Dschietzig T, Laule M, Alexiou K, Schrör K, Baumann G, Stangl K
Medizinische Klinik und Poliklinik I, Charité, Humboldt-Universität, Berlin, Germany.
Crit Care Med. 1998 Mar;26(3):510-7. doi: 10.1097/00003246-199803000-00024.
Myocardial ischemia plays a central role in the development of right ventricular failure after acute pulmonary embolism. This study investigates whether pulmonary mediators act specifically on coronary tone and cardiac contractile function in acute pulmonary microembolization and whether such effects are altered in the case of early systemic atherosclerosis. We employ a novel model of serial perfusion in which an isolated rabbit heart is perfused with the effluent of the same animal's isolated lung.
Controlled experiment using isolated organs.
Experimental laboratory.
Male New Zealand White rabbits (controls). Age-matched, male Watanabe rabbits (hypercholesterolemic, development of accelerated atherosclerosis).
Seven isolated control and seven isolated Watanabe hearts were perfused with the saline effluent of the same animal's isolated lung. After the assessment of the baseline data, the lungs were gradually embolized with glass beads measuring 100 microm in diameter to induce an increase in mean pulmonary arterial pressure from 6 to 8 mm Hg, at baseline, up to 25 mm Hg.
Pulmonary embolization to 25 mm Hg evoked a coronary constriction, measured as coronary flow decrease to 89 +/- 7% of the baseline value in controls. In the Watanabe group, coronary constriction was significantly enhanced, compared with controls, with coronary flow decreasing to 76 +/- 6% of the baseline value. In both groups, coronary constriction was followed by a deterioration in cardiac contractile performance. This cardiodepression was significantly deeper in Watanabe hearts with respect to both maximum ventricular pressures and maximum rates of pressure development and decline. Coronary constriction and cardiodepression were prevented by coronary infusion of the nonselective endothelin antagonist PD-145065, the endothelinA antagonists A-127722 and BQ-123, and the endothelin-converting enzyme inhibitor phosphoramidon. Concentration of big endothelin in pulmonary effluent increased from 5.6 +/- 0.3 pmol/L in controls and 5.6 +/- 0.2 pmol/L in the Watanabe group, at baseline, to 8.8 +/- 0.4 pmol/L in controls and 8.9 +/- 0.4 pmol/L in the Watanabe group, at 25 mm Hg pulmonary arterial pressure. Endothelin was not detectable at any time during the experiment in pulmonary effluent. The coronary gradient, calculated as a difference in concentration between coronary and pulmonary effluent, was negative for big endothelin and positive for endothelin in both groups.
We have demonstrated that an increase in pulmonary release of big endothelin occurs during lung embolism, which, in turn, results in coronary constriction and consequent cardiodepression. This action of big endothelin is based on its local coronary conversion into endothelin. In addition, coronary endothelial dysfunction, attributed to early systemic atherosclerosis, was shown to represent a specific risk factor in these events.
心肌缺血在急性肺栓塞后右心室衰竭的发生中起核心作用。本研究调查了肺介质在急性肺微栓塞中是否特异性作用于冠状动脉张力和心脏收缩功能，以及在早期系统性动脉粥样硬化情况下这些作用是否改变。我们采用了一种新型的连续灌注模型，即使用同一只动物的离体肺的流出液灌注离体兔心。
使用离体器官的对照实验。
实验实验室。
雄性新西兰白兔（对照组）。年龄匹配的雄性渡边兔（高胆固醇血症，加速动脉粥样硬化发展）。
对7个离体对照心脏和7个离体渡边心脏用同一只动物的离体肺的盐水流出液进行灌注。在评估基线数据后，用直径为100微米的玻璃珠逐渐栓塞肺，以使平均肺动脉压从基线时的6至8毫米汞柱升高至25毫米汞柱。
肺栓塞至25毫米汞柱时引起冠状动脉收缩，以对照组冠状动脉血流减少至基线值的89±7%来衡量。在渡边组中，与对照组相比，冠状动脉收缩明显增强，冠状动脉血流减少至基线值的76±6%。在两组中，冠状动脉收缩后心脏收缩性能均恶化。在最大心室压力以及压力上升和下降的最大速率方面，渡边心脏的这种心功能抑制明显更严重。冠状动脉内注入非选择性内皮素拮抗剂PD - 145065、内皮素A拮抗剂A - 127722和BQ - 12
