[The effects of calmodulin kinase II inhibitor on ventricular arrhythmias in rabbits with cardiac hypertrophy].

Abstract

OBJECTIVE:

To investigate the effect of KN-93, a calmodulin kinase II inhibitor, on ventricular arrhythmias in rabbits with cardiac hypertrophy.

METHODS:

Female New Zealand white rabbits were randomly divided into four groups (n = 10 each): Sham; LVH; LVH + KN-92 and LVH + KN-93 group. LVH was induced by partially constricting the abdominal aorta. In Sham group, the abdominal aorta was exposed without constriction. Eight weeks later, the arterially perfused left ventricular wedge preparations were made and transmembrane action potentials (TAP) from epicardium and endocardium and transmural ECG were simultaneously recorded. Incidence of early after depolarization (EAD) and torsade de pointes (Tdp), QT interval, action potential duration (APD) and transmural depolarization dispersion (TDR) at different cycle lengths were observed under slow stimulation (2000 - 4000 ms), hypokalemic (2 mmol/L) and hypomagnesaemic (0.25 mmol/L) Tyrode's solution perfusion.

RESULTS:

Left ventricular hypertrophy was detected in LVH group by echocardiography and not affected by KN-92 and KN-93. Perfused with hypokalemic, hypomagnesaemic Tyrode's solution and under slow stimulation (2000 - 4000 ms), the incidences of EAD and Tdp in Sham group, LVH group, LVH + KN-92 group (0.5 micromol/L) and LVH + KN-93 group (0.5 micromol/L) were 0/10, 10/10, 9/10, 5/10 and 0/10, 5/10, 4/10, 1/10, respectively. With 1 micromol/L KN-92 and KN-93, the incidences of EAD and Tdp in LVH + KN-92 and LVH + KN-93 group were 9/10, 3/10 and 4/10, 1/10 respectively. The QT interval, APD and TDR were not affected by KN-93.

CONCLUSION:

The calmodulin kinase II inhibitor KN-93 can effectively suppress ventricular arrhythmias in rabbits with cardiac hypertrophy by decreasing EAD.

• Authors: Jun Ke, Cun-tai Zhang, Ye-xin Ma, Jun Liu, Qing-yang Zhang, Nian Liu, Yan-fei Ruan, Li Lin
• Journal: Zhonghua xin xue guan bing za zhi (Zhonghua Xin Xue Guan Bing Za Zhi) Vol. 35 Issue 1 Pg. 33-6 (Jan 2007) ISSN: 0253-3758 [Print] China
• PMID: 17386161 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzylamines
• Protein Kinase Inhibitors
• Sulfonamides
• KN 93
• Calcium-Calmodulin-Dependent Protein Kinase Type 2

Topics

• Animals
• Arrhythmias, Cardiac (complications, drug therapy)
• Benzylamines (pharmacology)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (antagonists & inhibitors)
• Cardiomegaly (complications, drug therapy)
• Disease Models, Animal
• Male
• Protein Kinase Inhibitors (pharmacology)
• Rabbits
• Sulfonamides (pharmacology)