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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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

Fingerprint

Induced Hypothermia
Connexin 43
Gap Junctions
Rabbits
Protein Kinase C
Protein C Inhibitor
Protein Kinase Inhibitors
Rewarming
Optical Devices
Hypothermia
Immunoblotting
Microscopy
Myocardium
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Short-duration therapeutic hypothermia causesprompt connexin43 gap junction remodelingin isolated rabbit hearts. / Hsieh, Yu Cheng; Yeh, Hung I.; Lin, Shien-Fong; Hsu, Ya Wen; Huang, Jin Long; Lin, Tung Chao; Ting, Chih Tai; Wu, Tsu Juey.

In: Circulation Journal, Vol. 75, No. 7, 07.2011, p. 1706-1716.

Research output: Contribution to journalArticle

Hsieh, Yu Cheng ; Yeh, Hung I. ; Lin, Shien-Fong ; Hsu, Ya Wen ; Huang, Jin Long ; Lin, Tung Chao ; Ting, Chih Tai ; Wu, Tsu Juey. / Short-duration therapeutic hypothermia causesprompt connexin43 gap junction remodelingin isolated rabbit hearts. In: Circulation Journal. 2011 ; Vol. 75, No. 7. pp. 1706-1716.
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T1 - Short-duration therapeutic hypothermia causesprompt connexin43 gap junction remodelingin isolated rabbit hearts

AU - Hsieh, Yu Cheng

AU - Yeh, Hung I.

AU - Lin, Shien-Fong

AU - Hsu, Ya Wen

AU - Huang, Jin Long

AU - Lin, Tung Chao

AU - Ting, Chih Tai

AU - Wu, Tsu Juey

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

KW - Conduction velocity

KW - Connexin43

KW - Hypothermia

KW - Immunohistochemistry

KW - Optical mapping

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