The role played by glycogenolysis in the ischemic heart has been recently put into question because it is suspected that a slowing down of this process could be beneficial for the tolerance of the myocardium to
ischemia. The role of the intracellular effectors that control the rate of glycogenolysis has therefore regained interest. We aimed to understand the role played by those intracellular effectors which are directly related to the energy balance of the heart. To this end, we review some of the previously published data on this subject and we present new data obtained from P-31 and C-13 NMR spectroscopic measurement on isolated rat heart. Two conditions of
ischemia were studied: 15 min global no-flow and 25 min low-flow
ischemia. The hearts were isolated either from control animals or from rats pre-treated with
isoproterenol (5 mg.kg-1 b.w. i.p.) 1 h before the perfusion in order to C-13 label
glycogen stores. Our main results are as follows: (1) the biochemically determined glycogenolysis rate during the early phase of
ischemia (up to 10-15 min) was larger in no-flow
ischemia than in low-flow conditions for both groups, (2) direct measurement of the glycogenolysis rate, as determined by C-13 NMR, after labelling of the
glycogen pool in the hearts from
isoproterenol-treated rats, confirms the estimations from the biochemical data, (3) glycogenolysis was slower in the hearts from pre-treated animals than in control hearts for both conditions of
ischemia, (4) the total activity of
glycogen phosphorylase (a + b) increased, by 50%, after 5 min no-flow
ischemia, whereas it decreased by 42% after the same time of low-flow
ischemia. However, the ratio
phosphorylase a/a + b was not altered, whatever the conditions, (5) the concentration of
inorganic phosphate (Pi) increased sharply during the first minutes of
ischemia, to values above 8-10 mM, under all conditions studied. The rate of increase was larger during no-flow
ischemia than during low-flow
ischemia. The concentration of Pi was thereafter higher in controls than in the hearts from
isoproterenol-treated animals. The calculated cytosolic concentration of free 5'
AMP increased sharply at the onset on
ischemia, reaching in a few minutes values above 30 microM in controls and significantly lower values around 15 microM, in the hearts from
isoproterenol-treated rats. (6) The hearts from
isoproterenol-treated rats displayed a reduced intracellular
acidosis, when compared to controls, under both conditions of
ischemia. We conclude that the intracellular effectors, mainly free
AMP, play an essential role in the control of glycogenolysis via allosteric control of
phosphorylase b activity. The alteration in the concentration of free Pi, the substrate of both forms of
phosphorylase, can be considered as determinant in the control of the rate of glycogenolysis. The attenuation of
ischemia-induced intracellular
acidosis in the hearts from
isoproterenol-treated rats could be a consequence of a reduced glycogenolytic rate and is likely to be related to a better resumption of the mechanical function on reperfusion.