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 mumol of [13C]glucosyl units/g wet wt (P less than 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 mumol (P less than 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 less than 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 less than 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.
Kalil-Filho
R
R
Peter Belfer Laboratory Cardiology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Gerstenblith
G
G
Hansford
R G
RG
Chacko
V P
VP
Vandegaer
K
K
Weiss
R G
RG
D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D010710:Phosphates / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D005958:Glucosephosphates; D010710:Phosphates; D000249:Adenosine Monophosphate; D019298:Glucose-6-Phosphate; D006003:Glycogen; D006005:Phosphorylases