Thea experiments Flashcards
What was observed in the Pike’s Peak expedition regarding haematocrit levels?
Graded haematocrit increase above 55% with altitude.
What did blood samples from 132 miners indicate about haematocrit levels?
Higher haematocrit at higher altitude.
What was the overall conclusion regarding haematocrit levels and altitude?
Difficulty to extrapolate and all just causation.
What was found about erythrocytosis in Tibetans at high altitude?
Same distribution of Hb for Tibetans at 4000m altitude and US individuals at sea level.
How do Aymara individuals’ Hb levels compare to Tibetans at 4000m?
Aymara have higher Hb levels than Tibetans at 4000m.
What genetic association was found in Tibetan highlanders?
Natural selection on EPAS1 (HIF2A) associated with low haemoglobin concentration.
What was the significance of the SNPs found in Tibetans?
8 SNPs genome-wide significance (p < 2.81x 10-7), associated with EPAS1.
What was the association of EPAS1 genotype with haemoglobin levels in Tibetans?
Homozygotes (major allele) have a Hb ~1 g/dL lower than heterozygotes.
What was the finding regarding EPAS1 expression in CMS patients?
Higher EPAS1 expression in bone marrow erythroblasts of CMS patients.
What correlation was found with EPAS1 expression in CMS patients?
Positively correlated with erythrocyte number and negatively correlated with SaO2.
What was the limitation of the study on EPAS1 expression?
K562 cells derived from a cancerous line may be unrepresentative of normal lymphoblasts.
What was the conclusion regarding pulmonary artery pressure and vascular resistance at altitude?
Sustained increase in PAP and PVR with altitude.
What were the results of the hypobaric chamber study on male athletes?
Increase in pulmonary artery pressure and vascular resistance with altitude.
What was the conclusion regarding prolonged hypoxia and its effects?
Increased PAP and PVR can lead to RV hypertrophy, cor pulmonale, and precipitate HAPE.
What was the finding regarding HPV in Tibetans?
Absence of HPV in Tibetans at 3600m.
What was the effect of iron availability on pulmonary hypertension?
Iron supplementation can alleviate hypoxic pulmonary hypertension.
What was the conclusion regarding acclimatisation and acid-base status?
Evidence against acclimatisation triggered by acid-base status.
What was the significance of HIF mediation in ventilatory acclimatisation?
Inactivation of HIF-2alpha impaired ventilatory acclimatisation to chronic hypoxia.
What is the role of HIF in ventilatory acclimatisation?
HIF mediation is essential in modulating ventilatory sensitivity to hypoxia through acting at the carotid bodies.
What happens when PHD2 is inactivated?
Inactivation of PHD2 using tamoxifen results in enhanced hypoxic ventilatory responses, which can be compensated for by inactivating HIF-2alpha, but not HIF-1alpha.
How does HIF-2alpha inactivation affect acclimatisation to chronic hypoxia?
Inactivation of HIF-2alpha impairs ventilatory acclimatisation to chronic hypoxia and carotid body proliferation.
What is AMS and its cause?
AMS is due to hypoxia, not hypobaria.
What did Paul Bert’s 1978 study reveal about AMS?
A pressure chamber and a bird lost consciousness at the same PO2 regardless of pressure, indicating AMS is related to hypoxia.
What limitation was noted in AMS studies?
There was no control of PCO2, and loss of consciousness is not directly a symptom of AMS.
What did Karinen’s 2010 study link to AMS susceptibility?
The study linked hypoxemia with AMS susceptibility and measured resting and exercise Spo at various altitudes.
What was the outcome of the resting oxygen saturation study at 2600m?
30% of participants met Lake Louise criteria for AMS later on, but the difference in oxygen saturation was less than 1%, which was not clinically significant.
What distinguishes HACE from AMS?
Microbleeds are a feature of HACE but not AMS.
What did Kellenberg’s 2008 study find regarding HACE?
MRI imaging showed evidence of hemosiderin deposits in patients recovering from HACE but not in AMS controls.
What was the key finding of Severinghaus’s 1966 study?
There was a 24% increase in cerebral blood flow 6-8 hours after rapid ascent to 3810m.
What did Hacket’s 1998 study reveal about HACE?
Vasogenic oedema is most prominent along white matter tracts in the brain in HACE patients.
What did Wang’s 2018 study indicate about cytotoxic oedema in HACE?
Upregulation of the AQP4 channel may contribute to early cytotoxic oedema in HACE.
What did Gruenig’s 2000 study suggest about HAPE susceptibility?
Exercise testing could predict HAPE susceptibility based on pulmonary arterial systemic pressure responses.
What did Maggiorni’s 2001 study conclude about HAPE?
Early HAPE is caused by an increase in pulmonary capillary pressure, not an increase in permeability.
What is the conclusion of Swenson’s 2002 study regarding HAPE?
Inflammation is a tertiary consequence of hydrostatic oedema in HAPE, not a causative factor.
What did Groves’s 1987 study find about pulmonary hypertension?
Pulmonary vascular resistance rises with altitude, steepening the relationship between cardiac output and pulmonary pressure.
What characterizes HAPE?
HAPE is characterized by an increase in pulmonary arterial pressure that causes damage to the alveolar wall, leading to fluid leakage without initial inflammation. Observed inflammation is a tertiary consequence of hydrostatic edema and altered permeability.
What happens to pulmonary vascular resistance with altitude?
Pulmonary vascular resistance rises with altitude, and the relationship between cardiac output and pulmonary pressure steepens, indicating a progressively less distensible pulmonary circulation.
What was observed in the study of supraventricular arrhythmias in cold shock response?
In a study of breath-hold submersions in cold water, ectopic arrhythmias occurred in 11 of the 12 subjects tested. The incidence of these arrhythmias was noted around the time the diving response was initiated, leading to pronounced bradycardia.
What limitation was noted in the study of supraventricular arrhythmias?
The study had a limitation of no in vivo animal studies.
What was the significant finding in the study of pulmonary arterial pressure in IPO-predisposed individuals?
The first direct measurement of pulmonary arterial pressure showed significantly increased pressure in IPE-susceptible patients during moderate exercise in water, which was abolished when pre-treated with sildenafil.
What does the model for nitrogen narcosis suggest?
Computer simulations indicated that nitrogen solubilized within an aqueous solution takes only 100ns to partition in the lipid bilayer, which could explain nitrogen narcosis.
What limitation was noted in the nitrogen narcosis model study?
The limitation was that only one type of phospholipid (DPPC) was used in the lipid bilayer, which is not representative of human synapses.
What did the study on acute oxygen toxicity effect on lungs find?
The study found that combat swimmers exposed to hyperbaric challenges had increased DNA breaks and superoxide radical generation compared to non-diving endurance-trained controls.
What limitation was noted in the acute oxygen toxicity effect on lungs study?
The limitation was unclear regarding how many genetic aberrations were maintained, as breaks resolved within an hour, requiring single-cell sequencing for variability quantification.
What were the findings regarding acute oxygen toxicity effect on CNS?
Rats exposed to 5atm 100% O2 until seizures showed increased nitrotyrosine and carbonyl content, implicating NO as an intermediary in oxidative stress.
What limitation was noted in the acute oxygen toxicity effect on CNS study?
The limitation was that the used nNOS inhibitor seemed unselective, potentially affecting eNOS and preventing vasodilation.
What did the barotrauma study on dogs reveal?
The study indicated that transpulmonary pressures of more than 60-70 mmHg could cause alveolar ruptures, with necropsy showing arterial gas emboli and emphysema.
What limitation was noted in the barotrauma study?
The limitation was ethical concerns.
What were the findings on venous gas embolism and the endothelium?
The study found that more rapid ascent during simulated air dives correlated with increased bubble formation and endothelial damage, suggesting decompression bubbles are significant in assessing decompression stress.
What limitation was noted in the venous gas embolism study?
The limitation was that the findings were correlational; ex vivo studies could introduce bubbles with wire myography.
What did the study on exercise and diving find?
The study found that a single sub-maximal period of exercise before immersion reduced bubble grades in divers.
What limitation was noted in the exercise and diving study?
The limitation was that 45 minutes of exercise might not be feasible before many recreational dives, particularly at sea.
What did the Lorraine Smith effect of O2 study conclude?
The study concluded that exposure to different partial pressures of hyperbaric oxygen caused inflammation and lung damage, with significant endothelial cell damage observed.
What limitation was noted in the Lorraine Smith effect of O2 study?
The limitation was that even shorter exposure times were longer than most dives.
