Regimbal, Riley J.

This study investigated the first multiomics data for association with tolerance to central hypovolemia in humans. Analyzing gene expression, proteins, and genetic variants in individuals with high and low tolerance to simulated hemorrhage, the findings show that severe blood loss causes widespread transcriptional changes, including the activation of innate immune system pathways and inhibition of gas transport processes. This research can help identify molecular factors that influence individuals’ tolerance levels for progressive blood loss.

The maximal expiratory flow-volume (MEFV) curve is a valuable tool for assessing pulmonary function and diagnosing respiratory disease. Quantifying the shape of the MEFV curve may provide additional insight into pulmonary dysfunction compared to spirometry alone. We questioned if the shape of the MEFV curve could detect signs of abnormal lung emptying dynamics in asymptomatic ex-smokers when compared to never smokers free of cardiopulmonary disease. A retrospective analysis of routine spirometry from 22 asymptomatic ex-smokers (50% female) without a formal diagnosis of chronic obstructive pulmonary disease or other chronic respiratory disease was compared against 48 healthy never smokers (65% female). The shape of the MEFV curve was quantified via the slope-ratio method which generates a unitless value corresponding to the ratio between a line of tangency at a specific lung volume and a chord line intersecting the point of interest and residual volume. A SR of 1 would indicate a linear decrease in flow with decreasing lung volume, whereas a SR >1 or <1 would indicate a convex ( i.e., scooped) or concave ( i.e., bump) shape to the MEFV curve; respectively. Slope-ratio was assessed between 80-20% vital capacity in 2% vital capacity increments. A single average slope-ratio was taken as the mean of all slope-ratio values between 80-20% vital capacity per individual. Data are presented as mean ± SD. Patient demographics, including age, height and weight were not different between ex-smokers and never smokers (all p >0.05). No differences in pulmonary function between ex-smokers and never smokers were observed (FEV 1 : 89±22 vs. 95±20%predicted; FVC: 94±21 vs. 98±19%predicted; FEV 1 /FVC: 94±8 vs. 96±9%predicted, all p >0.05). The average slope-ratio was greater in ex-smokers compared to never smokers (1.74±0.29 vs. 1.45±0.41, p <0.0001). This difference was driven by a greater slope-ratio between 70-50% vital capacity (all, p <0.05). These preliminary data suggest slope-ratio analyses reveal a dysfunctional pattern of lung emptying in asymptomatic ex-smokers with no formal diagnosis of pulmonary disease compared to never smokers n that is not observed through spirometry alone. NSERC (PDF-577750-2023; AHR), NIH (HL139854; MJJ) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Humans with high affinity hemoglobin (HAH) develop compensatory polycythemia, an elevated hematocrit, which increases blood viscosity and may compromise cardiac output during exercise. In addition, humans with HAH have shown alterations in muscle blood flow during exercise in normoxia and hypoxia. As such, we aimed to investigate the influence of HAH and compensatory polycythemia on the central hemodynamic response during both normoxic and hypoxic exercise. METHODS Seven humans with HAH (4 females, 36 ± 13 years) and 11 healthy controls with normal oxygen binding affinity (4 females, 39 ± 10 years) performed cycling exercise at two intensities, 1) at a power output corresponding to 15% below normoxic gas exchange threshold (GET) for four minutes and 2) at a power output requiring 85% of normoxic maximal aerobic capacity until exhaustion. This protocol was performed during both normoxia and hypoxia (21% O 2 and 15% O 2 , respectively). Hemodynamic measurements were taken after three minutes of cycling at 15% below normoxic GET, three minutes at 85% V̇O 2max , and at exhaustion. Cardiac output (Q̇) was estimated using an open‐circuit acetylene wash‐in technique. Stroke volume (SV) was calculated by dividing Q̇ by heart rate (HR). Baseline characteristics were compared between groups with student’s two‐tailed unpaired t‐tests. Hemodynamics were analyzed using a two‐way repeated measures analysis of variance to examine the effects of group and exercise intensity. RESULTS As expected, hematocrit was ~15% greater in the HAH group than the control group (HAH: 58 ± 7 % vs CTL: 43 ± 3 %, P<0.001). Both groups elicited an increase in Q̇ and HR as exercise intensity increased during both normoxia (P<0.001 for both) and hypoxia (P<0.001 and P=0.002, respectively). There was no significant difference in Q̇ between groups during normoxia (P=0.85) or hypoxia (P=0.69). In addition, neither HR nor SV were different between groups during exercise in normoxia (P=0.13 and P=0.39, respectively) or hypoxia (P=0.89 and P=0.73, respectively). There was no group by intensity interaction for Q̇, HR, or SV during normoxia (all, P>0.42) or hypoxia (all, P>0.63). CONCLUSION Our data suggest that cardiac output is not compromised during normoxic or hypoxic exercise in humans with HAH and compensatory polycythemia. Therefore, compensatory polycythemia may improve exercise capacity in humans with HAH by raising oxygen carrying capacity without limiting cardiac output.

ABSTRACT Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO 3 − ) supplementation in young, healthy men and women, it is unclear if participant and environmental factors modulate the well-described ergogenic effects—particularly relevant factors include biological sex, aerobic fitness, and fraction of inspired oxygen (F i O 2 ) during exercise. To address this limitation, the literature was systematically reviewed for randomized, crossover, placebo-controlled studies reporting exercise performance outcome metrics with NO 3 − supplementation in young, healthy adults. Of the 2033 articles identified, 80 were eligible for inclusion in the meta-analysis. Random-effects meta-analysis demonstrated that exercise performance improved with NO 3 − supplementation compared with placebo ( d = 0.174; 95% confidence interval (CI), 0.120–0.229; P < 0.001). Subgroup analyses conducted on biological sex, aerobic fitness, and F i O 2 demonstrated that the ergogenic effect of NO 3 − supplementation was as follows: 1) not observed in studies with only women ( n = 6; d = 0.116; 95% CI, −0.126 to 0.358; P = 0.347), 2) not observed in well-trained endurance athletes (≥65 mL·kg −1 ·min −1 ; n = 26; d = 0.021; 95% CI, −0.103 to 0.144; P = 0.745), and 3) not modulated by F i O 2 (hypoxia vs normoxia). Together, the meta-analyses demonstrated a clear ergogenic effect of NO 3 − supplementation in recreationally active, young, healthy men across different exercise paradigms and NO 3 − supplementation parameters; however, the effect size of NO 3 − supplementation was objectively small ( d = 0.174). NO 3 − supplementation has more limited utility as an ergogenic aid in participants with excellent aerobic fitness that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g., women) are needed to advance the study of NO 3 − supplementation; however, additional descriptive studies of young, healthy men may have limited utility.

Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO 3 − ) supplementation ( e.g. beetroot juice) in young, healthy men and women, it is unclear if participant and environmental factors modulate the well‐described ergogenic effects—particularly relevant factors include biological sex, aerobic fitness and fraction of inspired oxygen (F i O 2 ) during exercise. To address this limitation, the literature was systematically reviewed for randomized, cross‐over, placebo‐controlled studies reporting exercise performance outcome metrics with NO 3 − supplementation in young, healthy adults. There were 2,033 articles identified, and 80 articles met inclusion criteria for the meta‐analysis. Random‐effects meta‐analysis demonstrated that exercise performance was improved with NO 3 − supplementation compared to placebo ( d =0.174, 95% CI [0.120–0.229], P <0.001). Subgroup analyses conducted on biological sex, aerobic fitness and F i O 2 demonstrated that the ergogenic effect of NO 3 − supplementation was: 1) not observed in studies with only women ( n =6, d=0.116, 95% CI [−0.126–0.358], P =0.347), 2) not observed in participants with moderate aerobic fitness (less than 45 mL·kg −1 ·min −1 ; n =4, d =0.168, 95% CI [−0.134–0.469], P =0.276) or elite aerobic fitness (65 mL·kg −1 ·min −1 or greater; n =26, d =0.021, 95% CI [−0.103–0.144], P =0.745) and 3) was not modulated by F i O 2 (hypoxia: n =17, d =0.214, 95% CI [0.054–0.375], P =0.009 vs. normoxia n =97, d =0.175, 95% CI [0.114–0.237], P <0.001). Together, the meta‐analyses demonstrated a clear ergogenic effect of NO 3 − supplementation in recreationally‐active, young, healthy men across many different exercise paradigms and NO 3 − supplementation parameters; however, the effect size of NO 3 − supplementation was objectively small . Although NO 3 − supplementation may be effective in moderately fit, healthy men, NO 3 − supplementation has limited utility as an ergogenic aid in participants that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects ( e.g. women) are needed to advance the study of NO 3 − supplementation; however, additional descriptive studies of young healthy men may have limited utility. Figure 1 Figure 2