Acetylcholine-regulated K+ current remodelling in the atrium after myocardial infarction and valsartan administration.

BACKGROUND

Atrial fibrillation (AF) is a common complication of myocardial infarction (MI). Angiotensin II receptor antagonists prevent the promotion and propagation of AF. However, the activation of the acetylcholine-regulated K(+) current (I(K,ACh)) in the atrium after MI and the effect of valsartan on I(K,ACh) are less understood.

METHODS

Twenty-four adult rabbits were randomly divided into three groups: sham-operated, MI and MI plus valsartan administration (MI+valsartan). The sham-operated group received a median sternotomy without left ventricular coronary artery ligation. Both the MI group and the MI+valsartan group received a median sternotomy followed by ligation of the midpoint of the left ventricular coronary artery. The MI+valsartan group was administered oral valsartan for 12 weeks. After 12 weeks, the initiation of AF was measured by vagal stimulation followed by quick excision of the heart. I(K,ACh) in the left atrial myocardium was measured by the patch clamp technique.

RESULTS

AF was induced in four animals in the MI group, two in the sham-operated and two in the MI+valsartan groups, with the total AF duration expectedly longer in the MI group than in the sham-operated and MI+valsartan groups (38 s versus 9 s and 9 s, respectively). Furthermore, the mean (+/- SEM) density of I(K,ACh) increased significantly more in the left atrial myocardia of the MI group than in the sham-operated and the MI+valsartan groups (-13+/-0.42 pA/pF versus -9+/-0.38 pA/pF and -10+/-0.37 pA/pF, respectively at -100 mV; and 4.1+/-0.28 pA/pF versus 3.1+/-0.27 pA/pF and 3.3+/-0.27 pA/pF, respectively at 20 mV; P<0.05). However, there was no statistically significant difference in I(K,ACh) between the sham-operated group and the MI+valsartan group.

CONCLUSIONS

AF is associated with increased I(K,ACh) after MI. Inhibition of increased IK,ACh may be the mechanism by which valsartan prevents AF following MI.