中国危重病急救医学
中國危重病急救醫學
중국위중병급구의학
CHINESE CRITICAL CARE MEDICINE
2011年
8期
471-474
,共4页
胡森%侯经元%李琳%杨明星%盛志勇
鬍森%侯經元%李琳%楊明星%盛誌勇
호삼%후경원%리림%양명성%성지용
失血性休克%丙戊酸%药物疗法%器官保护%生存率
失血性休剋%丙戊痠%藥物療法%器官保護%生存率
실혈성휴극%병무산%약물요법%기관보호%생존솔
Hemorrhage shock%Valproic acid%Drug therapy%Organ protection%Survival rate
目的 探讨组蛋白去乙酰化酶抑制剂丙戊酸(VPA)对致死性失血性休克犬器官功能和预后的影响.方法 20只成年雄性Beagle犬,采用颈总动脉放血(按全身血容量的42%计算)制备失血性休克模型.将模型犬按随机数字表法分为休克对照组和VPA治疗组,每组10只.VPA治疗组于失血后1.5 h静脉注射(静注)VPA 100 mg/kg(溶于20 ml生理盐水),休克对照组在失血后24 h内静注20 ml生理盐水;失血后24 h起两组犬均实施延迟静脉补液.在非麻醉状态下测定犬失血前(0 h)和失血后不同时间点平均动脉压(MAP)及血浆丙氨酸转氨酶(ALT)、肌酐(Cr)和肌酸激酶同工酶(CK-MB),记录尿量及72 h生存率.结果 两组失血后2 h MAP均显著降低;随后VPA治疗组MAP(mm Hg,1 mm Hg=0.133 kPa)迅速回升,于失血后4、8和24 h显著高于相应休克对照组(58.4±7.6比40.3±5.0,84.4±8.0比56.4±4.4,92.6±10.3比72.6±8.9,P＜0.05或P＜0.01).VPA治疗组0～8、8～24、24～48和48～72 h尿量均显著多于休克对照组,但仍显著少于失血前(0 h).两组失血后血浆ALT、Cr和CK-MB均较0 h显著升高;VPA治疗组失血后4 h起器官功能指标显著低于休克对照组[ALT(U/L):80.1±9.8比112.2±10.1;Cr(μmol/L):74.5±8.3比88.0±7.6;CK-MB(kU/L):10.39±1.10比13.67±1.46,P＜0.05或P＜0.01],但失血后72 h仍显著高于0 h(ALT:79.5±7.1比40.5±4.4;Cr:85.6±7.1比46.6±4.8;CK-MB:7.63±0.86比1.66±0.21,均P＜0.01).VPA治疗组失血后72 h生存率显著高于休克对照组[70%(7/10)比20%(2/10),P＜0.05].结论 犬42%血容量失血后静注VPA能有效提高MAP,增加尿量,减轻器官功能损害,提高72 h早期生存率,有潜力成为战争或突发事故及灾害时低血容量休克现场救治的有效药物.
目的 探討組蛋白去乙酰化酶抑製劑丙戊痠(VPA)對緻死性失血性休剋犬器官功能和預後的影響.方法 20隻成年雄性Beagle犬,採用頸總動脈放血(按全身血容量的42%計算)製備失血性休剋模型.將模型犬按隨機數字錶法分為休剋對照組和VPA治療組,每組10隻.VPA治療組于失血後1.5 h靜脈註射(靜註)VPA 100 mg/kg(溶于20 ml生理鹽水),休剋對照組在失血後24 h內靜註20 ml生理鹽水;失血後24 h起兩組犬均實施延遲靜脈補液.在非痳醉狀態下測定犬失血前(0 h)和失血後不同時間點平均動脈壓(MAP)及血漿丙氨痠轉氨酶(ALT)、肌酐(Cr)和肌痠激酶同工酶(CK-MB),記錄尿量及72 h生存率.結果 兩組失血後2 h MAP均顯著降低;隨後VPA治療組MAP(mm Hg,1 mm Hg=0.133 kPa)迅速迴升,于失血後4、8和24 h顯著高于相應休剋對照組(58.4±7.6比40.3±5.0,84.4±8.0比56.4±4.4,92.6±10.3比72.6±8.9,P＜0.05或P＜0.01).VPA治療組0～8、8～24、24～48和48～72 h尿量均顯著多于休剋對照組,但仍顯著少于失血前(0 h).兩組失血後血漿ALT、Cr和CK-MB均較0 h顯著升高;VPA治療組失血後4 h起器官功能指標顯著低于休剋對照組[ALT(U/L):80.1±9.8比112.2±10.1;Cr(μmol/L):74.5±8.3比88.0±7.6;CK-MB(kU/L):10.39±1.10比13.67±1.46,P＜0.05或P＜0.01],但失血後72 h仍顯著高于0 h(ALT:79.5±7.1比40.5±4.4;Cr:85.6±7.1比46.6±4.8;CK-MB:7.63±0.86比1.66±0.21,均P＜0.01).VPA治療組失血後72 h生存率顯著高于休剋對照組[70%(7/10)比20%(2/10),P＜0.05].結論 犬42%血容量失血後靜註VPA能有效提高MAP,增加尿量,減輕器官功能損害,提高72 h早期生存率,有潛力成為戰爭或突髮事故及災害時低血容量休剋現場救治的有效藥物.
목적 탐토조단백거을선화매억제제병무산(VPA)대치사성실혈성휴극견기관공능화예후적영향.방법 20지성년웅성Beagle견,채용경총동맥방혈(안전신혈용량적42%계산)제비실혈성휴극모형.장모형견안수궤수자표법분위휴극대조조화VPA치료조,매조10지.VPA치료조우실혈후1.5 h정맥주사(정주)VPA 100 mg/kg(용우20 ml생리염수),휴극대조조재실혈후24 h내정주20 ml생리염수;실혈후24 h기량조견균실시연지정맥보액.재비마취상태하측정견실혈전(0 h)화실혈후불동시간점평균동맥압(MAP)급혈장병안산전안매(ALT)、기항(Cr)화기산격매동공매(CK-MB),기록뇨량급72 h생존솔.결과 량조실혈후2 h MAP균현저강저;수후VPA치료조MAP(mm Hg,1 mm Hg=0.133 kPa)신속회승,우실혈후4、8화24 h현저고우상응휴극대조조(58.4±7.6비40.3±5.0,84.4±8.0비56.4±4.4,92.6±10.3비72.6±8.9,P＜0.05혹P＜0.01).VPA치료조0～8、8～24、24～48화48～72 h뇨량균현저다우휴극대조조,단잉현저소우실혈전(0 h).량조실혈후혈장ALT、Cr화CK-MB균교0 h현저승고;VPA치료조실혈후4 h기기관공능지표현저저우휴극대조조[ALT(U/L):80.1±9.8비112.2±10.1;Cr(μmol/L):74.5±8.3비88.0±7.6;CK-MB(kU/L):10.39±1.10비13.67±1.46,P＜0.05혹P＜0.01],단실혈후72 h잉현저고우0 h(ALT:79.5±7.1비40.5±4.4;Cr:85.6±7.1비46.6±4.8;CK-MB:7.63±0.86비1.66±0.21,균P＜0.01).VPA치료조실혈후72 h생존솔현저고우휴극대조조[70%(7/10)비20%(2/10),P＜0.05].결론 견42%혈용량실혈후정주VPA능유효제고MAP,증가뇨량,감경기관공능손해,제고72 h조기생존솔,유잠력성위전쟁혹돌발사고급재해시저혈용량휴극현장구치적유효약물.
Objective To investigate the effects of valproic acid (histone deacetylase inhibitor) on visceral function and outcome in a canine lethal hemorrhage model. Methods Twenty male Beagle canines were subjected to an about 42% of total blood volume loss to reproduce a lethal hemorrhage shock model.Animals were randomly divided into shock control group (SC group) and valproic acid treatment group (VPA group), each group n = 10. Canines in SC group and VPA group were intravenously injected either 20 ml saline or valproic acid (100 mg/kg) in 20 ml saline 1.5 hours after hemorrhage. Canines in each group were given delayed intravenous fluid resuscitation 24 hours after bleeding. The mean arterial pressure (MAP) was measured at 0 hour and at different time points without anesthesia, and the plasma levels of alanine aminotransferase (ALT), creatinine (Cr) and isoenzyme of creatine kinase (CK-MB) were measured before hemorrhage (0 hour), and at different time points after hemorrhage. Urinary output and survival rate 72 hours after hemorrhage were also recorded. Results The levels of MAP in both groups were significantly lowered from 2 hours after bleeding. The level of MAP (mm Hg, 1 mm Hg = 0. 133 kPa) in VPA group recovered rapidly and exceeded with statistically significant difference compared with those of SC group after hemorrhage (4 hours: 58. 4±7.6 vs. 40. 3±:5.0, 8 hours: 84.4±8. 0 vs. 56.4±4.4, 24 hours: 92.6±10. 3vs. 72. 6±8. 9, P＜0. 05 or P＜0. 01). The amount of urinary output of VPA group was significantly higher than that of SC group during the period of 0 -8 hours, 8 -24 hours, 24 -48 hours, and 48 -72 hours, but it was still lower than that before hemorrhage (0 hour). The plasma parameters for visceral function in both groups were significantly elevated compared with 0 hour. The plasma levels of ALT, Cr and CK-MB in VPA group were obviously lower than those in SC group from 4 hours after hemorrhage[at 4 hours after bleeding,ALT (U/L): 80.1±9.8 vs. 112.2±10.1, Cr (μmol/L): 74.5±8.3 vs. 88.0±7.6, CK-MB (kU/L):10. 39± 1.10 vs. 13.67±1.46, P＜0. 05 or P＜0. 01], but the visceral functional parameters at 72 hours after hemorrhage in VPA group were obviously higher than those at 0 hour[ALT (U/L):79.5±7.1 vs.40.5±4.4; Cr (μmol/L): 85.6±7.1 vs. 46.6±4.8; CK-MB (kU/L): 7.63±0.86 vs. 1.66±0.21, all P＜0. 01]. The survival rate of VPA group 72 hours after bleeding was significantly higher than that of SC group[70% (7/10) vs. 20% (2/10), P＜0. 05]. Conclusion The results indicate that intravenous injection of VPA promote MAP, increase urinary output, alleviate visceral injury and improve the survival rate at 72 hours in canines suffering from 42% blood volurne loss, it might be an effective drug for hypovolemic shock, especially in war or other site of mass casualties in an austere environment.
