Exercise exacerbates acute mountain sickness at simulated high altitude.

We hypothesized that exercise would cause greater severity and incidence of acute mountain sickness (AMS) in the early hours of exposure to altitude. After passive ascent to simulated high altitude in a decompression chamber [barometric pressure = 429 Torr, approximately 4,800 m (J. B. West, J. Appl. Physiol. 81: 1850-1854, 1996)], seven men exercised (Ex) at 50% of their altitude-specific maximal workload four times for 30 min in the first 6 h of a 10-h exposure. On another day they completed the same protocol but were sedentary (Sed). Measurements included an AMS symptom score, resting minute ventilation (VE), pulmonary function, arterial oxygen saturation (Sa(O(2))), fluid input, and urine volume. Symptoms of AMS were worse in Ex than Sed, with peak AMS scores of 4.4 +/- 1.0 and 1.3 +/- 0.4 in Ex and Sed, respectively (P < 0.01); but resting VE and Sa(O(2)) were not different between trials. However, Sa(O(2)) during the exercise bouts in Ex was at 76.3 +/- 1.7%, lower than during either Sed or at rest in Ex (81.4 +/- 1.8 and 82.2 +/- 2.6%, respectively, P < 0.01). Fluid intake-urine volume shifted to slightly positive values in Ex at 3-6 h (P = 0.06). The mechanism(s) responsible for the rise in severity and incidence of AMS in Ex may be sought in the observed exercise-induced exaggeration of arterial hypoxemia, in the minor fluid shift, or in a combination of these factors.     

Constructing Rigorous and Broad Biosurveillance Networks for Detecting Emerging Zoonotic Outbreaks

Determining optimal surveillance networks for an emerging pathogen is difficult since it is not known beforehand what the characteristics of a pathogen will be or where it will emerge. The resources for surveillance of infectious diseases in animals and wildlife are often limited and mathematical modeling can play a supporting role in examining a wide range of scenarios of pathogen spread. We demonstrate how a hierarchy of mathematical and statistical tools can be used in surveillance planning help guide successful surveillance and mitigation policies for a wide range of zoonotic pathogens. The model forecasts can help clarify the complexities of potential scenarios, and optimize biosurveillance programs for rapidly detecting infectious diseases. Using the highly pathogenic zoonotic H5N1 avian influenza 2006-2007 epidemic in Nigeria as an example, we determined the risk for infection for localized areas in an outbreak and designed biosurveillance stations that are effective for different pathogen strains and a range of possible outbreak locations. We created a general multi-scale, multi-host stochastic SEIR epidemiological network model, with both short and long-range movement, to simulate the spread of an infectious disease through Nigerian human, poultry, backyard duck, and wild bird populations. We chose parameter ranges specific to avian influenza (but not to a particular strain) and used a Latin hypercube sample experimental design to investigate epidemic predictions in a thousand simulations. We ranked the risk of local regions by the number of times they became infected in the ensemble of simulations. These spatial statistics were then complied into a potential risk map of infection. Finally, we validated the results with a known outbreak, using spatial analysis of all the simulation runs to show the progression matched closely with the observed location of the farms infected in the 2006-2007 epidemic.     

Effects of habitual smoking on cardiorespiratory responses to sub-maximal exercise

The effects of habitual cigarette smoking on cardiorespiratory responses to sub-maximal and maximal work were evaluated in nine adult nonsmokers and nine smokers with a mean age of 33 yr. A maximal treadmill test was followed by three tests at 45, 60 and 75% of each subject's VO(2)max. Compared to nonsmokers, the habitual smokers had a non-significantly lower VO(2)max in L/min and per lean body mass (9 and 6%, respectively), but had higher %fat (p<0.01), resulting in a significantly lower VO(2)max per kg body wt (13%, p<0.03). Maximal exercise ventilation (V(E)) was 16% lower in smokers. During sub-maximal work at equivalent exercise stress levels in the two groups, the V(E)/VO(2) ratio was higher in smokers by an average of 11% because VO(2) was lower and the respiratory exchange ratio values were significantly elevated in smokers at 75% of VO(2)max. Blood lactate concentrations in smokers were higher as workloads increased and O(2) pulse (VO(2)/HR) was significantly lower throughout, indicating reduced O(2) extraction, probably due to carbon monoxide. The resting HR was significantly higher in smokers and the HR recovery following all three submaximal exercises was significantly slower in smokers. These results show that detrimental cardiorespiratory effects of chronic cigarette smoking in apparently healthy individuals are evident at moderate exercise levels as reduced gas exchange efficiency in lungs and muscles.     

Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange.

To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency.     

Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia

Roach, Robert C., Jack A. Loeppky, and Milton V. Icenogle.Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia. J. Appl.Physiol. 81(5): 1908-1910, 1996.Acute mountainsickness (AMS) strikes those in the mountains who go too high too fast.Although AMS has been long assumed to be due solely to the hypoxia ofhigh altitude, recent evidence suggests that hypobaria may also make asignificant contribution to the pathophysiology of AMS. We studied ninehealthy men exposed to simulated altitude, normobaric hypoxia, andnormoxic hypobaria in an environmental chamber for 9 h on separateoccasions. To simulate altitude, the barometric pressure was lowered to432 ± 2 (SE) mmHg (simulated terrestrial altitude 4,564 m).Normobaric hypoxia resulted from adding nitrogen to the chamber(maintained near normobaric conditions) to match the inspiredPO₂ of the altitude exposure. Bylowering the barometric pressure and adding oxygen, we achievednormoxic hypobaria with the same inspiredPO₂ as in our laboratory at normalpressure. AMS symptom scores (average scores from 6 and 9 h ofexposure) were higher during simulated altitude (3.7 ± 0.8)compared with either normobaric hypoxia (2.0 ± 0.8;P < 0.01) or normoxic hypobaria (0.4 ± 0.2; P < 0.01). In conclusion,simulated altitude induces AMS to a greater extent than does eithernormobaric hypoxia or normoxic hypobaria, although normobaric hypoxiainduced some AMS.