Repetitive supply-demand ischemia with dobutamine increases glucose uptake in postischemic and remote myocardium.
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.
McFalls
Edward O
EO
Department of Medicine, VA Medical Center, University of Minnesota, Minneapolis, Minnesota, USA. mcfal001@tc.umn.edu
Murad
Bilal
B
Her
Doua
D
Liow
Jeih-San
JS
Kelly
Rosemary
R
Marx
David
D
Sikora
Joseph
J
Ward
Herbert B
HB
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
D001549:Benzamides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D004280:Dobutamine; C098101:dobupride; D005947:Glucose