Age-related differences of intraischemic gap junction uncoupling in hearts during ischemia

Abstract

Objective: Myocardial ischemia leads to energetic, morphologic, metabolic, and functional alterations. To evaluate differences in ischemia tolerance between neonatal and adult hearts, we investigated gap junction uncoupling (GJU) and its correlation to myocardial intracellular edema formation during normothermic ischemia.

Methods: Hearts of landrace piglets (neonates, 7.4 ± 1.9 days of age, body weight 2.9 ± 0.5 kg, n = 5 and adults, 84 ± 9 days of age, body weight 30.5 ± 3.9 kg, n = 5) were investigated. After we harvested the hearts, the bioelectrical impedance spectra were measured continuously during normothermic global ischemia (35°C). Spectra of the dielectric permittivity, ε'(frequency), and conductivity, σ(frequency), were calculated from the impedance measurements, and GJU was identified in the sigmoidal time course of ε' (13 kHz). The extracellular volume was estimated by the ratio σ (100Hz)/σ (1MHz). Dielectric data were correlated with electron-microscopical images.

Results: Intraischemic GJU was observed in neonates after 54 ± 9 minutes of ischemia and thus significantly earlier than in adults (90 ± 7 minutes, P < .05). A more than 20% increase of intercalated water was found in tissue samples of neonates after 20 ± 2 minutes, in contrast to adults after 137 ± 8 minutes (P < .05).

Conclusions: Intraischemic formation of edema and earlier GJU indicate faster intraischemic changes in neonates compared with adults. Intraischemic GJU and determination of intracellular water shifts are an experimental approach to establish the period of life-threatening damage. Because both parameters are linked and occur significantly earlier in neonates, they distinctly demonstrate the lower ischemia tolerance of neonatal hearts as both events interact.

Keywords: gap junction uncoupling; ischemia; neonates.