2,3-Butanedione monoxime suppresses excitation-contraction coupling in the canine blood-perfused left ventricle.

The negative inotropism of 2,3-butanedione monoxime (BDM)less than or equal to 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-E-max framework that we have developed, where VO2 is myocardial O-2 consumption, PVA is the systolic pressure-volume area as a measure of the total mechanical energy, and E-max is a contractility index. We gradually depressed E-max 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 E-max to the pre-BDM level by increasing intracoronary CaCl2. We compared the O-2 cost of E-max between BDM and Ca2+. We found that BDM and Ca2+ had a similar O-2 cost Of E-max. 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.