Inflammatory Reponse of the Lung to Hypothermia and Fluid Therapy after Hemorrhagic Shock in Rats / 대한흉부외과학회지

ABSTRACT

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 35~40 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 degrees C [normothermia] vs 33degrees 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+/-0.5 mL/100 g less than those of group II (3.9+/-0.8 mL/100 g) and group III (4.1+/-0.7 mL/100 g). Fluid volume infused in 2nd stage was 28.6+/-6.0 mL (group I), 20.6+/-4.0 mL (group II) and 14.7+/-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+/-437 pg/mL (group I), 1,006+/-532 pg/mL (group II), and 764+/-302 pg/mL (group III), retrospectively. In histologic score, the score of group III (1.6+/-0.6) was significantly lower than that of group I (2.8+/-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, it 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.