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| Title: | ION CHANNEL GENE PROFILING IN A MOUSE MODEL OF ACQUIRED QT PROLONGATION AND VENTRICULAR TACHYARRHYTHMIAS SECONDARY TO COMPLETE AV BLOCK | |
| DOI No: | 10.1142/9789812702234_0034 | |
| Source: | ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 127-130) | |
| Author(s): | JONG-KOOK LEE
Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan DAISUKE YUASA Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan MITSUNORI IWASE Toyota Memorial Hospital, Heiwa-cho, Toyota, Aichi 471-8513, Japan SUGIKO FUTAKI Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan MOTOHARU HAYASHI Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan MITSURU HORIBA Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan KENJI YASUI Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan YOSHITAKA HAYASHI Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan ITSUO KODAMA Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan |
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| Abstract: | Background: Marked bradycardia such as complete AV block (CAVB) predisposes to QT prolongation and torsade de pointes (TdP), however, molecular basis is not well understood. Methods: CAVB was produced in 8-wk-old mice by injecting 5 μL of 10% glycerol into AV nodal area following thoracotomy. Sham-operated mice were employed as control. ECGs were monitored continuously by telemetry. DNA microarray analysis (30,000 kinds of genes: 20,000 kinds analyzed) was conducted from left ventricles that survived longer than 10 days. Results: Twenty eight out of 35 CAVB mice died suddenly in an early stage (day 0-3 after operation) and 7 mice survived longer than 10 days. Spontaneous episodes of TdP were frequently documented in 14 out of 28 mice (50%) in the early stage, whereas 2 out of 7 (29%) in the chronic stage (day 4-10). Expression levels of mRNAs for Kvβl.5, Kv4.2, Kir2.1, Kir6.2 and Cav1.3 were significantly decreased, whereas these of Kir2.2 and Cavβ1 were significantly increased (n=3, p<0.05). Conclusion: A mouse model of sudden death with QT prolongation and TdP was created by surgically-induced CAVB. Altered expression of certain potassium and calcium channel subunits has been identified in the animal model that survived the early high-risk period after CAVB. | |
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