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内皮素转换酶的抑制可降低体外循环和循环停止后的肺动脉高压。

Blockade of endothelin-converting enzyme reduces pulmonary hypertension after cardiopulmonary bypass and circulatory arrest.

作者信息

Kirshbom P M, Tsui S S, DiBernardo L R, Meliones J N, Schwinn D A, Ungerleider R M, Gaynor J W

机构信息

Division of Surgery, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Surgery. 1995 Aug;118(2):440-4; discussion 444-5. doi: 10.1016/s0039-6060(05)80356-3.

DOI:10.1016/s0039-6060(05)80356-3
PMID:7638762
Abstract

BACKGROUND

Pulmonary dysfunction associated with elevated pulmonary vascular resistance is a significant problem after cardiopulmonary bypass (CPB) and circulatory arrest. Mediators of the pulmonary hypertensive response to CPB have not been fully elucidated. The purpose of this study was to examine the contribution of the endothelium-derived vasoconstrictor endothelin-1 to postbypass pulmonary hypertension.

METHODS

Twelve 1-month-old piglets were instrumented with left atrial and pulmonary artery (PA) micromanometers and a PA flow probe. Phosphoramidon (Phos, n = 6) pigs received a 30 mg/kg bolus of Phos, an endothelin converting enzyme inhibitor. Controls (n = 6) received saline solution. All animals were placed on CPB and underwent a 60-minute period of circulatory arrest. The indexed pulmonary vascular resistance (PVRI) was calculated at baseline for controls, both before and 10 minutes after drug infusion in the Phos group, and 15 minutes after separation from CPB in both groups.

RESULTS

Pre-CPB, mean PA pressure, and PVRI were not different between the control and Phos groups (14.6 +/- 1.1 versus 14.5 +/- 1.1 mm Hg and 7322 +/- 1269 versus 7260 +/- 947 dyne/sec/kg/cm-5, respectively). After CPB mean PA pressure was significantly higher in control than Phos animals (32.1 +/- 1.1 versus 22.5 +/- 1.3 mm Hg, p = 0.0003). PVRI was also significantly higher in the controls (30896 +/- 4714 versus 14972 +/- 1710, dyne/sec/kg/cm-5, p = 0.02).

CONCLUSIONS

Production of endothelin-1 during CPB and circulatory arrest is a mediator of postbypass pulmonary hypertension.

摘要

背景

与肺血管阻力升高相关的肺功能障碍是体外循环(CPB)和循环停止后的一个重要问题。CPB引起肺高血压反应的介质尚未完全阐明。本研究的目的是探讨内皮源性血管收缩剂内皮素-1对体外循环后肺动脉高压的作用。

方法

12只1月龄仔猪植入左心房和肺动脉(PA)微压计以及PA血流探头。磷酰胺(Phos,n = 6)组仔猪静脉注射30mg/kg磷酰胺,一种内皮素转化酶抑制剂。对照组(n = 6)注射生理盐水。所有动物均接受CPB并经历60分钟的循环停止。计算对照组基线时、Phos组药物输注前和输注后10分钟以及两组脱离CPB后15分钟的肺血管阻力指数(PVRI)。

结果

CPB前,对照组和Phos组的平均肺动脉压和PVRI无差异(分别为14.6±1.1与14.5±1.1mmHg,以及7322±1269与7260±947达因/秒/千克/厘米⁻⁵)。CPB后,对照组的平均肺动脉压显著高于Phos组动物(32.1±1.1与22.5±1.3mmHg,p = 0.0003)。对照组的PVRI也显著更高(30896±4714与14972±1710达因/秒/千克/厘米⁻⁵,p = 0.02)。

结论

CPB和循环停止期间内皮素-1的产生是体外循环后肺动脉高压的介质。

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Heart. 2003 Oct;89(10):1221-6. doi: 10.1136/heart.89.10.1221.
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Early therapeutic experience with the endothelin antagonist BQ-123 in pulmonary hypertension after congenital heart surgery.内皮素拮抗剂BQ-123用于先天性心脏病手术后肺动脉高压的早期治疗经验。
Heart. 1999 Oct;82(4):505-8. doi: 10.1136/hrt.82.4.505.