A Practical Approach, Second Edition=Ronald D. Ho.pdf

POSTNATAL DEVELOPMENTAL MILESTONES 1063decrease in right ventricular weight from 86% of the left ventricular at birth to 54% in adults, withpreferential growth of the left ventricle between postnatal days 1 and 7.For the beagle dog, Deavers et al. (1972) reported a small but significant decrease in relativeheart weights from birth to adulthood. The ratio of left ventricular volume and weight did notchange with age (Lee et al., 1975).Postnatal Development of Heart Cellular ConstituentsAt the cellular level, cardiac growth is due to both cellular proliferation and an increase in cellularvolume (Hudlicka and Brown, 1996). Myocyte hypertrophy is accompanied by an increase incellular DNA. Cardiac myocytes at birth contain one diploid nucleus. The number of binucleatedcells rapidly increases during the early postnatal stages. In human myocytes, the majority of thesenuclei subsequently fuse, leading to an increase in polyploidy. On the other hand, binucleatedcardiac myocytes remain predominant throughout life in rodents. Hearts from other experimentalanimals contain both binucleated and polyploid myocytes. Other significant intracellular maturationalchanges include a progressive increase in sarcoplasmic reticulum and myofibrils.HumanThe newborn heart contains about half the total number of myocytes present in the adult heart.Adult values are reached probably before the age of 4 months (Linzbach, 1950, 1952; Hort, 1953).At birth, the majority of cardiac myocytes are mononucleated. During postnatal development, thepercentage of binucleated cells increases up to 33% during late infancy or early childhood, with asubsequent decrease to adult values [5-13% of cells in the left ventricle are binucleated and 7% ofthe cells in the right ventricle are binucleated] (Schneider and Pfitzer, 1973). In infants, almost allnuclei of the cardiac myocyte are diploid. In adults, 60% are diploid, 30% are tetraploid and 10%are octoploid (Eisentein and Wied, 1970). Myocyte size is also reported to increase with age fromapproximately 5 µm at birth, 8 µm at 6 weeks, 11 µm at 3 years, 13 µm at 15 years to 14 µm inadults (Ashley, 1945; Rakusan, 1980).An increase in myocardial contractile function during the early postnatal period is accompaniedby intracellular changes such as increased sarcoplasmic reticulum and myofibrils, the organellesthat regulate and utilize calcium to produce cardiac contraction (Fisher and Towbin, 1988).Comparative SpeciesIn the rat, as in humans, myocyte cell volume increases nearly 25-fold and myocyte cell number3-4 fold from birth to 2 months of age, (Anversa et al., 1986; Englemann et al., 1986; Mattfeldtand Mall, 1987;Vliegen et al., 1987). The increase in cardiac mass is due to cell proliferation untilpostnatal day 3-6, hyperplasia and hypertrophy until postnatal day 14, and solely by hypertrophythereafter (Chubb and Bishop, 1984; Anversa et al., 1986, 1992; Batra and Rakusan, 1992; Li etal., 1996). Most of the muscle cell nuclei are diploid in the rat heart (Korecky and Rakusan, 1978;Rakusan, 1984). The frequency of polyploidy, which is rather low at birth, even decreases slightlywith age in the rat heart (Grove et al., 1969). Mast cells, which are postulated to play a role incapillary angiogenesis, are present in very low numbers in early rat pups, but start to increase inthe postnatal weeks 3 and 4 to maximum numbers by 100 days of age (Rakusan et al., 1990).In mice, the volume of myocytes remains relatively constant despite a concomitant increase inheart weight, indicating growth due to cell division during the first four postnatal days (Leu et al.,2001). After postnatal day 5, the volume of myocytes increases markedly until postnatal day 14,when the increase slows down. Myocytes reach their adult volume at around 3 months of age.In rabbits, myocyte diameter increases progressively (from ~ 5 µm) towards adult values(14 µm), starting on postnatal day 8 (Hoerter et al., 1981). Rabbit neonate studies show that, as in© 2006 by Taylor & Francis Group, LLC