Tuberc Respir Dis.  2000 Feb;48(2):210-222. 10.4046/trd.2000.48.2.210.

The Effects of Endothelin Receptor Antagonist on Hemodynamic and Respiratory Mechanics in Experimental Acute Pulmonary Thromboembolism

• Lee JH
• Jeon YG
• Choe KH
• Shim TS
• Lim CM
• Koh YS
• Kim WS
• Kim DS
• Kim WD
• Lee SD

• KMID: 1877190
• DOI: http://doi.org/10.4046/trd.2000.48.2.210

Abstract

BACKGROUND: Endothelin (ET) is the most potent vasoconstrictor and bronchoconstrictor. In patients with acute pulmonary thromboembolism (APTE), (delete) The plasma ET-1 level is elevated in patients with acute pulmonary thromboembolism (APTE). These findings suggest the possibility of ET-1 as an important mediator This finding suggest that ET-1 may be an important mediator in the cardiopulmonary derangement of APTE. But whether ET-1 is a pathogenic mediator or a simple marker of APTE is not known. We investigated the The role of ET-1 in the pathogenesis of cardiopulmonary dysfunction in APTE through evaluating (delete) was investigated through an evaluation of the effects of ETA-receptor antagonist on APTE. We also demonstrated that increased The increase in local levels of preproET-1 mRNA and ET-1 peptide in the embolized lung was also demonstrated.
METHODS
: In a canine autologous blood clot pulmonary embolism model, ETA-receptor antagonist (10 mg/kg intravenously, n = 6) was administered one hour after the onset of the embolism. Hemodynamic measurements, blood gas tensions and plasma levels of ET-1 immunoreactivity in this treatment group were compared with those in the control group (n = 5). After the experiment, preproET-1 mRNA expression (using Northern blot analysis) and the distribution of ET-1 (by immunohistochemical analysis) in the lung tissues were examined. RESULTS: Increase The increases in pulmonary arterial pressure and pulmonary vascular resistance were smaller in treatment group compared with of the treatment group were less than those of the control group. Decrease in cardiac output was also less in the treatment group. Complications such as systemic arterial hypotension and hypoxemia did not occur with the administration of ETA-receptor antagonist. While the The plasma level of ET-1 like (ED: what does 'like' mean?) immunoreactivity was increased after embolization in both the groups groups, it but was significantly higher in the treatment group. The preproET-1 mRNA and ET-1 peptide expressions were increased in the embolized lung.
CONCLUSION
ET-1 synthesis increases with embolization in the lung and may plays play an important role in the pathophys iology of cardiopulmonary derangement of APTE. Also Furthermore, ETA-receptor antagonist attenuates cardiopulmonary alterations seen in APTE, suggesting a potentially beneficial effect a potential benefit of this therapy.

Keyword

Acute pulmonary thromboembolism; endothelin-1; endothelin receptor antagonist

MeSH Terms

Anoxia
Arterial Pressure
Blotting, Northern
Cardiac Output
Embolism
Endothelin-1
Endothelins*
Hemodynamics*
Humans
Hypotension
Lung
Plasma
Pulmonary Embolism*
Receptors, Endothelin*
Respiratory Mechanics*
RNA, Messenger
Vascular Resistance
Endothelin-1
Endothelins
RNA, Messenger
Receptors, Endothelin