Szabó G, Bährle S, Fazekas L, MacDonald D, Stumpf N, Vahl C F, Hagl S
Department of Cardiac Surgery, University of Heidelberg, Germany.
Thorac Cardiovasc Surg. 1998 Aug;46(4):232-6. doi: 10.1055/s-2007-1010231.
This study was designed to investigate the effects of the selective endothelin-A receptor antagonist BQ123 on myocardial and endothelial function after reversible deep hypothermic ischemia and reperfusion.
Isogenic intra-abdominal heterotopic heart transplantation was performed in Lewis rats. After one hour of cold ischemic preservation reperfusion was started after application of either saline vehicle or BQ123 (1 micromol/L). Left-ventricular pressure-volume relations and myocardial blood flow were assessed after one and 24 hours of reperfusion. Responses to endothelium-dependent vasodilator acetylcholine and endothelium-independent vasodilator sodium nitroprusside were also determined.
BQ123 significantly improved myocardial contractility, as indicated by the leftward shift of the systolic pressure-volume relation and significantly increased myocardial blood flow during early reperfusion (p < 0.05). Although myocardial function and baseline myocardial blood flow were similar in both groups after 24 hours of reperfusion, endothelium-dependent vasodilatation was still significantly higher in the BQ123 group (p < 0.05).
These results suggest that endothelin-A receptor antagonists may be useful in reducing ischemia/reperfusion injury after heart transplantation by preservation of myocardial and endothelial function.
本研究旨在探讨选择性内皮素-A受体拮抗剂BQ123对可逆性深低温缺血再灌注后心肌和内皮功能的影响。
在Lewis大鼠中进行同基因腹腔异位心脏移植。在冷缺血保存1小时后，应用生理盐水或BQ123（1微摩尔/升）后开始再灌注。在再灌注1小时和24小时后评估左心室压力-容积关系和心肌血流量。还测定了对内皮依赖性血管扩张剂乙酰胆碱和内皮非依赖性血管扩张剂硝普钠的反应。
BQ123显著改善了心肌收缩力，表现为收缩压-容积关系向左移位，并且在再灌注早期显著增加了心肌血流量（p < 0.05）。尽管再灌注24小时后两组的心肌功能和基线心肌血流量相似，但BQ123组的内皮依赖性血管舒张仍显著更高（p < 0.05）。
这些结果表明，内皮素-A受体拮抗剂可能通过保护心肌和内皮功能，对减轻心脏移植后的缺血/再灌注损伤有用。
