Resuscitative effect of hyperoxia fluid on high-altitude hemorrhagic shock in rats and antishock mechanisms.

Pathophysiological characteristics of hemorrhagic shock at high altitude are different from that at plain which involve severe injury, high mortality, difficult treatment and compromised liquid tolerance. High-altitude pulmonary/cerebral edema and multiple-organ dysfunction render the conventional treatment ineffective. Herein, we evaluated the resuscitation effects of hyperoxia solution on high-altitude hemorrhagic shock in rats. For this purpose, a rat model of high-altitude (3,658 m) hemorrhagic shock was established on the plateau and hyperoxia solution (4 ml/kg) was infused through external jugular vein for resuscitation at 60 min post-hemorrhage. Blood pressure, blood gas, left and right ventricular pressure, lung and brain water content, survival time, survival rate at 2 h, levels of inflammatory cytokines and free oxygen radicals in blood and tissue were determined. After resuscitation with hyperoxia solution, blood pressure, arterial oxygen partial pressure, left and right ventricular systolic pressure, ±dp/dt max, survival time and rate were significantly increased. Lung and brain water content were unchanged, malondialdehyde activity in lung, brain and plasma and levels of TNF-α, IL-1, IL-6, and endothelin were significantly decreased. Besides, CGRP was elevated with reduced injury and improved lung and kidney functions. Concludingly, resuscitation with hyperoxia solution is feasible and more effective than other classical liquids, making it the first choice of treatment for high-altitude hemorrhagic shock.

[Gastrointestinal dysfunction in acute severe mountain sickness and its relation with multiple organ dysfunction syndrome].

OBJECTIVE: To investigate the relationship between gastrointestinal dysfunction (GD) and multiple organ dysfunction syndrome (MODS) in acute severe mountain sickness (ASMS), including high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE), by a retrospective study of medical records and prospective study of hospitalized patients. METHODS: In retrospective study, the clinical data of 3 184 inpatients of General Hospital of Tibetan Military Command suffering from ASMS in the past 50 years (from June, 1958 to June, 2007) were collected. Statistical analysis was performed to study the relationship between GD and MODS in these patients. For the prospective study, 10 admitted patients of ASMS were included. Gastroscopic examination was performed for the ASMS patients, and gastric and duodenal mucosa was scrutinized. At the same time, 30 g of glutamine (Gln) capsule was orally ingested each day for 3 days after the first day of admission. Ten healthy volunteers were included in the control group, and received the same treatment. The levels of serum diamine oxidase (DAO), malonic dialdehyde (MDA), endotoxin and lactulose/mannitol (L/M) ratio were detected before and after treatment in two groups. RESULTS: First, 49.8% of the patients with ASMS were complicated with GD, with 1.5% of fairy stool, and 1.0% with occult blood in stool. In 83 cases of ASMS complicated with MODS, 21.7% (18 cases) appeared GD, and the score of GD was 5.5 in the total score of all organ injury. Second, endoscopic examination showed extensive edema and localized hemorrhage in gastrointestinal mucous membrane, with dotted and patched erosion in gastric antrum and fundus. The pre-treatment DAO, MDA, and endotoxin were higher in the observation group than those in the control group (all P<0.01). After 3 days of Gln capsule treatment, DAO, MDA, and endotoxin were significantly decreased in the observation group (P<0.05 or P<0.01). The pre-treatment L/M ratio in observation group was significantly higher than that in healthy control group (150.69+/-19.91 vs. 117.91+/-17.78, P<0.01). The L/M ratio was significantly decreased after the treatment, as it decreased to 129.37+/-19.75 (P<0.05). However, no significant change in the healthy control group was observed. CONCLUSION: GD plays a major role in the pathogenesis of MODS in ASMS patients.

[Effects of liquids with different osmotic pressure and different oxygen concentration on resuscitation of hemorrhagic shock at high altitude in rat].

OBJECTIVE: To compare the effects of liquids with different osmotic pressure and different oxygen concentration on resuscitation of hemorrhagic shock at high altitude. METHODS: Hemorrhagic shock model of Sprague-Dawley (SD) rats was reproduced by Weigger method at the altitude of 3,658 meters. After 1 hour blood loss, the rats were treated either with normal saline, 75 g/L hypertonic saline solution, 60 g/L dextran 40 solution, solution of 75 g/L hypertonic saline solution with 60 g/L dextran 40, or hypertonic sodium chloride hydroxyethyl starch 40 solution, and all the above solutions were oxygenated with oxygen by high pressure. All the solutions were infused via external jugular vein (4 ml/kg) to resuscitate the rats, and the effects of different solutions on blood pressure (BP), blood gas, intraventricular pressure, water contents of lung or brain, survival time and survival rates were observed. RESULTS: The BP, mean arterial pressure (MAP), partial pressure of oxygen in artery (PaO2), left ventricular systolic pressures (LVSP), maximum upstroke velocity (+dp/dt max) and maximum descending velocity (-dp/dt max) of intraventricular pressure, survival time and survival rate were increased (P<0.05 or P<0.01), but the survival time of the rats in groups treated with hypertonic solutions or hypertonic colloid solutions was obviously prolonged. In particular, survival time and survival rate of the rats in the groups treated with hypertonic colloid solutions were raised more significantly than those of other groups. Besides, the results showed that BP rose steadily in all the groups, PaO2 and LVSP of these groups significantly increased, but partial pressure of carbon dioxide in artery (PaCO2) showed no significant change. Infusion of 4 ml/kg of liquids did not increase water contents of lung or brain. Hyperoxic solutions had no effect on the right ventricular pressure, but the oxygenated liquids could lower the right ventricular pressure at the beginning of resuscitation, suggesting that oxygen transfer through the vein could lower the pulmonary artery pressure and improve the right ventricle function. CONCLUSION: Liquids with different osmotic pressure and at different oxygen concentration showed therapeutical effect on hemorrhagic shock at high altitude in rat, with hypertonic colloid solution being the best among the liquids under examination.

[The clinical significance of leucocytosis and increase in interleukin content in acute mountain sickness complicated with multiple organ dysfunction syndrome].

OBJECTIVE: To study the role of white blood cell (WBC) and interleukins (ILs) in acute mountain sickness (AMS) complicated with multiple organ dysfunction syndrome (MODS). METHODS: Three thousand one hundred and eighty-four patients suffering from severe AMC in the past 50 years were surveyed with questionnaire. Correlation analysis was done to explore the relationship between differential count of WBC and elevation of ILs contents and MODS. RESULTS: There was no difference in differential count of WBC between essential high altitude pulmonary edema (HAPE) and secondary HAPE. No difference was also found between simple HAPE and high altitude cerebral edema (HACE). However, obvious difference in WBC was found between HACE accompanied by HAPE and simple HAPE or simple HACE in the differential counts of WBC, counts of WBC and neutrophil were significantly elevated, while lymphocyte was significantly declined (all P < 0.05). The count of WBC in people suffering from AMS accompanied by MODS was higher than patients only suffering from AMS, lymphocyte was significantly decreased, the difference was obviously (both P < 0.01). The content of tumor necrosis factor-alpha (TNF-alpha), IL-1, IL-2, IL-6 and IL-8 of severe AMS patients were obviously higher than that of normal people, therefore the content of IL-4 in severe AMS patients was obviously lower than that normal people the difference were obvious (all P < 0.01). CONCLUSION: People suffering from AMS also exist systemic inflammatory response syndrome (SIRS). SIRS play an important part in MODS which is a major cause of AMS, and it's a critical factor of high altitude MODS.

[The effect of inhaled nitric oxide on endothelium-derived angiokinetic factors in patients with acute high altitude disease].

OBJECTIVE: To study the effect of inhaled nitrogen monoxidum (NO) on endothelium-derived angiokinetic factors including NO, endothelin (ET), thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F(1a) (6-Keto-PGF(1a)) in patients with acute high altitude disease. METHODS: Forty-seven patients with acute high altitude disease were selected and divided into two groups randomly: twenty-three cases as a routine medical treatment group, for which oxygen, aminophylline, dexamethasone and furosemide were used, while 24 cases as a NO treatment group, for which only inhalation of 0.001% NO gas with air balanced in plateau (altitude 3658 m), were given twice daily (AM and PM each for an hour). The level of serum NO, ET, TXB(2) and 6-Keto-PGF(1a) were measured, and the changes of clinical symptoms were scored using the Lake Louise acute high altitude disease scoring. RESULTS: In the two groups, the level of ET [(78 +/- 8) and (69 +/- 5) ng/L], TXB(2) [(87 +/- 13) and (73 +/- 8) ng/L], ET/NO [(26.7 +/- 1.5) x 10(3) and (21.8 +/- 1.1) x 10(3)], TXB(2)/6-Keto-PGF(1a) (0.84 +/- 0.36 and 0.58 +/- 0.11, clinical symptom score 2.4 +/- 1.6 and 1.8 +/- 1.3) after treatment were decreased significantly as compared to the levels of ET [(83 +/- 8) and (84 +/- 4) ng/L], TXB(2) [(102 +/- 16) and (103 +/- 13) ng/L], ET/NO [(35.0 +/- 2.7) x 10(3) and (36.3 +/- 3.1) x 10(3)], TXB(2)/6-Keto-PGF(1a) (1.28 +/- 0.38 and 1.24 +/- 0.28), clinical symptom score (4.4 +/- 2.3 and 4.4 +/- 2.0) before treatment. After treatment, the level of NO [(2880 +/- 537) and (3167 +/- 192) microg/L] and 6-Keto-PGF(1a) [(122 +/- 46) and (128 +/- 15) ng/L] were significantly higher than the level of NO [(2372 +/- 144) and (2313 +/- 188) microg/L] and 6-Keto-PGF(1a) [(86 +/- 28) and (86 +/- 13) ng/L] before treatment. CONCLUSION: Inhaled NO is an effective treatment for high altitude disease in plateau, probably by modulating the angiokinetic factors.

[Analysis of 3,184 cases with acute mountain sickness complicated by multiple organ dysfunction syndrome].

OBJECTIVE: To investigate and analyze the probability of acute mountain sickness (AMS) [including high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE)] complicated by multiple organ dysfunction syndrome (MODS) and its pathogenetic mechanisms. METHODS: Questionnaire survey was made to retrospectively study the hospitalization cases in the past 50 years, and the incidence of high-altitude MODS (H-MODS) were statistically analyzed to determine the main causes and pathogenic mechanism of MODS. RESULTS: Among 3 184 cases with severe AMS, 83 cases conformed to the diagnostic criteria of diagnosis of H-MODS, and the incidence was 2.6%. The pathogenesis of acute H-MODS might be related to the activation of inflammation pathways, activation of blood clotting pathways and the damage to gastrointestinal mucosa barrier. Therefore, improving the diagnosis and the treatment effects of H-MODS is an important measure to increase cure rate of AMS and to decrease its death rate. CONCLUSION: AMS complicated by multiple organ damage (MOD) is the main factor that influences the therapeutic efficacy. Prompt effective remedy on the spot is a significant measure to reduce incidence of MOD.

[The clinical characteristics of acute severe high-altitude diseases in indigenous Tibetans].

OBJECTIVE: To describe the incidence and clinical characteristics of acute severe high-altitude diseases in indigenous Tibetans. METHODS: The medical records of indigenous Tibetan patients with high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema (HACE), who were treated in this hospital from June of 1956 to June of 2005, were retrospectively reviewed. RESULTS: A total of 3 184 cases of high-altitude disease were recorded in this period. Twenty four patients (0.75%, 24/3 184), 21 with HAPE and 3 with HACE, were indigenous Tibetans. Risk factors or precipitating factors were found in all the 24 cases, including getting into even higher altitude, exertion, cold, and alcohol drinking. From clinical symptoms, physical signs and laboratory examinations, it was found that 9 cases were complicated with multi-organ dysfunction. CONCLUSION: Indigenous Tibetans who travel between the plateau and the plain or to even higher altitude can suffer from hypoxic injury, even acute severe high-altitude disease, which may be complicated by multi-organ dysfunction.