Function of the CaMKII-ryanodine receptor signaling pathway in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia

doi:10.5847/wjem.j.issn.1920-8642.2012.01.012

Abstract

Abstract:

BACKGROUND: Calcium calmodulin-dependent kinase II (CaMKII) can be more active in patients with left ventricular hypertrophy (LVH), which in turn causes phosphorylation of ryanodine receptors, resulting in inactivation and the instability of intracellular calcium homeostasis. The present study aimed to determine the effect of CaMKII-ryanodine receptor pathway signaling in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia.

METHODS: Forty New Zealand rabbits were randomized into four groups (10 per group): sham group, LVH group, KN-93 group (LVH+KN-93), and ryanodine group (LVH+ryanodine). Rabbits in the LVH, KN-93, and ryanodine groups were used to establish a left ventricular hypertrophy model by the coarctation of the abdominal aorta, while those in the sham group did not undergo the coarctation. After eight weeks, action potentials (APs) were recorded simultaneously in the endocardium and epicardium, and a transmural electrocardiogram (ECG) was also recorded in the rabbit left ventricular wedge model. Drugs were administered to the animals in the KN-93 and ryanodine groups, and the frequency of triggered APs and ventricular tachycardia was recorded after the rabbits were given isoprenaline (1 μmol/L) and high-frequency stimulation.

RESULTS: The frequency (animals/group) of triggered APs was 0/10 in the sham group, 10/10 in the LVH group, 4/10 in the KN-93 group, and 1/10 in the ryanodine group. The frequencies of ventricular tachycardia were 0/10, 9/10, 3/10, and 1/10, respectively. The frequencies of polymorphic ventricular tachycardia or ventricular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The frequencies of triggered ventricular arrhythmias in the KN-93 and ryanodine groups were much lower than those in the LVH group (P<0.05).

CONCLUSIONS: KN-93 and ryanodine can effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMKII-ryanodine signaling pathway can be used as a new means of treating ventricular arrhythmia.

Key words: CaMKII, Ryanodine receptors, Signaling transduction pathway, Triggered action potential, Ventricular arrhythmia, Left ventricular hypertrophy

Jun Ke, Xing Xiao, Feng Chen, Li He, Mu-sen Dai, Xiao-ping Wang, Bing Chen, Min Chen, Cun-tai Zhang. Function of the CaMKII-ryanodine receptor signaling pathway in rabbits with left ventricular hypertrophy and triggered ventricular arrhythmia[J]. World Journal of Emergency Medicine, 2012, 3(1): 65-70.

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Groups	BW( kg )	LVM( g )	LVM/BW	LVFW( mm )
Sham	2.10±0.29	3.26±0.27	1.56±0.10	4.5±0.2
LVH	2.51±0.31	6.94±0.59^*	2.78±0.14^*	6.6±0.3^*
KN-93	2.49±0.32	6.90±0.58^*	2.79±0.18^*	6.5±0.2^*
Ryanodine	2.52±0.30	6.96±0.56^*	2.78±0.17^*	6.4±0.3^*

Groups	SW (mm)	LVPW (mm)	LVDd (mm)	LVM (g)	LVM/BW
Sham	3.04±0.23	3.03±0.28	10.90±0.64	3.76±0.55	1.79±0.12
LVH	4.18±0.24^*	4.06±0.23^*	11.08±0.60	6.11±0.69^*	2.44±0.10^*
KN-93	4.21±0.26^*	4.08±0.22^*	11.11±0.63	6.17±0.50^*	2.49±0.12^*
Ryanodine	4.23±0.30^*	4.09±0.25^*	11.02±0.55	6.15±0.64^*	2.45±0.12^*

Groups	Triggered AP^a	V-Tach^b	PMVT^c or V-Fib^d
Sham (n=10)	0	0	0
LVH (n=10)	10	9	7
KN-93 (n=10)	4	3	2
Ryanodine (n=10)	1	1	1

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