Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage

Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage
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DOI:
10.1016/j.jamcollsurg.2004.07.025
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发表时间:
2004-11-01
影响因子:
5.2
通讯作者:
Kashyap, VS
Kashyap, VS
中科院分区:
医学2区
文献类型:
--
作者:
Fitzpatrick, CM;Savage, SA;Kashyap, VS

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背景技术背景:本研究的目的是确定血红蛋白为基础的氧载体,HBOC-201(Hemopure,Biopure公司),改变内皮功能和一氧化氮生理学时,用于hemorrhagic shock.Study设计:雌性猪(猪)进行导管插入术的股动脉,旋髂动脉和肺动脉。对照组动物(n = 3)仅接受内固定。研究动物经历出血至平均动脉压30 +/- 5 mmHg,维持45分钟,并复苏至基线平均动脉压4小时。复苏液包括:脱落血(SB)(n = 8)、乳酸林格氏液+脱落血(LRSB)(n = 8)和HBOC(n = 8)。在基线、复苏后1小时和4小时,将乙酰胆碱注入近端髂动脉,用M型超声测量内皮依赖性舒张。结果:HBOC、SB和LRSB提供了等同的存活率和复苏率,通过平均动脉压(65.3 +/- 2.48 mmHg)、肺动脉平均压(15.8 +/- 0.84 mmHg)和乳酸水平(1.22 +/- 0.19 mmol/L)测量。HBOC组动物需要最低的复苏体积(SB,41.5 +/-3.5mL/kg; LRSB,76.4 +/-1.1mL/kg,HBOC,14.6 +/-2.1mL/kg,p < 0.001)。SB和LRSB组对乙酰胆碱的反应正常,但HBOC组的乙酰胆碱反应减弱(复苏结束时内皮依赖性舒张为29.5%,p < 0.001)。研究组之间的动脉一氧化氮水平没有差异(p = 0.69)。结论:HBOC可能是失血性休克患者的替代复苏剂。使用HBOC复苏需要的体积比血液或晶体少。这些数据表明HBOC-201具有血管收缩作用,不能仅归因于一氧化氮清除。((C)2004年由美国外科医生学会出版)。
BACKGROUND: The purpose of this study was to determine if a hemoglobin-based oxygen carrier, HBOC-201 (Hemopure, Biopure Corp), alters endothelial function and nitric oxide physiology when used for hemorrhagic shock.STUDY DESIGN: Female swine (Sus scrofa) underwent catheterization of the femoral, circumflex iliac, and pulmonary arteries. Control animals (n = 3) underwent instrumentation only. Study animals underwent hemorrhage to mean arterial pressure of 30 +/- 5 mmHg, were maintained for 45 minutes, and resuscitated to the baseline mean arterial pressure for 4 hours. Resuscitation fluids included: shed blood (SB) (n = 8), lactated Ringers plus shed blood (LRSB) (n = 8), and HBOC (n = 8). At baseline, 1, and 4 hours after resuscitation, acetylcholine was infused into the proximal iliac artery and endothelial-dependent relaxation was measured with M-mode ultrasonography. Nitric oxide levels were determined using a chemiluminescent assay.RESULTS: HBOC, SB, and LRSB provided equivalent survival and resuscitation as measured by mean arterial pressures (65.3 +/- 2.48 mmHg); pulmonary artery mean pressures (15.8 +/- 0.84 mmHg); and lactate levels (1.22 +/- 0.19 mmol/L). HBOC group animals required the lowest resuscitation volume (SB, 41.5 +/- 3.5 mL/kg; LRSB, 76.4 +/- 1.1 mL/kg, HBOC, 14.6 +/- 2.1 mL/kg, p < 0.001). Response to acetylcholine was normal in the SB and LRSB groups, but the HBOC group had diminished acetylcholine response (29.5% endothelial-dependent relaxation end resuscitation, p < 0.001). Arterial nitric oxide levels did not differ between study groups (p = 0.69).CONCULSIONS: HBOC might be an alternative resuscitation agent in patients with hemorrhagic shock. Resuscitation with HBOC requires less volume than blood or crystalloid. These data suggest HBOC-201 has a vasoconstrictive effect that cannot be attributed soley to nitric oxide scavenging. ((C) 2004 by the American College of Surgeons).