Accentuated hypoxemia at high altitude in subjects susceptible to high-altitude pulmonary edema T. M. HYERS, Cardiovascular and .University
J.
C. H. SCOGGIN, D. H. WILL, R. F. GROVER, AND J. T. REEVES Pulmonary Research Laboratory, Denver Veterans Administration Hospital, of Colorado Medical Center, Denver, Colorado 80262
HYERS, T. M., C. H. SCOGGIN, D. H. WILL, R. F. GROVER, T. REEVES. Accentuated hypoxemia at high altitude
subjects
susceptible
to high-altitude
pulmonary
edema.
AND
in JI 41-
Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46(l): 46, 1979. -To investigate the hypotheses that activated coagulation, catecholamine release, or arginine vasopressin release are involved in the pathogenesis of high-altitude pulmonary edema (HAPE), we measured these variables in seven subjects susceptible to HAPE and in nine control subjects at an altitude of 1,600 m, and after 6 and 12 h at a simulated altitude of 4,150 m. Each subject was studied twice, once after 3 days of placebo medication and once after 3 days of premedication with aspirin and dipyridamole. At high altitude, HAPE-susceptible subjects showed significantly exaggerated hypoxemia and a slightly higher end-tidal carbon dioxide partial pressure that did not account fully for the hypoxemia. Fibrinolytic activity was significantly accelerated in both groups at high altitude, whereas other coagulation measurements, catecholamines and arginine vasopressin levels, and pulmonary function tests were not significantly changed. Similar findings were obtained after both placebo and plateletinhibitor premeditation. The results indicate that none of the three hypothesized mechanisms, i.e., activated coagulation, excessive catecholamine release, or antidiuresis, would account for HAPE susceptibility. Instead, HAPE-susceptible subjects exhibited exaggerated hypoxemia associated with relative hypoventilation and a widened alveolar-arterial gas pressure difference. coagulation; sin
HIGH-ALTITUDE
fibrinolysis;
catecholamines;
PULMONARY
EDEMA
arginine
(HAPE)
vasopres-
is a rare
pulmonary hypertension and the accentuated hypoxemia was unclear, but neither abnormality was associated with frank pulmonary edema in these two studies. Recently, several hypotheses have been proposed either directly or indirectly to explain the pathogenesis of HAPE. The first hypothesis suggests that intravascular coagulation of platelets and fibrin obstructs the precapillary pulmonary circulation and subsequently leads to transvascular movement of fluid and cells. This idea is based on altered coagulation observed in normal adults and animals taken to high altitude (10, 12, 20). A second hypothesis is that excessive catecholamine release with sudden ascent to high altitude may predispose to acute pulmonary injury, and is based on work by Hoon et al. (13) with normal. subjects transported to high altitude at different rates of ascent. A third hypothesis comes mainly from isolated, uncontrolled experiences at high altitude and suggests that HAPEsusceptible individuals are prone to accentuated antidiuresis with acute hypoxemia in contrast to a milder antidiuresis described in normals (11). We studied these three hypotheses in a group of adolescents known to be susceptible to HAPE (25) and in a selected group of subjects without history of highaltitude dysfunction. In a prospective, controlled fashion, we evaluated coagulation, plasma catecholamine, and arginine vasopressin levels after decompressing the subjects to 4,150 m in a hypobaric chamber. We also evaluated the altered coagulation hypothesis by utilizing a crossover design whereby each subject was studied twice and was pretreated either with a placebo or with two platelet inhibitors, aspirin and dipyridamole.
form of noncardiogenic pulmonary edema that occurs most often in high-altitude residents who sojourn at low METHODS altitude for a few days and then return quickly to altitudes above 2,700 m (25). Because the syndrome is HAPE-susceptible subjects were adolescents ranging clinically and histologically similar to more common in age from 12 to 16 yr from Leadville, CO, elevation types of noncardiogenic pulmonary edema, an explica3,100 m, with a history of at least one episode of HAPE requiring hospitalization. One HAPE-susceptible subtion of its pathogenesis assumes additional importance. Hultgren et al. (14) and Viswanathan. et al. (29) ject was a resident of Denver, CO, at the time of the study. Control subjects, ranging in age from 9 to 33 yr, studied HAPE-susceptible subjects and found markedly increased mean pulmonary artery pressures, increased were residents of Denver, nonsmokers, and without a total pulmonary resistances, and increased alveolarhistory of problems at high altitude. HAPE-susceptible arterial gas pressure differences (AaDo2) when the sub- subjects were brought down to Denver’s altitude (1,600 jects were exposed to high altitude or hypoxia. In m) for 3 days and then decompressed in a hypobaric Hultgren’s study, subsequent administration of oxygen chamber to an altitude of 4,150 m at the rate of 50 m/ after ascent to 3,100 m only partially relieved the min. Control subjects had no high-altitude exposure for pulmonary hypertension. The relationship between the at least 1 wk prior to study. Baseline studies were 41
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on November 9, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
42
HYERS
performed immediately prior to decompression (altitude 1,600 m) and again 6 and 12 h at the simulated altitude of 4,150 m. In most cases, HAPE-susceptible subjects and controls were studied concurrently. All subjects and their parents gave informed consent before participation. The study was conducted as a crossover, double-blind experiment testing the efficacy of two anti .platelet drugs, aspirin and d ipyridamole, as preven tive agents. In this way, each subject received either 600 mg aspirin (ASA) and 50 mg dipyridamole (DP) twice a day for 3 days, or identically appearing placebos for 3 days prior to ascent to altitude. The crossover studies were separated by 3-4 wk in each instance. Except where indicated, results presented in this paper represent data obtained while subjects were taking placebo medication. All subjects ate a normal diet for the 3 days prior to ascent; while in the chamber for 12 h, each consumed 1,500-2,000 kcal composed of approximately 50% carbohydrate. Subjects were weighed immediately before ascent and immediately on descent 12 h later. Fluid intake and output during the 12 h were measured for each subject. No strenuous exercise was performed by subjects while in the chamber. The chamber was maintained at a temperature of 2224°C and an altitude of 4,150 -t- 10 m during the period of the study. Spirometry was always performed in duplicate with the subject standing. If there was more than 5% difference in the two forced vital capacities, spirometry was repeated. Forced vital capacity (FVC) and l-s forced expired volume (FEV, ()) were calculated from the curve of the larger forced vital capacity. All volumes were expressed as BTPS as described by Rahn and Hammond (23) and Ulvedal et al. (28) volume
(BTPS)
= volume
(ATPS)
[310/(273
+ T(“C))l x C(PB-
PH~o)/(PB
-
47)]
End-tidal CO, concentration was monitored at the mouth with a Beckman LB-l capnograph and recorded on a Brush Mark 280 recorder. The capnograph was recalibrated at each measurement with room air and with a mixture of nitrogen and 5.65% CO2 that had been analyzed by the Scholander technique. Arterial oxyhemoglobin saturation was monitored by a HewlettPackard ear oximeter model 47201A that had been calibrated against blood of known oxyhemoglobin saturations varying from 50 to 95% and known hematocrits varying from 26 to 76%. Closing volumes were performed in duplicate, with the subject seated, after a maximum breath of 100% 0, inhaled from a bag via a Collins three-way valve. Nitrogen concentration was monitored at the mouth using a Med-Science 505 nitrogen analyzer and displayed as the Y-axis variable on a Hewlett-Packard 7140A X-Y recorder. Volume of expired gas was measured by a potentiometer attached to the Collins spirometer and displayed on the X-axis of the recorder. Subjects were trained to perform slow vital capacity maneuvers and watch the tracing on the spirometer to keep expiratory flow constant , and less tha n 0.3 l/s. Closing volumes were expressed as percent of slow vital capac-
ET AL.
ity. Slopes of phase III were expressed as A%NZ/l (BTPSJ and represent the average of at least two determinations. Since many of the subjects were adolescents, approximately 150 ml of dead space were added to the breathing circuit as recommended by Manzell et al. (20) . Blood for biochemical assays was drawn through a 19gauge scalp vein needle placed cleanly in an antecubital vein. The line was first-cleared by withdrawing l-2 ml blood; blood was withdrawn rapidly and placed in separate tubes for platelet count and hematocrit (0.15% EDTA), fibrinogen, activated partial thromboplastin time (aPTT), and fibrinolysis assays (Na citrate 3.8% 1: 9 blood) and fibrinopeptide A (apoprotinin 1,000 U and Na heparin 1,000 U/l0 ml). Blood was also drawn for subsequent radioimmunoassay of arginine vasopressin (ADH). The line was filled with a dilute solution of heparin and the subjects were placed at rest for 15-20 min in the dark, prior to withdrawing blood for catecholamine levels. The scalp vein needle was removed and a new one placed in the opposite arm immediately prior to the next blood-draw ing period. All blood samples except that used for platelet count were immediately placed in ice, and the plasma was separated in a Sorval RC-2 centrifuge at 4°C. Platelet counts and tests of fibrinolysis were performed immediately. Plasma aliquots for fibrinopeptide A, fibrinogen, aPTT, ADH, and catecholamines were quickly frozen in dry ice and methanol, and stored at -75°C until assayed. Fibrinogen was measured in duplicate by the method of Jacobson (16), using alkaline urea dissolution of thrombin-clottable protein and spectrophotometric determination of protein concentration in a Beckman DU spectrophotometer at 282 nm. aPTI’ was measured by Fibrometer in duplicate with a commercial kaolincephalin reagent (Hyland Laboratories) and CaCl,, 0.15 M. Concurrent controls were run with pooled normal human plasma. Plasma euglobulin lysis time was measured by the method of Buckell (7) with a euglobulin fraction prepared at pH 5.4. Fibrin plates were prepared by the method of Astrup and Muellertz (3) utilizing Amour-Reheis bovine fibrinogen in an agarose gel. An aliquot of the plasma euglobulin fraction was placed in duplicate on the cut wells, and the plates were incubated at 37% for 24 h. Two diameters of each lytic area were measured and the product was expressed in mm? Concurrent standards using Oreganon urokinase were run at dilutions of 2, 4, 8, and 12 CTA units of urokinase. Fibrinopeptide A was measured by Nossel’s methodology (21) using radioimmunoassay and an antibody prepared by EMCO Laboratories, Stockholm. Plasma ADH was measured by a liquid-phase radioimmunoassay with a rabbit antibody prepared against ADH coupled to albumin. Arginine vasopressin was extracted from plasma by acidification and Bentonite precipitation (1). Serum catecholamine levels were measured by radiometric assay by use of the method of Passon and Peuler (22) at Laboratory Procedures, Inc., Inglewood, CA. Statistical methods. Group data for baseline and 6 and 12 h were analyzed by two-way analysis of variance using Scheffe’s method of testing multiple comparisons
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on November 9, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
HAPE
SUSCEPTIBILITY
AND
HYPOXEMIA
AT HIGH
43
ALTITUDE
(24). Group data for baseline and 12 h were analyzed by the t test for paired data. Intergroup comparisons between controls and HAPE-susceptible subjects were performed by a two-way repeated analysis of variance procedure with subjects nestled within groups (31).
96
OXYGEN SATURATION
0 /0
88
RESULTS
The striking finding in all HAPE-susceptible subjects was the marked degree of hypoxemia that developed within 1 h at altitude and persisted during the 12-h period (Fig. 1). This accentuated hypoxemia was always observed and there was essentially no overlap in oxyhemoglobin saturations between the two groups of subjects. When concurrent end-tidal carbon dioxide partial pressure (Pco,) was measured, the HAPE-susceptible subjects showed a tendency to relative hypoventilation at hour 6, but by hour 12, the mean end-tidal PcoZ was almost the same in the two groups despite a widening difference in oxyhemoglobin saturation (Fig. 2). It should also be noted that the tendency to greater hypoxemia not only appeared rapidly (within 1 h) but also resolved by the time the HAPE-susceptible subjects had been decompressed and left the chamber (30 min). The accentuated hypoxemia was seen in the six subjects who were residents of Leadville (3,100 m) and also in the one subject who was a resident of Denver (Fig. 2). These data indicated a significant difference for both (P < 0.001) and end-tid .a1 oxyhemoglobin saturationPCO~ (P < 0.05) between the subjects susceptible to HAPE and the controls at 4,150 m altitude. The differences between the groups at baseline altitude of 1,650 m were not significant. There were no significant time, or group by time, interaction effects for either oxyhemoglobin saturation or end-tidal PcoZ at either altitude. Despite this marked difference in oxyhemoglobin saturation at altitude, pulmonary function tests were similar in the two groups. Forced vital capacity declined minimally in both groups and there was very little change in FE& .o (Table 1). The slope of phase III of the desingle-breath nitrogen exhalation curve actually the changes were not creased in both groups although significant. The baseline phase III slope was signifi-
96
n=9
CONTROL HAPE-SlJSC.
92 OXY - Hb 88 SATURA STION 84 % 80
0
n=7
q
84
80
76
132 torr 128
124 / II 0 ‘/2
PC.001
76 b BASELINE
6 hrs 4150m.
12 hrs 4150m.
FIG. 1. Oxyhemoglobin saturation for all control and HAPE-susceptible subjects are shown. Acute altitude exposure produces exaggerated hypoxemia in HAPE-susceptible subjects at altitude: saturation was significantly lower in HAPE-susceptible subjects at 6 and 12 h at high altitude (P < 0.001).
6h HOURS
12h %p
AT 4150m.
FIG. 2. Oxyhemoglobin saturation for those control and HAPEsusceptible subjects with concurrent end-tidal Pco2 measurements are shown. At high altitude, HAPE-susceptible subjects had lower oxyhemoglobin saturation (P < 0.001) and higher end-tidal Pco2 levels (P < 0.05).
TABLE 1. Spirometry and single- breath (BTPS) curves at altitude n
Forced vital capacity, % baseline Control HAPE-susceptible Forced expiratory volume at 1 s, YO baseline Control HAPE-susceptible Slope phase III, A%N,/l Control HAPE-susceptible Values
P
J.
C. H. SCOGGIN, D. H. WILL, R. F. GROVER, AND J. T. REEVES Pulmonary Research Laboratory, Denver Veterans Administration Hospital, of Colorado Medical Center, Denver, Colorado 80262
HYERS, T. M., C. H. SCOGGIN, D. H. WILL, R. F. GROVER, T. REEVES. Accentuated hypoxemia at high altitude
subjects
susceptible
to high-altitude
pulmonary
edema.
AND
in JI 41-
Appl. Physiol.: Respirat. Environ. Exercise Physiol. 46(l): 46, 1979. -To investigate the hypotheses that activated coagulation, catecholamine release, or arginine vasopressin release are involved in the pathogenesis of high-altitude pulmonary edema (HAPE), we measured these variables in seven subjects susceptible to HAPE and in nine control subjects at an altitude of 1,600 m, and after 6 and 12 h at a simulated altitude of 4,150 m. Each subject was studied twice, once after 3 days of placebo medication and once after 3 days of premedication with aspirin and dipyridamole. At high altitude, HAPE-susceptible subjects showed significantly exaggerated hypoxemia and a slightly higher end-tidal carbon dioxide partial pressure that did not account fully for the hypoxemia. Fibrinolytic activity was significantly accelerated in both groups at high altitude, whereas other coagulation measurements, catecholamines and arginine vasopressin levels, and pulmonary function tests were not significantly changed. Similar findings were obtained after both placebo and plateletinhibitor premeditation. The results indicate that none of the three hypothesized mechanisms, i.e., activated coagulation, excessive catecholamine release, or antidiuresis, would account for HAPE susceptibility. Instead, HAPE-susceptible subjects exhibited exaggerated hypoxemia associated with relative hypoventilation and a widened alveolar-arterial gas pressure difference. coagulation; sin
HIGH-ALTITUDE
fibrinolysis;
catecholamines;
PULMONARY
EDEMA
arginine
(HAPE)
vasopres-
is a rare
pulmonary hypertension and the accentuated hypoxemia was unclear, but neither abnormality was associated with frank pulmonary edema in these two studies. Recently, several hypotheses have been proposed either directly or indirectly to explain the pathogenesis of HAPE. The first hypothesis suggests that intravascular coagulation of platelets and fibrin obstructs the precapillary pulmonary circulation and subsequently leads to transvascular movement of fluid and cells. This idea is based on altered coagulation observed in normal adults and animals taken to high altitude (10, 12, 20). A second hypothesis is that excessive catecholamine release with sudden ascent to high altitude may predispose to acute pulmonary injury, and is based on work by Hoon et al. (13) with normal. subjects transported to high altitude at different rates of ascent. A third hypothesis comes mainly from isolated, uncontrolled experiences at high altitude and suggests that HAPEsusceptible individuals are prone to accentuated antidiuresis with acute hypoxemia in contrast to a milder antidiuresis described in normals (11). We studied these three hypotheses in a group of adolescents known to be susceptible to HAPE (25) and in a selected group of subjects without history of highaltitude dysfunction. In a prospective, controlled fashion, we evaluated coagulation, plasma catecholamine, and arginine vasopressin levels after decompressing the subjects to 4,150 m in a hypobaric chamber. We also evaluated the altered coagulation hypothesis by utilizing a crossover design whereby each subject was studied twice and was pretreated either with a placebo or with two platelet inhibitors, aspirin and dipyridamole.
form of noncardiogenic pulmonary edema that occurs most often in high-altitude residents who sojourn at low METHODS altitude for a few days and then return quickly to altitudes above 2,700 m (25). Because the syndrome is HAPE-susceptible subjects were adolescents ranging clinically and histologically similar to more common in age from 12 to 16 yr from Leadville, CO, elevation types of noncardiogenic pulmonary edema, an explica3,100 m, with a history of at least one episode of HAPE requiring hospitalization. One HAPE-susceptible subtion of its pathogenesis assumes additional importance. Hultgren et al. (14) and Viswanathan. et al. (29) ject was a resident of Denver, CO, at the time of the study. Control subjects, ranging in age from 9 to 33 yr, studied HAPE-susceptible subjects and found markedly increased mean pulmonary artery pressures, increased were residents of Denver, nonsmokers, and without a total pulmonary resistances, and increased alveolarhistory of problems at high altitude. HAPE-susceptible arterial gas pressure differences (AaDo2) when the sub- subjects were brought down to Denver’s altitude (1,600 jects were exposed to high altitude or hypoxia. In m) for 3 days and then decompressed in a hypobaric Hultgren’s study, subsequent administration of oxygen chamber to an altitude of 4,150 m at the rate of 50 m/ after ascent to 3,100 m only partially relieved the min. Control subjects had no high-altitude exposure for pulmonary hypertension. The relationship between the at least 1 wk prior to study. Baseline studies were 41
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on November 9, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
42
HYERS
performed immediately prior to decompression (altitude 1,600 m) and again 6 and 12 h at the simulated altitude of 4,150 m. In most cases, HAPE-susceptible subjects and controls were studied concurrently. All subjects and their parents gave informed consent before participation. The study was conducted as a crossover, double-blind experiment testing the efficacy of two anti .platelet drugs, aspirin and d ipyridamole, as preven tive agents. In this way, each subject received either 600 mg aspirin (ASA) and 50 mg dipyridamole (DP) twice a day for 3 days, or identically appearing placebos for 3 days prior to ascent to altitude. The crossover studies were separated by 3-4 wk in each instance. Except where indicated, results presented in this paper represent data obtained while subjects were taking placebo medication. All subjects ate a normal diet for the 3 days prior to ascent; while in the chamber for 12 h, each consumed 1,500-2,000 kcal composed of approximately 50% carbohydrate. Subjects were weighed immediately before ascent and immediately on descent 12 h later. Fluid intake and output during the 12 h were measured for each subject. No strenuous exercise was performed by subjects while in the chamber. The chamber was maintained at a temperature of 2224°C and an altitude of 4,150 -t- 10 m during the period of the study. Spirometry was always performed in duplicate with the subject standing. If there was more than 5% difference in the two forced vital capacities, spirometry was repeated. Forced vital capacity (FVC) and l-s forced expired volume (FEV, ()) were calculated from the curve of the larger forced vital capacity. All volumes were expressed as BTPS as described by Rahn and Hammond (23) and Ulvedal et al. (28) volume
(BTPS)
= volume
(ATPS)
[310/(273
+ T(“C))l x C(PB-
PH~o)/(PB
-
47)]
End-tidal CO, concentration was monitored at the mouth with a Beckman LB-l capnograph and recorded on a Brush Mark 280 recorder. The capnograph was recalibrated at each measurement with room air and with a mixture of nitrogen and 5.65% CO2 that had been analyzed by the Scholander technique. Arterial oxyhemoglobin saturation was monitored by a HewlettPackard ear oximeter model 47201A that had been calibrated against blood of known oxyhemoglobin saturations varying from 50 to 95% and known hematocrits varying from 26 to 76%. Closing volumes were performed in duplicate, with the subject seated, after a maximum breath of 100% 0, inhaled from a bag via a Collins three-way valve. Nitrogen concentration was monitored at the mouth using a Med-Science 505 nitrogen analyzer and displayed as the Y-axis variable on a Hewlett-Packard 7140A X-Y recorder. Volume of expired gas was measured by a potentiometer attached to the Collins spirometer and displayed on the X-axis of the recorder. Subjects were trained to perform slow vital capacity maneuvers and watch the tracing on the spirometer to keep expiratory flow constant , and less tha n 0.3 l/s. Closing volumes were expressed as percent of slow vital capac-
ET AL.
ity. Slopes of phase III were expressed as A%NZ/l (BTPSJ and represent the average of at least two determinations. Since many of the subjects were adolescents, approximately 150 ml of dead space were added to the breathing circuit as recommended by Manzell et al. (20) . Blood for biochemical assays was drawn through a 19gauge scalp vein needle placed cleanly in an antecubital vein. The line was first-cleared by withdrawing l-2 ml blood; blood was withdrawn rapidly and placed in separate tubes for platelet count and hematocrit (0.15% EDTA), fibrinogen, activated partial thromboplastin time (aPTT), and fibrinolysis assays (Na citrate 3.8% 1: 9 blood) and fibrinopeptide A (apoprotinin 1,000 U and Na heparin 1,000 U/l0 ml). Blood was also drawn for subsequent radioimmunoassay of arginine vasopressin (ADH). The line was filled with a dilute solution of heparin and the subjects were placed at rest for 15-20 min in the dark, prior to withdrawing blood for catecholamine levels. The scalp vein needle was removed and a new one placed in the opposite arm immediately prior to the next blood-draw ing period. All blood samples except that used for platelet count were immediately placed in ice, and the plasma was separated in a Sorval RC-2 centrifuge at 4°C. Platelet counts and tests of fibrinolysis were performed immediately. Plasma aliquots for fibrinopeptide A, fibrinogen, aPTT, ADH, and catecholamines were quickly frozen in dry ice and methanol, and stored at -75°C until assayed. Fibrinogen was measured in duplicate by the method of Jacobson (16), using alkaline urea dissolution of thrombin-clottable protein and spectrophotometric determination of protein concentration in a Beckman DU spectrophotometer at 282 nm. aPTI’ was measured by Fibrometer in duplicate with a commercial kaolincephalin reagent (Hyland Laboratories) and CaCl,, 0.15 M. Concurrent controls were run with pooled normal human plasma. Plasma euglobulin lysis time was measured by the method of Buckell (7) with a euglobulin fraction prepared at pH 5.4. Fibrin plates were prepared by the method of Astrup and Muellertz (3) utilizing Amour-Reheis bovine fibrinogen in an agarose gel. An aliquot of the plasma euglobulin fraction was placed in duplicate on the cut wells, and the plates were incubated at 37% for 24 h. Two diameters of each lytic area were measured and the product was expressed in mm? Concurrent standards using Oreganon urokinase were run at dilutions of 2, 4, 8, and 12 CTA units of urokinase. Fibrinopeptide A was measured by Nossel’s methodology (21) using radioimmunoassay and an antibody prepared by EMCO Laboratories, Stockholm. Plasma ADH was measured by a liquid-phase radioimmunoassay with a rabbit antibody prepared against ADH coupled to albumin. Arginine vasopressin was extracted from plasma by acidification and Bentonite precipitation (1). Serum catecholamine levels were measured by radiometric assay by use of the method of Passon and Peuler (22) at Laboratory Procedures, Inc., Inglewood, CA. Statistical methods. Group data for baseline and 6 and 12 h were analyzed by two-way analysis of variance using Scheffe’s method of testing multiple comparisons
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on November 9, 2018. Copyright © 1979 American Physiological Society. All rights reserved.
HAPE
SUSCEPTIBILITY
AND
HYPOXEMIA
AT HIGH
43
ALTITUDE
(24). Group data for baseline and 12 h were analyzed by the t test for paired data. Intergroup comparisons between controls and HAPE-susceptible subjects were performed by a two-way repeated analysis of variance procedure with subjects nestled within groups (31).
96
OXYGEN SATURATION
0 /0
88
RESULTS
The striking finding in all HAPE-susceptible subjects was the marked degree of hypoxemia that developed within 1 h at altitude and persisted during the 12-h period (Fig. 1). This accentuated hypoxemia was always observed and there was essentially no overlap in oxyhemoglobin saturations between the two groups of subjects. When concurrent end-tidal carbon dioxide partial pressure (Pco,) was measured, the HAPE-susceptible subjects showed a tendency to relative hypoventilation at hour 6, but by hour 12, the mean end-tidal PcoZ was almost the same in the two groups despite a widening difference in oxyhemoglobin saturation (Fig. 2). It should also be noted that the tendency to greater hypoxemia not only appeared rapidly (within 1 h) but also resolved by the time the HAPE-susceptible subjects had been decompressed and left the chamber (30 min). The accentuated hypoxemia was seen in the six subjects who were residents of Leadville (3,100 m) and also in the one subject who was a resident of Denver (Fig. 2). These data indicated a significant difference for both (P < 0.001) and end-tid .a1 oxyhemoglobin saturationPCO~ (P < 0.05) between the subjects susceptible to HAPE and the controls at 4,150 m altitude. The differences between the groups at baseline altitude of 1,650 m were not significant. There were no significant time, or group by time, interaction effects for either oxyhemoglobin saturation or end-tidal PcoZ at either altitude. Despite this marked difference in oxyhemoglobin saturation at altitude, pulmonary function tests were similar in the two groups. Forced vital capacity declined minimally in both groups and there was very little change in FE& .o (Table 1). The slope of phase III of the desingle-breath nitrogen exhalation curve actually the changes were not creased in both groups although significant. The baseline phase III slope was signifi-
96
n=9
CONTROL HAPE-SlJSC.
92 OXY - Hb 88 SATURA STION 84 % 80
0
n=7
q
84
80
76
132 torr 128
124 / II 0 ‘/2
PC.001
76 b BASELINE
6 hrs 4150m.
12 hrs 4150m.
FIG. 1. Oxyhemoglobin saturation for all control and HAPE-susceptible subjects are shown. Acute altitude exposure produces exaggerated hypoxemia in HAPE-susceptible subjects at altitude: saturation was significantly lower in HAPE-susceptible subjects at 6 and 12 h at high altitude (P < 0.001).
6h HOURS
12h %p
AT 4150m.
FIG. 2. Oxyhemoglobin saturation for those control and HAPEsusceptible subjects with concurrent end-tidal Pco2 measurements are shown. At high altitude, HAPE-susceptible subjects had lower oxyhemoglobin saturation (P < 0.001) and higher end-tidal Pco2 levels (P < 0.05).
TABLE 1. Spirometry and single- breath (BTPS) curves at altitude n
Forced vital capacity, % baseline Control HAPE-susceptible Forced expiratory volume at 1 s, YO baseline Control HAPE-susceptible Slope phase III, A%N,/l Control HAPE-susceptible Values
P
