Abstract
Background: In the broad field of cardiology, pediatric research has lagged behind in establishing appropriate models to study the developing heart. Human cardiomyocytes exhibit a limited life span and immortalized cell lines lack physiologically relevant automaticity. Pediatric animal models include caveats related to action potential morphology, ion channel expression, and excitation-contraction coupling. Changes that occur in these parameters as the animal transition from neonate to adult are relatively unknown, especially as it may be translated to a human model. In quantifying the toxicological effect of plasticizer exposure in a pediatric population, we first sought to establish the limits of using hearts from developing neonatal rats as a viable model. Objective: This study aimed to quantify the advantages and limitations associated with using neonatal rat hearts as a model for toxicological screening. Methods/Design: The heart from rats ranging in age from 2 days old, up to adult were excised, and the aorta was cannulated. It was placed on a Langendorff system and retrograde perfused. Calcium and voltage sensitive dyes were used to stain the heart for imaging. It was mechanically uncoupled with blebbistatin to eliminate motion artifacts and an ECG was recorded continuously. Results/Discussion: Preliminary results showed that compared to adult cohorts, neonatal rats displayed a longer action potential duration (APD80: adult= 85.9ms, neonatal=95.5ms, p=0.026), likely associated with delayed Ito expression. Likewise, calcium handling was also slower in the neonatal hearts as shown by the calcium imaging. (Cad80: Adults: 128.9ms, neonatal=138.8, p=.004) Without autonomic modulation, we observed an increase in heart rate from 320 to 350bpm between neonatal and adult populations which has been shown in vivo . The developing excitation contraction coupling machinery will be further probed for the mechanism behind these phenomena.
Published Version
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