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Biomedical subjects

P H Hackett

Publications and source records attributed to P H Hackett.

At least 37 records · Page 2Linked to original sources
PubMed1987

Respiratory stimulants and sleep periodic breathing at high altitude. Almitrine versus acetazolamide.

We studied the effects of almitrine, acetazolamide, and placebo on the hypoxic ventilatory response (HVR), sleep periodic breathing, and arterial oxygen saturation (SaO2) in 4 healthy climbers. In a laboratory on Denali (Mt. McKinley) at 4,400 m (PB = 440 mm Hg), we used a double-blind, randomized, three-way crossover design. The HVR was measured during the waking state. Periodic breathing and SAO2% were measured during 3-h sleep studies. Almitrine and acetazolamide both increased SaO2% during sleep, although almitrine increased periodic breathing, whereas acetazolamide decreased periodic breathing. The HVR (delta VE/delta SaO2%) was doubled with almitrine (p less than 0.05), but unchanged with acetazolamide. The HVR was positively related to periodic breathing (p less than 0.05). We conclude that periodic breathing during sleep at high altitude is related to the hypoxic ventilatory response, and that acetazolamide is a superior agent to almitrine for ameliorating periodic breathing.

Acetazolamide↗
PubMed1986

High-altitude pulmonary edema. Characteristics of lung lavage fluid.

To evaluate the cellular and biochemical composition of bronchoalveolar fluid in high-altitude pulmonary edema (HAPE), we performed bronchoalveolar lavage in three climbers with HAPE in a research facility at 4400 m on Mount McKinley. Three healthy climbers were used as controls. The HAPE fluids contained marked increases in high-molecular-weight proteins, erythrocytes, and leukocytes, most of which were alveolar macrophages. The HAPE fluids also contained detectable amounts of leukotriene B4 and other lipoxygenase products of arachidonic acid metabolism, complement fragments (C5a), inhibitors of neutrophil chemotaxis, and acid proteases but not hydroxyproline, a constituent of collagen. The data from this study indicate that HAPE involves a transient "large pore" leak in the pulmonary circulation. Despite the presence of two potent mediators of inflammation, leukotriene B4 and C5a, HAPE is not characterized by the intense neutrophil accumulation that is typical of other forms of acute lung injury.

Adult↗
PubMed1986

Hemodilution of polycythemic mountaineers: effects on exercise and mental function.

We studied the effects of acute, isovolemic hemodilution on the exercise ability and mental function of four polycythemic mountain climbers (mean hematocrit 58 +/- 1.25%) during the American Medical Research Expedition to Mt. Everest (AMREE). The subjects were studied at 5400 m (PB = 400 mm Hg). Approximately 15% of their blood volume was removed and replaced with an equal volume of 5% human albumin solution. Final hematocrits were 50.5 +/- 1.5%. Before and after hemodilution, the subjects performed psychological and exercise tests. Maximum work level, oxygen uptake, minute ventilation, and blood oxygen saturation did not change. After hemodilution, heart rate increased slightly at all work levels, and there was a small but significant improvement on the psychological tests. It is concluded that this degree of hemodilution was well tolerated and that a hematocrit of greater than 50% conferred no advantage for exercise and may have impaired cerebral function. Although, in these circumstances, isovolemic hemodilution improved cerebration, we feel that this potentially hazardous maneuver is rarely indicated.

Adult↗
PubMed1985

High altitude pulmonary edema and exercise at 4,400 meters on Mount McKinley. Effect of expiratory positive airway pressure.

Breathing against positive expiratory pressure has been used to improve gas exchange in many forms of pulmonary edema, and forced expiration against resistance during exercise has been advocated for climbing at high altitude as a method to optimize performance. To evaluate the effect of expiratory positive airway pressure (EPAP) on climbers with high altitude pulmonary edema (HAPE) and on exercise at high altitude, we studied four climbers with HAPE at rest and 13 healthy climbers during exercise on a bicycle ergometer at 4400 m. We measured minute ventilation (VI, L/min), arterial oxygen saturation (SaO2 percent), end-tidal carbon dioxide (PACO2, mm Hg), respiratory rate (RR), and heart rate (HR) during the last minute of a five minute interval at rest in the climbers with HAPE, and at rest, 300, and 600 kpm/minute workloads on a bicycle ergometer in the healthy subjects. The HAPE subjects demonstrated an increased SaO2 percent, no change in HR or VI, and a decrease in RR on EPAP as compared to control. In normal subjects, SaO2 percent, VI, and heart rate were significantly higher on EPAP 10 cm H2O than 0 cm H2O control (p less than 0.01, 0.01, and 0.05, respectively). The RR and PaCO2 were not significantly different. In summary, EPAP improves gas exchange in HAPE subjects at rest. The EPAP in normal subjects at high altitude resulted in a higher SaO2 percent at the expense of a higher VI and higher HR. These results suggest that the work of breathing is higher and the stroke volume lower on EPAP. The positive pressure mask may be an effective temporizing measure for victims of HAPE who cannot immediately go to a lower altitude.

Adult↗
PubMed1985

Acetazolamide and exercise in sojourners to 6,300 meters--a preliminary study.

To examine the effect of acetazolamide on resting acid-base balance and on exercise performance at extreme altitude, we studied four members of the American Medical Research Expedition to Mount Everest at an altitude of 6,300 meters. After an initial progressive exercise test to exhaustion on a bicycle ergometer, subjects were re-studied after taking acetazolamide 250 mg every 8 h for three doses. We measured venous blood during rest for determination of hemoglobin, hematocrit, 2,3-diphosphoglycerate (DPG), bicarbonate, pH, P50, and arterial oxygen saturation by ear oximeter. The results showed that pH, bicarbonate, and DPG:hemoglobin ratio were lower on acetazolamide, whereas P50 at in vivo conditions was unchanged. Exercise ventilation and oxygen consumption for the same workload were slightly higher after acetazolamide, whereas VCO2/VO2 respiratory exchange ratio (R) was lower, and oxygen saturation was unchanged. Two of four subjects had decreased time at maximum workload on acetazolamide; none had an increased performance. The results of this study show that partial carbonic anhydrase inhibition in individuals sojourning to very high altitude produces a further base deficit and a metabolic acidosis, stimulates ventilation, and may impair maximum exercise performance. Although acetazolamide effectively prevents acute mountain sickness, it does not improve performance, and may even impair exercise performance at extreme altitude.

Acetazolamide↗
PubMed1984

Relationship of hypoxic ventilatory response to exercise performance on Mount Everest.

At very high altitude, exercise performance in the human sojourner may depend on a sufficient hypoxic ventilatory response (HVR). To study the relationship of HVR to exercise performance at high altitude, we studied HVR at sea level and 5,400 m and exercise ventilation at sea level, 5,400 m, and 6,300 m in nine members of the American Medical Research Expedition to Everest. The relationship of HVR between individuals was maintained when HVR was repeated after acclimatization to 5,400 m (P less than 0.05). There was a significant correlation in all subjects between HVR and ventilatory equivalent during exercise at sea level (r = 0.704, P less than 0.05). Subjects were then grouped into high (H) and low (L) HVR responders (ventilation increase to end-tidal PO2 of 40 Torr = 21.2 +/- 5.4 and 5.6 +/- 0.9 1 X min-1, respectively. At low and moderate levels of exercise, ventilation at sea level and after acclimatization to 6,300 m was higher in the high HVR group. At 6,300 m blood O2 saturation (Sao2%) decreased from rest to maximum exercise: H = 8.3 +/- 1.8%, L = 20.0 +/- 2.5% (P less than 0.01). HVR correlated inversely in all subjects with the decrease in Sao2 from rest to maximum exercise (P less than 0.05). Climbers with the highest HVR values reached and slept at higher altitudes. We conclude that the relative value of HVR in our group of climbers was not significantly altered after acclimatization; HVR predicts exercise ventilation at sea level and high altitude; the drop in Sao2% that occurs with exercise is inversely related to HVR; and sojourners with high HVR may perform better at extreme altitude.

Altitude↗
PubMed1983

Pulmonary gas exchange on the summit of Mount Everest.

Pulmonary gas exchange was studied on members of the American Medical Research Expedition to Everest at altitudes of 8,050 m (barometric pressure 284 Torr), 8,400 m (267 Torr) and 8,848 m (summit of Mt. Everest, 253 Torr). Thirty-four valid alveolar gas samples were taken using a special automatic sampler including 4 samples on the summit. Venous blood was collected from two subjects at an altitude of 8,050 m on the morning after their successful summit climb. Alveolar CO2 partial pressure (PCO2) fell approximately linearly with decreasing barometric pressure to a value of 7.5 Torr on the summit. For a respiratory exchange ratio of 0.85, this gave an alveolar O2 partial pressure (PO2) of 35 Torr. In two subjects who reached the summit, the mean base excess at 8,050 m was -7.2 meq/l, and assuming the same value on the previous day, the arterial pH on the summit was over 7.7. Arterial PO2 was calculated from changes along the pulmonary capillary to be 28 Torr. In spite of the severe arterial hypoxemia, high pH, and extremely low PCO2, subjects on the summit were able to perform simple tasks. The results allow us to construct for the first time an integrated picture of human gas exchange at the highest point on earth.

Acid-Base Equilibrium↗
PubMed1983

Maximal exercise at extreme altitudes on Mount Everest.

Maximal exercise at extreme altitudes was studied during the course of the American Medical Research Expedition to Everest. Measurements were carried out at sea level [inspired O2 partial pressure (PO2) 147 Torr], 6,300 m during air breathing (inspired PO2 64 Torr), 6,300 m during 16% O2 breathing (inspired PO2 49 Torr), and 6,300 m during 14% O2 breathing (inspired PO2 43 Torr). The last PO2 is equivalent to that on the summit of Mt. Everest. All the 6,300 m studies were carried out in a warm well-equipped laboratory on well-acclimatized subjects. Maximal O2 uptake fell dramatically as the inspired PO2 was reduced to very low levels. However, two subjects were able to reach an O2 uptake of 1 l/min at the lowest inspired PO2. Arterial O2 saturations fell markedly and alveolar-arterial PO2 differences increased as the work rate was raised at high altitude, indicating diffusion limitation of O2 transfer. Maximal exercise ventilations exceeded 200 l/min at 6,300 m during air breathing but fell considerably at the lowest values of inspired PO2. Alveolar CO2 partial pressure was reduced to 7-8 Torr in one subject at the lowest inspired PO2, and the same value was obtained from alveolar gas samples taken by him at rest on the summit. The results help to explain how man can reach the highest point on earth while breathing ambient air.

Adult↗
PubMed1982

Fluid retention and relative hypoventilation in acute mountain sickness.

The presence of pulmonary, cerebral, and/or peripheral edema in acute mountain sickness (AMS) implies a derangement in the body's handling of water. Previously, we demonstrated water retention and increased symptoms of AMS when hypocapnia was prevented in subjects exposed to simulated high altitude. This led us to the hypothesis that upon ascent to high altitude, those persons who fail to increase their ventilation adequately and hence do not become hypocapnic will retain water reflected as weight gain and will develop AMS. To test this hypothesis, we studied in Kathmandu, Nepal (1,377 m) 42 healthy western tourists; all were restudied in Pheriche (4,243 m) within 6 days of exposure to high altitude. Symptoms of AMS were highly correlated (p less than 0.001) with weight change, suggesting that persons becoming symptomatic retained fluid. On going from low to high altitude, those persons who lost weight and remained well increased their resting ventilation, whereas those who gained weight did not (p = 0.03). This relative hypoventilation in the latter group was confirmed by higher values of Pco2 (heated hand vein blood) and lower values of arterial saturation (ear oximeter) at Pheriche. Vital capacity measured in Kathmandu was correlated with arterial saturation at Pheriche (p = 0.02); persons with low vital capacity were more hypoxemic with more symptoms of AMS. We conclude that relative hypoventilation and weight gain appear early in the development of AMS suggesting links between altitude hypoxia, hyperventilation, hypocapnia, and the body's handling of water.

Acute Disease↗
PubMed1981

Acute mountain sickness and the edemas of high altitude: a common pathogenesis?

Within days of ascent to high altitude when symptoms of acute mountain sickness (AMS) are common, pulmonary and cerebral edema may also develop. Although peripheral edema of the hands, face or feet may also appear, its association with AMS is unclear. In addition, persons with high altitude pulmonary edema often report an antidiuresis. Hence, altitude sickness appears to result from abnormalities in the handling of body water. To test this hypothesis, we studied 102 men and women who were trekking in the Mount Everest region of Nepal. Most were seen both at low (1377 m) and at high (4243 m) altitude. Severity of AMS was measured by an established Symptom Score derived from a questionnaire and physical examination. Change in body water was inferred from change in body weight in less than 10 days. Peripheral edema was assessed separately by physical examination. AMS Symptom Score correlated directly with weight change; those who remained well lost weight, whereas increasing signs and symptoms of AMS occurred in those with increasing weight gain. The symptomatic subjects also developed peripheral edema and reported decreased urinary output. These findings support the hypothesis that with rapid ascent to high altitude, abnormalities in the handling of body water, with antidiuresis, result in fluid retention (weight gain) manifest as peripheral, pulmonary, and/or cerebral edema.

Adolescent↗
PubMed1980

Control of breathing in Sherpas at low and high altitude.

Sherpas are well known for their physical performance at extreme altitudes, yet they are reported to have blunted ventilatory responses to acute hypoxia and relative hypoventilation in chronic hypoxia. To examine this paradox, we studied ventilatory control in Sherpas in comparison to that in Westerners at both low and high altitude. At low altitude, 25 Sherpas had higher minute ventilation, higher respiratory frequency, and lower end-tidal carbon dioxide tension than 25 Westerners. The hypoxic ventilatory response of Sherpas was found to be similar to that in Westerners, even though long altitude exposure had blunted the responses of some Sherpas. At high altitude, Sherpas again had higher minute ventilation and a tendency toward higher arterial oxygen saturation than Westerners. Oxygen administration increased ventilation further in Sherpas but decreased ventilation in Westerners. We conclude that Sherpas differ from other high-altitude natives; their hypoxic ventilatory response is not blunted, and they exhibit relative hyperventilation.

Adaptation, Physiological↗