Takasago T, Goto Y, Kawaguchi O, Hata K, Saeki A, Taylor T W, Nishioka T, Suga H
Department of Cardiovascular Dynamics, National Cardiovascular Center, Suita, Japan.
Jpn J Physiol. 1997 Apr;47(2):205-15. doi: 10.2170/jjphysiol.47.205.
The negative inotropism of 2,3-butanedione monoxime (BDM) < or = 5 mmol/l has been attributed primarily to directly suppressed crossbridge force development without much suppressed intracellular Ca2+ handling. However, there is evidence that BDM simultaneously or even primarily suppresses myocardial excitation-contraction (E-C) coupling. We therefore studied the mechanoenergetic effects of intracoronary BDM in the left ventricle (LV) of 11 canine excised cross-circulated hearts. We fully utilized the VO2-PVA-Emax framework that we have developed, where VO2 is myocardial O2 consumption, PVA is the systolic pressure-volume area as a measure of the total mechanical energy, and Emax is a contractility index. We gradually depressed Emax from 5.9 to 3.4 mmHg/(ml/100 g) on average by increasing intracoronary BDM to 2.6 +/- 2.1 mmol/l, and then gradually restored Emax to the pre-BDM level by increasing intracoronary CaCl2. We compared the O2 cost of Emax between BDM and Ca2+. We found that BDM and Ca2+ had a similar O2 cost of Emax. BDM did not affect the concentrations of blood-borne catecholamines. We therefore conclude that the negative inotropism of BDM is primarily due to suppressed E-C coupling in canine blood-perfused hearts.
2,3-丁二酮一肟（BDM）浓度≤5 mmol/l时的负性肌力作用，主要归因于其直接抑制横桥力的产生，而对细胞内Ca2+处理的抑制作用较小。然而，有证据表明BDM同时甚至主要抑制心肌兴奋-收缩（E-C）偶联。因此，我们研究了冠状动脉内注射BDM对11只犬离体交叉循环心脏左心室（LV）的机械能学效应。我们充分利用了我们开发的VO2-PVA-Emax框架，其中VO2是心肌耗氧量，PVA是收缩压-容积面积，作为总机械能的度量，Emax是收缩性指数。通过将冠状动脉内BDM增加到2.6±2.1 mmol/l，我们平均将Emax从5.9逐渐降低到3.4 mmHg/(ml/100 g)，然后通过增加冠状动脉内CaCl2将Emax逐渐恢复到BDM注射前的水平。我们比较了BDM和Ca2+之间Emax的氧耗成本。我们发现BDM和Ca2+具有相似的Emax氧耗成本。BDM不影响血中儿茶酚胺的浓度。因此，我们得出结论，BDM的负性肌力作用主要是由于犬血液灌注心脏中E-C偶联受到抑制。
