ABSTRACT
This research is to explore the effects of traditional Chinese medicine Ginseng-spikenard heart-nourishing capsule on the inactivation of c-type Kv1.4 channels [Kv1.4[DELTA]N] in Xenopus laevis oocytes with two-electrode voltageclamp technique. Defolliculated oocytes [stage V-VI] were injected with transcribed cRNAs of ferret Kv1.4[DELTA]N channels. During recording, oocytes were continuously perfused with ND96 solution [control group] and solution prepared from Ginseng-spikenard heart-nourishing capsule [experimental group]. Results found that, at the command potential of +50 mV, the current of experimental group was reduced to 48.33+/-4.0% of that in control group. The inactivation time constants in control and experimental groups were 2962.56+/-175.35 ms and 304.13+/-36.22ms, respectively [P<0.05, n= 7]. The recovery time of fKv1.4[DELTA]N channel after inactivation in control group and experimental groups was 987+/-68.39 ms and 1734.15+/-98.45 ms, respectively [P<0.05, n=5]. Ginseng-spikenard heart-nourishing capsule can inhibit the Kv1.4[DELTA]N channel, which may be one of the mechanisms of underlying antiarrhythmia
ABSTRACT
BACKGROUND:Ventricular arrhythmia (VA) is one of the most common complications of myocardial infarction (MI), and ventricular tachycardia and fibrillation are the main causes for sudden cardiac death. This study aimed to explore the effect of ramipril on the occurrence of VA and its mechanism after MI in rabbits. METHODS:Twenty-four New Zealand rabbits purchased from the Wuhan Laboratory Animal Research Center were divided into three groups:sham-operated (SHAM) group (n=8), MI group (n=8) and MI with ramipril (RAM) group (n=8). Rabbits in the SHAM group received a median sternotomy without ligation of the left ventricular coronary artery. Rabbits in the MI and RAM groups received a median sternotomy followed by ligation of the left coronary artery. The successful anterior MI was confirmed by elevation of the ST segment with more than 0.2 mV in lead II and III. After MI, rabbits in the RAM group were fed with intragastric ramipril (1 mg/kg per day ) for 12 weeks. Before and 12 weeks after MI in the three groups, ventricular tachycardia or fibrillation (VT/VF) episodes and MAP in cadiocytes of the epicardium, mid-myocardium and endocardium were recorded by a multichannel physiograph. Student'st test and ANOVA were used for statistical analysis. RESULTS:VT/VF episodes were decreased more markedly in the RAM group than in the MI group after 12 weeks (2.6±0.8 vs. 12.4±2.9,P<0.05). Twelve weeks after MI, the duration of repolarization for 90％ (APD90) of three-tier ventricular myocytes in the MI group was longer than that before MI (258.2±21.1 vs. 230.1±23.2, 278.0±23.8 vs. 245.8±25.4, 242.6±22.7 vs. 227.0±21.7,P<0.05). However, the APD90 was not significantly different at 12 weeks before and after MI in the RAM group (P>0.05). Moreover, the transmural dispersion of repolarization (TDR) was increased more markedly 12 weeks after MI in the MI group than in the SHAM and RAM groups (36.2±10.2 vs. 18.7±6.2, 24.9±8.7,P<0.05). But the TDR was not significantly different between the RAM and SHAM groups (18.7±6.2 vs. 24.9±8.7,P>0.05). CONCLUSION:Ramipril may reduce the incidence of malignant ventricular arrhythmia via improvement of transmembrance repolarization heterogeneity after MI.