Meadow W L, Meus P J
Pediatr Res. 1984 Oct;18(10):960-5. doi: 10.1203/00006450-198410000-00011.
Using a piglet model of neonatal sepsis, we have determined that Group B streptococcal (GBS) bacteremia is associated with a state of vascular hyper-resistance in both the pulmonary and systemic circulations. This elevated vascular resistance is accompanied by a significant fall in cardiac output despite the assurance of constant intravascular fluid volume. Pulmonary artery pressure rises extensively while systemic blood pressure remains essentially unchanged during this GBS infusion protocol. We report here our attempts to relieve the vascular hyperresistance of GBS infusion by administration of an alpha-sympathetic antagonist, tolazoline (Tz). We found that Tz, in a dose-related fashion, decreased both systemic and pulmonary vascular resistance over the entire range from 2 to 25 mg/kg. Further, at all doses tested, the resistance-reducing effect of Tz was equal in the systemic and pulmonary vascular beds. No selective pulmonary or systemic vasodilatory effect was demonstrated by Tz in this model of neonatal pulmonary hypertension. The reduction of systemic vascular resistance was accompanied by a significant elevation in total body cardiac output at all Tz doses. Compared to pre-Tz values, cardiac output rose by 24, 55, and 55% after Tz at 2, 8.3, and 25 mg/kg respectively. In addition, administration of Tz to septic normovolemic piglets reliably produced a transient decrease of systemic blood pressure. For Tz doses of 2 and 8.3 mg/kg, steady state systemic blood pressure returned to pre-Tz levels within 10 min. However, after Tz at 25 mg/kg, steady state systemic blood pressure remained significantly below pre-Tz levels.
利用新生仔猪败血症模型,我们已确定B组链球菌(GBS)菌血症与肺循环和体循环中的血管高阻力状态相关。尽管血管内容量保持恒定,但这种升高的血管阻力伴随着心输出量的显著下降。在该GBS输注方案中,肺动脉压力大幅上升,而体循环血压基本保持不变。我们在此报告我们尝试通过给予α-交感神经拮抗剂妥拉唑啉(Tz)来缓解GBS输注引起的血管高阻力。我们发现,Tz以剂量相关的方式在2至25mg/kg的整个范围内降低了体循环和肺循环血管阻力。此外,在所有测试剂量下,Tz在体循环和肺循环血管床中的阻力降低效果相同。在这个新生儿肺动脉高压模型中,Tz未表现出选择性肺或体循环血管舒张作用。在所有Tz剂量下,体循环血管阻力的降低伴随着全身心输出量的显著升高。与Tz给药前的值相比,在2、8.3和25mg/kg的Tz剂量下,心输出量分别在Tz给药后升高了24%、55%和55%。此外,给败血症血容量正常的仔猪施用Tz可靠地导致体循环血压短暂下降。对于2和8.3mg/kg的Tz剂量,稳态体循环血压在10分钟内恢复到Tz给药前的水平。然而,在25mg/kg的Tz给药后,稳态体循环血压仍显著低于Tz给药前的水平。