Protective effect of urinary trypsin inhibitor on myocardial mitochondria during hemorrhagic shock and reperfusion
Protective effect of urinary trypsin inhibitor on myocardial mitochondria during hemorrhagic shock and reperfusion
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DOI：
10.1097/01.ccm.0000057037.44171.ba
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发表时间：
2003-07-01
影响因子：
8.8
通讯作者：
Izumi, T
中科院分区：
文献类型：
--
作者：
Masuda, T;Sato, K;Izumi, T
目的：观察失血性休克及再灌注后心肌线粒体功能的变化，评价尿胰蛋白酶抑制剂（UTI）对线粒体的保护作用。设计：动物实验。环境：大学研究实验室。实验对象：Wistar大鼠接受50,000单位/kg/hr UTI治疗（27只，UTI组），对照组26只，对照组。干预措施：将大鼠置于低灌注缺血状态下，通过出血使左心室收缩压维持在50 mm Hg 60分钟，然后再输血60分钟。从出血前10分钟开始持续输注尿路感染。测定出血前、出血后、输血后的心功能；酶促法测定各测点心肌三磷酸腺苷（ATP）、磷酸肌酸（P-Cr）、丙酮酸（Pyr）、乳酸（Lac）含量。计算胞质磷酸化电位（PP）、线粒体内氧化型烟酰胺腺嘌呤二核苷酸/还原型烟酰胺腺嘌呤二核苷酸对的氧化还原电位（Eh(NAD)+/NADH）和ATP水解时吉布斯自由能的变化(DeltaG（ATP)（水解）能）。测量结果和主要结果：与对照组相比，UTI组输血后心功能明显改善，但失血性休克时心功能下降。尿路感染组输血后Lac和Lac/Pyr比值明显低于对照组。尿路感染组输血后ATP和P-Cr明显高于对照组。输血后，对照组的pp （x10(3) M-1）、Eh(NAD)+(/NADH) （x -1 mV）和DeltaG(ATP)（水解）（x -1 kcal/mol）分别为1.9 +/- 0.4、266 +/- 4和9.7 +/- 0.2，UTI组分别为4.0 +/- 0.9、274 +/- 5和13.0 +/- 0.2 （p < 0.001、p < 0.001、p < 0.001）。结论：在失血性休克后的再灌注中，心肌线粒体的氧化磷酸化受损，即使在再灌注后能量产生仍然减少。UTI有助于再灌注后心功能的恢复，可能是通过降低休克状态下线粒体功能障碍的严重程度和维持能量产生。
Objective: To examine the mitochondrial function in the myocardium after hemorrhagic shock and reperfusion and to evaluate the protective effect of urinary trypsin inhibitor (UTI) on mitochondria.Design: Animal experiment.Setting: University research laboratory.Subjects: Wistar rats receiving 50,000 units/kg/hr of UTI (n 27; UTI group) and control rats (n = 26; control group).Interventions: Rats were subjected to low-perfusion ischemia with the left ventricular systolic pressure maintained at 50 mm Hg for 60 mins by bleeding, followed by a 60-min reperfusion by transfusion of shed blood. UTI was infused continuously from 10 mins before bleeding. Cardiac function was measured before bleeding, after bleeding, and after transfusion; at each determination point, the myocardial contents of adenosine triphosphate (ATP), creatine phosphate (P-Cr), pyruvate (Pyr), and lactate (Lac) were measured enzymatically. The cytosolic phosphorylation potential (PP) as well as the redox potential of the oxidized form of nicotinamide adenine dinucleotide/reduced form of nicotinamide adenine dinucleotide couple in mitochondria (Eh(NAD)+/NADH) and change of Gibbs free energy in ATP hydrolysis (DeltaG(ATP) (hydrolysis) energy) were calculated.Measurements and Main Results: Cardiac function decreased during hemorrhagic shock but improved significantly in the UTI group after transfusion compared with the control group. Lac and the Lac/Pyr ratio were significantly lower in the UTI group than in the control group after transfusion. ATP and P-Cr were significantly higher in the UTI group than in the control group after transfusion. pp (x10(3) M-1), Eh(NAD)+(/NADH) (x - 1 mV), and DeltaG(ATP) (hydrolysis) (x - 1 kcal/mol) were 1.9 +/- 0.4, 266 +/- 4, and 9.7 +/- 0.2, respectively, in the control group and 4.0 +/- 0.9, 274 +/- 5 and 13.0 +/- 0.2, respectively, in the UTI group after transfusion (p < .001, p < .001, and p < .001, respectively).Conclusions: In reperfusion after hemorrhagic shock, oxidative phosphorylation in myocardial mitochondria is impaired and energy production remains reduced, even after reperfusion. UTI contributed to the recovery of cardiac function after reperfusion, probably by reducing the severity of mitochondrial dysfunction during a state of shock and by maintaining energy production.