title: Short-duration therapeutic hypothermia causes prompt connexin43 gap junction remodeling in isolated rabbit hearts.
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 remains unclear.
  
  
  RESULTS
  Using an optical mapping system, ventricular CV was evaluated by S₁ pacing in 29 Langendorff-perfused isolated rabbit hearts at baseline (37°C, n=9), 30-min MH (n=6), 30-min SH (n=9), and rewarming (R, 30-min SH followed by 30-min 37°C, n=5). After CV evaluation, myocardium was collected to measure the level and distribution of non-phosphorylated (NP-Cx43) and total (T-Cx43) Cx43 by immunoblotting and immunoconfocal 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 of CV 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- and T-Cx43 were increased in MH, SH, and R hearts. Pretreatment of PKC inhibitor attenuated SH-induced NP-Cx43 lateralization (P=0.0495).
  
  
  CONCLUSIONS
  Short-duration (30 min) therapeutic hypothermia causes prompt Cx43 GJs remodeling, in which the PKC pathway is involved. Rewarming abolished hypothermia-induced conduction disturbance, while Cx43 GJs lateralization did not completely recover.
authors: Cardiovascular Center, Taichung Veterans General Hospital and Department of Internal Medicine, Faculty of Medicine, Institute of Clinical Medicine, Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors: Yu-Cheng
authors: YC
authors: Hsieh
authors: Hung-I
authors: HI
authors: Yeh
authors: Shien-Fong
authors: SF
authors: Lin
authors: Ya-Wen
authors: YW
authors: Hsu
authors: Jin-Long
authors: JL
authors: Huang
authors: Tung-Chao
authors: TC
authors: Lin
authors: Chih-Tai
authors: CT
authors: Ting
authors: Tsu-Juey
authors: TJ
authors: Wu