Protective Effect of Wenxin Granula on Heart from Myocardial Infarction through Regulating Intracellular Ca2+ / 中草药·英文版

Objective To assess the anti-arrhythmic activity and cardioprotective effects of Wenxin Granula, a traditional Chinese formula (consisting of Salviae Miltiorrhizae Radix, Polygonati Rhizoma, Notoginseng Radix et Rhizoma, Nardostachyos Radix et Rhizoma, Angelicae Sinensis Radix, and Succinum), on heart in ischemic-induced myocardial infarction (MI) rats and compare with those of Amiodarone which have been demonstrated in clinic. Methods Rats were randomly divided into Sham-operated (control), Ml + Amiodarone [5 mg/(kg·d)] (MI), and MI + Wenxin Granula [10 mg/(kg·d)] groups and left anterior descending coronary artery was occluded in each group. After left anterior descending for 12 h, standard lead Ⅱ of administration electrocardiogram was recorded in order to analyze the occurrence of arrhythmia. After one month, the size of the infarct area of heart was evaluated by TTC staining method and haemodynamic function was assessed to detect the heart function. Laser scanning confocal microscope and the technique of patch clamp were used to detect the intracellular Ca2+ ([Ca2+]j) and L-type calcium current (ICa-L), respectively. Results Both Wenxin Granula [10 mg/(kg·d)] and Amiodarone [5 mg/(kg·d)] could markedly decrease the incidence of arrhythmia in heart of rats which were subjected to ischemic injury. After one month, Wenxin Granula could significantly decrease mortality to 22.22% and reduce the infarct area (P < 0.05), but Amiodarone did not. The mechanism may involve that Wenxin Granula attenuated [Ca2+]j decreasing in MI rats. Additionally, Wenxin Granula could obviously ameliorate the impaired heart function of MI rats by decreasing the elevated left ventricular end-diastolic pressure and increasing the attenuated maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period. On the other hand, electrophysiological experiment results revealed that Wenxin Granula administration one month later also increased the reduced ICa-L density in rat ventricular myocytes in MI rats. The results of LSCM showed that Wenxin Granula could recover the amplitude of [Ca2+]j decreased by heart failure during long term. Conclusion Wenxin Granula could not only inhibit the incidence of arrhythmia but also decrease the mortality, which was accompanied by recovering the amplitude of [Ca2+]j. This protective effect of Wenxin Granula may partially be mediated through changing ICa-L.as well as increasing [Ca2+]j.

Functional impairment of cardiac transient outward K+ current as a result of abnormally altered cellular environment.

1. Physiological functions of cardiac cells require a normal cellular environment. Under pathological conditions, there is a loss of normal cellular environment due to metabolic perturbations and other abnormalities. To test the hypothesis that cellular environmental stresses can create an electrophysiological substrate for electrical disorders in the heart, we investigated the effects of hypoxia, acidosis and ischaemia on transient outward K+ current (I(to)) in single canine ventricular myocytes. 2. The I(to) was studied because it plays a critical role in initiating cardiac repolarization and, thereby, arrhythmias. It was found that I(to) was significantly depressed by some 30% under hypoxic conditions relative to that in a normal cellular environment with normal Tyrode's solution. 3. Acidosis created by lowering the pH of the external solution from 7.4 to 7.2 produced a substantial (approximately 35%) reduction of the I(to) amplitude. 4. A marked impairment of I(to) function was consistently observed in ischaemic hearts in the canine coronary artery ligation model, with an approximate 30% decrease in the size of I(to). 5. Importantly, the impairment of I(to) under these environmental stresses was largely reversible following restoration to normal conditions. 6. The results of the present study suggest that I(to) is susceptible to changes in the cellular environment and the functional impairment of I(to) under environmental stresses contributes to arrhythmias under relevant pathological conditions of the heart.

Inhibition of matrine on potassium currents in guinea pig ventricular myocytes / 中国药理学与毒理学杂志

AIM To elucidate the possible antiarrhythmic mechanism of matrine. METHODS Whole-cell patch-clamp technique was used to record ionic currents in ventricular myocytes. RESULTS In guinea pig ventricular myocytes, matrine 100 μmol·L-1 prolonged 90% action potential duration (APD90) by 40% at a stimulation of 0.1 Hz in a frequency-independent manner, inhibited IK1 by 47% at the test potential of -120 mV, reduced IKr,tail by 50% and had no effect on IKs,tail. CONCLUSION Matrine prolonged APD through blockade of multiple potassium currents, which may relate to its antiarrhythmic efficacy.