Immunodiffusion assay of C1 inhibitor function in serum: prospective analysis in angioedema-urticaria.

An immunodiffusion assay for detecting C1 inhibitor function in human serum was described recently by Ziccardi and Cooper. In our present study, the applicability of this assay for C1 inhibitor deficiency or C1 inhibitor dysfunction was evaluated. Of the 39 patients evaluated, all eight patients with the common (C1 inhibitor deficiency) form of hereditary angioedema and all three patients with the variant (dysfunctional C1 inhibitor) form of hereditary angioedema were identified correctly. Treatment of patients with hereditary angioedema with stanozolol or danocrine increased their serum C1 inhibitor concentrations and normalized the immunodiffusion assay for C1 inhibitor function. In addition, the assay allowed the correct identification of three patients with the acquired form of C1 inhibitor deficiency, because the sera of these patients exhibited a distinctive pattern. The 25 samples from patients (chronic angioedema, chronic urticaria, or hypocomplementemic vasculitis) without C1 inhibitor deficiency had normal assays.

The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema.

High-altitude pulmonary edema (HAPE), a severe form of altitude illness that can occur in young healthy individuals, is a noncardiogenic form of edema that is associated with high concentrations of proteins and cells in bronchoalveolar lavage (BAL) fluid (Schoene et al., J. Am. Med. Assoc. 256: 63-69, 1986). We hypothesized that acute mountain sickness (AMS) in which gas exchange is impaired to a milder degree is a precursor to HAPE. We therefore performed BAL with 0.89% NaCl by fiberoptic bronchoscopy in eight subjects at 4,400 m (barometric pressure = 440 Torr) on Mt. McKinley to evaluate the cellular and biochemical responses of the lung at high altitude. The subjects included one healthy control (arterial O2 saturation = 83%), three climbers with HAPE (mean arterial O2 saturation = 55.0 +/- 5.0%), and four with AMS (arterial O2 saturation = 70.0 +/- 2.4%). Cell counts and differentials were done immediately on the BAL fluid, and the remainder was frozen for protein and biochemical analysis to be performed later. The results of this and of the earlier study mentioned above showed that the total leukocyte count (X10(5)/ml) in BAL fluid was 3.5 +/- 2.0 for HAPE, 0.9 +/- 4.0 for AMS, and 0.7 +/- 0.6 for controls, with predominantly alveolar macrophages in HAPE. The total protein concentration (mg/dl) was 616.0 +/- 3.3 for HAPE, 10.4 +/- 8.3 for AMS, and 12.0 +/- 3.4 for controls, with both large- (immunoglobulin M) and small- (albumin) molecular-weight proteins present in HAPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Barometric pressures at extreme altitudes on Mt. Everest: physiological significance.

Barometric pressures were measured on Mt. Everest from altitudes of 5,400 (base camp) to 8,848 m (summit) during the American Medical Research Expedition to Everest. Measurements at 5,400 m were made with a mercury barometer, and above this most of the pressures were obtained with an accurate crystal-sensor barometer. The mean daily pressures were 400.4 +/- 2.7 (SD) Torr (n = 35) at 5,400 m, 351.0 +/- 1.0 Torr (n = 16) at 6,300 m, 283.6 +/- 1.5 Torr (n = 6) at 8,050 m, and 253.0 Torr (n = 1) at 8,848 m. All these pressures are considerably higher than those predicted from the ICAO Standard Atmosphere. The chief reason is that pressures at altitudes between 2 and 16 km are latitude dependent, being higher near the equator because of the large mass of cold air in the stratosphere of that region. Data from weather balloons show that the pressure at the altitude of the summit of Mt. Everest varies considerably with season, being about 11.5 Torr higher in midsummer than in midwinter. Although the mountain has been climbed without supplementary O2, the very low O2 partial pressure at the summit means that it is at the limit of man's tolerance, and even day-by-day variations in barometric pressure apparently affect maximal O2 uptake.

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.

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.

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.