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Circ J. 2011;75(7):1706-16. Epub 2011 May 25.

Short-duration therapeutic hypothermia causes prompt connexin43 gap junction remodeling in isolated rabbit hearts.

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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.



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.


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).


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.

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