Gap Junction Regulation and Edema Formation in Neonatal and Adult Hearts

Objectives: In congenital heart surgery, ischemia-induced myocardial edema formation often influences postoperative care, especially after long lasting ischemic periods, since delayed sternal closure is necessary. To evaluate differences in ischemic processes between neonatal and adult hearts we investigated gap junction closure (GJC) and edema formation during normothermic ischemia (35°C) using bioelectrical impedance spectroscopy.

Methods: Hearts of landrace piglets (NEONATES, 7.4 days old, body weight (bw) 2.9kg, n = 5) and pigs (ADULTS, 90 days old, bw 30.5kg, n = 5) were investigated. All animals were premedicated, intubated and ventilated. After median thoracotomy both caval veins were occluded and the aorta x-clamped. Subsequently the hearts were harvested and immediately put into a thermostat at 35°C. A flat probe containing 4 parallel platinum covered electrodes was placed on the epicardial layer of the left ventricle. All hearts were kept under these conditions for 24 hour. Induction of ischemia-induced GJC and edema formation was analyzed by bioimpedance spectroscopy. Applying an alternating current (100Hz to 1MHZ) every 3 minute complex electrical impedance spectra of the hearts were measured and registered. We calculated the dielectric spectrum from the impedance measurements and identified GJC in the sigmoidal time course of dielectric permittivity at 13kHz. Information about myocardial edema formation and intercalation of water, respectively, was obtained by morphology. Samples were taken at predefined time intervals and prepared for electron microscopy.

Results: Intraischemic GJC was observed in NEONATES after 54 ± 9min of ischemia and thus significantly earlier than in ADULTS (90 ± 7min, p< 0.05). More than 20% increase of intercalated water was found in NEONATES after 20 ± 2min but in ADULTS after 137 ± 8min (p< 0.05). Both parameters indicate that the intensity of morphological alterations and the duration to complete GJC differed significantly among both groups.

Conclusion: The development of intraischemic edema formation and the earlier GJC demonstrate faster intraischemic changes in NEONATES compared with ADULTS. Intraischemic GJC is a parameter for evaluating the period of life-threatening damage and distinctly demonstrates the smaller ischemia tolerance of neonatal hearts.