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Astragalosides were the main active components from a native Chinese herb Astragalus membranaceus. Recent studies have shown that Astragalosides have a protective effect on myocardial injury in rats. The present study was designed to investigate the effect of Astragalosides on intracellular calcium overload and sarcoplasmic reticulum calcium load (SR Ca²⁺ load) in cultured cardiac myocytes from neonatal rats. Astragalosides (100 μg/ml) were incubated in the presence of isoproterenol (ISO) (10^-5 M) for 72 hours in cardiomyocytes. Metoprorol (10^-6 M), a β₁-selective antagonist, was cultured in the same condition as Astragalosides. The result showed that intracellular calcium concentration ([Ca²⁺]_i) and SR Ca²⁺ load increased in ISO-treated cardiac myocytes as compared to control (P<0.01). Astragalosides prevented ISO-induced increase in [Ca²⁺]_i and SR Ca²⁺ load. Metoprolol also inhibited those increase. The mRNA expression and activity of sarcoplasmic reticulum Ca²⁺ ATPase (SERCA) were enhanced following ISO treatment in cardiac myocytes, and these increases were inhibited by Astragalosides or metoprolol (P<0.05). The decrease of superoxide dismutase (SOD) activity and the elevation of intracellular maleic dialdehyde (MDA) were observed after ISO treatment in cardiac myocytes. Both Astragalosides and metoprolol restored the SOD activity and reduced the level of MDA. We conclude that Astragalosides have the effects on reducing [Ca²⁺]_i and SR Ca²⁺ load, enhancing free radical removal and decreasing lipid peroxidation in ISO-treated cardiomyocytes, which might account for their protective effect on myocardial injury.

Genetic and drug-induced abnormalities of cardiac repolarization have been linked to fatal arrhythmias. These arrhythmias result from a complex interaction of the remaining currents during excitation and repolarization. In this review, we examine recent advancement in investigations of genetic heart diseases and mechanisms of arrhythmia generation. We also present our simulation of repolarization during rapid pacing for different levels of block of the rapid delayed rectifier current, I_Kr, and pharmacological interventions using the Luo–Rudy model. Control simulations showed the development of alternans at a basic cycle length (BCL) of 131 ms. Two levels of I_Kr block were simulated corresponding to type 2 of familial long QT syndrome, LQT2. At 100% I_Kr block, the threshold BCL for the appearance of alternans increased to 145 ms and for shorter cycle lengths showed increasingly complex patterns of periodic and chaotic behavior. We examined the potential of other currents to correct this complex behavior. Improvement of the threshold for bifurcation as a function of BCL was achieved by: (1) 100% block of a nonspecific Ca²⁺-activated current; (2) 15% block of L-type Ca²⁺ current; (3) 20% increase of Na⁺/K⁺ pump current; (4) 50% increase of SERCA2 pump activity. Conversely, increased L-type Ca²⁺ current, decreased Na⁺/K⁺ pump current, or decreased SERCA2 pump activity increased the threshold BCL. Modification of several other currents had little effect. Alternans and chaotic activity develop at fast pacing rates in model guinea pig ventricular myocytes through a sequence of bifurcations. We elucidated mechanisms that modify the development of alternans which may provide novel targets for treatment of patients with LQT2.