Oxygen wastage of stunned myocardium in vivo is due to an increased oxygen cost of contractility and a decreased myofibrillar efficiency.
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.
Trines
S A
SA
Department of Cardiology, Thoraxcentre, Erasmus Medical Centre Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Slager
C J
CJ
Onderwater
T A
TA
Lamers
J M
JM
Verdouw
P D
PD
Krams
R
R
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
D013829:Thiadiazines; C088204:EMD 60263; D004280:Dobutamine; D010100:Oxygen; D002118:Calcium