Regulation of myocardial glycogenolysis during post-ischemic reperfusion

Myocardial glycogen and the factors which primarily regulate its metabolism were studied during post-ischemic reperfusion. Myocardial [¹³C]glycogen was continuously monitored by ¹³C-NMR spectroscopy in beating rat hearts perfused with oxygenated solutions containing [1-¹³C]glucose (5 mm) and insulin, during normal flow at 15 ml/min (n = 5), and during reperfusion after 30 min of 1 ml/min (n = 5), or 0 ml/min (n = 4) ischemia. Mean myocardial [¹³C]glycogen fell during reperfusion from 1.1 ± 0.6 at the end of zero-flow ischemia to 0.4 ± 0.4 μmol of [¹³C]glucosyl units/g wet wt (P<0.02) over the first 7 min of reperfusion; it also fell during reflow following 1 ml/min ischemia, from 2.3 ± 1.4 to 1.7 ± 1.0 μmol (P<0.03) over the same interval. In parallel experiments, glycogen phosphorylase % a(GPA%) content was higher at the end of 30 min of 0 ml/min (37.3 ± 7.3%, P<0.01), and trended higher after 1 ml/min flow (30.8 ± 12.1%, P=0.18) than under baseline conditions (20.1 ± 7.4%). However GPA% returned to baseline values within 1 min of reflow after both 0 and 1 ml/min ischemic periods (20.6 ± 3.0% and 19.0 ± 8.0%, respectively). Inorganic phosphate, as determined by simultaneous ³¹P-NMR, remained elevated during early reperfusion relative to baseline, and significantly correlated with the extent of decline in [¹³C]glycogen during reperfusion (r = 0.79, P<0.01). Thus, glycogen breakdown continues to occur during early post-ischemic reperfusion, but the mechanism is not related to elevated GPA%, and may be due to persistently increased inorganic phosphate at that time.