High-altitude hypoxia and echocardiographic indices of pulmonary hypertension in male and female chickens at adulthood.

BACKGROUND: By combining the chick embryo model with incubation at high altitude (HA), the effects of chronic hypoxia on fetal growth, fetal cardiac and aortic wall remodeling and systemic arterial blood pressure at adulthood were reported. Using non-invasive functional echocardiography, here we investigated the in vivo effects of HA hypoxia on the pulmonary circulation at adulthood in male and female chickens. METHODS AND RESULTS: Chick embryos were incubated, hatched and raised at sea level (SL) or at HA. At 6 months of age, functional echocardiography was performed and the body and heart weights were taken. Heart weight was heavier in males but not in female HA chickens compared to their same sex SL counterparts. Similarly, male but not female HA chickens had greater in vivo right ventricular wall thickness compared to their same sex SL counterparts. The tricuspid pressure gradient was greatly enhanced in HA male and HA female chickens. However, the increment in the tricuspid pressure gradient was greater in HA males than in HA females. The pulmonary artery diameter was also enhanced in HA males than in SL males. In contrast, HA did not affect this variable in female chickens. CONCLUSIONS: The data show that chronic hypoxia during development at HA is associated with echocardiocraphic indices of pulmonary hypertension at adulthood in a highly sex-dependent manner.

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Acute hypoxia-reoxygenation and vascular oxygen sensing in the chicken embryo.

Fetal/perinatal hypoxia is one of the most common causes of perinatal morbidity and mortality and is frequently accompannied by vascular dysfunction. However, the mechanisms involved have not been fully delineated. We hypothesized that exposure to acute hypoxia-reoxygenation induces alterations in vascular O2 sensing/signaling as well as in endothelial function in the chicken embryo pulmonary artery (PA), mesenteric artery (MA), femoral artery (FA), and ductus arteriosus (DA). Noninternally pipped 19-day embryos were exposed to 10% O2 for 30 min followed by reoxygenation with 21% O2 or 80% O2 Another group was constantly maintained at 21% O2 or at 21% O2 for 30 min and then exposed to 80% O2 Following treatment, responses of isolated blood vessels to hypoxia as well as endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside and forskolin) relaxation were investigated in a wire myograph. Hypoxia increased venous blood lactate from 2.03 ± 0.18 to 15.98 ± 0.73 mmol/L (P < 0.001) and reduced hatchability to 0%. However, ex vivo hypoxic contraction of PA and MA, hypoxic relaxation of FA, and normoxic contraction of DA were not significantly different in any of the experimental groups. Relaxations induced by acetylcholine, sodium nitroprusside, and forskolin in PA, MA, FA, and DA rings were also similar in the four groups. In conclusion, exposure to acute hypoxia-reoxygenation did not affect vascular oxygen sensing or reactivity in the chicken embryo. This suggests that direct effects of acute hypoxia-reoxygenation on vascular function does not play a role in the pathophysiology of hypoxic cardiovascular injury in the perinatal period.

Students with autism spectrum disorder in college: Results from a preliminary mixed methods needs analysis.

BACKGROUND: There is a growing call for empirically based programming to support the success of students with autism spectrum disorder (ASD) as they transition to college. AIMS: The purpose of this study was to identify the needs and challenges faced by adolescents and young adults with ASD in postsecondary education. METHODS: A mixed methods approach was taken to explore the needs of college-bound and college-enrolled students with ASD. Primary stakeholders (i.e., parents, educators/support staff from secondary and postsecondary institutions, and students) participated in an online survey (n=67) and focus groups (n=15). RESULTS: Across the stakeholder groups, commonly identified areas of difficulty included limited interpersonal competence, managing competing demands in postsecondary education, and poor emotional regulation. There was a high degree of agreement across stakeholders in the identified needs and challenges. IMPLICATIONS: Findings from this preliminary needs analysis will inform the development of programming to support students with ASD.

Adrenocortical suppression in highland chick embryos is restored during incubation at sea level.

By combining the chick embryo model with incubation at high altitude, this study tested the hypothesis that development at high altitude is related to a fetal origin of adrenocortical but not adrenomedullary suppression and that hypoxia is the mechanism underlying the relationship. Fertilized eggs from sea-level or high altitude hens were incubated at sea level or high altitude. Fertilized eggs from sea-level hens were also incubated at altitude with oxygen supplementation. At day 20 of incubation, embryonic blood was taken for measurement of plasma corticotropin, corticosterone, and Po(2). Following biometry, the adrenal glands were collected and frozen for measurement of catecholamine content. Development of chick embryos at high altitude led to pronounced adrenocortical blunting, but an increase in adrenal catecholamine content. These effects were similar whether the fertilized eggs were laid by sea-level or high altitude hens. The effects of high altitude on the stress axes were completely prevented by incubation at high altitude with oxygen supplementation. When chick embryos from high altitude hens were incubated at sea level, plasma hormones and adrenal catecholamine content were partially restored toward levels measured in sea-level chick embryos. There was a significant correlation between adrenocortical blunting and elevated adrenal catecholamine content with both asymmetric growth restriction and fetal hypoxia. The data support the hypothesis tested and provide evidence to isolate the direct contribution of developmental hypoxia to alterations in the stress system.

The role of oxygen in prenatal growth: studies in the chick embryo.

The compelling evidence linking small size at birth with later cardiovascular disease has renewed and amplified scientific and clinical interests into the determinants of fetal growth. It is accepted that genes and nutrition control fetal growth; however, prior to this study, it had been impossible to isolate the effect of increases and decreases in fetal oxygenation on the regulation of prenatal growth. We investigated the role of oxygen in the control of fetal growth in the chicken because in contrast to mammals, the effects on the fetus of changes in oxygenation could be isolated, by assessing them directly without alteration to the maternal or placental physiology or maternal nutrition during development. The data show that incubation at high altitude of fertilized eggs laid by sea level hens markedly restricted fetal growth. Incubation at high altitude of fertilized eggs laid by high altitude hens also restricted fetal growth, but to a lesser extent compared to eggs laid by sea level hens. By contrast, incubation at sea level of fertilized eggs laid by high altitude hens not only restored, but enhanced, fetal growth relative to sea level controls. Incubation at high altitude of sea level eggs with oxygen supplementation completely prevented the high altitude-induced fetal growth restriction. Thus, fetal oxygenation, independent of maternal nutrition during development, has a predominant role in the control of fetal growth. Further, prolonged high altitude residence confers protection against the deleterious effects of hypoxia on fetal growth.