The Mechanism Of Transmural Dispersion Of Repolarization In Rabbits With Hypertrophy Myocardium

Backgrounds Myocardial hypertrophy is an adaptive response of the myocardium to the increase in load, and seen in various cardiovascular diseases including valvular heart disease and ischemic cardiomyopathy, as well as hypertension. In addition, myocardial hypertrophy predispose to malignant ventricular arrhythmias and sudden cardiac death. Therefore, myocardial hypertrophy is an independent risk factor of cardiovascular events, and the mechanisms of cardiac electrophysiology provide theoretical basis for the study of myocardial hypertrophic cardiac arrhythmias. Recently study found, the different characteristics of epicardium, suben-docardium and endocardium, especially the difference of repolarization characteristics, result in transmural dispersion of repolarization(TDR) and interventricular dispersion of repolarization in normal heart. However, myocardial hypertrophy is associated with preferential prolongation of action potential duration in epicardium, suben-docardium and endocardium that leads to a marked increase in transmural dispersion of repolarization and interventricular dispersion of repolarization, resulting in reentrant arrhythmias even torsades de points(Td P). Several lines of evidence suggest that slowly activating delayed rectifier potassium(IKs) isoutward currents in repolarization phase, the decreases of outward current density result in the prolonged repolarization. Up to now, the expression changes of IKs channel in hypertrophic myocardium is still controversial. In the studies here, a canine model of myocardial hypertrophy, Akar scholars found that it did not affect the m RNA expression and protein expression of subunits underlying IKs. However, a mouse model of ventricular tachypacing induced myocardial hypertrophy, was exposured the increased the m RNA expression and protein expression of KCNE1 gene, but not corresponding KCNQ1 gene. Therefore, it will be necessary to study the IKs channel expression changes in myocardial hypertrophy in further research.Objective To reveal the regional heterogeneity of KCNQ1 and KCNE1 in m RNA level between epicardium and endocardium in right and left ventricle, and explore the effect of IKs in the amplified transmural dispersion of repolarization in rabbits with hypertrophy myocardium.Methods Male Japanese white rabbit were randomly divided into 30 rabbits in hypertension group, and 25 rabbits in sham group. In hypertension group, rabbits underwent abdominal artery constriction(50% to 60%) to produce left ventricular hypertrophy(LVH) within 8 weeks. The sham group were similar to hypertension group without aortic ligation. Electrocardiographic examinations were used in all rabbits before and after operation 8 weeks. When anesthesia was achieved, the heart was excised. Hearts were washed in cold normal saline to clear thechambers of blood. After a quick blotting, the left ventricle were weighted(LVW), and the left ventricular weight index(LVWI) were calculated. HE staining was used in myocardial tissue. Real-time quantitative reverse transcription PCR was used to detect the level of KCNQ1 m RNA and KCNE1 m RNA.Results 1. The comparison of electrocardiogram examination:(1)Compared with the sham group and preoperative, QRS-wave amplitude in hypertension group were increased in inferior leads and precardiac leads(P<0.05).(2)Compared with the sham group and preoperative, QRS duration and QTc in hypertension group were remarkable extended(P<0.05). 2. The comparison of LVWI: The changes of bodyweight between the sham group and the hypertension group had no significant difference(P > 0.05); Compared with the sham group, the LVW and LVWI in hypertension group were remarkable increased(P<0.05). 3. The comparison of myocardial tissue HE staining: In sham group, myocardial fibers arranged in neat rows, and extracellular had no significant proliferation; In hypertension group, myocardial hypertrophy, myofibrillar disarrays and significant proliferation of extracellular. 4. The comparison of the expression changes of IKs in m RNA level between epicardium and endocardium in right and left ventricle(1)In sham group, the expression of KCNQ1 in m RNA level between epicardium and endocardium in right and left ventricle: The expression of KCNQ1(α-subunit of IKs) was 2.12 times in left epicardium(L-Epi) than left endocardium(L-Endo)(P<0.05); The expression of KCNQ1 was 1.53 times in right epicardium(R-Epi) than right endocardium(R-Endo)(P<0.05); The expression of KCNQ1 in R-Epi and R-Endo was remarkable more than L-Epi and L-Endo(P<0.05).(2)In sham group, the expression of KCNE1 in m RNA level between epicardium and endocardium in right and left ventricle: The expression of KCNE1(β-subunitof IKs) was 1.83 times in L-Epi than L-Endo(P<0.05); The expression of KCNE1 was 1.94 times in R-Epi than R-Endo(P<0.05); The expression of KCNE1 in R-Epi and R-Endo was remarkable more than L-Epi and L-Endo(P<0.05).(3)In sham group and hypertension group, the expression of KCNQ1 in m RNA level between L-Epi and L-Endo: Compared with the sham group, in hypertension group, the expression of KCNQ1 was decreased 37.57% in L-Epi(P<0.05); Theexpression of KCNQ1 was decreased 28.29% in L-Endo(P<0.05).(4)In sham group and hypertension group, the expression of KCNE1 in m RNA level between L-Epi and L-Endo: Compared with the sham group, in hypertension group, the expression of KCNE1 was decreased 47.66% in L-Epi(P<0.05); The expression of KCNE1 was decreased 35.56% in L-Endo(P<0.05).Conclusions 1. It has certain feasibility to make pressure overload–induced LVH by the lateral abdominal artery constriction. 2. IKs may be the ionic basis of ventricular regional heterogeneity, leading to transmural dispersion of repolarization and interventricular dispersion of repolarization in normal heart. 3. The decrease of IKs could prolong ventricular repolarization duration; The decreased heterogeneity of IKs may be the reason of amplified transmural dispersion of repolarization in hypertrophy myocardium.