Short-duration therapeutic hypothermia causesprompt connexin43 gap junction remodelingin isolated rabbit hearts

Yu Cheng Hsieh, Hung I. Yeh, Shien Fong Lin, Ya Wen Hsu, Jin Long Huang, Tung Chao Lin, Chih Tai Ting, Tsu Juey Wu

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7 Scopus citations

Abstract

Background: Whether connexin43 gap junctions (Cx43 GJs) and spatial heterogeneity of conduction velocity(CV) restitutions are altered in hearts during moderate (MH; 33°C) and severe (SH; 30°C) hypothermia remainsunclear.Methods and Results: Using an optical mapping system, ventricular CV was evaluated by S 1 pacing in 29Langendorff-perfused isolated rabbit hearts at baseline (37°C, n=9), 30-min MH (n=6), 30-min SH (n=9), andrewarming (R, 30-min SH followed by 30-min 37°C, n=5). After CV evaluation, myocardium was collected to measurethe level and distribution of non-phosphorylated (NP-Cx43) and total (T-Cx43) Cx43 by immunoblotting andimmunoconfocal microscopy. In 6 additional hearts, Cx43 GJ remodeling was evaluated at 30-min SH with (n=3)or without (n=3) pretreatment of a protein kinase C (PKC) inhibitor. CV slowing and spatial heterogeneities ofCV restitutions were enhanced in MH and SH hearts. NP-Cx43 was downregulated in MH (P=0.002) and SH(P<0.001) hearts. NP-Cx43 levels among 4 different ventricular sites became inhomogeneous in MH (P=0.017)and SH (P=0.046) hearts. However, T-Cx43 levels were unchanged. The percentages of lateralized NP- andT-Cx43 were increased in MH, SH, and R hearts. Pretreatment of PKC inhibitor attenuated SH-induced NP-Cx43lateralization (P=0.0495).Conclusions: Short-duration (30 min) therapeutic hypothermia causes prompt Cx43 GJs remodeling, in whichthe PKC pathway is involved. Rewarming abolished hypothermia-induced conduction disturbance, while Cx43GJs lateralization did not completely recover.

Original languageEnglish (US)
Pages (from-to)1706-1716
Number of pages11
JournalCirculation Journal
Volume75
Issue number7
DOIs
StatePublished - Jul 1 2011

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Keywords

  • Conduction velocity
  • Connexin43
  • Hypothermia
  • Immunohistochemistry
  • Optical mapping

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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