A high
glycogen level may be beneficial to the ischemic heart by providing glycolytic
ATP or detrimental by increasing intracellular
lactate and
protons. To determine the effect of high
glycogen on the ischemic myocardium, the
glycogen content of Langendorff-perfused rat hearts was either depleted or elevated before 32 minutes of low-flow (0.5 mL/min)
ischemia with
Krebs-Henseleit buffer with or without 11 mmol/
L glucose, followed by 32 minutes of reperfusion with
buffer containing 11 mmol/
L glucose. 31P nuclear magnetic resonance spectra were acquired sequentially throughout. Further experiments involved early reperfusion or the addition of
HOE 694, a Na+-H+ exchange inhibitor, during reperfusion. When
glucose was supplied throughout
ischemia, no
ischemic contracture occurred, and postischemic recovery of contractile function was highest, at 88% of preischemic function. In the absence of
glucose, normal-
glycogen hearts underwent
ischemic contracture at 5 minutes, had an end-ischemic pH of 6.87, and recovered to 54%, whereas in high-
glycogen hearts,
contracture was delayed to 13 minutes, the end-ischemic pH was 6.61, and functional recovery decreased to 13%.
Contracture onset coincided with the decrease in glycolysis, which occurred as
glycogen became fully depleted. Functional recovery in the high-
glycogen hearts increased to 89% when reperfused before
contracture and to 56% when reperfused in the presence of
HOE 694. Thus, during brief
ischemia in the high-
glycogen hearts, ischemic
glycogen depletion and
contracture were avoided, and the hearts were protected from injury. In contrast, during prolonged
ischemia in the high-
glycogen hearts,
glycogen became fully depleted, and myocardial injury occurred; the injury was exacerbated by the lower
ischemia pH in these hearts, leading to increased Na+-H+ exchange during reperfusion. The contradictory findings of past studies concerning the effect of high
glycogen on the ischemic myocardium may thus be due to differences in the extent of
glycogen depletion during
ischemia.