Summary
The negative inotropic effect of the calcium antagonist, verapamil, was compared in isolated hearts from 15-, 30-, 45-, 60-, and 90-day-old rats. Electrically paced hearts were perfused in vitro according to Langendorff, either under constant pressure or under constant flow conditions. An intraventricular-pressure curve was measured isovolumetrically and analyzed on-line using a microcomputer. Changes in pressure amplitude and maximum rate of pressure development were evaluated during a stepwise increase of the verapamil concentration in the perfusion solution (10−9–3.3×10−7 mol·l−1). It was found that the sensitivity of cardiac contractile function to verapamil declines gradually in the course of postnatal ontogeny. The higher sensitivity of the developing heart to calcium channel blockade is probably a consequence of a higher functional dependence of the immature myocardium on trans-sarcolemmal calcium influx.
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References
Anderson TW, Hirsch C, Kavalier F (1977) Mechanisms of activation in frog ventricular muscle. Circ Res 41:472–480
Artman M, Graham TP, Boucek RJ (1985) Effects of postnatal maturation on myocardial contractile responses to calcium antagonists and changes in contraction frequency. J Cardiovasc Pharmacol 7:850–855
Boucek RJ, Shelton M, Artman M, Mushlin PS, Starncs VA, Olson RD (1984) Comparative effects of verapamil, nifedipine and diltiazem on contractile function in the isolated immature and adult rabbit heart. Pediat Res 18:948–952
Boucek RJ, Shelton ME, Artman M, Landon E (1985) Myocellular calcium regulation by the sarcolemmal membrane in the adult and immature rabbit heart. Basic Res Cardiol 80:316–325
Fabiato A, Fabiato F (1978) Calcium-induced release of calcium from the sarcoplasmic reticulum of skinned cells from adult human, dog, cat, rabbit, rat and frog hearts and from fetal and newborn rat ventricles. Ann New York Acad Sci 307:491–522
George BL, Shimizu T, Jarmakani JM (1984) Caffeine effect on myocardial mechanical function in the neonatal rabbit heart. Dev Pharmacol Ther 7:398–408
Gibson R, Driscoll D, Gillette P, Hartley C, Entman ML (1981) The comparative electrophysiologic and hemodynamic effects of verapamil in puppies and adult dogs. Dev Pharmacol Ther 2:104–116
Hoerter J, Mazct F, Vassort G (1981) Perinatal growth of the rabbit cardiac cell: Possible implications for the mechanisms of relaxation. J Mol Cell Cardiol 13:725–740
Jarmakani JM, Nakanishi T, George BL, Bers D (1982) Effect of extracellular calcium on myocardial mechanical function in the neonatal rabbit. Dev Pharmacol Ther 5:1–13
Kazazoglou T, Schmid A, Renaud JF, Lazdunski M (1983) Ontogenic appearance of Ca2+ channels characterized as binding sites for nitrendipine during development of nervous, skeletal and cardiac muscle systems in the rat. FEBS Lett 164:75–79
Maylie JG (1982) Excitation-contraction coupling in neonatal and adult myocardium of cat. Am J Physiol 242:H834-H843
Nakanishi T, Jarmakani JM (1984) Developmental changes in myocardial mechanical function and subcellular organellcs. Am J Physiol 246:H615-H625
Nayler WC, Fassold E (1977) Calcium-accumulating and ATPase activity of cardiac sarcoplasmic reticulum before and after birth. Cardiovasc Res 111:231–237
Nishioka K, Nakanishi T, George BL, Jarmakani JM (1981) The effect of calcium on the inotropy of catecholamine and paired electrical stimulation in the newborn and adult myocardium. J Mol Cell Cardiol 13:511–520
Page E, Earley J, Power B (1974) Normal growth of ultrastructures in rat left ventricular myocardial cells. Circ Res 34 (Suppl 2):12–16
Pučelík P, Ježek K, Barták F (1982) Postnatal development of electrophysiological manifestation of the working ventricular myocardium of albino rats. Physiol bohemoslov 31:217–224
Reder RF, Miura DS, Danilo P, Rosen MR (1981) The electrophysiological properties of normal neonatal and adult canine cardiac Purkinje fibers. Circ Res 48:658–668
Reiter M, Vierling W, Seibel K (1984) Where is the origin of the activator calcium in cardiac ventricular contraction? Basic Res Cardiol 79:1–8
Seguchi M, Jarmakani JM, George BL, Harding JA (1986) Effect of Ca2+ antagonists on mechanical function in the neonatal heart. Pediat Res 20:838–842
Škovránek J, Ošt'ádal B, Pelouch V, Procházka J (1986) Ontogenetic difference in cardiac sensitivity to verapamil in rats. Pediat Cardiol 7:25–29
Vetter R, Will H (1986) Sarcolemmal Na−Ca exchange and sarcoplasmic reticulum calcium uptake in developing chick heart. J Mol Cell Cardiol 18:1267–1275
Vornanen M (1984) Activation of contractility and sarcolemmal Ca2+-ATPase by Ca2+ during postnatal development of the rat heart. Comp Biochem Physiol (A) 78:691–695
Vornanen M (1987) Postnatal changes in the inotropic effect of ouabain on the rat heart ventricle. Basic Res Cardiol 82:82–91
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Kolář, F., Ošt'ádal, B. & Papoušek, F. Effect of verapamil on contractile function of the isolated perfused rat heart during postnatal ontogeny. Basic Res Cardiol 85, 429–434 (1990). https://doi.org/10.1007/BF01931488
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DOI: https://doi.org/10.1007/BF01931488