Circulation, Vol 87, 900-908, Copyright © 1993 by American Heart Association
BA Finegan, GD Lopaschuk, CS Coulson and AS Clanachan
BACKGROUND. Adenosine possesses marked cardioprotective properties, but the
mechanisms for this beneficial effect are unclear. The objective of this
study was to determine the effect of adenosine given before ischemia or at
reperfusion on mechanical function, glucose oxidation, glycolysis, and
metabolite levels in isolated, paced (280 beats per minute) working rat
hearts. METHODS AND RESULTS. Hearts were perfused with Krebs-Henseleit
buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microU.mL-1
insulin at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload.
Adenosine (100 microM) pretreatment or adenosine (100 microM) at
reperfusion markedly increased the recovery of mechanical function (from
44% to 81% and 96%, respectively) after 60 minutes of low-flow ischemia
(coronary flow, 0.5 mL.min-1). Glucose oxidation (mumol.min-1 x g dry wt-1)
was inhibited during ischemia (from 0.44 +/- 0.04 to 0.12 +/- 0.01), and
this was not altered by adenosine (100 microM). During reperfusion, glucose
oxidation recovered (to 0.38 +/- 0.02) and adenosine (100 microM), given at
reperfusion, further increased glucose oxidation (to 0.52 +/- 0.06). The
rate of glycolysis (mumol.min-1 x g dry wt-1), which was unaffected by
ischemia per se, was inhibited by adenosine pretreatment (from 4.7 +/- 0.3
to 2.6 +/- 0.3). During reperfusion, glycolysis was also inhibited by
adenosine relative to control (3.9 +/- 0.8) either when present during
ischemia (2.6 +/- 0.6) or during reperfusion (1.4 +/- 0.4). These effects
of adenosine on glucose metabolism reduced the calculated rate of H+
production attributable to glucose metabolism during the ischemic and
reperfusion periods. Tissue lactate levels (mumol.g dry wt-1), which
increased during ischemia (from 9.3 +/- 1.1 to 87.4 +/- 10.3) and then
declined during reperfusion (to 26.2 +/- 3.7), were depressed further by
adenosine pretreatment (to 19.7 +/- 4.1) and by adenosine at reperfusion
(to 13.6 +/- 2.1). ATP levels (mumol.g dry wt-1), which were depressed by
ischemia (from 18.1 +/- 1.1 to 10.6 +/- 1.3) and tended to be further
depressed during reperfusion (to 7.1 +/- 0.7), were increased by adenosine
pretreatment (to 14.1 +/- 1.2) and by adenosine at reperfusion (to 15.6 +/-
2.4). CONCLUSIONS. The effects of adenosine on glucose metabolism that
would tend to decrease cellular acidosis and hence, Ca2+ overload, may
explain the beneficial effects of adenosine on mechanical function observed
in these hearts during reperfusion after ischemia.
ARTICLES
Adenosine alters glucose use during ischemia and reperfusion in isolated rat hearts
Department of Anaesthesia, Faculty of Medicine, University of Alberta, Edmonton, Canada.
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