Post-ischaemic changes in the response time of oxygen consumption to demand in the isolated rat heart are mediated partly by calcium and glycolysis.
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.
Zuurbier
C J
CJ
Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.j.zuurbier@amc.uva.nl
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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
D002118:Calcium