title: Oxygen wastage of stunned myocardium in vivo is due to an increased oxygen cost of contractility and a decreased myofibrillar efficiency.
abstract: OBJECTIVE
  We investigated whether an increased oxygen cost of contractility and/or a decreased myofibrillar efficiency contribute to oxygen wastage of stunned myocardium. Because Ca(2+)-sensitizers may increase myofibrillar Ca(2+)-sensitivity without increasing cross-bridge cycling, we also investigated whether EMD 60263 restores myofibrillar efficiency and/or the oxygen cost of contractility.
  
  
  METHODS
  Regional fiber stress and strain were calculated from mesomyocardially implanted ultrasound crystals and left ventricular pressure in anesthetized pigs (n=18). Regional myocardial oxygen consumption (MVO(2)) was measured before contractility (end-systolic elastance, E(es)) and total myofibrillar work (stress-strain area, SSA) were determined from stress-strain relationships. Atrial pacing at three heart rates and two doses of dobutamine were used to vary SSA and E(es), respectively. After stunning (two times 10-min ischemia followed by 30-min reperfusion), measurements were repeated following infusion of saline (n=8) or EMD 60263 (1.5 mg.kg(-1) i.v., n=10). Linear regression was performed using: MVO(2)=alpha.SSA+beta.E(es)+gamma.HR(-1) (alpha(-1), myofibrillar efficiency; beta, oxygen cost of contractility; and gamma, basal metabolism/min).
  
  
  RESULTS
  Stunning decreased SSA by 57% and E(es) by 64%, without affecting MVO(2), while increasing alpha by 71% and beta by 134%, without affecting gamma. From the wasted oxygen, 72% was used for myofibrillar work and 18% for excitation-contraction coupling. EMD 60263 restored both alpha and beta.
  
  
  CONCLUSIONS
  Oxygen wastage in stunning is predominantly caused by a decreased myofibrillar efficiency and to a lesser extent by an increased oxygen cost of contractility. Considering that EMD 60263 reversed both causes of oxygen wastage, it is most likely that this drug increases myofibrillar Ca(2+)-sensitivity without increasing myofibrillar cross-bridge cycling.
authors.affiliation: Department of Cardiology, Thoraxcentre, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Trines
authors.forename: C J
authors.initials: CJ
authors.lastname: Slager
authors.forename: T A
authors.initials: TA
authors.lastname: Onderwater
authors.forename: J M
authors.initials: JM
authors.lastname: Lamers
authors.forename: P D
authors.initials: PD
authors.lastname: Verdouw
authors.forename: R
authors.initials: R
authors.lastname: Krams
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004280:Dobutamine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D016014:Linear Models; D009200:Myocardial Contraction; D017682:Myocardial Stunning / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011897:Random Allocation; D013552:Swine; D013829:Thiadiazines / Q000494:pharmacology
chemical_list: D013829:Thiadiazines; C088204:EMD 60263; D004280:Dobutamine; D010100:Oxygen; D002118:Calcium