Hilzenrat N, Arish A, Yaari A, Sikuler E
Liver Research Laboratory and Department of Medicine B', The Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
J Gastroenterol Hepatol. 2001 Jul;16(7):796-800. doi: 10.1046/j.1440-1746.2001.02514.x.
Recently, we found in a portal hypertensive rat model that hemorrhage and volume restitution with Haemaccel, a low viscosity plasma expander, induced an increase in cardiac output and portal venous inflow. The present study was conducted to evaluate whether pretreatment with propranolol will attenuate these hyperdynamic changes.
Portal hypertension was induced by portal vein constriction. Treatment was initiated 14--21 days later. Propranolol (30 mg/kg per day) or water were administered for 7 days via a gastric gavage. Under ketamine anesthesia, 18 h after the last given dose, blood was withdrawn at a constant rate of 0.3 mL/min for 15 min followed by a 15-min stabilization. Haemaccel was infused at the same rate and volume used for withdrawal. Hemodynamic measurements were performed after volume restitution in both groups by using radioactive microspheres.
Eight rats were studied in each group. In the propranolol-treated animals, portal venous inflow was decreased (2.4 +/- 0.8 vs 3.8 +/- 0.7 mL/min per 100 g bodyweight; P < 0.01), while splanchnic arteriolar and porto-collateral resistance were increased (52.8 +/- 21.0 vs 32.8 +/- 13.0 and 6.0 +/- 1.4 vs 4.1 +/- 0.7 mmHg x min x 100 g bodyweight/mL; P < 0.05, respectively). Cardiac output, mean arterial pressure, heart rate, total peripheral resistance and portal pressure were not significantly different between the two groups.
In this model, pretreatment with propranolol prevented the increase in portal venous inflow, which occurs following hemorrhage and volume restitution with Haemaccel. Although caution should be taken in extrapolating data from animal models to humans, our results suggest that volume replacement during a portal hypertensive-related bleeding episode may be safer in a patient treated with non-selective beta-adrenoreceptor antagonists.
最近，我们在门脉高压大鼠模型中发现，使用低粘度血浆扩容剂贺斯进行出血和容量恢复后，心输出量和门静脉血流量增加。本研究旨在评估普萘洛尔预处理是否会减弱这些高动力变化。
通过门静脉缩窄诱导门脉高压。14 - 21天后开始治疗。通过胃管给予普萘洛尔（30毫克/千克/天）或水，持续7天。在氯胺酮麻醉下，最后一次给药18小时后，以0.3毫升/分钟的恒定速率抽血15分钟，随后稳定15分钟。以与抽血相同的速率和体积输注贺斯。两组在容量恢复后均使用放射性微球进行血流动力学测量。
每组研究8只大鼠。在普萘洛尔治疗的动物中，门静脉血流量降低（每100克体重2.4±0.8对3.8±0.7毫升/分钟；P < 0.01），而内脏小动脉和门体侧支循环阻力增加（52.8±21.0对32.8±13.0以及6.0±1.4对4.1±0.7毫米汞柱×分钟×100克体重/毫升；P分别< 0.05）。两组之间的心输出量、平均动脉压、心率、总外周阻力和门静脉压力无显著差异。
在该模型中，普萘洛尔预处理可防止使用贺斯进行出血和容量恢复后门静脉血流量的增加。尽管在将动物模型数据外推至人类时应谨慎，但我们的结果表明，在与门脉高压相关的出血发作期间进行容量替代，对于接受非选择性β - 肾上腺素能受体拮抗剂治疗的患者可能更安全。
