Effects of different inotropic interventions on myocardial function in the developing rabbit heart.
The development of the mammalian heart is characterized by substantial changes in myocardial performance. We studied the ontogeny of myocardial function with and without various inotropic interventions in the developing isolated, antegrade-perfused rabbit heart (2d, 8d, 14d, 28d, n = 96). Myocardial function was related to the protein expression of the sarcolemmal Na(+)-Ca2+ exchanger and to the sarcoplasmic Ca(2+)-ATPase. In neonatal hearts an age-dependent increase in maximal developed pressure velocity (dP/dtmax) by 45% and peak negative pressure velocity (dP/ dtmin) by 75% within days 2 to 8 were observed. In response to inotropic intervention with isoproterenol, ouabain, calcium and the Na(+)-channel modulator BDF 9148, dP/dtmax and dP/dtmin increased in a concentration dependent manner. Significant differences between neonatal, juvenile and adult hearts could be demonstrated in a repeated measurement ANOVA model on the concentration-response curves for BDF 9148 (dP/dtmax and dP/dtmin), ouabain (dP/dtmin) and calcium (dP/dtmin), but not for isoproterenol. At the maximum isoproterenol concentration of 1 micromol/l, the increase in dP/dtmax and dP/dtmin was significantly higher in adult compared to neonatal hearts (t-test, p < 0.01). The significant decline of the Na(+)-Ca2+ exchanger protein expression from neonatal (1822 +/- 171) to adult hearts (411 +/- 96 S.E.M. [units per 20 microg protein], p < 0.01) was related to an increase in myocardial function (dP/dtmax r = 0.63, p < 0.01, dP/dtmin r = 0.62, p < 0.01). Contractility, relaxation and the observed positive inotropic effects were in general significantly lower in neonatal compared to adult hearts. In the individual heart an increase in contractility and relaxation was related to a decrease in Na(+)-Ca2+ exchanger expression.
Schiffmann
Holger
H
Department of Pediatrics, University of Göttingen, Germany. schiffi@med.uni-goettingen.de
Flesch
Markus
M
Häuseler
Claudia
C
Pfahlberg
Annette
A
Böhm
Michael
M
Hellige
Gerhard
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001384:Azetidines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000032:analysis; D017725:Ventricular Pressure / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D001384:Azetidines; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D019831:Sodium-Calcium Exchanger; C071117:BDF 9148; D010042:Ouabain; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium