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This Article Full Text Full Text (PDF) All Versions of this Article: 285/1/H316    most recent 00906.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Southworth, R. Articles by Garlick, P. B. Search for Related Content PubMed PubMed Citation Articles by Southworth, R. Articles by Garlick, P. B.

Dobutamine responsiveness, PET mismatch, and lack of necrosis in low-flow ischemia: is this hibernation in the isolated rat heart?

Department of Radiological Sciences, Guy's Hospital, London SE1 9RT, United Kingdom

Submitted 21 October 2002 ; accepted in final form 10 March 2003

The clinical hallmarks of hibernating myocardium include hypocontractility while retaining an inotropic reserve (using dobutamine echocardiography), having normal or increased [¹⁸F]fluoro-2-deoxyglucose-6-phosphate (¹⁸FDG6P) accumulation associated with decreased coronary flow [flow-metabolism mismatch by positron emission tomography (PET)], and recovering completely postrevascularization. In this study, we investigated an isolated rat heart model of hibernation using experimental equivalents of these clinical techniques. Rat hearts (n = 5 hearts/group) were perfused with Krebs-Henseleit buffer for 40 min at 100% flow and 3 h at 10% flow and reperfused at 100% flow for 30 min (paced at 300 beats/min throughout). Left ventricular developed pressure fell to 30 ± 8% during 10% flow and recovered to 90 ± 7% after reperfusion. In an additional group, this recovery of function was found to be preserved over 2 h of reperfusion. Electron microscopic examination of hearts fixed at the end of the hibernation period demonstrated a lack of ischemic injury and an accumulation of glycogen granules, a phenomenon observed clinically. In a further group, hearts were challenged with dobutamine during the low-flow period. Hearts demonstrated an inotropic reserve at the expense of increased lactate leakage, with no appreciable creatine kinase release. PET studies used the same basic protocol in both dual- and globally perfused hearts (with 250MBq ¹⁸FDG in Krebs buffer ± 0.4 mmol/l oleate). PET data showed flow-metabolism "mismatch;" whether regional or global, ¹⁸FDG6P accumulation in ischemic tissue was the same as (glucose only) or significantly higher than (glucose + oleate) control tissue (0.023 ± 0.002 vs. 0.011 ± 0.002 normalized counts · s^-1 · g^-1 · min^-1, P < 0.05) despite receiving 10% of the flow. This isolated rat heart model of acute hibernation exhibits many of the same characteristics demonstrated clinically in hibernating myocardium.

hibernation; positron emission topography; isolated heart; dobutamine; morphology