title: Repetitive supply-demand ischemia with dobutamine increases glucose uptake in postischemic and remote myocardium.
abstract: The goal of this study was to determine whether myocardial glucose uptake after repetitive ischemia differs in response to coronary occlusion-reperfusion versus supply-demand ischemia induced by dobutamine. Although glucose metabolism is increased after myocardial ischemia, the metabolic effect of supply-demand ischemia induced by dobutamine may increase glucose metabolism within remote myocardium. This would make it difficult to discriminate postischemic from remote myocardium with glucose tracers.
  
  
  METHODS
  Eighteen swine with a hydraulic occluder and flow probe on the circumflex artery underwent repetitive ischemia. In group 1 (n = 9), the circumflex artery was occluded, whereas in group 2 (n = 9), circumflex flow was decreased by 30% before dobutamine (40 micro g/kg/min intravenously). Each pig underwent 15 min of ischemia, twice per day for 5 d. Echocardiography and PET to determine myocardial glucose ((18)F-FDG) uptake were performed after final ischemia, and tissue was later analyzed for activation of Akt, p38 mitogen-activated protein, and adenosine monophosphate (AMP) kinase.
  
  
  RESULTS
  Wall thickening in the circumflex region was lower than in remote regions in both groups. (18)F-FDG uptake in the circumflex region was similar in groups 1 and 2 (0.22 +/- 0.03 and 0.23 +/- 0.04 micro mol/min/g, respectively; not statistically significant). In the remote region, (18)F-FDG uptake was lower than in the circumflex region in group 1 (0.14 +/- 0.03 micro mol/min/g; P < 0.05) but was similar to that in the circumflex region in group 2 (0.20 +/- 0.03 micro mol/min/g; not statistically significant). AMP kinase activity in the remote region was significantly lower than in the circumflex region in group 1 but was similar to that in the circumflex region in group 2.
  
  
  CONCLUSIONS
  Unlike repetitive coronary artery occlusion-reperfusion, repetitive supply-demand ischemia with dobutamine alters glucose uptake within the remote myocardium, possibly as a result of AMP kinase activation. Clinically, these data suggest that (18)F-FDG studies have a limited role in discriminating postischemic from remote myocardium after dobutamine stress.
authors.affiliation: Department of Medicine, VA Medical Center, University of Minnesota, Minneapolis, Minnesota, USA. mcfal001@tc.umn.edu
authors.forename: Edward O
authors.initials: EO
authors.lastname: McFalls
authors.forename: Bilal
authors.initials: B
authors.lastname: Murad
authors.forename: Doua
authors.initials: D
authors.lastname: Her
authors.forename: Jeih-San
authors.initials: JS
authors.lastname: Liow
authors.forename: Rosemary
authors.initials: R
authors.lastname: Kelly
authors.forename: David
authors.initials: D
authors.lastname: Marx
authors.forename: Joseph
authors.initials: J
authors.lastname: Sikora
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Ward
mesh_terms: D000818:Animals; D001549:Benzamides; D004280:Dobutamine / Q000008:administration & dosage*; D005215:Fasting / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000378:metabolism; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000000981:diagnostic imaging / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013552:Swine; D014055:Tomography, Emission-Computed
chemical_list: D001549:Benzamides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D004280:Dobutamine; C098101:dobupride; D005947:Glucose