Antecedent ischemia reverses adenosine-induced alterations of
glycolysis and recovery of mechanical function of working rat
hearts.
Finegan, Barry A., Manoj Gandhi, Gary D. Lopaschuk, & Alexander S.
Clanachan.
DEPARTMENTS OF ANAESTHESIA, AND PHARMACOLOGY, FACULTY OF MEDICINE,
UNIVERSITY OF ALBERTA, EDMONTON, ALBERTA, CANADA, T6G 2H7
APStracts 3:0185H, 1996.
This study compared the effects of adenosine on the coupling of
glycolysis and glucose oxidation and on mechanical function in normal
hearts and in hearts subjected to transient ischemia. Isolated
working rat hearts, paced at 300 beats x min-1, were perfused with
Krebs solution, containing 1.2 mM palmitate and 100 FEU x ml-1
insulin. Rates of glycolysis and glucose oxidation were measured from
the production of 3H2O and 14CO2 from [5-3H/U-14C]glucose. Left
ventricular minute work (LV work) served as an index of mechanical
function. After 15 min of aerobic perfusion, hearts were subjected to
either two cycles of 10 min ischemia and 5 min reperfusion (Stressed)
or 30 min of aerobic perfusion (Control). After 45 min, hearts
underwent either aerobic perfusion for 35 min (Series A) or 30 min
sustained ischemia and 30 min reperfusion (Series B). In Series A, LV
work was similar in Control and Stressed hearts and was not affected
by adenosine (500 FEM) or N6-cyclohexyladenosine (CHA 0.5 FEM).
Adenosine reduced glycolysis by 49% in Control hearts but increased
glycolysis by 74% in Stressed hearts. CHA inhibited glycolysis in
both groups by 50% and 62%, respectively. Glucose oxidation was not
affected by adenosine or CHA in either group. In Series B, LV work
during reperfusion recovered to a similar extent in untreated Control
and Stressed hearts. In Control hearts, adenosine reduced glycolysis
by 50%, while enhancing the recovery of LV work to 81 +/- 7% of pre
-ischemic values. In Stressed hearts, adenosine increased glycolysis
by 34% and depressed the recovery of LV work to 9 +/- 4%, while CHA
inhibited glycolysis by 53% and enhanced the recovery of LV work to
91 +/- 5% of pre-ischemic values. These data support the hypothesis
that the coupling of glycolysis to glucose oxidation is an important
determinant of the recovery of mechanical function of the post
-ischemic myocardium. They also demonstrate that the metabolic and
cardioprotective effects of adenosine are dependent on the status of
the heart prior to sustained ischemia.
Received 16 November 1995; accepted in final form 17 April 1996.
APS Manuscript Number H1080-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96