Using modified Fenn diagrams to assess ventilatory acclimatization during ascent to high altitude: Effect of acetazolamide.

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self-administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ measurements were collected on 46 acetazolamide-free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. HIGHLIGHTS: What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide-free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

Hemorrhage at high altitude: impact of sustained hypobaric hypoxia on cerebral blood flow, tissue oxygenation, and tolerance to simulated hemorrhage in humans.

With ascent to high altitude (HA), compensatory increases in cerebral blood flow and oxygen delivery must occur to preserve cerebral metabolism and consciousness. We hypothesized that this compensation in cerebral blood flow and oxygen delivery preserves tolerance to simulated hemorrhage (via lower body negative pressure, LBNP), such that tolerance is similar during sustained exposure to HA vs. low altitude (LA). Healthy humans (4F/4 M) participated in LBNP protocols to presyncope at LA (1130 m) and 5-7 days following ascent to HA (3800 m). Internal carotid artery (ICA) blood flow, cerebral delivery of oxygen (CDO2) through the ICA, and cerebral tissue oxygen saturation (ScO2) were determined. LBNP tolerance was similar between conditions (LA: 1276 ± 304 s vs. HA: 1208 ± 306 s; P = 0.58). Overall, ICA blood flow and CDO2 were elevated at HA vs. LA (P ≤ 0.01) and decreased with LBNP under both conditions (P < 0.0001), but there was no effect of altitude on ScO2 responses (P = 0.59). Thus, sustained exposure to hypobaric hypoxia did not negatively impact tolerance to simulated hemorrhage. These data demonstrate the robustness of compensatory physiological mechanisms that preserve human cerebral blood flow and oxygen delivery during sustained hypoxia, ensuring cerebral tissue metabolism and neuronal function is maintained.

Adolescent experiences of the safe surgical checklist and surgical care processes.

PURPOSE: To explore the perceptions, satisfaction, and needs of adolescent surgical patients with their perioperative pathway, including consent, the Safe Surgical Checklist (SSC), and post-operative care. METHODS: We used qualitative methodology to examine adolescent experiences with surgical consent, SSC, and post-operative care. We purposively recruited ten patients aged 13-17 undergoing emergency and elective surgery and obtained consent from parents and patients. Semi-structured interview scripts were co-developed with an adolescent patient advisor, and interviews were performed, recorded, and transcribed verbatim. Thematic analysis was based on grounded theory and Participants were recruited and interviewed until thematic saturation was achieved. RESULTS: Four themes emerged in thematic analysis: (1) Autonomy and Inclusion-Adolescents desire to participate in the consent process, including signing their own consent when appropriate, (2) Value of Repetition-Adolescents value the repetition of information in the pre-operative check and feel safer when the team reinforces the information, (3) Importance of Caregiver Involvement - Adolescents valued their caregivers being involved in critical conversations and decision making, and (4) Importance of Transparency in Communication-Adolescents desire to be directly given information about their surgery post-operatively and not told to parents alone. CONCLUSION: Adolescents are situated uniquely between childhood and adulthood. Adolescents desired to be directly involved in the decision-making process of their surgery, including participation in the SSC and discussion of post-operative complications.

Duration at high altitude influences the onset of arrhythmogenesis during apnea.

PURPOSE: Autonomic control of the heart is balanced by sympathetic and parasympathetic inputs. Excitation of both sympathetic and parasympathetic systems occurs concurrently during certain perturbations such as hypoxia, which stimulate carotid chemoreflex to drive ventilation. It is well established that the chemoreflex becomes sensitized throughout hypoxic exposure; however, whether progressive sensitization alters cardiac autonomic activity remains unknown. We sought to determine the duration of hypoxic exposure at high altitude necessary to unmask cardiac arrhythmias during instances of voluntary apnea. METHODS: Measurements of steady-state chemoreflex drive (SS-CD), continuous electrocardiogram (ECG) and SpO2 (pulse oximetry) were collected in 22 participants on 1 day at low altitude (1045 m) and over eight consecutive days at high-altitude (3800 m). SS-CD was quantified as ventilation (L/min) over stimulus index (PETCO2/SpO2). RESULTS: Bradycardia during apnea was greater at high altitude compared to low altitude for all days (p < 0.001). Cardiac arrhythmias occurred during apnea each day but became most prevalent (> 50%) following Day 5 at high altitude. Changes in saturation during apnea and apnea duration did not affect the magnitude of bradycardia during apnea (ANCOVA; saturation, p = 0.15 and apnea duration, p = 0.988). Interestingly, the magnitude of bradycardia was correlated with the incidence of arrhythmia per day (r = 0.8; p = 0.004). CONCLUSION: Our findings suggest that persistent hypoxia gradually increases vagal tone with time, indicated by augmented bradycardia during apnea and progressively increased the incidence of arrhythmia at high altitude.

Bringing Enhanced Recovery After Surgery to the NICU: An Implementation Trial.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) guidelines are bundled evidence-informed recommendations implemented to improve quality and safety of perioperative care. This study aims to determine feasibility of NICU implementation of an ERAS Guideline for Intestinal Resection, describing clinical outcomes and adherence to recommendations following light-touch implementation. METHODS: Infants <28 days undergoing laparotomy for intestinal resection in a closed-NICU were prospectively enrolled. Exclusion criteria included prematurity (<32wks), instability, or major comorbidity. Clinical data reflecting 13 ERAS recommendations were collected through chart review. Descriptive statistics are presented as median [interquartile range]. Thirty-day post-discharge outcomes include NICU and hospital length of stay (LOS), ventilator days, surgical site infection (SSI), re-intubation, readmission, reoperation, and mortality. Adherence was calculated as the percentage of patients eligible for each recommendation whose care was adherent. RESULTS: Ten infant-parent dyads were enrolled (five females; GA 37 weeks [35, 38.8]; birthweight 2.97 kg [2.02, 3.69]). Surgical diagnoses included intestinal atresia/web (n = 6), anorectal malformation (n = 3), and segmental volvulus (n = 1). NICU LOS was 16 days [11, 21], hospital LOS 20 days [18, 30], and 2.5 ventilator days/patient [2, 3]. There was reduced opioid use, no SSIs, one re-intubation, three readmissions, three reoperations, and no mortalities. Adherence to ERAS recommendations ranged 0-100 % with a pooled adherence rate of 73 %. CONCLUSION: It is feasible to introduce ERAS to the NICU with acceptable overall adherence. Assessing adherence was challenging for some measures. There were promising early clinical findings including a reduction in opioid use. This implementation trial will inform development of an ERAS protocol for surgical NICUs. LEVEL OF EVIDENCE: IV (Cohort Study).

Sex Differences in Orthostatic Tolerance Are Mainly Explained by Blood Volume and Oxygen Carrying Capacity.

OBJECTIVES: The reduced orthostatic tolerance (OT) that is characteristic of the female sex may be explained by multiple phenotypic differences between sexes. This study aimed to elucidate the mechanistic role of blood volume (BV) and oxygen carrying capacity on sex differences in OT. DESIGN: Experimental intervention. SETTING: University of Calgary, Main Campus, Calgary, AB, Canada. SUBJECTS: Healthy women and men (n = 90) throughout the adult lifespan (20-89 yr) matched by age and physical activity. INTERVENTIONS: Incremental lower body negative pressure (LBNP) in all individuals. Blood withdrawal and oxygen carrying capacity reduction in men to match with women's levels. MEASUREMENTS AND MAIN RESULTS: Transthoracic echocardiography and central blood pressures were assessed throughout incremental LBNP for 1 hour or until presyncope. Blood uniformization resulted in a precise sex match of BV and oxygen carrying capacity (p ≥ 0.598). A third of women (14/45) and two thirds of men (31/45) prior to blood uniformization completed the orthostatic test without presyncopal symptoms (p-for-sex < 0.001). After blood uniformization, seven out of 45 men completed the test (p-for-sex = 0.081). Left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) were progressively reduced with LBNP in both sexes, with women showing markedly lower volumes than men (p < 0.001). Blood uniformization did not eliminate sex differences in LVEDV and SV. CONCLUSIONS: Sex differences in OT are not present when BV and oxygen carrying capacity are experimentally matched between sexes throughout the adult lifespan.

Differences in Cardiac Output and Aerobic Capacity Between Sexes Are Explained by Blood Volume and Oxygen Carrying Capacity.

Whether average sex differences in cardiorespiratory fitness can be mainly explained by blood inequalities in the healthy circulatory system remains unresolved. This study evaluated the contribution of blood volume (BV) and oxygen (O2) carrying capacity to the sex gap in cardiac and aerobic capacities in healthy young individuals. Healthy young women and men (n = 28, age range = 20-43 years) were matched by age and physical activity. Echocardiography, blood pressures, and O2 uptake were measured during incremental exercise. Left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q), peak O2 uptake (VO2peak ), and BV were assessed with precise methods. The test was repeated in men after blood withdrawal and reduction of O2 carrying capacity, reaching women's levels. Before blood normalization, exercise cardiac volumes and output (LVEDV, SV, Q) adjusted by body size and VO2peak (42 ± 9 vs. 50 ± 11 ml⋅min-1⋅kg-1, P < 0.05) were lower in women relative to men. Blood normalization abolished sex differences in cardiac volumes and output during exercise (P ≥ 0.100). Likewise, VO2peak was similar between women and men after blood normalization (42 ± 9 vs. 40 ± 8 ml⋅min-1⋅kg-1, P = 0.416). In conclusion, sex differences in cardiac output and aerobic capacity are not present in experimental conditions matching BV and O2 carrying capacity between healthy young women and men.

Sex differences in cardiorespiratory fitness are explained by blood volume and oxygen carrying capacity.

AIMS: Intrinsic sex differences in fundamental blood attributes have long been hypothesized to contribute to the gap in cardiorespiratory fitness between men and women. This study experimentally assessed the role of blood volume and oxygen (O2) carrying capacity on sex differences in cardiac function and aerobic power. METHODS AND RESULTS: Healthy women and men (n = 60) throughout the mature adult lifespan (42-88 yr) were matched by age and physical activity levels. Transthoracic echocardiography, central blood pressure, and O2 uptake were assessed throughout incremental exercise (cycle ergometry). Main outcomes such as left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q), and peak O2 uptake (VO2peak), as well as blood volume (BV) were determined with established methods. Measurements were repeated in men following blood withdrawal and O2 carrying capacity reduction matching women's levels. Prior to blood normalization, BV and O2 carrying capacity were markedly reduced in women compared with men (P < 0.001). Blood normalization resulted in a precise match of BV (82.36 ± 9.83 vs. 82.34 ± 7.70 ml·kg-1, P = 0.993) and O2 carrying capacity (12.0 ± 0.6 vs. 12.0 ± 0.7 g·dl-1, P = 0.562) between women and men. Body size-adjusted cardiac filling and output (LVEDV, SV, Q) during exercise as well as VO2peak (30.8 ± 7.5 vs. 35.6 ± 8.7 ml·min-1·kg-1, P < 0.001) were lower in women compared with men prior to blood normalization. VO2peak did not differ between women and men after blood normalization (30.8 ± 7.5 vs. 29.7 ± 7.4 ml·min-1·kg-1, P = 0.551). CONCLUSIONS: Sex differences in cardiorespiratory fitness are abolished when blood attributes determining O2 delivery are experimentally matched between adult women and men.

Effects of blood withdrawal on cardiac, hemodynamic, and pulmonary responses to a moderate acute workload in healthy middle-aged and older females.

OBJECTIVES: To investigate the effects of blood withdrawal on cardiac, hemodynamic, and pulmonary responses to submaximal exercise in females. DESIGN AND METHODS: 30 healthy females (63.8 ±â€¯8.3 years) were recruited for this experimental study. Transthoracic echocardiography, non-invasive blood pressure monitoring, and oxygen uptake were assessed during a fixed submaximal workload (100 W) prior to (day 1) and immediately after (day 2) a 10% reduction of blood volume. Main measurements included left ventricular end-diastolic volume, stroke volume, cardiac output, mean arterial pressure, systolic blood pressure, diastolic blood pressure, and oxygen uptake. Blood volume was determined via carbon monoxide rebreathing. RESULTS: Participant's blood volume ranged from 3.8 to 6.6 L. Following 10% reduction in blood volume (0.5 ±â€¯0.1 L), left ventricular end-diastolic volume (p ≤ 0.030) and stroke volume (p < 0.019) were reduced during submaximal exercise while cardiac output was unchanged (p = 0.139) due to increased heart rate (p < 0.026). Hemodynamic variables including mean arterial pressure (p < 0.015), systolic blood pressure (p < 0.005), and diastolic blood pressure (p < 0.038) were reduced while oxygen uptake was unaltered (p = 0.250). CONCLUSIONS: Blood withdrawal results in marked reductions in cardiac filling with compensatory chronotropic responses that preserve cardiac output at a moderate submaximal workload in healthy females. Thus, blood volume determines the relative exercise intensity, as typically determined by heart rate, of submaximal efforts in this population.

Lean body mass and the cardiovascular system constitute a female-specific relationship.

Recent evidence points toward a link between lean body mass (LBM) and cardiovascular capacity in women. This study aimed at determining the sex-specific relationship of LBM with central and peripheral circulatory variables in healthy women and men (n=70) matched by age (60±12 years versus 58±15 years), physical activity, and cardiovascular risk factors. Regional (legs, arms, and trunk) and whole-body (total) body composition were assessed via dual-energy x-ray absorptiometry. Cardiac structure, function, and central/peripheral hemodynamics were measured via transthoracic echocardiography and the volume-clamp method at rest and peak incremental exercise. Regression analyses determined sex-specific relationships between LBM and cardiovascular variables. Regional and total LBM were lower in women than men (P<0.001), with little overlap between sexes. Leg and arm LBM positively associated with left ventricular (LV) internal resting dimensions in women (r≥0.53, P≤0.002) but not men (P≥0.156). Leg, arm, and total LBM only associated with LV relaxation in women (r≥0.43, P≤0.013). All LBM variables strongly associated with LV volumes at peak exercise in women (r≥0.54, P≤0.001) but not men and negatively associated with total peripheral resistance at peak exercise in women (r≥0.43, P≤0.023). Adjustment by adiposity-related or cardiovascular risk factors did not alter results. In conclusion, leg and arm LBM independently associate with internal cardiac dimensions, ventricular relaxation, and systemic vascular resistance in a sex-specific manner, with these relationships exclusively present in women.

Sex dimorphism in cardiac and aerobic capacities: The influence of body composition.

OBJECTIVE: The contribution of body composition to sex differences in strong prognostic cardiorespiratory variables remains unresolved. This study aimed to elucidate whether body composition determines sex differences in cardiac and oxygen (O2 ) uptake responses to incremental exercise. METHODS: Healthy, moderately active women and men (n = 60, age = 60.7 [12.3] years) matched by age and cardiorespiratory fitness were included. Body composition was determined via dual-energy x-ray absorptiometry. Transthoracic echocardiography and O2 uptake were assessed at rest and throughout incremental exercise with established methods. Major cardiac and pulmonary outcomes were normalized by body surface area (BSA), total lean body mass (LBM), or leg LBM. RESULTS: Women presented with smaller anthropometrical indices (height, weight, BSA) and LBM compared with men (p < 0.001). Peak exercise cardiac dimensions and output (i.e., peak cardiac outout [Qpeak ]), commonly normalized by BSA, were reduced in women relative to men (p ≤ 0.019). Cardiac sex differences were abolished after normalization by total or leg LBM (p ≥ 0.115). Strong linear relationships of total and leg LBM with Qpeak and peak oxygen uptake were detected exclusively in women (r ≥ 0.53, p ≤ 0.003), independent of body fat percentage. CONCLUSIONS: Total and leg LBM stand out as strong independent determinants of cardiac and aerobic capacities in women, regardless of body fat percentage, relationships that are not present in age- and fitness-matched men.

Blood withdrawal acutely impairs cardiac filling, output and aerobic capacity in proportion to induced hypovolemia in middle-aged and older women.

Blood donation entails acute reductions of cardiorespiratory fitness in healthy men. Whether these effects can be extrapolated to blood donor populations comprising women remains uncertain. The purpose of this study was to comprehensively assess the acute impact of blood withdrawal on cardiac function, central hemodynamics and aerobic capacity in women throughout the mature adult lifespan. Transthoracic echocardiography and O2 uptake were assessed at rest and throughout incremental exercise (cycle ergometry) in healthy women (n = 30, age: 47-77 yr). Left ventricular end-diastolic volume (LVEDV), stroke volume (SV), cardiac output (Q̇) and peak O2 uptake (V̇O2peak), and blood volume (BV) were determined with established methods. Measurements were repeated following a 10% reduction of BV within a week period. Individuals were non-smokers, non-obese and moderately fit (V̇O2peak = 31.4 ± 7.3 mL·min-1·kg-1). Hematocrit and BV ranged from 38.0 to 44.8% and from 3.8 to 6.6 L, respectively. The standard 10% reduction in BV resulted in 0.5 ± 0.1 L withdrawal of blood, which did not alter hematocrit (P = 0.953). Blood withdrawal substantially reduced cardiac LVEDV and SV at rest as well as during incremental exercise (≥10% decrements, P ≤ 0.009). Peak Q̇ was proportionally decreased after blood withdrawal (P < 0.001). Blood withdrawal induced a 10% decrement in V̇O2peak (P < 0.001). In conclusion, blood withdrawal impairs cardiac filling, Q̇ and aerobic capacity in proportion to the magnitude of hypovolemia in healthy mature women. Novelty: The filling of the heart and therefore cardiac output are impaired by blood withdrawal in women. Oxygen delivery and aerobic capacity are reduced in proportion to blood withdrawal.

Intravascular albumin loss is strongly associated with plasma volume withdrawal in dialysis patients.

INTRODUCTION: Low circulating albumin closely predicts mortality in end-stage renal disease (ESRD) patients. The cause(s) of hypoalbuminemia (hALB) in ESRD patients remains to be elucidated. The aim of the present study was to determine the role of plasma volume (PV) withdrawal in the reduction of total circulating albumin and essential blood solutes induced by hemodialysis (HD). METHODS: PV determined with high-precision automated carbon monoxide-rebreathing, total circulating as well as concentration of plasma albumin and electrolytes were assessed prior to and after 4-hour HD in 10 ESRD patients. FINDINGS: Baseline PV ranged from 3.5 to 6.2 l. After HD, PV was decreased by 689 ± 566 mL (-16%) (P = 0.004). Total circulating albumin was largely reduced after HD (170.8 ± 35.1 vs. 146.1 ± 48.9 g, P = 0.008), while albumin concentration was unaltered. According to a strong linear relationship (r = 0.91, P < 0.001), one-third of total circulating albumin is lost from the intravascular compartment for every liter of PV removed. Similar results were found regarding Na+ and Ca2+ electrolytes. DISCUSSION: Total circulating albumin, but not albumin concentration, is substantially reduced by HD in proportion to the amount of PV removed from the circulation. This study highlights the potential contributing role of PV withdrawal to hALB in ESRD patients.

Peaks and valleys: oscillatory cerebral blood flow at high altitude protects cerebral tissue oxygenation.

Introduction.Oscillatory patterns in arterial pressure and blood flow (at ∼0.1 Hz) may protect tissue oxygenation during conditions of reduced cerebral perfusion and/or hypoxia. We hypothesized that inducing oscillations in arterial pressure and cerebral blood flow at 0.1 Hz would protect cerebral blood flow and cerebral tissue oxygen saturation during exposure to a combination of simulated hemorrhage and sustained hypobaric hypoxia.Methods.Eight healthy human subjects (4 male, 4 female; 30.1 ± 7.6 year) participated in two experiments at high altitude (White Mountain, California, USA; altitude, 3800 m) following rapid ascent and 5-7 d of acclimatization: (1) static lower body negative pressure (LBNP, control condition) was used to induce central hypovolemia by reducing chamber pressure to -60 mmHg for 10 min(0 Hz), and; (2) oscillatory LBNP where chamber pressure was reduced to -60 mmHg, then oscillated every 5 s between -30 mmHg and -90 mmHg for 10 min(0.1 Hz). Measurements included arterial pressure, internal carotid artery (ICA) blood flow, middle cerebral artery velocity (MCAv), and cerebral tissue oxygen saturation (ScO2).Results.Forced 0.1 Hz oscillations in mean arterial pressure and mean MCAv were accompanied by a protection of ScO2(0.1 Hz: -0.67% ± 1.0%; 0 Hz: -4.07% ± 2.0%;P = 0.01). However, the 0.1 Hz profile did not protect against reductions in ICA blood flow (0.1 Hz: -32.5% ± 4.5%; 0 Hz: -19.9% ± 8.9%;P = 0.24) or mean MCAv (0.1 Hz: -18.5% ± 3.4%; 0 Hz: -15.3% ± 5.4%;P = 0.16).Conclusions.Induced oscillatory arterial pressure and cerebral blood flow led to protection of ScO2during combined simulated hemorrhage and sustained hypoxia. This protection was not associated with the preservation of cerebral blood flow suggesting preservation of ScO2may be due to mechanisms occurring within the microvasculature.

Time course and magnitude of ventilatory and renal acid-base acclimatization following rapid ascent to and residence at 3,800 m over nine days.

Rapid ascent to high altitude imposes an acute hypoxic and acid-base challenge, with ventilatory and renal acclimatization countering these perturbations. Specifically, ventilatory acclimatization improves oxygenation, but with concomitant hypocapnia and respiratory alkalosis. A compensatory, renally mediated relative metabolic acidosis follows via bicarbonate elimination, normalizing arterial pH(a). The time course and magnitude of these integrated acclimatization processes are highly variable between individuals. Using a previously developed metric of renal reactivity (RR), indexing the change in arterial bicarbonate concentration (Δ[HCO3-]a; renal response) over the change in arterial pressure of CO2 (Δ[Formula: see text]; renal stimulus), we aimed to characterize changes in RR magnitude following rapid ascent and residence at altitude. Resident lowlanders (n = 16) were tested at 1,045 m (day [D]0) prior to ascent, on D2 within 24 h of arrival, and D9 during residence at 3,800 m. Radial artery blood draws were obtained to measure acid-base variables: [Formula: see text], [HCO3-]a, and pHa. Compared with D0, [Formula: see text] and [HCO3-]a were lower on D2 (P < 0.01) and D9 (P < 0.01), whereas significant changes in pHa (P = 0.072) and RR (P = 0.056) were not detected. As pHa appeared fully compensated on D2 and RR did not increase significantly from D2 to D9, these data demonstrate renal acid-base compensation within 24 h at moderate steady-state altitude. Moreover, RR was strongly and inversely correlated with ΔpHa on D2 and D9 (r≤ -0.95; P < 0.0001), suggesting that a high-gain renal response better protects pHa. Our study highlights the differential time course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization following rapid ascent and residence at high altitude.NEW & NOTEWORTHY We assessed the time course, magnitude, and variability of integrated ventilatory and renal acid-base acclimatization with rapid ascent and residence at 3,800 m. Despite reductions in [Formula: see text] upon ascent, pHa was normalized within 24 h of arrival at 3,800 m through renal compensation (i.e., bicarbonate elimination). Renal reactivity (RR) was unchanged between days 2 and 9, suggesting a lack of plasticity at moderate steady-state altitude. RR was strongly correlated with ΔpHa, suggesting that a high-gain renal response better protects pHa.