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M J Legato

Publications and source records attributed to M J Legato.

7 recordsLinked to original sources

The morphology of the developing canine conducting system: bundle branch and Purkinje cell architecture from birth to week 12 of life.

This is a qualitative and quantitative study of dog bundle branch and Purkinje cell development from day 0 to week 12 of life; we correlate the morphologic data with changes observed in the functional properties of developing dog Purkinje tissue. The bundle branch itself has a roughly cylindrical shape and is surrounded by a collagen sheath covered with endocardium. Within the bundle, Purkinje cells are packed closely together in fascicles distributed evenly around a central artery. Cross-sectional area doubles in the right bundle and increases 5-fold in the left bundle system between day 0 and week 12 of life. About one third of the bundle by volume is Purkinje tissue; the rest is extracellular space containing an increasing amount of collagen as the animal ages. Purkinje cell cross-sectional area is constant during the first week of life, but its length doubles and the cell changes from a relatively round to a more cylindrical shape. Between day 7 and week 12, cell diameter doubles; Purkinje cell surface area increases 5-fold and its volume almost 10-fold. As a consequence, the surface to volume ratio halves and approaches the value reported for adult dogs by week 12 of life. The percent of the intercalated disc occupied by nexal junctions virtually doubles by week 12, the same period over which Purkinje fiber conduction velocity increases. The disc itself becomes less dominant as the cell enlarges; the total percent of sarcolemma involved in its formation decreases by a fourth and has achieved the adult value by week 12 of life. As this happens, the percent of cell membrane facing on clefts increases almost 6-fold, so that the total percent of sarcolemma facing on small spaces (approximately 340A wide) is constant over the age period studied. The paucity of clefts in newborn tissue compared with the value reported for the adult dog may help explain the relative lack of responsiveness to extracellular potassium concentration of the resting membrane potential described for fetal Purkinje tissue. Within the Purkinje cell itself, the percent by volume occupied by mitochondria remains relatively constant over the age span studied, while sarcomeric mass increases 3-fold over the same period of time; these data are consonant with the relative resistance of this tissue to hypoxia.

Animals

Phospholipase C modulates automaticity of canine cardiac Purkinje fibers.

Alpha-1 adrenergic agonists increase cardiac Purkinje fiber automaticity and elevate D-myo-inositol-trisphosphate (IP3) levels. To learn about the relationship between phosphoinositide metabolism and the modulation of cardiac rhythm, we used phospholipase C to activate phosphoinositide hydrolysis in an alpha-1 receptor-independent fashion and determined whether this intervention modulated automaticity. We used standard microelectrode techniques to study automaticity in adult Purkinje fiber bundles, fluorescence microscopy to study fura-2 fluorescence in isolated Purkinje and ventricular myocytes and standard biochemical techniques to measure inositol phosphate production in ventricular myocytes. Phospholipase C increased Purkinje fiber automaticity, a process that was enhanced by 10 mM lithium (which had no effect alone) and suppressed by verapamil or ryanodine (both 10 microM). Superfusion with 12-O-tetradecanoyl-phorbol-13-acetate phorbol ester, phospholipase D and A2, as well as L-alpha-phosphatidic acid, trypsin and D-myo-inositol-1-phosphate, D-myo-inositol-1,4-bisphosphate, IP3 and D-myo-inositol-1,4,5,6-tetrakisphosphate did not affect automatic rate or transmembrane potentials. Biochemical studies of ventricular myocytes demonstrated a phospholipase C-induced increase in intracellular and extracellular IP3, D-myo-inositol-1,4-bisphosphate and D-myo-inositol-1-phosphate at 3 min, with the extracellular increase persisting thereafter. Fluorescence microscopy with fura-2 revealed that phospholipase C increased systolic-free calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cellular mechanisms of normal growth in the mammalian heart. I. Qualitative and quantitative features of ventricular architecture in the dog from birth to five months of age.

This paper describes the qualitative and quantitative composition of dog myocardium over the first 5 months of life. The quantitative composition of dog right and left ventricle over this period does not vary. A stereological analysis of electron micrographs representing 32,000 micron2 of tissue surface revealed that 79% of the heart is made up of myofibers, whereas 21% is extracellular space. Twenty-eight percent of the extracellular compartment by volume is vasculature (tissue was preserved by immersion rather than vascular perfusion); 72% is occupied by nonvascular elements and "empty" space. In contrast to the remarkable constancy of quantitative composition of the whole myocardium, myocyte shape and dimensions and the arrangement of intercellular connections vary dramatically over the age period studied. In early postnatal life, the morphology of blood vessels, many of which have completely partitioned lumina, also changes significantly.

Aging

Cellular mechanisms of normal growth in the mammalian heart. II. A quantitative and qualitative comparison between the right and left ventricular myocytes in the dog from birth to five months of age.

This paper describes and contrasts the changes in myocytes taken from the right and left ventricules of dog heart over the first 5 months of life. The development of the two populations of cells differs in important respects: sarcomeric volume, the proportion of the myocyte occupied by the contractile apparatus, and the volume and surface area of the transverse tubular system all were greater on the average in the left than in the right ventricle (P less than 0.001). Other intracellular structures also changed significantly as development progressed, but did so in both chambers; the surface area and surface-to-volume (s/v) ratio of both right and left ventricular myocytes increased with age (P less than 0.001) as did mitochondrial and mitochondrial-myocyte volume (P less than 0.001). The surface area (P less than 0.01) and the s/v ratio of the mitochondria (P less than 0.001) also increased with development. Nuclear and nuclear myocyte volume grew smaller with age in both chambers (P less than 0.002), as did the surface area (P less than 0.001) and the s/v ratio of the nucleus (P less than 0.01). Not only does myocyte composition change quantitatively, striking changes in intracellular architecture and the appearance and arrangement of intracellular organelles occur during postnatal life.

Aging