Alexiou K, Dschietzig T, Simsch O, Laule M, Hundertmark J, Baumann G, Stangl K
Medizinische Klinik und Poliklinik I, Charité, Humboldt-Universität zu Berlin, Germany.
J Am Coll Cardiol. 1998 Nov 15;32(6):1773-8. doi: 10.1016/s0735-1097(98)00440-9.
We investigated whether endogenous pulmonary big endothelin has arrhythmogenic properties under normal conditions and in heritable hyperlipidemia.
Endothelin (ET), one of the most potent vasoconstrictors, is known to induce ventricular arrhythmias. It is unclear, however, whether its precursor, big endothelin, released from the lung, contributes to arrhythmogenesis.
In a lung-heart model in which a Langendorff heart is serially perfused with the effluent from the isolated lung of the same animal, we evaluated arrhythmias in control and in Watanabe heritable hyperlipidemic (WHHL) rabbits.
In both controls (n=12) and WHHL (n=8), serial perfusion evoked a decrease in coronary flow (controls, -11+/-3%; WHHL, -25+/-6%) and a fourfold increase of ventricular extrasystoles (VES) (controls, 40.7+/-8; WHHL, 40.2+/-5 VES/40 min, p < 0.05). However, WHHL developed more and longer nonsustained ventricular tachycardias (VT) compared with controls (incidence, 1.38+/-1.1 vs. 0.33+/-0.5 VT/40 min, p < 0.05; length, 14.36+/-3.1 vs. 7.25+/-1.5 beats/VT, p < 0.05). Arrhythmias were not ischemia-induced because corresponding mechanical flow reduction had no arrhythmogenic effect (n=6 in controls and WHHL). Although vasoconstriction disappeared entirely, arrhythmias were only partly suppressed by ET(A) antagonists (BQ-123, 2 micromol/liter; A-127722, 20 micromol/liter). The ET-converting enzyme inhibitor phosphoramidon (50 micromol/liter) completely suppressed arrhythmias and vasoconstriction. The ET(B) antagonists (IRL-1038, 4 micromol/liter; IRL-1025, 5 micromol/liter) had no effect (n=6).
Endogenous pulmonary big ET produces arrhythmogenic effects that are aggravated in heritable hyperlipidemia. These effects, requiring coronary conversion of big ET into ET, are partly ET(A)-mediated and ET(B)-independent.
我们研究了内源性肺大内皮素在正常条件下及遗传性高脂血症状态下是否具有致心律失常特性。
内皮素（ET）是最有效的血管收缩剂之一，已知可诱发室性心律失常。然而，其前体——从肺释放的大内皮素是否参与心律失常的发生尚不清楚。
在一个心肺模型中，用同一动物分离肺的流出液连续灌注Langendorff心脏，我们评估了对照兔和渡边遗传性高脂血症（WHHL）兔的心律失常情况。
在对照组（n = 12）和WHHL组（n = 8）中，连续灌注均导致冠状动脉血流减少（对照组，-11±3%；WHHL组，-25±6%）以及室性期前收缩（VES）增加四倍（对照组，40.7±8；WHHL组，40.2±5次VES/40分钟，p < 0.05）。然而，与对照组相比，WHHL组出现更多且持续时间更长的非持续性室性心动过速（VT）（发生率，1.38±1.1 vs. 0.33±0.5次VT/40分钟，p < 0.05；持续时间，14.36±3.1 vs. 7.25±1.5次搏动/VT，p < 0.05）。心律失常并非由缺血诱导，因为相应的机械性血流减少无致心律失常作用（对照组和WHHL组各n = 6）。尽管血管收缩完全消失，但心律失常仅部分被ET(A)拮抗剂（BQ - 123，2微摩尔/升；A - 127722，20微摩尔/升）抑制。内皮素转化酶抑制剂磷酰胺素（50微摩尔/升）完全抑制了心律失常和血管收缩。ET(B)拮抗剂（IRL - 1038，4微摩尔/升；IRL - 1025，5微摩尔/升）无效（n = 6）。
内源性肺大内皮素产生致心律失常作用，在遗传性高脂血症中会加重。这些作用需要将大内皮素在冠状动脉中转化为内皮素，部分由ET(A)介导且不依赖ET(B)。
