Downregulation of immunodetectable atrial Connexin40 in a canine model of chronic left ventricular myocardial infarction

Implications to atrial fibrillation

Keiko Oahara, Yasushi Miyauchi, Toshihiko Ohara, Michael C. Fishbein, Shengmei Zhou, Moon Hyoung Lee, William J. Mandel, Peng-Sheng Chen, Hrayr S. Karagueuzian

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability. Methods and Results: The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (<5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 ± 4% of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 ± 1.2 μm vs. 10.2 ± 1.2 μm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 ± 0.09% vs. 0.82 0.13%; P <0.01). Conclusions: Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume7
Issue number2
StatePublished - 2002
Externally publishedYes

Fingerprint

Atrial Fibrillation
Canidae
Down-Regulation
Myocardial Infarction
Dogs
Heart Atria
Muscle Cells
Coronary Vessels
Coronary Occlusion
Heart Ventricles
Fibrosis
Wounds and Injuries

Keywords

  • Atrial fibrillation
  • Connexin40
  • Gap junction
  • Left ventricular myocardial infarction
  • Remodeling

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Downregulation of immunodetectable atrial Connexin40 in a canine model of chronic left ventricular myocardial infarction : Implications to atrial fibrillation. / Oahara, Keiko; Miyauchi, Yasushi; Ohara, Toshihiko; Fishbein, Michael C.; Zhou, Shengmei; Lee, Moon Hyoung; Mandel, William J.; Chen, Peng-Sheng; Karagueuzian, Hrayr S.

In: Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 7, No. 2, 2002, p. 89-94.

Research output: Contribution to journalArticle

Oahara, Keiko ; Miyauchi, Yasushi ; Ohara, Toshihiko ; Fishbein, Michael C. ; Zhou, Shengmei ; Lee, Moon Hyoung ; Mandel, William J. ; Chen, Peng-Sheng ; Karagueuzian, Hrayr S. / Downregulation of immunodetectable atrial Connexin40 in a canine model of chronic left ventricular myocardial infarction : Implications to atrial fibrillation. In: Journal of Cardiovascular Pharmacology and Therapeutics. 2002 ; Vol. 7, No. 2. pp. 89-94.
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abstract = "Background: The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability. Methods and Results: The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (<5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 ± 4{\%} of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 ± 1.2 μm vs. 10.2 ± 1.2 μm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 ± 0.09{\%} vs. 0.82 0.13{\%}; P <0.01). Conclusions: Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.",
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T1 - Downregulation of immunodetectable atrial Connexin40 in a canine model of chronic left ventricular myocardial infarction

T2 - Implications to atrial fibrillation

AU - Oahara, Keiko

AU - Miyauchi, Yasushi

AU - Ohara, Toshihiko

AU - Fishbein, Michael C.

AU - Zhou, Shengmei

AU - Lee, Moon Hyoung

AU - Mandel, William J.

AU - Chen, Peng-Sheng

AU - Karagueuzian, Hrayr S.

PY - 2002

Y1 - 2002

N2 - Background: The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability. Methods and Results: The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (<5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 ± 4% of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 ± 1.2 μm vs. 10.2 ± 1.2 μm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 ± 0.09% vs. 0.82 0.13%; P <0.01). Conclusions: Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.

AB - Background: The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability. Methods and Results: The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (<5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 ± 4% of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 ± 1.2 μm vs. 10.2 ± 1.2 μm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 ± 0.09% vs. 0.82 0.13%; P <0.01). Conclusions: Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.

KW - Atrial fibrillation

KW - Connexin40

KW - Gap junction

KW - Left ventricular myocardial infarction

KW - Remodeling

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