glycogen and Contracture

Preconditioning hastens the time to onset of ischaemic contracture and increases peak contracture in an isolated perfused rat heart, but improves recovery of function. The preconditioning ischaemic episode is also known to deplete glycogen stores. We tested whether a depletion in glycogen is related to the protection conferred by preconditioning. The isolated Langendorff perfused rat heart, with a left ventricular balloon to record function, was perfused with either glucose 11 mM, acetate 5 mM, or glucose 11 mM + insulin to alter pre-ischaemic glycogen levels prior to 30 min total global ischaemia. In addition, hearts were preconditioned by an episode of 5 min ischaemia and 5 min reperfusion. Time to onset of contracture (TOC-min), peak contracture and recovery of developed pressure after 20 min reperfusion with glucose-containing perfusate (both expressed as percentage pre-ischaemic developed pressure) were measured (n = 9-10). Parallel groups of hearts were clamped at various times for assessment of tissue metabolites. Acetate pre-perfusion reduced glycogen levels compared to glucose hearts, from 16.27 +/- 0.44 to 10.77 +/- 0.96 mumol/g wet wt. TOC was reduced and peak contracture increased, with poor functional recovery. Glucose + insulin pre-perfusion increased glycogen (21.39 +/- 1.08 mumol/g wet wt) with opposite effects on contracture, but functional recovery was still poor. Preconditioning hastened the time to onset of contracture, which could be partially attributed to glycogen depletion. Preconditioning significantly improved functional recovery in glucose hearts, but had little or no effect in the other groups. Thus the protective effect on functional recovery could not be linked to glycogen depletion. Pre-ischaemic glycogen appeared to play a dual role. When low, preconditioning was ineffective, presumably because of lack of production of glycolytic ATP, and severe contracture. When pre-ischaemic glycogen was increased, preconditioning was also relatively ineffective, presumably because of excess accumulation of the metabolites of glycogenolysis.

Topics: Acetates; Animals; Contracture; Glycogen; Heart; Ischemic Preconditioning, Myocardial; Male; Myocardium; Perfusion; Rats

We report on the autopsy study of a premature boy with multiple joint contractures who died soon after birth of severe lung hypoplasia. Muscle histology showed PAS-positive vacuoles, and electronmicroscopy revealed massive subsarcolemmal and intermyofibrillar accumulation of glycogen. Biochemical analysis of fresh-frozen muscle tissue disclosed increased glycogen content and a complete lack of phosphofructokinase (PFK) activity. The brain showed focal cerebral and diffuse cerebellar white matter gliosis, and patchy loss of internal granular and Purkinje cells in the cerebellar cortex. The spinal cord was normal. This report describes the first case of PFK deficiency, presenting as a lethal fetal akinesia sequence.

Topics: Abnormalities, Multiple; Brain; Contracture; Fatal Outcome; Gliosis; Glycogen; Glycogen Storage Disease Type VII; Humans; Infant, Newborn; Infant, Premature; Joints; Male; Muscles; Phosphofructokinase-1

The clinical course of metabolic myopathies is dominated by progressive muscle weakness and wasting or aching contraction and recurrent rhabdomyolysis with intense exercise. Vacuolar muscle fibre degeneration is the leading pathological finding on routine histological examination. For further characterization of those histologically empty looking vacuoles, histochemistry and electron microscopy are employed. Increase of glycogen, lipid droplets or mitochondria can often be demonstrated and indicate the need for subsequent biochemical identification of the underlying metabolic defect. Some other metabolic myopathies that cause recurrent rhabdomyolysis lack myopathological abnormalities. These can only be diagnosed biochemically, but additional new histochemical screening methods might be helpful.

Topics: Biopsy; Contracture; Glycogen; Glycogen Storage Disease; Humans; Lipid Metabolism; Lipid Metabolism, Inborn Errors; Microscopy, Electron; Mitochondria, Muscle; Muscle Hypotonia; Muscles; Muscular Atrophy; Muscular Diseases; Rhabdomyolysis; Vacuoles

Topics: Adenine Nucleotides; Adenosine Triphosphate; Blood Chemical Analysis; Contracture; Electromyography; Glycogen; Humans; In Vitro Techniques; Lactates; Metabolism, Inborn Errors; Muscle Contraction; Muscle Cramp; Muscle Proteins; Muscles; Muscular Diseases; Myoglobinuria; Phosphocreatine; Phosphotransferases; Physical Exertion; Spectrophotometry