Fitzpatrick Colleen M, Savage Stephanie A, Kerby Jeffrey D, Clouse W Darrin, Kashyap Vikram S
Department of Surgery, Wilford Hall Medical Center, Lackland Air Force Base, TX, USA.
J Am Coll Surg. 2004 Nov;199(5):693-701. doi: 10.1016/j.jamcollsurg.2004.07.025.
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.
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.
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).
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.
本研究的目的是确定一种基于血红蛋白的氧载体HBOC - 201（Hemopure，生物纯公司）在用于失血性休克时是否会改变内皮功能和一氧化氮生理。
雌性猪（野猪）接受股动脉、旋髂动脉和肺动脉插管。对照动物（n = 3）仅接受仪器植入。研究动物出血至平均动脉压为30±5 mmHg，维持45分钟，然后复苏至基线平均动脉压并维持4小时。复苏液包括：自体失血（SB）（n = 8）、乳酸林格氏液加自体失血（LRSB）（n = 8）和HBOC（n = 8）。在复苏后基线、1小时和4小时，将乙酰胆碱注入近端髂动脉，并用M型超声测量内皮依赖性舒张。使用化学发光分析法测定一氧化氮水平。
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、SB和LRSB提供了等效的生存率和复苏效果。HBOC组动物所需的复苏液量最低（SB，41.5±3.5 mL/kg；LRSB，76.4±1.1 mL/kg，HBOC，14.6±2.1 mL/kg，p < 0.001）。SB组和LRSB组对乙酰胆碱的反应正常，但HBOC组乙酰胆碱反应减弱（复苏结束时内皮依赖性舒张为29.5%，p < 0.001）。研究组之间动脉一氧化氮水平无差异（p = 0.69）。
HBOC可能是失血性休克患者的一种替代复苏药物。与血液或晶体液相比，使用HBOC进行复苏所需的液体量更少。这些数据表明HBOC - 201具有血管收缩作用，且不能仅归因于一氧化氮清除。
