Desmecht D, Linden A, Amory H, Lekeux P
Department of Pathology, Faculty of Veterinary Medicine, University of Liège, Belgium.
Can J Physiol Pharmacol. 1996 May;74(5):572-9.
The effects of saline (control, group C) and metrenperone (treated, group M) on systemic and pulmonary hemodynamics were determined in conscious 7- to 15-day-old calves after they were intratracheally inoculated with Pasteurella haemolytica. Metrenperone, a specific serotonin (5-hydroxytryptamine) receptor antagonist, was injected intramuscularly (100 micrograms.kg-1) 2 h after the calves were inoculated. Central venous, pulmonary arterial and capillary wedge, and systemic arterial pressures were measured, using fluid-filled catheters. Cardiac output was measured by the thermodilution technique. Heart rate, stroke volume, and pulmonary and systemic vascular resistances were calculated. The parameters were measured hourly from the 1st to the 10th h after inoculation. In group C, cardiovascular response to P. haemolytica inoculation was marked and typically consisted of two systemic hypotensive phases and two pulmonary hypertensive phases. The first phase occurred by the 2nd h post inoculation and was induced by a transient bradycardia and a systemic vasodilation, leading to profound hypotension and reduced venous return. Cardiac performance then transiently recovered, but systemic hypotension persisted. The second hypotensive hypodynamic phase occurred by the 7th h after inoculation, and was associated with a decline in stroke volume, an increase in heart rate, and pulmonary hypertension and vasoconstriction. In group M, the early response to P. haemolytica exposure was similar to that in controls, indicating that, as in sheep, 5-hydroxytryptamine does not contribute to the early hypodynamic response to endotoxemia. In contrast, metrenperone completely abolished late increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that 5-hydroxytryptamine contributes to the late pulmonary vasoconstriction. Metrenperone treatment also allowed better restoration of heart rate, and hence, cardiac output was maintained. In conclusion, 5-hydroxytryptamine might have a role in mediating pasteurellic endotoxin induced changes in pulmonary hemodynamics through its type-2 receptors.
在7至15日龄的清醒犊牛经气管内接种溶血巴斯德菌后，测定了生理盐水（对照组，C组）和甲硫哒嗪（处理组，M组）对全身和肺血流动力学的影响。甲硫哒嗪是一种特异性5-羟色胺受体拮抗剂，在犊牛接种后2小时肌肉注射（100微克·千克-1）。使用充液导管测量中心静脉压、肺动脉压、毛细血管楔压和体动脉压。通过热稀释技术测量心输出量。计算心率、每搏量以及肺和全身血管阻力。在接种后第1小时至第10小时每小时测量这些参数。在C组中，对溶血巴斯德菌接种的心血管反应明显，通常包括两个全身低血压期和两个肺动脉高压期。第一期在接种后第2小时出现，由短暂的心动过缓和全身血管舒张引起，导致严重低血压和静脉回流减少。然后心脏功能短暂恢复，但全身低血压持续存在。第二个低血压低动力期在接种后第7小时出现，与每搏量下降、心率增加以及肺动脉高压和血管收缩有关。在M组中，对溶血巴斯德菌暴露的早期反应与对照组相似，表明与绵羊一样，5-羟色胺对内毒素血症的早期低动力反应没有作用。相比之下，甲硫哒嗪完全消除了后期肺动脉压和肺血管阻力的增加，表明5-羟色胺促成了后期肺血管收缩。甲硫哒嗪治疗还使心率得到更好的恢复，因此心输出量得以维持。总之，5-羟色胺可能通过其2型受体在介导巴氏杆菌内毒素引起的肺血流动力学变化中起作用。
