Susceptibility to high-altitude pulmonary edema is associated with a more uniform distribution of regional specific ventilation.

High-altitude pulmonary edema (HAPE) is a potentially fatal condition affecting high-altitude sojourners. The biggest predictor of HAPE development is a history of prior HAPE. Magnetic resonance imaging (MRI) shows that HAPE-susceptible (with a history of HAPE), but not HAPE-resistant (with a history of repeated ascents without illness) individuals develop greater heterogeneity of regional pulmonary perfusion breathing hypoxic gas (O2 = 12.5%), consistent with uneven hypoxic pulmonary vasoconstriction (HPV). Why HPV is uneven in HAPE-susceptible individuals is unknown but may arise from regionally heterogeneous ventilation resulting in an uneven stimulus to HPV. We tested the hypothesis that ventilation is more heterogeneous in HAPE-susceptible subjects (n = 6) compared with HAPE-resistant controls (n = 7). MRI specific ventilation imaging (SVI) was used to measure regional specific ventilation and the relative dispersion (SD/mean) of SVI used to quantify baseline heterogeneity. Ventilation heterogeneity from conductive and respiratory airways was measured in normoxia and hypoxia (O2 = 12.5%) using multiple-breath washout and heterogeneity quantified from the indexes Scond and Sacin, respectively. Contrary to our hypothesis, HAPE-susceptible subjects had significantly lower relative dispersion of specific ventilation than the HAPE-resistant controls [susceptible = 1.33 ± 0.67 (SD), resistant = 2.36 ± 0.98, P = 0.05], and Sacin tended to be more uniform (susceptible = 0.085 ± 0.009, resistant = 0.113 ± 0.030, P = 0.07). Scond was not significantly different between groups (susceptible = 0.019 ± 0.007, resistant = 0.020 ± 0.004, P = 0.67). Sacin and Scond did not change significantly in hypoxia (P = 0.56 and 0.19, respectively). In conclusion, ventilation heterogeneity does not change with short-term hypoxia irrespective of HAPE susceptibility, and lesser rather than greater ventilation heterogeneity is observed in HAPE-susceptible subjects. This suggests that the basis for uneven HPV in HAPE involves vascular phenomena.NEW & NOTEWORTHY Uneven hypoxic pulmonary vasoconstriction (HPV) is thought to incite high-altitude pulmonary edema (HAPE). We evaluated whether greater heterogeneity of ventilation is also a feature of HAPE-susceptible subjects compared with HAPE-resistant subjects. Contrary to our hypothesis, ventilation heterogeneity was less in HAPE-susceptible subjects and unaffected by hypoxia, suggesting a vascular basis for uneven HPV.

The Cushing-Dandy conflict­the Dandy family perception of the discord.

The rivalry between Harvey Cushing and Walter Dandy has long fascinated neurosurgeons. Once a mentor to Dandy, Cushing saw his pupil's cunning prowess in the laboratory and unique surgical skill rival his own, and he took years to embrace some of Dandy's innovations, the most well-known of which was the technique of ventriculography. In this report, Dandy's great grandson draws on his family archives and personal letters of Dandy to lineate the evolution of the Dandy-Cushing relationship.

Dead space mask eliminates central apnea at altitude.

Travelers to high altitude may have disturbed sleep due to periodic breathing with frequent central apneas. We tested whether a mask with added dead space could reduce the central apneas of altitude. 16 subjects were recruited, age 18-35, residing at 4600 ft (1400 m). They each slept one night with full polysomnographic monitoring, including end tidal CO2, in a normobaric hypoxia tent simulating 12,000 ft. (3658 m) altitude. Those who had a central apnea index (CAI) >20/h returned for a night in the tent for dead space titration, during which they slept with increasing amounts of dead space, aiming for a CAI <5/h or <10% of baseline. Then each subject slept another night with the titrated amount of dead space. Of the 16 subjects, 5 had a central apnea index >20/h mean 49.1, range 21.4-131.5/hr. In each of the 5, the dead space mask reduced the CAI by at least 88% to a mean of 3.1, range 0.9-7.1/h, (p=0.04). Hypopnea index was unchanged. Three subjects required 500 cc of dead space or less. One subject required 860 cc, and one required 2.1 L. Morning symptoms and arousal index were not significantly affected by the dead space mask. Dead space did not appear to increase the CO2 reserve. At 12,000 ft., central apneas can be effectively reduced with a dead space mask, but clinical utility will require further evaluation.

Modulation of the hypothalamo-pituitary-adrenocortical axis by caffeine.

Although caffeine is the most consumed psychoactive substance in the world, the extents of many of its effects are unknown. High doses of caffeine have been shown to activate the HPA axis while the effects of low to moderate doses have usually not been described in detail. Moreover, although several lines of evidence suggest that low doses of caffeine may restrain some negative affective states, the possible modulatory role of caffeine on HPA axis activation induced by a stressful stimulus has not been described. Thus, the present studies investigated the possible modulatory effects of low to moderate doses of caffeine on moderate to high HPA axis activation induced by different intensities of loud noise. First, in order to test this modulation, time courses for adrenocorticotropic hormone (ACTH) and corticosterone responses to loud noise stress and to caffeine were defined, in rats. Plasma ACTH and corticosterone levels peaked 30 min from the onset of noise presentation, and rapidly declined after noise termination. A low caffeine dose of 2 mg/kg significantly increased plasma corticosterone and ACTH levels 30 min following injections, but levels returned to baseline 60 min following injections. Caffeine doses of 30 mg/kg and higher elevated plasma hormone levels for at least 2h. Doses of 2 or 10mg/kg, however, did not modulate endocrine responses to loud noise presentation. It is concluded that although caffeine activates the HPA axis, low to moderate doses do not modulate HPA axis responses to stressful stimuli.