelial cells. In young healthy adults, ischemic preconditioning, caused by repeated periods of brief ischemia induced by local cuff inflation prior to reperfusion, attenuates endothelial dysfunction following an ischemia‐reperfusion injury. However, ischemic preconditioning does not consistently protect against ischemia‐reperfusion injury in older adults. Intermittent systemic hypoxemia, induced via brief bouts of breathing low levels of oxygen, attenuates endothelial dysfunction following an ischemia‐reperfusion injury in young healthy adults. Therefore, the aim of the present study was to determine whether intermittent hypoxia protects against ischemia‐reperfusion injury in older adults. Eleven older adults (4 women, age: 57±9 years, height: 173±8 cm, body weight: 76±13 kg) visited the laboratory on two separate occasions. Endothelium‐dependent vasodilation was assessed by brachial artery flow‐mediated dilation using a semiautomated diagnostic ultrasound system before and after 20 minutes of blood flow occlusion to induce an ischemia‐reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia (IH), consisting of three 4‐min hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with 4‐min room air cycles, or intermittent normoxia (IN), consisting of three 4‐min normoxic cycles separated by 4‐min room air cycles. Intermittent hypoxia resulted in an arterial oxygen saturation of 80±2%, which corresponded to oxygen levels of 11.6±1.0%. When preceded by intermittent normoxia, blood flow occlusion reduced flow‐mediated dilation by 4.0±2.6% (6.4±1.7 to 2.4±1.8%). In contrast, flow‐mediated dilation was reduced by 1.8±1.5% when blood flow occlusion was preceded by intermittent hypoxia (5.6±1.8 to 3.7±2.4%: p=0.05). Intermittent hypoxia increased cardiac output (5.2±1.5 to 5.7±1.8 L·min‐1, p=0.03) mainly due to an increase in heart rate (61±12 to 69±10 bpm, p<0.01). In conclusion, hypoxic preconditioning attenuated the reduction in flow‐mediated dilation induced by blood flow occlusion in older adults. Thus, exposure to intermittent hypoxia represents a potential strategy to protect against ischemia‐reperfusion injury in populations at risk for ischemic events.

We tested the hypotheses that spontaneous baroreflex control of integrated muscle sympathetic nerve activity (MSNA) burst occurrence and action potential (AP) subpopulations would be blunted in older compared with young adults and that sympathetic transduction will be blunted in older adults relative to young adults. Integrated muscle sympathetic nerve activity (MSNA) and the underlying sympathetic APs were obtained using microneurography and a continuous wavelet analysis approach, respectively, during 5 min of supine rest in 13 older (45-75 yr, 6 females) and 14 young (21-30 yr, 7 females) adults. Baroreflex threshold relationships were quantified as the slope of the linear regression between MSNA burst occurrence (%) and diastolic blood pressure (mmHg), or AP cluster firing probability (%) and diastolic blood pressure (mmHg). Integrated MSNA baroreflex threshold gain was greater in older compared with young adults (older: -5.7 +/- 2.6%/mmHg vs. young: -2.7 +/- 1.4%/mmHg, P < 0.001). Similarly, the baroreflex threshold gain of AP clusters was modified by aging (group-by-cluster effect: P < 0.001) such that older adults demonstrated greater baroreflex threshold gains of medium-sized AP clusters (e.g., Cluster 4, older: -8.2 +/- 3.2%/mmHg vs. young: -3.6 +/- 1.9%/mmHg, P = 0.003) but not for the smallest-sized (Cluster 1, older: -1.6 +/- 1.9%/mmHg vs. young: -1.0 +/- 1.7%/mmHg, P > 0.999) and largest-sized (Cluster 10, older: -0.5 +/- 0.5%/mmHg vs. young: -0.2 +/- 0.1%/mmHg, P = 0.819) AP clusters compared with young adults. In contrast, the peak change in mean arterial pressure (MAP) following a spontaneous MSNA burst (i.e., sympathetic transduction) was impaired with aging (older: -0.7 +/- 0.3 mmHg vs. young: 1.8 +/- 1.2 mmHg, P < 0.001). We conclude that aging is associated with elevated baroreflex control over high-probability AP content of sympathetic bursts that may compensate for impaired sympathetic neurovascular transduction. NEW & NOTEWORTHY The present study demonstrates for the first time that the spontaneous baroreflex threshold gains of integrated muscle sympathetic nerve activity burst occurrence and medium-sized action potential clusters are greater in older compared with young adults. Since sympathetic transduction was blunted in older compared with young adults, we interpret the data to indicate that the central arc of the baroreflex is enhanced in older adults to compensate for impairments in the peripheral arc.

Few minutes of hypoxia exposure stabilizes hypoxia-inducible factors, resulting in erythropoietin (EPO) gene transcription and production. A brief intermittent hypoxia exposure increased EPO levels in young healthy individuals, suggesting that a single session of intermittent hypoxia has the potential to increase oxygen-carrying capacity. Thus, the objective of this study was to determine the effect of a single session of intermittent hypoxia on serum EPO levels and hemoglobin mass among older individuals. We hypothesized that a single session of intermittent hypoxia would raise serum EPO levels and lead to an increase in hemoglobin mass in older individuals. Seventeen participants (8 women, age: 54 ± 8 years, height: 177 ± 10 cm, weight: 76 ± 14 kg, BMI: 24 ± 4 kg/m ) were randomly assigned to an intermittent hypoxia group (IH, n=11) or an intermittent normoxia group (IN, n=6). Intermittent hypoxia consisted of eight 4-minute cycles at a targeted arterial oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into the breathing circuit. Intermittent normoxia consisted of the same protocol, but nitrogen was not added to the breathing circuit. Pulmonary gas exchange, arterial oxygen saturation, and hemodynamics were continuously measured throughout both protocols. EPO levels were measured before and 4.5 hours after the beginning of each protocol. Hemoglobin mass was assessed via carbon monoxide rebreathing the day before and seven following intermittent hypoxia or normoxia. Intermittent hypoxia lowered arterial oxygen saturation (--98 ±- 1 to 82 ± 3 %, p<0.01), which resulted in a lower fraction of inspired oxygen (20.8 ±- 0.1 to 10.9 ± 1.0 %, p<0.01). There was no significant change in EPO levels in either condition (IH:10.4 ±- 2.9 to 13.3 ± 4.2; IN: 5.6 ±- 2.4 to 6.5 ± 2.9 mU/ml, main effect for time p=0.12). Similarly, there was no change in hemoglobin mass in response to both conditions (IH: 752 ±- 189 to 754 ± 189; IN: 858 ± 177 to 879 ± 157 g, main effect for time p=0.87). Intermittent hypoxia did not affect mean arterial pressure (87 ± 15 to 88 ± 14 mmHg, p=0.18) or cardiac output (5.5 ± 1.5 to 5.7 ± 1.5 L/min, p=0.22), but increased heart rate (62 ± 9 to 68 ± 9 bpm, p<0.01). In conclusion, a single session of eight 4-minute cycles of intermittent hypoxia did not increase serum EPO levels in older individuals.

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.

The current study evaluated the hypothesis that 6 mo of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in 11 patients with IHD (1 female; 61 ± 9 yr) pre (pre-CR) and post (post-CR) 6 mo of aerobic and resistance training-based CR. Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1 min of baseline and the second half of apneas. At baseline, overall sympathetic activity was less post-CR (all P < 0.01). During EI-APN, AP recruitment was not observed pre-CR (all P > 0.05), but increases in both within-burst AP firing frequency (Δpre-CR: 2 ± 3 AP spikes/burst vs. Δpost-CR: 4 ± 3 AP spikes/burst; P = 0.02) and AP cluster recruitment (Δpre-CR: -1 ± 2 vs. Δpost-CR: 2 ± 2; P < 0.01) were observed in post-CR tests. In contrast, during EE-APN, AP firing frequency was not different post-CR compared with pre-CR tests (Δpre-CR: 269 ± 202 spikes/min vs. Δpost-CR: 232 ± 225 spikes/min; P = 0.54), and CR did not modify the recruitment of new AP clusters (Δpre-CR: -1 ± 3 vs. Δpost-CR: 0 ± 1; P = 0.39), or within-burst firing frequency (Δpre-CR: 3 ± 3 AP spikes/burst vs. Δpost-CR: 2 ± 2 AP spikes/burst; P = 0.21). These data indicate that CR improves some of the sympathetic nervous system dysregulation associated with cardiovascular disease, primarily via a reduction in resting sympathetic activation. However, the benefits of CR on sympathetic neural recruitment may depend upon the magnitude of initial impairment.

Currently, the effect of aging on sympathetic baroreflex control is equivocal, with some studies finding that integrated sympathetic baroreflex threshold gain is not affected by age, and others finding that it is blunted in older compared to young adults. While these studies evaluated the effect of aging on baroreflex control of integrated sympathetic burst frequency, it remains unclear how aging modulates the baroreflex control of postganglionic action potentials (AP). In young adults, the arterial baroreflex exerts non-uniform control over varying-sized APs spontaneously firing within bursts of muscle sympathetic nerve activity (MSNA), with the strongest control over medium sized AP clusters, and less control over the smallest and largest APs. Therefore, we tested the hypothesis that resting baroreflex control of AP subpopulations and integrated sympathetic bursts would be blunted in older compared to young adults. Baroreflex threshold relationships for integrated MSNA bursts and the underlying subpopulations of AP clusters (obtained using microneurography and a continuous wavelet transform) were assessed during 5 minutes of supine rest in eleven older (45-75 years, 5 females) and eleven young (21-30 years, 5 females) adults. Baroreflex threshold was quantified as the slope of the linear regression between AP probability (%) and MSNA burst probability (%) versus diastolic blood pressure (DBP, mmHg; Finger plethysmography). AP discharge was greater in older compared to young adults (Older: 614 ± 327 spikes/100 beats vs. Young: 211 ± 107 spikes/100 beats, P < 0.001), and the baroreflex control of AP subpopulations was reset towards greater firing probabilities in older adults (group-by-cluster effect: P < 0.001). Specifically, the arterial baroreflex threshold gain of medium AP clusters was greater in older compared to young adults (e.g. Cluster 4, Older: -7.8 ± 3.1 %/mmHg vs. Young: -4.1 ± 2.9 %/mmHg, P = 0.010), whereas the baroreflex threshold gains for the smallest (e.g. Cluster 1, Older: -1.2 ± 1.1 %/mmHg vs. Young: -0.7 ± 0.4 %/mmHg, P = 0.197) and largest (e.g. Cluster 10, Older: -0.5 ± 0.4 %/mmHg vs. Young: -0.6 ± 0.6 %/mmHg, P = 0.673) AP clusters were not modified by aging. Additionally, integrated sympathetic burst threshold gain was greater in older compared to young adults (Older: -7.9 ± 3.8 %/mmHg vs. Young: -3.9 ± 1.8 %/mmHg, P = 0.005), and the operating point was shifted rightward towards a higher DBP (Older: 76 ± 8 mmHg vs. Young: 68 ± 7 mmHg, P = 0.021). Contrary to our hypothesis, the strength of baroreflex control over medium sized AP clusters as well as integrated sympathetic baroreflex threshold gain was greater in this group of older adults compared to young adults.

Ischemia-reperfusion injury induced by restoration of blood flow following occlusion impairs flow-mediated dilation, a marker of endothelium-dependent vasodilation. In young healthy adults, exposure to intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, before an ischemia-reperfusion injury significantly attenuated the reduction in flow-mediated dilation. Thus, hypoxic preconditioning represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events.