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Published on: November 3, 2020
Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research
Luther M Swift1,2, Morgan Burke1,2, Devon Guerrelli1,2
1Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Health System, Washington, District of Columbia.
Insights
This study reveals significant postnatal changes in rat heart function, showing faster electrical conduction and improved calcium handling in adults compared to neonates. These findings establish a crucial baseline for pediatric cardiovascular research.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Biophysics
Background:
- Pediatric cardiac physiology understanding relies heavily on simplified cell studies, lacking whole-heart developmental data.
- Postnatal development involves changes in genes and proteins affecting cell coupling, ion channels, and calcium handling.
Purpose of the Study:
- To investigate dynamic alterations in whole heart electrophysiology and calcium handling during postnatal maturation.
- To establish a comprehensive baseline for pediatric cardiovascular research and preclinical testing.
Main Methods:
- Utilized multiparametric imaging and electrophysiological techniques in Sprague-Dawley rats from neonate to adult.
- Collected in vivo electrocardiograms and performed optical mapping on whole hearts in a Langendorff-perfusion system.
- Assessed voltage, calcium dynamics, heart rate, atrioventricular conduction, action potential duration, and refractoriness.
Main Results:
- Postnatal development led to increased heart rate, faster atrioventricular conduction, and shortened action potential durations and ventricular refractoriness.
- Calcium handling matured, evidenced by shorter calcium transient durations and a decreased propensity for calcium transient alternans.
- Significant differences (P < 0.05) were observed between neonatal and adult groups for all measured parameters.
Conclusions:
- Cardiac electrophysiology and calcium handling undergo dynamic maturation throughout postnatal development.
- This study provides the first comprehensive assessment of these changes using integrated in vivo and whole-heart models.
- The findings serve as a vital reference for future pediatric disease modeling and therapeutic development.
Abstract:
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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