Stangl K, Dschietzig T, Laule M, Alexiou K, Wernecke K D, Baumann G
Medizinische Klinik und Poliklinik I, Charité, Humboldt-Universität zu Berlin, Germany.
Circulation. 1997 Nov 4;96(9):3192-200. doi: 10.1161/01.cir.96.9.3192.
Lung tissue produces a variety of mediators; however, little is known regarding how these mediators affect coronary regulation and myocardial contractility. In a novel rabbit lung-heart model, we investigated the possible influence exerted by pulmonary mediators on coronary tone both under normal conditions and in early endothelial dysfunction.
In our model, the effluent from the isolated lung is used to serially perfuse the coronary vessels of the isolated heart of the same animal. Compared with the hearts of control rabbits, isolated hearts of Watanabe rabbits revealed pharmacological evidence of endothelial dysfunction and a significant steeper decrease of coronary flow during serial perfusion of the coronary vessels with lung effluent (75+/-6% versus 89+/-3%). This decline in coronary flow was prevented by the nonselective endothelin (ET) antagonist PD-145065, the ET(A) antagonists BQ-123 and A-127722, and the endothelin-converting enzyme inhibitor phosphoramidon. The concentration of big ET in lung effluent ranged from 5.5 to 5.8 pmol/L in both control and Watanabe groups, with levels in corresponding coronary effluent falling to 0.9 to 1.1 pmol/L in controls and to 1.0 to 1.2 pmol/L in the Watanabe group. In either group, ET was not detected in lung effluent, but it rose significantly in coronary effluent during serial perfusion.
Pulmonary big ET, locally converted into ET during coronary passage, causes an ET(A)-mediated elevation in coronary tone under basal conditions as well as an enhanced coronary constriction when early endothelial dysfunction is present.
肺组织可产生多种介质；然而，关于这些介质如何影响冠状动脉调节和心肌收缩性，我们知之甚少。在一个新型兔肺-心模型中，我们研究了在正常条件下以及早期内皮功能障碍时，肺介质对冠状动脉张力可能产生的影响。
在我们的模型中，来自离体肺的流出液被用于连续灌注同一只动物离体心脏的冠状动脉。与对照兔的心脏相比，渡边兔的离体心脏显示出内皮功能障碍的药理学证据，并且在用肺流出液连续灌注冠状动脉时，冠状动脉血流显著更陡峭地下降（75±6%对89±3%）。冠状动脉血流的这种下降可被非选择性内皮素（ET）拮抗剂PD-145065、ET(A)拮抗剂BQ-123和A-127722以及内皮素转化酶抑制剂磷酰胺素所阻止。在对照组和渡边组中，肺流出液中大分子ET的浓度范围为5.5至5.8 pmol/L，相应冠状动脉流出液中的水平在对照组降至0.9至1.1 pmol/L，在渡边组降至1.0至1.2 pmol/L。在任一组中，肺流出液中均未检测到ET，但在连续灌注期间冠状动脉流出液中ET显著升高。
肺大分子ET在冠状动脉通过过程中局部转化为ET，在基础条件下导致ET(A)介导的冠状动脉张力升高，并且在存在早期内皮功能障碍时导致冠状动脉收缩增强。
