Role of glycolysis in the energy production for the non-mechanical myocardial work in isolated pig hearts.

Background: The dissociation of mechanical from non-mechanical energy utilisation can be studied using BDM (2,3-butanedione monoxime), which inhibits the actin-myosin interaction without inhibiting Ca2+ transport. The objective of the present study was to establish if increasing the non-mechanical energy demand of perfused isolated pig hearts by dobutamine stimulation requires glycolysis with increased exogenous glucose uptake.

Methods: Five isolated pig hearts (CTRL) were perfused for 90 min at constant flow (1 ml g(-1) min(-1)) with non-recirculating blood containing 30 mM BDM and 26 MBq/l of fluorine-18 2-fluoro-2-deoxyglucose (IFDG). This was compared with five hearts (DOBU) subjected to the same protocol for the first 30 min and then to dobutamine (1.5 microM) for the following 30 min and dobutamine (4 microM) for the last 30 min. Five other isolated hearts were perfused as for the DOBU group but without BDM (CTRLDOBU). Using a clinical PET scanner, glucose uptake was assessed by estimating 18FDG uptake using linear regression. The slope variations were compared using a global test of coincidence.

Results: Heart rate was at 100 +/- 2 b.p.m. in the CTRL group and at 180 +/- 7 b.p.m. in the DOBU group. 18FDG uptake was homogeneous within the whole myocardium and we observed a linear and regular increase in both the CTRL and DOBU groups (p, NS). In the CTRLDOBU group, 18FDG uptake was also homogeneous within the whole myocardium, but slopes of 18FDG uptake during dobutamine perfusion were higher than without dobutamine.

Conclusion: In blood-perfused isolated pig hearts, exogenous glucose is not necessarily required when non-mechanical energy is increased by dobutamine stimulation. These findings suggest that ATP derived from glycolysis is not necessary to preserve myocardial Ca2+ transport during beta-adrenergic stimulation.