Role of CaMKII in an experimental model of ventricular fibrillation storm

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461074
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagasaki University
• Principal Investigator: TSUJI Yukiomi 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60432217)
• Co-Investigator(Renkei-kenkyūsha): MAKITA Naomasa 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00312356)
• Research Collaborator: DOBREV Dobromir ; NATTEL Stanley
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 心室細動 / トルサード・ド・ポアンツ / CaMKII / 遅延ナトリウム電流

Outline of Final Research Achievements

To elucidate mechanisms of ventricular tachycardia and fibrillation (VT/VF), we studied a rabbit model of electrical storm featuring multiple defibrillator-firings for repetitive VT/VF by electrical remodeling (QT-prolongation) due to chronic atrioventricular block. Optical mapping revealed that although a vortex-like reentrant activity called a rotor underlies both VT and VF, they have the rotor frequency and dynamics particular to themselves. VT resulted from a rotor in the distinctive manner, possibly explaining the ECG pattern of Torsades de Pointes (TdP), and VF was sustained by a high frequency stable rotor. Late Na-current was a major contributor to the substrate favoring TdP-related rotor, based on our findings that Na-channel Nav1.5 was hyperphosphorylated by Ca/calmodulin-dependent protein kinase II and that late Na-current blockade with lidocaine suppressed TdP. Conversion to a rapidly stationary rotor from a disease-specific rotor may be essential for VT-transition to VF.

Free Research Field

循環器内科学・不整脈学・心臓電気生理学