During hemodialysis, cardiopulmonary decompensation may appear in uremic patients, possibly caused by plugging of pulmonary vessels by leukocytes. In 34 patients we noted leukopenia (20% of initial levels) during hemodialysis that in 15 was associated with impaired pulmonary function. When we infused autologous plasma, incubated with dialyzer cellophane, into rabbits and sheep, sudden leukopenia and hypoxia occurred, with doubling of pulmonary-artery pressures and quintupling of pulmonary-lymph effluent. Histologic examination showed severe pulmonary-vessel-leukostasis and interstitial edema. The syndrome was prevented by preinactivation of complement but was reproduced by infusions of plasma in which complement was activated by zymosan. Thus, acute pulmonary dysfunction from complement-mediated leukostasis may play a major part in the acute cardiopulmonary complications of cellophane-membrane hemodialysis.

A B S T R A C T The response of ventilation and of heart rate to hypoxia and hypercapnia was determined in eight young normal men age 22-30 yr and eight elderly men age 64-73. The elderly men were selected and carefully screened to eliminate the possibility of cardiopulmonary disease. All the subjects were born at low altitude and had no significant prior exposure to hypoxia. The ventilatory response to hypoxia was measured as the exponential slope constant, k, of regression lines relating the logarithm of incremental ventilation to PAo, during isocapnic progressive hypoxia. The heart rate response to hypoxia was measured as the percentage change in heart rate between PAO2 = 100 and PAO2 = 40 mm Hg. The ventilatory response to hypercapnia was measured as the slope of regression lines relating ventilation to PACO2 during rebreathing with PAO2> 200 mm Hg. The heart rate response to hypercapnia was measured as the percentage change in heart rate between control values at the start of the rebreathing test and PACO2= 55 mm Hg.The ventilatory and heart rate responses to both hypoxia and hypercapnia were significantly decreased in the elderly men as compared to the young men. Hypoxic ventilatory drive was decreased by 51±6% (mean +-SEM; P < 0.001) and hypercapnic drive by 41±7% (P < 0.025). The percentage change in heart rate produced by hypoxia was 34±5% (mean +SEM) in the young normals and 12±2% in the old normals (P < 0.005). Similar figures for heart rate in response to hypercapnia were 15±3% and -1±1% for the young and old normal groups (P < 0.001).We conclude that ventilatory and heart rate responses to hypoxia and hypercapnia diminish with age. These alterations in both ventilatory and circulatory controls could make older individuals more vulnerable to hypoxic disease states.

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A B S T R A C T Pulmonary hemodynamics and Rotta, Canepa, Hurtado, Velasquez, and Chavez in 1956 (1) and has been confirmed many times since, both in acclimatized natives (2, 3) and in newcomers (4). The relationship of this pulmonary hypertension to the development of high altitude pulmonary edema (HAPE) is uncertain, but pulmonary artery pressure is higher during episodes of HAPE than during control observations in the same individuals (5), and persons who have had such episodes previously have higher pulmonary artery pressures when reexposed to altitude than nonsusceptible individuals under the same conditions (6). Although it is recognized that the peak incidence of HAPE occurs 1-3 days after entry to high altitude (7), it has not been established whether pulmonary arterial pressure rises in a progressive fashion over the same time course. A progressive rise in pulmonary arterial pressure during a 6 wk period at 12,700 ft has been reported in steers, apparently associated with the right heart failure termed "brisket disease" (8), but was not observed in lambs in a matched experiment (9). Therefore, we decided to investigate in ourselves the time course of the pulmonary arterial pressure both at rest and during exercise at 12,470 ft and to examine other aspects of cardiovascular function over the same time span. We also explored the possibility suggested by Haab, Held, Ernst, and Farhi (10) and Reeves, Halpin, Cohn, and Daoud (11) that hypoxia widens the alveolar to arterial 02 difference.

Ventilatory and heart rate responses to hypoxia and hypercapnia were measured in eight normal subjects (5 women, 3 men, ages 22-27 yr) during wakefulness (W), slow-wave sleep (SWS), and rapid-eye-movement sleep (REM). Ventilatory responses to progressive isocapnic hypoxia were measured as k, the slope of the line relating the logarithm of incremental ventilation to alveolar O2 partial pressure (PAO2) and as the incremental ventilation at PAO2 = 40 Torr delta V 40. Values for k (mean +/- SE) were 40.5 +/- 2.4 Torr during W, 42.1 +/- 2.5 during SWS, and 29.9 +/- 2.3 (5 subj) during REM (P less than 0.02 vs. W). Comparable values for delta V 40 were 5.4 +/- 0.3, 6.3 +/- 1.0, and 5.4 +/- 0.31/min. Hypoxia increased heart rate 19 +/- 1.3% during W, 18 +/- 1.8% during SWS, and 15 +/- 2.2% during REM. Ventilatory responses to rebreathing CO2 (6 subj) were 1.7 +/- 0.3 1 X min-1 X Torr-1 during W and 1.3 +/- 0.2 during SWS. Hypercapnia consistently produced arousal from sleep in all eight subjects at levels between 6 and 15 Torr (11.2 +/- 1.1) above resting alveolar CO2 partial pressure. No consistent arousal was noted during hypoxia. Arousal occurred in 87% of the CO2-rebreathing tests compared with only 28% of the progressive isocapnic hypoxia tests (P less than 0.001). We conclude that ventilatory and heart rate responses to hypoxia and ventilatory responses to hypercapnia are not significantly altered by SWS. Arousal from sleep during hypercapnia is reproducible and predictable, but there is no consistent arousal during hypoxia.