S52
Microcirculafion and High Altitude Edema G. Ueda, M. Takeoka, A. Sakai, T Kobayashi Department of Environ Physiology, Shinshu University School of Medicine, 390 Matsumoto, Japan
Materials and Methods Abstract
ashi, Microcirculation and High High Altitude Altitude Edema. Edema. Tnt Int J SportsMed,Vol l3,Suppl 13,Suppl l,ppS52—S54, l,ppSS2—SS4, 1992. 1992. Physiological functions are are aa conglomeraconglomeraPhysiological functions tion of cell functions, and all cells are regulated by informa-
tion processing and energy distributing distributing systems. systems. The The
consists of former consists of nervous nervous systems systems and and the the latter latterconsists consistsof of respiro-circulatory systems. Defensive reactions appear in response to local cold stress which can induce frostbite or edema. We analyzed the cold cold vasoreaction vasoreaction time time course course in in which which rhythmical changes and trends were found found using using rabrabbit's ear blood vessels. In sheep, hypobaric hypoxia corre-
sponding to 6600 m altitude was applied for 3 hrs. Lung Lung lymph volume increased in response to this stress. Most sheep exposed recovered later. The factors influencing the increase in lung lymph flow and the conditions to induce in-
Rabbits weighing weighing about about 3 3 kg were used in vasoRabbits
motion and edema experiments. The distal one-third of the earlobe was immersed in liquid liquid of of —4 —4 to to — —10 °C. The The time time 10 °C. course of thermoregulatory oscillation was recorded without anesthesia, using thermistor pickups placed on the ear central artery. Sheep, 25 to 32 kg, were exposed to hypobaric hypoxia in a climatic chamber. Lung lymph was collected by the technique of Staub (1). Eight normal male subjects were exposed to hypobaria to study symptoms 88). The age ranged from 20 to 36 years old. A 22 year-old male who died on a winter mountain was dissected at the department of legal medicine (10).
Results and Discussion
Cold stress The pattern of vasoreaction in peripheral vessels in response to cold is either regular or irregular (5). In one -6 °C vasoreactions were recorded for six hrs. The rabbit -6 thirty-seven wave patterns were recognized for the record,
terstitial edema were analyzed. Simulated-altitude symptoms were, then, analyzed by Sampson's method. In eight subjects exposed to 3700 m condition, the nervous system symptoms were well correlated with the respiro-circulatory symptoms. Thus we concluded that the distinction between system-specific diseases, viz., that between acute mountain
wave height average values showed staircase pattern and
sickness cerebral type (AMS-C) and respiratory type
plied to the external ear, and the recovery period was pro-
(AMS-R) was somewhat fuzzy. A common AMS condition, AMS-general, exists. Lastly, a case of 22-year-old male who died of lung and cerebral edema on a winter mountain was reported. The lung weighed 1506 g and the brain I610g. l610g.
longed (9).
Key words
Vasomotion, lung lymph, high altitude pulmonary edema
Introduction
At high altitude humans are exposed to hypobaric hypoxia and sometimes to cold. The circulatory response to simulated altitude or cold, strong enough, shows an alarm signal, for example, blood pressure oscillation (4). Vasomotor oscillation shows a specific time course in response to local cold stress (3), and to the extent of its limits preserves homeostasis. Beyond Beyond aa certain certain stress stress level, level, impairments impairments
appear. Both experimental and field data concerned are presented here. Tnt. J. SportsMed.l3(1992)S52—S54 13(1992)S52—S54 Int.J.SportsMed. Georg Thieme Verlag Stuttgart New York GeorgThieme StuttgartNew
with each pattern consisting of 5 to 10 waves. The successive fatigue fatigue during during the the course, course, although although the the periods periods were were stable stable (3) (3) (Fig. 1). No edema appeared here. The time course of edema at — 20 °C — 30 mm stimulus was greater when massage was ap-
Hypobaric hypoxia Basic permeability characteristics of lung fluid flow were reported in (6). (6). Collected Collected lung lung lymph lymph volume volumeJJis inis in. fluenced fluenced by X, which is mean vascular pressure minus minus osmotic osmotic pressure, and filtration coefficient L, which consists of capil-
lary filtration LB and lymph-vessel filtration LL. At 6600 m simulated altitude exposure, the increase in J was found to be influenced by both L and X. With left atrial pressure elevation, it was mainly affected by X (Fig. 2). With endotoxin infusion, it was increase in L was greater than that in X. In air bubble infusion, increase in X was greater than that in L. Interstitial edema occurs when increase in J is noticed and LB > LL. After endotoxin infusion no significant significant edema edema was was noticed noticed because becauseLB LB was nearly LL (7). nearly equal equal to toLL
Subjective symptoms of hypobaric hypoxia In eight eight subjects subjectsexposed exposed to toa a3700 3700rn-simum-simulated altitude altitude for lated for 24 hrs, Sampson (2) symptom scores for acute mountain sickness cerebral type (AMS-C) were well correlated with those for respiratory type (AMS-R). The dis-
Downloaded by: National University of Singapore. Copyrighted material.
G. Ueda, M Takeoka, A. A. Sakai Sakai and and T. T Kobay-
mt. i Sports Med. 13(1992) S53
Microcirculation and High Altitude Edema
Fig. 1 Rabbit ear vasomotion in
p
.E
0. 0 E a
Z D-
> Ce
4:
x
>-
30
60
90
120
180
150
210
240
300
270
—6 °Cliquidat25 °C room. The XBAR values show a staircase phenomenon unti' 60 until 60 mm mn and
decrease thereafter due to fatigue. fafigue. The YBAR values are relatively relativefy stable. Each wave here indicated is the mean for a similar group of original vasooscillatory waves (3).
330
flg.22Factors, Fig. Factors,XXand andL, L, affecting affecting sheep Endotoxin
6.600 m
X
lung lymph volume J. X: driving forces of leaky flow in pulmonary flow pathway. L is the filtration of the pathways. The control values are graphed as a rectangular cubicle with a unit unit ?ength length in test in each axis. The test values (6600 m altitude: n = 8, left atrial pressure elevation: n = 5), endotoxin infusion: n = 6 and air bubble infusion: n = 6) are indicated ndicated by the respective respective outer outer cucubicles shown here (7).
Mr Bubble Air
Left Atrfal Atrial
x
7
tinction is fuzzy. In the case of local cold exposure, the impairment ment is is local. local. In In the the case case of of hypoxia, hypoxia, the the effect effect is is not not localized. localized.
Thus AMS is classified as AMS-general and AMS-local. Fuzziness in diagnosis of AMS arises from disease structure and from sense-receptor threshold characteristics (8).
Cold and hypobaric hypoxia in winter mountain A 22-yr-old male who was one of four-man expedition that entered the Japan Alps on Dec. 30th, 1990 died of altitude disease on Jan. 4th, 1991. the main points in this case have already been reported (10). Although his initial subjective physical conditions conditions had had been been excellent, excellent, on on Jan Jan 2nd 2ndhe he developed a slight fever. However, his state on the morning of the 3rd was good. In the afternoon, his activity was curtailed by
severe weather conditions. On the morning of the 4th, he showed progressive deterioration. At noon a helicopter rescue was requested, but access was hindered by the weather condi-
tions. After urinary incontinence at 16:00 and sudden expectoration of foamy exudate at 20:00, the man died. He had received no medical treatment other than the first aid provided by his comrades. At autopsy in our legal medicine department, lung weight was 1506 g. Interstitial edema and alveolar flooding were marked. Brain weight was 1610 g and vessels were congestive, showing multiple petechiae. Evidence of cold injury was present on the face and peripheral parts of the extremities. Our background study into the victim's previous medical history revealed constitutional elements to high altitude disease and vulnerability to accident. References 1
Staub N. C., Bland R. D., Brigham K. L., Demling R., Erdman A.
J.: Preparation of chronic lung lymph fistulas in sheep. J. SurgRes 19:315—320,1975. 22 Sampson J. B., B., Cymerman Cymerman A., A., Burse Burse R. R. L., L., Maber Maber J. J. T., T., Rock Rock P. P. B.: B.: Sampson J. Procedures for the measurement of acute mountain sickness. A viaand EnvMed54:1063—1073,1983. 1063—1073,1983. tion, Space SpaceandEnvMed54:
Downloaded by: National University of Singapore. Copyrighted material.
Time (mm)
S54 mt. mt.J.J.Sports SportsMed. Med. 13(1992) 13(1992) Ueda G., Takeoka M., Koshihara Y.: Wave pattern analyses for
symptoms in acute mountain sickness. Jpn J Mountain Med 10:
cold vasooscillation. lntlJBiomeleor lntlJBiomeleor 27: 27: 157—164, 157—164,1983. 1983.
145— 149, 1990. 145—149,1990.
Ueda G., Sakai A., Kobayashi T., Kubo K., Fukushima M., Yoshimura K.: Low atmospheric pressure and third-order blood pressure waves in sheep. In Miyakawa K. (ed): Mechanisms of Blood Pressure Waves. Waves. Tokyo Tokyo and and Berlin, Berlin, Springer-Verlag Springer-Verlag1984, 1984,
Ueda G., Takeoka M.: Microcirculatory responses during frost injury in rabbit ear. In Tsuchiya M. (ed): Microcirculation Annual, Tokyo, Nihon-Igakukan 1991, pp 177—178. Tokyo, Ueda G., Kubo K., Yanagidaira Y., Takeoka M., Hasekura H., Yonemura K., K., Shigematsu ShigematsuH., H.,Ebara EbaraT., Hirose T.: T.:AAcase casereport reportofof T., Hirose high altitude pulmonary edema victim. Jpn J Mountain high Mountain Med Med 11: 11:
pp 137—146. pp137— 146.
Ueda G., Takeoka M.: Computer analyses for thermoregulatory cold vasooscillation. In Hales J. R. S. (ed): Thermal Physiology, 6
G. Ueda, M. Takeoka, A. Sakai, T Kobayashi
10
17—21, 1991. 17—21,1991.
New York, Raven Press 1984, pp.209—212. Ueda G.: The permeability characteristics of high altitude pulmo-
nary edema model. In Courtice F. C. (ed): Microcirculation Research II, 1—475. TI,Univ. Univ.ofNSW, ofNSW,Sydney Sydney1984, 1984,pp.47 pp.471—475.
Gou Ueda
edema model. In Tsuchiya M. (ed): Microcirculation an update I, Amsterdam, Excerpta Medica 1987, pp 171—172. Ueda G., Sakai A., AsanoK.,TakeokaM.,FujiwaraT.,Kobayashi UedaG.,SakaiA., Asano K., Takeoka M., FujiwaraT., Kobayashi T., Matsuzawa Y.: Fuzzy theoretical interpretation of cause and
Dept. of Environ Physiology Shinshu University School of Medicine 390 Matsumoto 390 Matsumoto
8
Japan Japan
High Altitude Pulmonary Edema is Caused by Stress Failure of Pulmonary Capillaries .1. B. West and 0. Mathieu-Costello Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623
Abstract
J. B. West and 0. Mathieu-Costello, High Altitude Pulmonary Edema is Caused by Stress Failure of Pulmonary Capillaries. Tnt J Sports Med, Vol 13, Suppl 1, ppS54—S58, 1992.
The pathogenesis of high altitude pulmonary edema (HAPE) is disputed. We propose that the mechanism is stress failure of pulmonary capillaries. The main features to be accounted for are the strong association with
pulmonary hypertension, the high permeability characteristics of the edema, and the presence of inflammatory markers in the lung lavage fluid. When the capillary pressure is raised to about 40 mmHg in anesthetized rabbits, ultrastructural damage to the capillary walls is seen including breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. This results in a
high permeability form of edema with the escape of high molecular weight proteins and blood cells into the alveolar spaces. In addition the basement membrane of the en-
Int.J.SportsMed. 13(l992)S54—S58 GeorgThieme Verlag StuttgartNew York
dothelial layer is frequently exposed, and we suggest that this highly reactive surface attracts and activates platelets
and neutrophils. The result is the formation of small thrombi which are frequently seen in HAPE, and the presence of inflammatory markers such as leukotriene B4 and the complement fragment C5a in the lung lavage fluid. Hy-
poxic pulmonary vasoconstriction raises the pressure in some capillaries because the constriction is uneven. Since HAPE has its origin in the high pulmonary artery pressure, the objective of treatment should be to reduce the pressure by descent, administering oxygen, or giving drugs such as calcium channel blockers (e.g. nifedipine) which relax pulmonary vasoconstriction. Stress failure of pulmonary capillaries satisfactorily accounts for the features of HAPE. Key words
Hypoxia, pulmonary circulation, rabbit, high permeability edema, inflammatory markers, vasoconstriction
Downloaded by: National University of Singapore. Copyrighted material.
Ueda G.: Composite membrane theory in sheep pulmonary
Microcirculafion and High Altitude Edema G. Ueda, M. Takeoka, A. Sakai, T Kobayashi Department of Environ Physiology, Shinshu University School of Medicine, 390 Matsumoto, Japan
Materials and Methods Abstract
ashi, Microcirculation and High High Altitude Altitude Edema. Edema. Tnt Int J SportsMed,Vol l3,Suppl 13,Suppl l,ppS52—S54, l,ppSS2—SS4, 1992. 1992. Physiological functions are are aa conglomeraconglomeraPhysiological functions tion of cell functions, and all cells are regulated by informa-
tion processing and energy distributing distributing systems. systems. The The
consists of former consists of nervous nervous systems systems and and the the latter latterconsists consistsof of respiro-circulatory systems. Defensive reactions appear in response to local cold stress which can induce frostbite or edema. We analyzed the cold cold vasoreaction vasoreaction time time course course in in which which rhythmical changes and trends were found found using using rabrabbit's ear blood vessels. In sheep, hypobaric hypoxia corre-
sponding to 6600 m altitude was applied for 3 hrs. Lung Lung lymph volume increased in response to this stress. Most sheep exposed recovered later. The factors influencing the increase in lung lymph flow and the conditions to induce in-
Rabbits weighing weighing about about 3 3 kg were used in vasoRabbits
motion and edema experiments. The distal one-third of the earlobe was immersed in liquid liquid of of —4 —4 to to — —10 °C. The The time time 10 °C. course of thermoregulatory oscillation was recorded without anesthesia, using thermistor pickups placed on the ear central artery. Sheep, 25 to 32 kg, were exposed to hypobaric hypoxia in a climatic chamber. Lung lymph was collected by the technique of Staub (1). Eight normal male subjects were exposed to hypobaria to study symptoms 88). The age ranged from 20 to 36 years old. A 22 year-old male who died on a winter mountain was dissected at the department of legal medicine (10).
Results and Discussion
Cold stress The pattern of vasoreaction in peripheral vessels in response to cold is either regular or irregular (5). In one -6 °C vasoreactions were recorded for six hrs. The rabbit -6 thirty-seven wave patterns were recognized for the record,
terstitial edema were analyzed. Simulated-altitude symptoms were, then, analyzed by Sampson's method. In eight subjects exposed to 3700 m condition, the nervous system symptoms were well correlated with the respiro-circulatory symptoms. Thus we concluded that the distinction between system-specific diseases, viz., that between acute mountain
wave height average values showed staircase pattern and
sickness cerebral type (AMS-C) and respiratory type
plied to the external ear, and the recovery period was pro-
(AMS-R) was somewhat fuzzy. A common AMS condition, AMS-general, exists. Lastly, a case of 22-year-old male who died of lung and cerebral edema on a winter mountain was reported. The lung weighed 1506 g and the brain I610g. l610g.
longed (9).
Key words
Vasomotion, lung lymph, high altitude pulmonary edema
Introduction
At high altitude humans are exposed to hypobaric hypoxia and sometimes to cold. The circulatory response to simulated altitude or cold, strong enough, shows an alarm signal, for example, blood pressure oscillation (4). Vasomotor oscillation shows a specific time course in response to local cold stress (3), and to the extent of its limits preserves homeostasis. Beyond Beyond aa certain certain stress stress level, level, impairments impairments
appear. Both experimental and field data concerned are presented here. Tnt. J. SportsMed.l3(1992)S52—S54 13(1992)S52—S54 Int.J.SportsMed. Georg Thieme Verlag Stuttgart New York GeorgThieme StuttgartNew
with each pattern consisting of 5 to 10 waves. The successive fatigue fatigue during during the the course, course, although although the the periods periods were were stable stable (3) (3) (Fig. 1). No edema appeared here. The time course of edema at — 20 °C — 30 mm stimulus was greater when massage was ap-
Hypobaric hypoxia Basic permeability characteristics of lung fluid flow were reported in (6). (6). Collected Collected lung lung lymph lymph volume volumeJJis inis in. fluenced fluenced by X, which is mean vascular pressure minus minus osmotic osmotic pressure, and filtration coefficient L, which consists of capil-
lary filtration LB and lymph-vessel filtration LL. At 6600 m simulated altitude exposure, the increase in J was found to be influenced by both L and X. With left atrial pressure elevation, it was mainly affected by X (Fig. 2). With endotoxin infusion, it was increase in L was greater than that in X. In air bubble infusion, increase in X was greater than that in L. Interstitial edema occurs when increase in J is noticed and LB > LL. After endotoxin infusion no significant significant edema edema was was noticed noticed because becauseLB LB was nearly LL (7). nearly equal equal to toLL
Subjective symptoms of hypobaric hypoxia In eight eight subjects subjectsexposed exposed to toa a3700 3700rn-simum-simulated altitude altitude for lated for 24 hrs, Sampson (2) symptom scores for acute mountain sickness cerebral type (AMS-C) were well correlated with those for respiratory type (AMS-R). The dis-
Downloaded by: National University of Singapore. Copyrighted material.
G. Ueda, M Takeoka, A. A. Sakai Sakai and and T. T Kobay-
mt. i Sports Med. 13(1992) S53
Microcirculation and High Altitude Edema
Fig. 1 Rabbit ear vasomotion in
p
.E
0. 0 E a
Z D-
> Ce
4:
x
>-
30
60
90
120
180
150
210
240
300
270
—6 °Cliquidat25 °C room. The XBAR values show a staircase phenomenon unti' 60 until 60 mm mn and
decrease thereafter due to fatigue. fafigue. The YBAR values are relatively relativefy stable. Each wave here indicated is the mean for a similar group of original vasooscillatory waves (3).
330
flg.22Factors, Fig. Factors,XXand andL, L, affecting affecting sheep Endotoxin
6.600 m
X
lung lymph volume J. X: driving forces of leaky flow in pulmonary flow pathway. L is the filtration of the pathways. The control values are graphed as a rectangular cubicle with a unit unit ?ength length in test in each axis. The test values (6600 m altitude: n = 8, left atrial pressure elevation: n = 5), endotoxin infusion: n = 6 and air bubble infusion: n = 6) are indicated ndicated by the respective respective outer outer cucubicles shown here (7).
Mr Bubble Air
Left Atrfal Atrial
x
7
tinction is fuzzy. In the case of local cold exposure, the impairment ment is is local. local. In In the the case case of of hypoxia, hypoxia, the the effect effect is is not not localized. localized.
Thus AMS is classified as AMS-general and AMS-local. Fuzziness in diagnosis of AMS arises from disease structure and from sense-receptor threshold characteristics (8).
Cold and hypobaric hypoxia in winter mountain A 22-yr-old male who was one of four-man expedition that entered the Japan Alps on Dec. 30th, 1990 died of altitude disease on Jan. 4th, 1991. the main points in this case have already been reported (10). Although his initial subjective physical conditions conditions had had been been excellent, excellent, on on Jan Jan 2nd 2ndhe he developed a slight fever. However, his state on the morning of the 3rd was good. In the afternoon, his activity was curtailed by
severe weather conditions. On the morning of the 4th, he showed progressive deterioration. At noon a helicopter rescue was requested, but access was hindered by the weather condi-
tions. After urinary incontinence at 16:00 and sudden expectoration of foamy exudate at 20:00, the man died. He had received no medical treatment other than the first aid provided by his comrades. At autopsy in our legal medicine department, lung weight was 1506 g. Interstitial edema and alveolar flooding were marked. Brain weight was 1610 g and vessels were congestive, showing multiple petechiae. Evidence of cold injury was present on the face and peripheral parts of the extremities. Our background study into the victim's previous medical history revealed constitutional elements to high altitude disease and vulnerability to accident. References 1
Staub N. C., Bland R. D., Brigham K. L., Demling R., Erdman A.
J.: Preparation of chronic lung lymph fistulas in sheep. J. SurgRes 19:315—320,1975. 22 Sampson J. B., B., Cymerman Cymerman A., A., Burse Burse R. R. L., L., Maber Maber J. J. T., T., Rock Rock P. P. B.: B.: Sampson J. Procedures for the measurement of acute mountain sickness. A viaand EnvMed54:1063—1073,1983. 1063—1073,1983. tion, Space SpaceandEnvMed54:
Downloaded by: National University of Singapore. Copyrighted material.
Time (mm)
S54 mt. mt.J.J.Sports SportsMed. Med. 13(1992) 13(1992) Ueda G., Takeoka M., Koshihara Y.: Wave pattern analyses for
symptoms in acute mountain sickness. Jpn J Mountain Med 10:
cold vasooscillation. lntlJBiomeleor lntlJBiomeleor 27: 27: 157—164, 157—164,1983. 1983.
145— 149, 1990. 145—149,1990.
Ueda G., Sakai A., Kobayashi T., Kubo K., Fukushima M., Yoshimura K.: Low atmospheric pressure and third-order blood pressure waves in sheep. In Miyakawa K. (ed): Mechanisms of Blood Pressure Waves. Waves. Tokyo Tokyo and and Berlin, Berlin, Springer-Verlag Springer-Verlag1984, 1984,
Ueda G., Takeoka M.: Microcirculatory responses during frost injury in rabbit ear. In Tsuchiya M. (ed): Microcirculation Annual, Tokyo, Nihon-Igakukan 1991, pp 177—178. Tokyo, Ueda G., Kubo K., Yanagidaira Y., Takeoka M., Hasekura H., Yonemura K., K., Shigematsu ShigematsuH., H.,Ebara EbaraT., Hirose T.: T.:AAcase casereport reportofof T., Hirose high altitude pulmonary edema victim. Jpn J Mountain high Mountain Med Med 11: 11:
pp 137—146. pp137— 146.
Ueda G., Takeoka M.: Computer analyses for thermoregulatory cold vasooscillation. In Hales J. R. S. (ed): Thermal Physiology, 6
G. Ueda, M. Takeoka, A. Sakai, T Kobayashi
10
17—21, 1991. 17—21,1991.
New York, Raven Press 1984, pp.209—212. Ueda G.: The permeability characteristics of high altitude pulmo-
nary edema model. In Courtice F. C. (ed): Microcirculation Research II, 1—475. TI,Univ. Univ.ofNSW, ofNSW,Sydney Sydney1984, 1984,pp.47 pp.471—475.
Gou Ueda
edema model. In Tsuchiya M. (ed): Microcirculation an update I, Amsterdam, Excerpta Medica 1987, pp 171—172. Ueda G., Sakai A., AsanoK.,TakeokaM.,FujiwaraT.,Kobayashi UedaG.,SakaiA., Asano K., Takeoka M., FujiwaraT., Kobayashi T., Matsuzawa Y.: Fuzzy theoretical interpretation of cause and
Dept. of Environ Physiology Shinshu University School of Medicine 390 Matsumoto 390 Matsumoto
8
Japan Japan
High Altitude Pulmonary Edema is Caused by Stress Failure of Pulmonary Capillaries .1. B. West and 0. Mathieu-Costello Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0623
Abstract
J. B. West and 0. Mathieu-Costello, High Altitude Pulmonary Edema is Caused by Stress Failure of Pulmonary Capillaries. Tnt J Sports Med, Vol 13, Suppl 1, ppS54—S58, 1992.
The pathogenesis of high altitude pulmonary edema (HAPE) is disputed. We propose that the mechanism is stress failure of pulmonary capillaries. The main features to be accounted for are the strong association with
pulmonary hypertension, the high permeability characteristics of the edema, and the presence of inflammatory markers in the lung lavage fluid. When the capillary pressure is raised to about 40 mmHg in anesthetized rabbits, ultrastructural damage to the capillary walls is seen including breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. This results in a
high permeability form of edema with the escape of high molecular weight proteins and blood cells into the alveolar spaces. In addition the basement membrane of the en-
Int.J.SportsMed. 13(l992)S54—S58 GeorgThieme Verlag StuttgartNew York
dothelial layer is frequently exposed, and we suggest that this highly reactive surface attracts and activates platelets
and neutrophils. The result is the formation of small thrombi which are frequently seen in HAPE, and the presence of inflammatory markers such as leukotriene B4 and the complement fragment C5a in the lung lavage fluid. Hy-
poxic pulmonary vasoconstriction raises the pressure in some capillaries because the constriction is uneven. Since HAPE has its origin in the high pulmonary artery pressure, the objective of treatment should be to reduce the pressure by descent, administering oxygen, or giving drugs such as calcium channel blockers (e.g. nifedipine) which relax pulmonary vasoconstriction. Stress failure of pulmonary capillaries satisfactorily accounts for the features of HAPE. Key words
Hypoxia, pulmonary circulation, rabbit, high permeability edema, inflammatory markers, vasoconstriction
Downloaded by: National University of Singapore. Copyrighted material.
Ueda G.: Composite membrane theory in sheep pulmonary
