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 (∆[HCO3-]a; renal response) over the change in arterial pressure of CO2 (∆PaCO2; 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-hours of arrival, and D9 during residence at 3,800 m. Radial artery blood draws were obtained to measure acid-base variables: PaCO2, [HCO3-]a and pHa. Compared to D0, PaCO2 and [HCO3-]a were lower on D2 (P<0.01) and D9 (P<0.01), whereas significant changes in pHa (P>0.058) 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-hours at moderate steady-state altitude. Moreover, RR was strongly and inversely correlated with ∆pHa 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.

Voluntary apnoea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in haemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation (S pO 2), which may cause tonic splenic contraction, which may contribute to haematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, S pO 2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0) to 3440 m (day 3), 4240 m (day 7) and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnoea-induced responses in HR, S pO 2 and splenic volume were measured before and after two separate voluntary maximal apnoeas (A1

Maintenance of arterial blood gases is achieved through sophisticated regulation of ventilation, mediated by central and peripheral chemoreflexes. Respiratory chemoreflexes are important during exposure to high altitude owing to the competing influence of hypoxia and hypoxic hyperventilation-mediated hypocapnia on steadystate ventilatory drive. Inter-individual variability exists in ventilatory acclimatization to high altitude, potentially affecting the development of acute mountain sickness (AMS). We aimed to quantify ventilatory acclimatization to high altitude by comparing differential ascent and descent values (i.e. hysteresis) in steady-state cardiorespiratory variables. We hypothesized that: (i) the hysteresis area formed by cardiorespiratory variables during ascent and descent would quantify the magnitude of ventilatory acclimatization; and (ii) larger hysteresis areas would be associated with lower AMS symptom scores during ascent. In 25 healthy, acetazolamide-free trekkers ascending to and descending from 5160 m, cardiorespiratory hysteresis was measured in the partial pressure of end-tidal CO 2 , peripheral oxygen saturation, minute ventilation, chemoreceptor stimulus index (end-tidal CO 2 /peripheral oxygen saturation) and the calculated steady-state chemoreflex drive (SS-CD; minute ventilation/chemoreceptor stimulus index) using portable devices (capnograph, peripheral pulse oximeter and respirometer, respectively). Symptoms of AMS were assessed daily using the Lake Louise questionnaire. We found that: (i) ascent-descent hysteresis was present in all cardiorespiratory variables; (ii) SS-CD is a valid metric for tracking ventilatory acclimatization to high altitude; and (iii) the highest AMS scores during ascent exhibited a significant, moderate and inverse correlation with the magnitude of SS-CD hysteresis (r s = −0.408, P = 0.043). We propose that ascent-descent hysteresis is a

No abstract

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 SpO 2 (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 (P ET CO 2 /SpO 2 ). 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.