title: Post-ischaemic changes in the response time of oxygen consumption to demand in the isolated rat heart are mediated partly by calcium and glycolysis.
abstract: This study examined whether different durations of ischaemia (I) and reperfusion (R) altered the kinetics of O(2) consumption-to-demand matching and the contribution of changes in calcium and metabolic pathways to possible alterations. The response time of mitochondrial O(2) consumption (t(mito)) to a step in heart rate in isolated rat hearts was used as index for the response time of O(2) consumption-to-demand matching. At baseline, t(mito) was 8.9 +/- 0.4 s for all groups. At 5 min reperfusion, after both reversible (I=5 or I=15 min) or irreversible (I=25 min) ischaemia, matching was accelerated (t(mito) relative to baseline: 53 +/- 8%, 64 +/- 8%, 51+/- 6% and 100 +/- 5% for I=5, 15, 25 min and control). At late reperfusion (>30 min), reversible ischaemia resulted in a slowing of the matching, whereas after irreversible ischaemia t(mito) recovered to control values (156 +/- 16%, 153 +/- 13%, 92 +/- 7%, 114 +/- 6%, for I=5,15, 25 min and control, respectively). High perfusate Ca(2+) mimicked (t(mito): 44 +/- 11%), whereas blocking mitochondrial Ca(2+) uptake attenuated the acceleration observed at early reperfusion (t(mito): 7 +/- 5%). Replacing glucose with substrates used downstream of glycolysis (11 mM lactate or 11 mM pyruvate) abolished the reversible ischaemia-induced slowing of the matching at late reperfusion. It is concluded that I/R-induced changes in the kinetics of O(2) consumption-to demand matching depend critically on the duration of ischaemia and reperfusion. The data indicate that I/R-induced increases in Ca(2+) may, at least partly, explain the faster kinetics at early reperfusion, whereas I/R-induced increases in glycolysis from exogenous glucose result in slower matching of O(2) consumption-to-demand at late reperfusion.
authors.affiliation: Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.j.zuurbier@amc.uva.nl
authors.forename: C J
authors.initials: CJ
authors.lastname: Zuurbier
authors.forename: C
authors.initials: C
authors.lastname: Ince
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology
chemical_list: D002118:Calcium