2,3-Butanedione monoxime suppresses excitation-contraction coupling in the canine blood-perfused left ventricle.
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.
Takasago
T
T
Department of Cardiovascular Dynamics, National Cardiovascular Center, Suita, Japan.
Goto
Y
Y
Kawaguchi
O
O
Hata
K
K
Saeki
A
A
Taylor
T W
TW
Nishioka
T
T
Suga
H
H
D000704:Analysis of Variance; D000818:Animals; D002122:Calcium Chloride / Q000378:metabolism / Q000494:pharmacology; D002138:Calibration; D002395:Catecholamines / Q000097:blood; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D019188:Organ Preservation Solutions; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D012044:Regression Analysis
D002395:Catecholamines; D002801:Cholinesterase Reactivators; D019188:Organ Preservation Solutions; C004717:diacetylmonoxime; D003931:Diacetyl; D002122:Calcium Chloride