Drug-induced cardiac abnormalities in premature infants and neonates

Pesco-Koplowitz, Luana; Gintant, Gary A.; Ward, Robert M.; Heon, Dominique; Saulnier, Muriel; Heilbraun, Jeff

doi:10.1016/j.ahj.2017.07.014

Cited by 4 publications

(2 citation statements)

References 96 publications

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“…Moreover, neonatal cardiomyocytes lack fully developed transverse tubules and sarcoplasmic reticulum (66), which influences calcium cycling (4,13,56) and contractile function (32,41). Because of the extended period of postnatal maturation, the juvenile mammalian heart is uniquely dynamic and often considered a "moving target" (39). As such, there are considerable gaps in our understanding of normal cardiac physiology throughout the postnatal developmental period.…”

Section: Introductionmentioning

confidence: 99%

Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research

Swift

Burke

Guerrelli

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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Rodent models are frequently employed in cardiovascular research, yet our understanding of pediatric cardiac physiology has largely been deduced from more simplified two-dimensional cell studies. Previous studies have shown that postnatal development includes an alteration in the expression of genes and proteins involved in cell coupling, ion channels, and intracellular calcium handling. Accordingly, we hypothesized that postnatal cell maturation is likely to lead to dynamic alterations in whole heart electrophysiology and calcium handling. To test this hypothesis, we employed multiparametric imaging and electrophysiological techniques to quantify developmental changes from neonate to adult. In vivo electrocardiograms were collected to assess changes in heart rate, variability, and atrioventricular conduction (Sprague-Dawley rats). Intact, whole hearts were transferred to a Langendorff-perfusion system for multiparametric imaging (voltage, calcium). Optical mapping was performed in conjunction with an electrophysiology study to assess cardiac dynamics throughout development. Postnatal age was associated with an increase in the heart rate (181 ± 34 vs. 429 ± 13 beats/min), faster atrioventricular conduction (94 ± 13 vs. 46 ± 3 ms), shortened action potentials (APD80: 113 ± 18 vs. 60 ± 17 ms), and decreased ventricular refractoriness (VERP: 157 ± 45 vs. 57 ± 14 ms; neonatal vs. adults, means ± SD, P < 0.05). Calcium handling matured with development, resulting in shortened calcium transient durations (168 ± 18 vs. 117 ± 14 ms) and decreased propensity for calcium transient alternans (160 ± 18- vs. 99 ± 11-ms cycle length threshold; neonatal vs. adults, mean ± SD, P < 0.05). Results of this study can serve as a comprehensive baseline for future studies focused on pediatric disease modeling and/or preclinical testing. NEW & NOTEWORTHY This is the first study to assess cardiac electrophysiology and calcium handling throughout postnatal development, using both in vivo and whole heart models.

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Section: Introductionmentioning

confidence: 99%

Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research

Swift

Burke

Guerrelli

et al. 2020

American Journal of Physiology-Heart and Circulatory Physiology

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“…With their large I CaT , lower dependence on CICR from the SR and absence of T-tubules, zebrafish ventricular myocytes more closely resemble perinatal ventricular myocytes than adult ventricular myocytes of the human heart. Considering that there is a paucity of information regarding the cardiac safety pharmacology of human neonates and premature infants (Pesco-Koplowitz et al, 2018), zebrafish could be a useful model for this population.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Expression of calcium channel transcripts in the zebrafish heart: dominance of T-type channels

Haverinen

Hassinen

Dash

et al. 2018

Journal of Experimental Biology

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Calcium channels are necessary for cardiac excitation-contraction (E-C) coupling, but Ca channel composition of fish hearts is still largely unknown. To this end, we determined transcript expression of Ca channels in the heart of zebrafish (), a popular model species. Altogether, 18 Ca channel α-subunit genes were expressed in both atrium and ventricle. Transcripts for 7 L-type (Ca1.1a, Ca1.1b, Ca1.2, Ca1.3a, Ca1.3b, Ca1.4a, Ca1.4b), 5 T-type (Ca3.1, Ca3.2a, Ca3.2b, Ca3.3a, Ca3.3b) and 6 P/Q-, N- and R-type (Ca2.1a, Ca2.1b, Ca2.2a, Ca2.2b, Ca2.3a, Ca2.3b) Ca channels were expressed. In the ventricle, T-type channels formed 54.9%, L-type channels 41.1% and P/Q-, N- and R-type channels 4.0% of the Ca channel transcripts. In the atrium, the relative expression of T-type and L-type Ca channel transcripts was 64.1% and 33.8%, respectively (others accounted for 2.1%). Thus, at the transcript level, T-type Ca channels are prevalent in zebrafish atrium and ventricle. At the functional level, peak densities of ventricular T-type () and L-type () Ca current were 6.3±0.8 and 7.7±0.8 pA pF, respectively. mediated a sizeable sarcolemmal Ca influx into ventricular myocytes: the increment in total cellular Ca content via was 41.2±7.3 µmol l, which was 31.7% of the combined Ca influx (129 µmol l) via and (88.5±20.5 µmol l). The diversity of expressed Ca channel genes in zebrafish heart is high, but dominated by the members of the T-type subfamily. The large ventricular is likely to play a significant role in E-C coupling.

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Current Resources for Evidence-Based Practice, May 2018

Carlson¹

2018

Journal of Obstetric, Gynecologic & Neonatal Nursing

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Drug-induced cardiac abnormalities in premature infants and neonates

Cited by 4 publications

References 96 publications

Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research

Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research

Expression of calcium channel transcripts in the zebrafish heart: dominance of T-type channels

Current Resources for Evidence-Based Practice, May 2018

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