去甲肾上腺素诱导的高血压灌注对猪心搏骤停复苏后肝脏的影响

Effects of hypertension state induced by norepinephrine on liver in a swine model of cardiopulmonary resuscitation

目的研究去甲肾上腺素（NE）诱导的高血压灌注状态对猪心肺复苏成功后肝脏功能及组织形态的影响。方法诱导猪出现心室纤颤4min后给予标准心肺复苏，自主循环恢复（ROSC）后应用NE干预治疗，然后按随机数字表法将ROSC的10只猪均分为两组；高血压组维持平均动脉压（MAP）为基础血压的130％，正常血压组维持MAP为基础血压水平，均予以10ml．kg^-1·h^-1的生理盐水补液；同时监测血流动力学；分别于基础状态及ROSC后10min、2h、4h抽血检测血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和乳酸脱氢酶（LDH）；于ROSC后24h处死动物，取肝脏组织检测Na＋-K＋-ATP酶和Ca2＋-ATP酶活性；光镜和电镜下观察肝组织病理改变。结果高血压组在ROSC后心率、MAP、心排血量和冠状动脉灌注压均显著高于正常血压组，氧摄取率较正常血压组降低。与正常血压组同时间点比较，高血压组血清AST于ROSC后2h、4h显著降低[R0sC后2h：（110．5±12；1）U／L比（141．8±8．1）U／L，R0sc后4h：（118．2±14．1）U／L比（175．0±14．3）U／L，均P〈O．053，ROSC后4hLDH显著降低[（18．1±1．9）μmol·s^-1·L^-1比（20．7±1．9）μmol·s^-1·L^1-，P〈0．053，而两组间ROSC后各时间点ALT变化不明显。高血压组肝脏ATP酶活性[Na＋-K＋-ATP酶：（2．054±0．716）U，Ca2＋-ATP酶：（1．889±0．450）U]较正常血压组[Na＋-K＋-ATP酶：（3．274±0．710）U，Ca2＋-ATP酶：（2．746±0．788）U]有所下降，但并无显著差异（均P〉0．05）。与正常血压组相比，高血压组肝脏细胞水肿、坏死，炎性细胞浸润以及线粒体结构破坏程度较轻。结论NE诱导的高血压灌注状态对维持ROSC后血流动力学稳定及氧代谢平衡有重要作用，对ROSC后肝脏功能及组织形态都有一定的保护作用。

Objective To study the effects of norepinephrine （NE）-induced hypertension （HT） on hepatic function and pathology after restoration of spontaneous circulation （ROSE） by cardiopulmonary resuscitation （CPR） in swine. Methods After 4 minutes of induced ventricular fibrillation （VF）, standard CPR was carried out, and then the NE was pumped after ROSC. The survivors were then divided into two groups by the random digits table. In the HT group （n=5） the mean arterial pressure （MAP） was maintained at 130% of the baseline （MAP before VF）, and in the normal pressure （NP） group （n=5） the MAP was maintained at the baseline level. At the same time, the animals of two groups received normal saline at the speed of 10 ml·kg^-1·h^-1. Hemodynamic status was monitored and aspartate aminotransferase （AST）, alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） were measured in blood samples obtained at baseline and at 10 minutes, 2 hours and 4 hours after ROSE. At 24 hours after ROSE, the animals were killed and the liver was removed to determine Na＋-K＋-ATPase and Ca2＋-ATPase activities and pathological changes under light and electron microscopy. Results The heart rate （HR）, MAP, cardiac output （CO） and coronary perfusion pressure （CPP） were obviously higher, while the oxygen extraction ratio was lower in the HT group than in the NP group. Compared with NP group, AST in the HT group was lower at ROSC 2 hours, 4 hours [ROSC 2 hours： （110.5±12.1） U/L vs. （141.8=k8.1） U/L; ROSE 4 hours： （118.2±14. 1） U/L vs. （175.0±14.3） U/L, both P〈0.05], LDH was lower at ROSC 4 hours （（18.1±1. 9） μmol·s^-1·L^-1 vs. （20.7±1. 9） μmol·s^-1·L^-1, P〈0.05], but ALT showed no significant difference between two groups after ROSE. ATPase activity in the HT group [Na＋-K＋-ATPase： （2.054±0.716） U, Ca2＋-ATPase： （1.889±0.450） U] was a little lower than that of the NP group [Na＋-K＋-ATPase： （3. 274 ±0. 710） U, Ca2＋-ATPase： （2. 746±0. 778） U], but without statistical significance （both P〉0. 05）. Compared with the NP group, there was less cellular edema, necrosis or inflammatory cells infiltration, and less damaged mitochondria in HT group. Conclusion These data suggest that HT induced by NE helps to maintain stable hemodynamic status and oxygen metabolism, and may protect the liver in terms of function and cellular injury after CPR.