• Journal of Chest Surgery
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• v.39 no.12 s.269
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• pp.879-890
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• 2006

Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.236-249
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• 1993

Background: Among the injurious agents to which the lung airspaces are constantly exposed are reactive species of oxygen. It has been widely believed that reactive oxygen species may be implicated in the etiology of lung injuries. In order to elucidated how this oxidant causes lung cell injury, we investigated the effects of exogenous $H_2O_2$ on alveolar epithelial barrier characteristics. Methods: Rat type II alveolar epithelial cells were plated onto tissue culture-treated polycarbonate membrane filters. The resulting confluent monolayers on days 3 and 4 were mounted in a modified Ussing chamber and bathed on both sides with HEPES-buffered Ringer solution. The changes in short-circuit current (Isc) and monolayer resistance (R) in response to the exogenous hydroperoxide were measured. To determine the degree of cellular catalase participation in protection against $H_2O_2$ injury to the barrier, experiments were repeated in the presence of 20 mM aminotriazole (ATAZ, an inhibitor of catalase) in the same bathing fluid as the hydroperoxide. Results: These monolayers have a high transepithelial resistance (>2000 ohm-$cm^2$) and actively transport $Na^+$ from apical fluid. $H_2O_2$(0-100 mM) was then delivered to either apical or basolateral fluid. Resulting indicated that $H_2O_2$ decreased Isc and R gradually in dose-dependent manner. The effective concentration of apical $H_2O_2$ at which Isc (or R) was decreased by 50% at one hour ($ED_{50}$) was about 4 mM. However, basolateral $H_2O_2$ exposure led to $ED_{50}$ for Isc (and R) of about 0.04 mM. Inhibition of cellular catalase yielded $ED_{50}$ for Isc (and R) of about 0.4 mM when $H_2O_2$ was given apically, while $ED_{50}$ for basolateral exposure to $H_2O_2$ did not change in the presence of ATAZ. The rate of $H_2O_2$ consumption in apical and basolateral bathing fluids was the same, while cellualr catalase activity rose gradually with time in culture. Conclusion: Our data suggest that basolateral $H_2O_2$ may affect directly membrane component (e.g., $Na^+,\;K^+$-ATPase) located on the basolateral cell surface. Apical $H_2O_2$, on the other hand, may be largely degraded by catalase as it passes through the cells before reaching these membrane components. We conclude that alveolar epithelial barrier integrity as measured by Isc and R are compromised by $H_2O_2$ being relatively sensitive to basolateral (and insensitive to apical) $H_2O_2$.