Summary
The degree of a negative inotropic response of the isolated right ventricle to verapamil as well as the mortality rate were studied in rats during their postnatal development. Male Wistar rats aged 3, 15, 30, and 90 days were used. The isolated right ventricle was incubated in a glucose-free solution with a mixture of 95% O2 and 5% CO2 and electrically stimulated. The amplitude of isotonic contractions (AIC) was registered. In 90-day-old rats, AIC was 74.1±6.2% of initial amplitude 45 min after administration of verapamil; in 30-day-old, 41.1±6.4%; in 15-day-old, 38.2±4.1%; and in 3-day-old rats, only 2.6±1.5. The difference between the 3-day-old rats and all older groups was statistically highly significant. The mortality rate of verapamil-treated rats increased with decreasing age of animals. It is concluded that the sensitivity of the rat myocardium to verapamil is age dependent: the negative inotropic effect of this drug increases with decreasing age of the animal. This indicates a possible risk in the therapeutic use of verapamil when given to newborns and infants.
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References
Abinader E, Borochowitz Z, Berger A (1981) A hemodynamic complication of verapamil therapy in a neonate.Helv Paediatr Acta 36:451–455
Apitz J, Gaissmaier U (1971) Zwischenfall mit tödlichen Ausgang nach intravenöser Injektion von Isoptin.Med Klin 66:751–753
Bers DM, Philipson KD, Langer GA (1981) Cardiac contractility and sarcolemmal calcium binding in several cardiac muscle preparations.Am J Physiol 240 (Heart Circ Physiol 9):H576-H583
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 NY Acad Sci 307:491–522
Fleckenstein A (1971) Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention of production of myocardial lesions. In: Harris P, Opie LH (eds)Calcium and the heart. Academic Press, London, 135–188
Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle.Ann Rev Pharmacol Toxicol 17:149–166
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
Greco R, Musto B, Arienzo V, Alborino A, Garofalo S, Marsico F (1982) Treatment of paroxysmal supraventricular tachycardia in infancy with digitalis, adenosin-5′-triphosphate, and verapamil: a comparative study.Circulation 66:504–508
Hamm CW, Opie LH (1983) Protection of infarcting myocardium by slow channel inhibitors. Comparative effects of verapamil, nifedipine, and diltiazem in the coronary-ligated, isolated working rat heart.Circ Res [Suppl I]52:129–138
Hohlhardt M, Bauer B, Krause H, Fleckenstein A (1972) Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors.Pflugers Arch 335:309–322
Hösemann R, Diekmann L, Hilgenberg F (1970) Zur Behandlung von Herzrhytmusstörungen im Kindesalter mit Verapamil (Isoptin).Herz-Kreislauff 2:333–340
Langer GA, Brady AJ, Tan ST, Serena SD (1975) Correlation of the glycoside response, the force staircase, and the action potential configuration in the neonatal heart.Circ Res 36:744–752
McGrath JJ, Procházka J, Pelouch V, Ošťádal B (1973) Physiological responses of rats to intermittent high-altitude stress: effects of age.J Appl Physiol 34:389–393
Nayler WG (1980) Calcium antagonists.Eur Heart J 1:225–237
Nayler WG, Fassold E (1977) Calcium-accumulating and ATPase activity of cardiac sarcoplasmatic reticulum before and after birth.Cardiovasc Res 11:231–237
Nayler WG, Szeto J (1972) Effect of verapamil on contractility, oxygen utilization and calcium exchange ability in human heart muscle.Cardiovasc Res 6:120–128
Olivetti G, Anversa P, Loud AV (1980) Morphometric study of early postnatal development in the left and right ventricular myocardium of the rat. II. Tissue compositions, capillary growth, and sarcoplasmic alterations.Circ Res 46:503–512
Page E, Buecker JL (1981) Development of dyadic junctional complexes between sarcoplasmic reticulum and plasmalemma in rabbit left ventricular myocardial cells. Morphometric analysis.Circ Res 48:519–522
Porter CJ, Gillette PC, Garson A Jr, Hesslein PS, Karpawich PP, McNamara DG (1981) Effects of verapamil on supraventricular tachycardia in children.Cardiol 48:487–491
Poupa O, Krofta K, Procházka J, Turek Z (1966) Acclimatization to simulated high altitude and to acute cardiac necrosis.Fed Proc 25:1243–1246
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
Quinn P, Briscol MG, Nuttall A, Smith HJ (1981) Species variation in arterial-myocardial sensitivity to verapamil.Cardiovasc Res 15:398–403
Sapire DW, O'Riordan AC, Black IFS (1981) Safety and efficacy of short- and long-term verapamil therapy in children with tachycardia.Am J Cardiol 48:1091–1097
Schiebler TH, Wolff HH (1966) Elektronmikroskopische Untersuchungen am Herzmuskel der Ratte während der Entwicklung.Zellforsch 69:22–40
Shahar E, Barzilay Z, Frand M (1981) Verapamil in the treatment of paroxysmal supraventricular tachycardia in infants and children.J Pediatr 98:323–326
Siegl PKS, McNeill JH (1980) The negative inotropic potency of compound D 600 in rat, guinea pig, and rabbit cardiac preparations.Can J Physiol Pharmacol 58:1406–1411
Singh BN, Collett JT, Chow CYC (1980) New perspectives in the pharmacologic therapy of cardiac arrhythmias.Cardiovasc Dis 22:243–401
Soler-Soler J, Sagristá-Sauleda J, Cabrera A, Sauleda-Parés J, Iglesias-Berengué J, Permanyer-Miralda G, Roca-Llop J (1979) Effect of verapamil in infants with paroxysmal supraventricular tachycardia.Circulation 59:876–879
Stone PH, Antman EM, Muller JE, Braunwald E (1980) Calcium channel blocking agents in the treatment of cardiovascular disorders. II. Hemodynamic effects and clinical applications.Ann Intern Med 93:886–904
Thomas ML, Anast CS, Forte LR (1981) Regulation of calcium homeostasis in the fetal and neonatal rat.Am J Physiol 240 (Endocrin Metabol 3):E367-E372A0946025 00006 CS-SPJRNPDF [HEADSUP]
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Škovránek, J., Ošťádal, B., Pelouch, V. et al. Ontogenetic differences in cardiac sensitivity to verapamil in rats. Pediatr Cardiol 7, 25–29 (1986). https://doi.org/10.1007/BF02315478
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DOI: https://doi.org/10.1007/BF02315478