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 in comparison 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.

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.

Mechanisms underlying the health benefits of intermittent hypoxia conditioning.

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.

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.

Aging is associated with enhanced central but impaired peripheral arms of the sympathetic baroreflex arc.

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.

Influence of ischemia-reperfusion injury on endothelial function in men and women with similar serum estradiol concentrations.

Prior data suggest that, relative to the early follicular phase, women in the late follicular phase are protected against endothelial ischemia-reperfusion (I/R) injury when estradiol concentrations are highest. In addition, endothelial I/R injury is consistently observed in men with naturally low endogenous estradiol concentrations that are similar to those of women in the early follicular phase. Therefore, the purpose of this study was to determine whether the vasodeleterious effect of I/R injury differs between women in the early follicular phase of the menstrual cycle and age-matched men. We tested the hypothesis that I/R injury would attenuate endothelium-dependent vasodilation to the same extent in women and age-matched men with similar circulating estradiol concentrations. Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasound) in young healthy men (n = 22) and women (n = 12) before (pre-I/R) and immediately after (post-I/R) I/R injury, which was induced via 20 min of arm circulatory arrest followed by 20-min reperfusion. Serum estradiol concentrations did not differ between sexes (men 115.0 ± 33.9 pg·mL-1 vs. women 90.5 ± 40.8 pg·mL-1; P = 0.2). The magnitude by which I/R injury attenuated endothelium-dependent vasodilation did not differ between men (pre-I/R 5.4 ± 2.4% vs. post-I/R 3.0 ± 2.7%) and women (pre-I/R 6.1 ± 2.8% vs. post-I/R 3.7 ± 2.7%; P = 0.9). Our data demonstrate that I/R injury similarly reduces endothelial function in women in the early follicular phase of the menstrual cycle and age-matched men with similar estradiol concentrations.

Four-Second Power Cycling Training Increases Maximal Anaerobic Power, Peak Oxygen Consumption, and Total Blood Volume.

INTRODUCTION: High-intensity interval training is an effective tool to improve cardiovascular fitness and maximal anaerobic power. Different methods of high-intensity interval training have been studied but the effects of repeated maximal effort cycling with very short exercise time (i.e., 4 s) and short recovery time (15-30 s) might suit individuals with limited time to exercise. PURPOSE: We examined the effects of training at near maximal anaerobic power during cycling (PC) on maximal anaerobic power, peak oxygen consumption (V˙O2peak), and total blood volume in 11 young healthy individuals (age: 21.3 ± 0.5 yr) (six men, five women). METHODS: Participants trained three times a week for 8 wk performing a PC program consisting of 30 bouts of 4 s at an all-out intensity (i.e., 2 min of exercise per session). The cardiovascular stress progressively increased over the weeks by decreasing the recovery time between sprints (30-24 s to 15 s), and thus, total session time decreased from 17 to <10 min. RESULTS: Power cycling elicited a 13.2% increase in V˙O2peak (Pre: 2.86 ± 0.18 L·min-1, Post: 3.24 ± 0.21 L·min-1; P = 0.003) and a 7.6% increase in total blood volume (Pre: 5139 ± 199 mL, Post: 5529 ± 342 mL; P < 0.05). Concurrently, maximal anaerobic power increased by 17.2% (Pre: 860 ± 53 W, Post: 1,009 ± 71 W; P < 0.001). CONCLUSIONS: A PC training program employing 30 bouts of 4 s duration for a total of 2 min of exercise, resulting in a total session time of less than 10 min in the last weeks, is effective for improving total blood volume, V˙O2peak and maximal anaerobic power in young healthy individuals over 8 wk. These observations require reconsideration of the minimal amount of exercise needed to significantly increase both maximal aerobic and anaerobic power.

The impact of 6 months of exercise-based cardiac rehabilitation on sympathetic neural recruitment during apneic stress.

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.

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.

Hypoxic preconditioning attenuates ischemia-reperfusion injury in young healthy adults.

Ischemic preconditioning attenuates the reduction in brachial artery endothelial function following an ischemia-reperfusion injury. Brief bouts of systemic hypoxemia could similarly mitigate the blunted vasodilatory response induced by an ischemia-reperfusion injury. The aim of the present study was to determine whether an acute bout of intermittent hypoxia protects against an ischemia-reperfusion injury in young healthy individuals. Brachial artery endothelial function was assessed by flow-mediated dilation in 16 young healthy individuals before and after a 20-min upper arm blood flow occlusion to induce ischemia-reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia or intermittent normoxia. Intermittent hypoxia consisted of three 4-min hypoxic cycles at an arterial oxygen saturation of 87 ± 3% separated by 4-min normoxic cycles. Intermittent hypoxia resulted in a lower arterial oxygen saturation than intermittent normoxia (hypoxia: 87 ± 3% vs. normoxia: 99 ± 1%, P < 0.01), which was equivalent to a lower fraction of inspired oxygen (hypoxia: 0.123 ± 0.013 and normoxia: 0.210 ± 0.003, P < 0.01). When preceded by intermittent normoxia, blood flow occlusion resulted in a blunted flow-mediated dilation. In contrast, the reduction in flow-mediated dilation following blood flow occlusion was attenuated by prior exposure to intermittent hypoxia (hypoxia: 6.4 ± 1.9 to 4.4 ± 2.3% and normoxia: 7.1 ± 2.5 to 4.0 ± 2.4%, time × condition interaction P = 0.048). Exposure to intermittent hypoxia did not affect mean arterial pressure (hypoxia: 92 ± 9 mmHg and normoxia: 89 ± 8 mmHg, P = 0.19) or cardiac output (hypoxia: 5.8 ± 1.1 L·min-1 and normoxia: 5.3 ± 1.1 L·min-1, P = 0.29). In conclusion, hypoxic preconditioning attenuates the reduction in flow-mediated dilation induced by blood flow occlusion in young healthy individuals. Intermittent hypoxia represents a potential strategy to mitigate the effect of ischemia-reperfusion injury associated with ischemic events.NEW & NOTEWORTHY 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.

Effect of a Single Session of Intermittent Hypoxia on Erythropoietin and Oxygen-Carrying Capacity.

Intermittent hypoxia, defined as alternating bouts of breathing hypoxic and normoxic air, has the potential to improve oxygen-carrying capacity through an erythropoietin-mediated increase in hemoglobin mass. The purpose of this study was to determine the effect of a single session of intermittent hypoxia on erythropoietin levels and hemoglobin mass in young healthy individuals. Nineteen participants were randomly assigned to an intermittent hypoxia group (Hyp, n = 10) or an intermittent normoxia group (Norm, n = 9). Intermittent hypoxia consisted of five 4-min hypoxic cycles at a targeted arterial oxygen saturation of 90% interspersed with 4-min normoxic cycles. Erythropoietin levels were measured before and two hours following completion of the protocol. Hemoglobin mass was assessed the day before and seven days after exposure to intermittent hypoxia or normoxia. As expected, the intermittent hypoxia group had a lower arterial oxygen saturation than the intermittent normoxia group during the intervention (Hyp: 89 ± 1 vs. Norm: 99 ± 1%, p < 0.01). Erythropoietin levels did not significantly increase following exposure to intermittent hypoxia (Hyp: 8.2 ± 4.5 to 9.0 ± 4.8, Norm: 8.9 ± 1.7 to 11.1 ± 2.1 mU·mL-1, p = 0.15). Hemoglobin mass did not change following exposure to intermittent hypoxia. This single session of intermittent hypoxia was not sufficient to elicit a significant rise in erythropoietin levels or hemoglobin mass in young healthy individuals.

Effect of virtual reality-simulated exercise on sympathovagal balance.

Discovery of therapeutic avenues to provide the benefits of exercise to patients with enforced sedentary behavior patterns would be of transformative importance to health care. Work in model organisms has demonstrated that benefits of exercise can be provided to stationary animals by daily intermittent stimulation of adrenergic signaling. Here, we examine as a proof of principle whether exposure of human participants to virtual reality (VR) simulation of exercise can alter sympathovagal balance in stationary humans. In this study, 24 participants performed 15 minutes of cycling exercise at standardized resistance, then repeated the exercise with a virtual reality helmet that provided an immersive environment. On a separate day, they each controlled a virtual environment for 15 minutes to simulate exercise without actual cycling exercise. Response to each treatment was assessed by measuring heart rate (HR), norepinephrine, and heart rate variability, and each participant's response to virtual exercise was compared internally to his/her response to the actual cycling. We found that neither post-exercise norepinephrine nor post-exercise HR was significantly increased by VR simulation. However, heart rate variability measured during virtual exercise was comparable to actual cycling in participants that engaged in moderate exercise, but not in those that engaged in high-intensity exercise. These findings suggest that virtual exercise has the potential to mimic some effects of moderate exercise. Further work will be needed to examine the longitudinal effects of chronic exposure to VR-simulated exercise.

Exercise Intolerance in Heart Failure: Central Role for the Pulmonary System.

We propose that abnormalities of the pulmonary system contribute significantly to the exertional dyspnea and exercise intolerance observed in patients with chronic heart failure. Interventions designed to address the deleterious pulmonary manifestations of heart failure may, therefore, yield promising improvements in exercise tolerance in this population.

Impact of Menstrual Blood Loss and Oral Contraceptive Use on Oxygen-carrying Capacity.

PURPOSE: The effect of menstrual blood loss on oxygen-carrying capacity remains equivocal. The purpose of this study was to determine the effect of menstrual blood loss on hemoglobin mass in young, healthy women. METHODS: Twenty-one women (age, 23 ± 6 yr; height, 168 ± 7 cm; weight, 66.1 ± 12.6 kg) with regular menstrual cycles, either using (n = 10) or not using oral contraceptives, participated in the study. Hemoglobin mass was assessed using carbon monoxide rebreathing on three separate occasions over the course of one menstrual cycle. RESULTS: Visits for women not using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (1 ± 1 d after the surge of luteinizing hormone in urine), and luteal phase (9 ± 1 d after the late follicular visit). Visits for women using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (15 ± 3 d after the onset of menses), and luteal phase (9 ± 2 d after the late follicular visit). Hemoglobin mass was not affected by menstrual cycle phase (early follicular, 618 ± 61; late follicular, 610 ± 65; luteal, 607 ± 68 g; P = 0.52). Interestingly, when normalized to weight, hemoglobin mass was 12% higher in women using oral contraceptives in comparison to nonusers (10.0 ± 1.2 vs 8.9 ± 1.2 g·kg, P < 0.05). CONCLUSION: Menstrual blood loss had no measurable effect on hemoglobin mass in eumenorrheic women. However, oral contraceptive use resulted in a greater oxygen-carrying capacity, potentially leading to a greater maximal oxygen uptake.

The interactions between respiratory and cardiovascular systems in systolic heart failure.

Heart failure (HF) is a complex and multifaceted disease. The disease affects multiple organ systems, including the respiratory system. This review provides three unique examples illustrating how the cardiovascular and respiratory systems interrelate because of the pathology of HF. Specifically, these examples outline the impact of HF pathophysiology on 1) respiratory mechanics and the mechanical "cost" of breathing; 2) mechanical interactions of the heart and lungs; and on 3) abnormalities of pulmonary gas exchange during exercise, and how this may be applied to treatment. The goal of this review is to, therefore, raise the awareness that HF, though primarily a disease of the heart, is accompanied by marked pathology of the respiratory system.

Determinants of Gambling Disorders in Elderly People-A Systematic Review.

Background: Despite the growth in the number of studies on gambling disorders (GDs) and the potentially severe harm it may cause, problem gambling in older adults is rarely apparent in literature. Driven by the need to overcome this limitation, a broad systematic review is essential to cover the studies that have already assessed the determinants of GD in the elderly. Objectives: The aim of this systematic review is to understand the determinants related to GDs in elderly people. Methods: A total of 51 studies met the inclusion criteria, and data were synthesized. Results: Three major types of determinants were identified in this review: individual, socio-financial and environmental. Conclusions: This review explored the determinants influencing GDs in older people. The findings are relevant to academics, policymakers, patients, and practitioners interested in the identification and prevention of GD in older people.

Effects of 6 Months of Exercise-Based Cardiac Rehabilitation on Autonomic Function and Neuro-Cardiovascular Stress Reactivity in Coronary Artery Disease Patients.

Background Autonomic dysregulation represents a hallmark of coronary artery disease (CAD). Therefore, we investigated the effects of exercise-based cardiac rehabilitation (CR) on autonomic function and neuro-cardiovascular stress reactivity in CAD patients. Methods and Results Twenty-two CAD patients (4 women; 62±8 years) were studied before and following 6 months of aerobic- and resistance-training-based CR. Twenty-two similarly aged, healthy individuals (CTRL; 7 women; 62±11 years) served as controls. We measured blood pressure, muscle sympathetic nerve activity, heart rate, heart rate variability (linear and nonlinear), and cardiovagal (sequence method) and sympathetic (linear relationship between burst incidence and diastolic blood pressure) baroreflex sensitivity during supine rest. Furthermore, neuro-cardiovascular reactivity during short-duration static handgrip (20s) at 40% maximal effort was evaluated. Six months of CR lowered resting blood pressure (P<0.05), as well as muscle sympathetic nerve activity burst frequency (48±8 to 39±11 bursts/min; P<0.001) and burst incidence (81±7 to 66±17 bursts/100 heartbeats; P<0.001), to levels that matched CTRL and improved sympathetic baroreflex sensitivity in CAD patients (P<0.01). Heart rate variability (all P>0.05) and cardiovagal baroreflex sensitivity (P=0.11) were unchanged following CR, yet values were not different pre-CR from CTRL (all P>0.05). Furthermore, before CR, CAD patients displayed greater blood pressure and muscle sympathetic nerve activity reactivity to static handgrip versus CTRL (all P<0.05); yet, responses were reduced following CR (all P<0.05) to levels observed in CTRL. Conclusions Six months of exercise-based CR was associated with marked improvement in baseline autonomic function and neuro-cardiovascular stress reactivity in CAD patients, which may play a role in the reduced cardiac risk and improved survival observed in patients following exercise training.

Multimorbid outpatients: A high frequency of FP appointments and/or family difficulties, should alert FPs to the possibility of death or acute hospitalization occurring within six months; A primary care feasibility study.

BACKGROUND: The European General Practitioners Research Network (EGPRN) designed and validated a comprehensive definition of multimorbidity using a systematic literature review and qualitative research throughout Europe. This definition was tested as a model to assess death or acute hospitalization in multimorbid outpatients. OBJECTIVE: To assess which criteria in the EGPRN concept of multimorbidity could detect outpatients at risk of death or acute hospitalization in a primary care cohort at a 6-month follow-up and to assess whether a large scale cohort with FPs would be feasible. METHOD: Family Physicians included a random sample of multimorbid patients who attended appointments in their offices from July to December 2014. Inclusion criteria were those of the EGPRN definition of Multimorbidity. Exclusion criteria were patients under legal protection and those unable to complete the 2-year follow-up. Statistical analysis was undertaken with uni- and multivariate analysis at a 6-month follow-up using a combination of approaches including both automatic classification and expert decision making. A Multiple Correspondence Analysis (MCA) completed the process with a projection of illustrative variables. A logistic regression was finally performed in order to identify and quantify risk factors for decompensation. RESULTS: 19 FPs participated in the study. 96 patients were analyzed. 3 different clusters were identified. MCA showed the central function of psychosocial factors and peaceful versus conflictual relationships with relatives in all clusters. While taking into account the limit of a small cohort, age, frequency of family physician visits and extent of family difficulties were the factors which predicted death or acute hospitalization. CONCLUSION: A large scale cohort seems feasible in primary care. A sense of alarm should be triggered to prevent death or acute hospitalization in multimorbid older outpatients who have frequent family physician visits and who experience family difficulties.