The independent effects of hypovolemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800 m

We aimed to determine the isolated and combined contribution of hypovolemia and hypoxic pulmonary vasoconstriction in limiting left ventricular (LV) function and exercise capacity under chronic hypoxemia at high altitude. In a double‐blinded, randomized and placebo‐controlled design, twelve healthy participants underwent echocardiography at rest and during submaximal exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5–10 days at 3800 m. Plasma volume was normalised to SL values, and hypoxic pulmonary vasoconstriction was reversed by administration of Sildenafil (50 mg) to create four unique experimental conditions that were compared with SL values; high altitude (HA), Plasma Volume Expansion (HA‐PVX), Sildenafil (HA‐SIL) and Plasma Volume Expansion with Sildenafil (HA‐PVX‐SIL). High altitude exposure reduced plasma volume by 11% (P < 0.01) and increased pulmonary artery systolic pressure (19.6 ± 4.3 vs. 26.0 ± 5.4, P < 0.001); these differences were abolished by PVX and SIL respectively. LV end‐diastolic volume (EDV) and stroke volume (SV) were decreased upon ascent to high altitude, but were comparable to sea level in the HA‐PVX. LV EDV and SV were also elevated in the HA‐SIL and HA‐PVX‐SIL trials compared to HA, but to a lesser extent. Neither PVX or SIL had a significant effect on the LV EDV and SV response to exercise, or the maximal oxygen consumption or peak power output. In summary, at 3800 m both hypovolemia and hypoxic pulmonary vasoconstriction contribute to the decrease in LV filling, however, restoring LV filling does not confer an improvement in maximal exercise performance

Use of simplified claustrophobia questionnaire in predicting adherence to positive airway pressure (PAP) therapy in obstructive sleep apnea (OSA) patients

TITLE: Use of simplified claustrophobia questionnaire in predicting adherence to continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) patients. Introduction: Claustrophobia could affect adherence to CPAP in sleep apnea patients. High score in a claustrophobia questionnaire containing 12 restriction and 14 suffocation items was associated to poor CPAP adherence in previous research. The restriction and suffocation items were equivalent on predicting CPAP adherence which allowed to limit the survey to only the suffocation questionnaire. The goal of this study is to find the predictability of CPAP adherence for each question of the suffocation questionnaire. Methods: We performed a prospective chart review of 114 patients with newly diagnosed OSA using home sleep apnea testing (HSAT). On initial consultation, patients were provided with a suffocation claustrophobia questionnaire. Patients’ demographics, home sleep study data and objective adherence data were collected within the first 3 months of usage.Results: Items 2 (OR =1.67, p-value = 0.049), 3 (OR=1.60, p-value = 0.021), and 13 (OR= 1.52, p-value = 0.056) are most promising in association with non-adherence. Results indicate that higher scores on item 2 is associated with higher odds of non-adherence to CPAP. Specifically, each point increase on item 2 was associated with a 67% increase in odds of non-adherence. However, these items alone do not show a large effect in providing accurate classification of adherence. Of these items, item 3 had the lower rate of missing data, suggesting that it may be the most patient-friendly item. Conclusions: Based on these results, the 3 questions with highest predictability for CPAP adherence will be studied in the clinical arena to address feasibility and predictability.https://scholarlycommons.henryford.com/merf2019clinres/1013/thumbnail.jp

UBC-Nepal Expedition: An experimental overview of the 2016 University of British Columbia Scientific Expedition to Nepal Himalaya

The University of British Columbia Nepal Expedition took place over several months in the fall of 2016 and was comprised of an international team of 37 researchers. This paper describes the objectives, study characteristics, organization and management of this expedition, and presents novel blood gas data during acclimatization in both lowlanders and Sherpa. An overview and framework for the forthcoming publications is provided. The expedition conducted 17 major studies with two principal goals—to identify physiological differences in: 1) acclimatization; and 2) responses to sustained high-altitude exposure between lowland natives and people of Tibetan descent. We performed observational cohort studies of human responses to progressive hypobaric hypoxia (during ascent), and to sustained exposure to 5050 m over 3 weeks comparing lowlander adults (n = 30) with Sherpa adults (n = 24). Sherpa were tested both with (n = 12) and without (n = 12) descent to Kathmandu. Data collected from lowlander children (n = 30) in Canada were compared with those collected from Sherpa children (n = 57; 3400–3900m). Studies were conducted in Canada (344m) and the following locations in Nepal: Kathmandu (1400m), Namche Bazaar (3440m), Kunde Hospital (3480m), Pheriche (4371m) and the Ev-K2-CNR Research Pyramid Laboratory (5050m). The core studies focused on the mechanisms of cerebral blood flow regulation, the role of iron in cardiopulmonary regulation, pulmonary pressures, intra-ocular pressures, cardiac function, neuromuscular fatigue and function, blood volume regulation, autonomic control, and micro and macro vascular function. A total of 335 study sessions were conducted over three weeks at 5050m. In addition to an overview of this expedition and arterial blood gas data from Sherpa, suggestions for scientists aiming to perform field-based altitude research are also presented. Together, these findings will contribute to our understanding of human acclimatization and adaptation to the stress of residence at high-altitude

One session of remote ischemic preconditioning does not improve vascular function in acute normobaric and chronic hypobaric hypoxia

Application of repeated short duration bouts of ischemia to the limbs, termed remote ischemic preconditioning (RIPC), is a novel technique that may have protective effects on vascular function during hypoxic exposures. In separate parallel-design studies, at sea-level (SL; n=16), and after 8-12 days at high-altitude (HA; n=12; White Mountain, 3800m), participants underwent either a sham protocol or one session of 4x5 minutes of dual-thigh cuff occlusion with 5-minutes recovery. Brachial artery flow-mediated dilation (FMD; ultrasound), pulmonary artery systolic pressure (PASP; echocardiography), and internal carotid artery flow (ICA; ultrasound) were measured at SL in normoxia and isocapnic hypoxia [end-tidal PO (PETO ) maintained to 50mmHg], and during normal breathing at HA. The hypoxic ventilatory response (HVR) was measured at each location. All measures at SL and HA were obtained at baseline (BL), 1 hour, 24 hours, and 48 hours post-RIPC or sham. At SL, RIPC produced no changes in FMD, PASP, ICA flow, end-tidal gases or HVR in normoxia or hypoxia. At HA, although HVR increased 24 hours post RIPC compared to BL (2.05{plus minus}1.4 vs. 3.21{plus minus}1.2 L•min-1•%SaO2-1, p<0.01), there were no significant differences in FMD, PASP, ICA flow, resting end-tidal gases. Accordingly, a single session of RIPC is insufficient to evoke changes in peripheral, pulmonary, and cerebral vascular function in healthy adults. Although chemosensitivity may increase following RIPC at HA, this did not confer any vascular changes. The utility of a single RIPC session seems unremarkable during acute and chronic hypoxia

Pulmonary vascular reactivity to supplemental oxygen in Sherpa and lowlanders during gradual ascent to high altitude

Abstract Prolonged alveolar hypoxia leads to pulmonary vascular remodelling. We examined the time course at altitude, over which hypoxic pulmonary vasoconstriction goes from being acutely reversible to potentially irreversible. Study subjects were lowlanders (n = 20) and two Sherpa groups. All Sherpa were born and raised at altitude. One group (ascent Sherpa, n = 11) left altitude and after de‐acclimatization in Kathmandu for ∼7 days re‐ascended with the lowlanders over 8–10 days to 5050 m. The second Sherpa group (non‐ascent Sherpa, n = 12) remained continuously at altitude. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured while breathing ambient air and following supplemental oxygen. During ascent PASP and PVR increased in lowlanders and ascent Sherpa; however, with supplemental oxygen, lowlanders had significantly greater decrease in PASP (P = 0.02) and PVR (P = 0.02). After ∼14 days at 5050 m, PASP decreased with supplemental oxygen (mean decrease: 3.9 mmHg, 95% CI 2.1–5.7 mmHg, P < 0.001); however, PVR was unchanged (P = 0.49). In conclusion, PASP and PVR increased with gradual ascent to altitude and decreased via oxygen supplementation in both lowlanders and ascent Sherpa. Following ∼14 days at 5050 m altitude, there was no change in PVR to hypoxia or O2 supplementation in lowlanders or either Sherpa group. These data show that both duration of exposure and residential altitude influence the pulmonary vascular responses to hypoxia

Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation : alterations with hyperoxia

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O₂ fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O₂ fraction, 1.0; n = 12). Dynamic CA was assessed using transferfunction gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after arrival at HA (~5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (-11 ± 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (-12 ± 3 vs. -5 ± 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by ~50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.9 page(s

Influence of iron manipulation on hypoxic pulmonary vasoconstriction and pulmonary reactivity during ascent and acclimatization to 5050 m

To examine the adaptational role of iron bioavailability on the pulmonary vascular responses to acute and chronic hypobaric hypoxia, the hematological and cardiopulmonary profile of lowlanders and Sherpa were determined during: 1) a nine-day ascent to 5050m (20 lowlanders; 12 Sherpa), and 2) following partial acclimatization (11±4 days) to 5050m (18 lowlanders; 20 Sherpa), where both groups received either an i.v. infusion of iron (iron (III)-hydroxide sucrose) or an iron chelator (desferrioxamine). During ascent, there were reductions in iron status in both lowlanders and Sherpa; however, Sherpa appeared to demonstrate a more efficient capacity to mobilize stored iron, compared to lowlanders, when expressed as a hepcidin per unit change in either body iron or the soluble transferrin receptor index, between 3400-5050m (p=0.016 and p=0.029 respectively). The rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders during ascent; however, PASP was comparable in both groups upon arrival to 5050m. Following partial acclimatization, despite Sherpa demonstrating a blunted hypoxic ventilatory response and greater resting hypoxemia, they had similar hypoxic pulmonary vasoconstriction when compared to lowlanders at rest. Iron-infusion attenuated PASP in both groups at rest (p=0.005), while chelation did not exaggerate PASP in either group at rest or during exaggerated hypoxemia (PIO2=67 mmHg). During exercise at 25% peak wattage, PASP was only consistently elevated in Sherpa, which persisted following both iron infusion or chelation. These findings provide new evidence on the complex interplay of iron regulation on pulmonary vascular regulation during acclimatization and adaptation to high altitude