Protection of ischemic myocardium in dogs using intracoronary 2,3-butanedione monoxime (BDM).
BACKGROUND
Actomyosin ATPase is one of the major ATP consuming enzymes in the myocardium. We tested whether 2,3-butanedione monoxime (BDM), a reversible inhibitor of actomyosin ATPase, given before coronary occlusion, limits infarct size in anesthetized open-chest dogs.


RESULTS
After circumflex artery catheterization using fluoroscopic guidance, BDM (125 mM) or buffer vehicle was infused (12.0 ml/min) for 20 min (BDM-20, n = 5 and Buffer-20, n = 6) or for 5 min (BDM-5, n = 6 and Buffer-5, n = 6) prior to 60 min of ischemia and 3 h of reperfusion. BDM administration increased subendocardial blood flow 271% above baseline flow (radioactive microspheres), and systolic wall thickening was converted to wall bulging (wall thickening by sonomicrometry was -27 +/- 29% and -22 +/- 13% of baseline in BDM-20 and BDM-5, respectively). Adjusted mean infarct size (% area-at-risk) was 11.0 +/- 2.8% and 11.9 +/- 2.6% in BDM-20 and BDM-5 vs. 20.2 +/- 2.5% and 20.5 +/- 2.5% in Buffer-20 and Buffer-5 (ancova, P < 0.05 for each BDM vs. Buffer group). Measurement of glycolytic metabolites and the adenine nucleotide pool of myocardium paced electronically at 150 beats per minute during total ischemia at 37 degrees C following BDM showed a metabolic response similar to that seen in ischemic preconditioning. ATP depletion, nucleoside production, and lactate accumulation were slowed in ischemic tissue treated with BDM.


CONCLUSIONS
BDM given before the onset of ischemia markedly limited infarct size and reduced energy demand after the onset of ischemia. The explanation for the reduced infarct size induced by BDM treatment is hypothesized to be the persistent reduction in energy demand found in ischemic BDM treated myocardium.
Sebbag
Laurent
L
Pole de transplantation, Hôpital cardiologique Louis-Pradel, BP Lyon Montchat, 69394 Lyon cedex 3, France. sebbag@univ-lyon1.fr
Verbinski
Steven G
SG
Reimer
Keith A
KA
Jennings
Robert B
RB
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003931:Diacetyl / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009218:Myosins / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; C004717:diacetylmonoxime; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D009218:Myosins; D003931:Diacetyl