caa a22 4500 445825839 CHVBK 20180317145259.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00246-011-9899-6 doi (NATIONALLICENCE)springer-10.1007/s00246-011-9899-6 The Neonatal But Not the Mature Heart Adapts to Acute Tachycardia by Beneficial Modification of the Force-Frequency Relationship [Elektronische Daten] [M. Schmidt, P. White, S. Khambadkone, G. Gross, H. Bøtker, M. Vogel, V. Hjortdal, K. Sørensen, A. Redington] The force-frequency relationship (FFR) reflects alterations in intracellular calcium cycling during changing heart rate (HR). Tachycardia-induced heart failure is associated with depletion of intracellular calcium. We hypothesized (1) that the relative resistance to tachycardia-induced heart failure seen in neonatal pigs is related to differences in calcium cycling, resulting in different FFR responses and (2) that pretreatment with digoxin to increase intracellular calcium would modifies these changes. LV +dP/dt was measured during incremental right atrial pacing in 16 neonatal and 14 adult pigs. FFR was measured as the change in +dP/dt as HR was increased. Animals were randomized to control or intravenous bolus digoxin (n=8 neonate pigs in the 0.05mg/kg group and n=7 adult pigs in the 0.025mg/kg group) and paced for 90min at 25bpm greater than the rate of peak +dP/dt. Repeat FFR was then obtained. The postpacing FFR in neonatal control pigs shifted rightward, with peak force occurring 30bpm greater than baseline (P<0.03). There was no vertical shift; thus, force at 150bpm decreased (P<0.03) and force at 300beats/min increased (P<0.08). In adult control pigs, FFR shifted downward (P<0.01), with decreased force generation at all HRs. In both neonates and adult pigs, digoxin increased +dP/dt at all HRs; however, in neonate pigs digoxin decreased the contractile reserve by abrogation of the rightward shift of FFR. An adaptive response to tachycardia in the neonate pig leads to improved force generation at greater HRs. Conversely, the response of the mature pig heart is maladaptive with decreased force generation. Pretreatment with digoxin modifies these responses. Springer Science+Business Media, LLC, 2011 Neonatal tachycardia nationallicence Heart failure nationallicence Force-frequency relationship nationallicence Schmidt M. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut White P. Papworth Hospital NHS Trust, Cambridge, Cambridgeshire, UK aut Khambadkone S. Great Ormond Street Hospital for Sick Children, London, UK aut Gross G. Toronto Hospital for Sick Children, Toronto, Canada aut Bøtker H. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut Vogel M. Great Ormond Street Hospital for Sick Children, London, UK aut Hjortdal V. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut Sørensen K. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut Redington A. Toronto Hospital for Sick Children, Toronto, Canada aut Pediatric Cardiology Springer-Verlag 32/5(2011-06-01), 562-567 0172-0643 32:5<562 2011 32 246 https://doi.org/10.1007/s00246-011-9899-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00246-011-9899-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schmidt M. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut NATIONALLICENCE 700 1- White P. Papworth Hospital NHS Trust, Cambridge, Cambridgeshire, UK aut NATIONALLICENCE 700 1- Khambadkone S. Great Ormond Street Hospital for Sick Children, London, UK aut NATIONALLICENCE 700 1- Gross G. Toronto Hospital for Sick Children, Toronto, Canada aut NATIONALLICENCE 700 1- Bøtker H. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut NATIONALLICENCE 700 1- Vogel M. Great Ormond Street Hospital for Sick Children, London, UK aut NATIONALLICENCE 700 1- Hjortdal V. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut NATIONALLICENCE 700 1- Sørensen K. Aarhus University Hospital, Skejby Sygehus, Aarhus, Denmark aut NATIONALLICENCE 700 1- Redington A. Toronto Hospital for Sick Children, Toronto, Canada aut NATIONALLICENCE 773 0- Pediatric Cardiology Springer-Verlag 32/5(2011-06-01), 562-567 0172-0643 32:5<562 2011 32 246 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer