Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition
Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition
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DOI：
10.1097/ccm.0b013e3181a00597
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发表时间：
2009-06-01
影响因子：
8.8
通讯作者：
Irwin, David C.
中科院分区：
文献类型：
--
作者：
Gotshall, Robert W.;Hamilton, Karyn L.;Irwin, David C.
目标。几种类型的基于血红蛋白的氧气载体(HBOC)从血管系统中清除一氧化氮，导致血管收缩和高血压，包括全身和肺的。磷酸二酯酶-5(PDE5)抑制剂促进一氧化氮活性，增强血管扩张。这项研究的目的是确定戊二醛聚合牛血红蛋白(HBOC)与PDE5抑制剂联合治疗是否能对抗HBOC单独治疗的血流动力学负面影响，从而改善血流动力学和氧气输送。设计：对照实验研究。地点：一所大学的研究实验室。受试者：清醒的雄性SD大鼠。干预：戊二醛聚合牛血红蛋白(HBOC)、西地那非(PDE5抑制剂)和乳酸林格液(对照)。测量和主要结果：输注HBOC导致显著(P<；0.05)全身和肺血管收缩，心输出量减少，外周氧气输送减少。输注乳酸林格氏液对测量的变量没有影响。单独输注西地那非可降低体动脉和肺动脉血压，同时维持心输出量和氧气输送。HBOC和西地那非联合输注可使全身血压、心输出量和氧输送稳定。然而，在HBOC中加入西地那非并不能完全改善HBOC引起的肺血管收缩。结论：本研究中使用的HBOC导致了肺和全身的高血压，心输出量和氧输送减少。HBOC治疗的这些负面后果可以通过将HBOC治疗与PDE5抑制剂(西地那非)结合起来在很大程度上克服。因此，这些数据支持在考虑HBOC治疗的情况下继续研究HBOC和PDE5抑制剂的联合治疗。(《急症护理医学》2009；37：1988-1993)
Objective. Hemoglobin-based oxygen carriers (HBOC) of several types scavenge nitric oxide from the vasculature resulting in vasoconstriction and hypertension, both systemic and pulmonary. Phosphodiesterase-5 (PDE5) inhibitors promote nitric oxide activity and enhance vasodilation. The purpose of this study was to determine whether combined therapy of glutaraldehyde-polymerized bovine hemoglobin (HBOC) with a PDE5 inhibitor would counter the negative hemodynamic consequences of HBOC therapy alone, resulting in improved hemodynamics and oxygen delivery.Design: A controlled, experimental study.Setting: A research laboratory at a university.Subjects: Conscious male Sprague-Dawley rats.Interventions: Glutaraldehyde-polymerized bovine hemoglobin (HBOC), sildenafil (PDE5 inhibitor), and lactated Ringer's solution (control).Measurements and Main Results: Infusion of the HBOC resulted in significant (p < 0.05) systemic and pulmonary vasoconstriction, with reduced cardiac output and reduced oxygen delivery to the periphery. Infusion of lactated Ringer's demonstrated no changes in the measured variables. Infusion of sildenafil alone reduced systemic and pulmonary artery blood pressure, while maintaining cardiac output and oxygen delivery. Combined HBOC and sildenafil infusion resulted in stable systemic blood pressure, cardiac output, and oxygen delivery. However, the addition of sildenafil to HBOC did not fully ameliorate the pulmonary vasoconstriction caused by HBOC.Conclusion: The HBOC used in this study resulted in pulmonary and systemic hypertension, reduced cardiac output, and oxygen delivery. These negative consequences of HBOC treatment can be largely overcome by combing HBOC treatment with a PDE5 inhibitor (sildenafil). Thus, these data support the continued investigation of combined HBOC and PDE5 inhibitor treatment in circumstances in which HBOC therapy is being considered. (Crit Care Med 2009; 37:1988-1993)