The Protect Effect Of STVNa In Rats With Myocardial Infarction And Hypertrophy

Background: Cardiovascular diseases are the leading cause of death globally. Thus, it is important to search for cardiac protective drugs that are safe and effective. Isosteviol sodium(STVNa) is a sodium formation of isosteviol which is a tetracyclic diterpenoid wit h a beyerane skeleton extracted from steviol leaves. It has been reported that STVNa pre-treatment has cardiac protective and anti-arrhythmic effect. However, it is unclear that whether STVNa post-treatment can alleviate decrease of cardiac function and whether long-term STVNa administration has effect on arrhythmia. This study was to explore whether STVNa post-treatment can preserve cardiac function after myocardial infarction, and whether STVNa protects cardiac from decompensate hypertrophy. Methods:(1) The left anterior descending coronary artery(LAD) was used to induce myocardial infarction(MI). LAD rats were random divided into 4 groups, namely LAD group, LAD treated with 1mg/kg, 5mg/kg or 10mg/kg group. STVNa was given intragastric and lasted for 4 weeks. After that, cardiac function test and electrocardiogram analysis were performed on experimental rats.(2) Transverse aortic constriction(TAC) model were used in this study to induce hypertrophy. TAC rats were random divided into 2 groups, TAC group and TAC rats treated with 1 mg/kg STVNa. After 9 weeks of STVNa treatment, cardiac function test and electrocardiogram analysis were performed on experimental rats. Results:(1) LAD induced cardiac function decreased showed by dp/dtmax decrease(P<0.05) and dp/dtmin increase(P<0.01). STVNa(1mg/kg) administrated after MI improved cardiac function: dp/dtmax increased from 8102±671 mm Hg/sto 11129±1008mm Hg/s(P<0.05) and dp/dtmin decreasedfrom-6714 ± 592 mm Hg/sto-11324 ± 1734 mm Hg/s(P<0.05), alleviated cardiac ischemia performance, and stablized autonomic nervous system(LF to HF ratio was recovered).(2) TAC induced an overall decrease of cardiac function. STVNa administration reversed such adverse events. Compared to TAC group, dp/dtmax increased from 6442±545 mm Hg/s to 10130±470mm Hg/s(P<0.001) and dp/dtmin decreased from-7233±303 mm Hg/s to-10503±486mm Hg/s(P<0.01). According to heart rate variability analysis, STVNa treatment protected cardiac regulatory effect of autonomic nervous system.(3) STVNa not only protectd heart from MI, but also significantly improved cardiac function which is decreased by TAC. Therefore we compared STVNa effect on two different disease models. Our data indicated that STVNa seem to have better effect on improvement of cardiac diastolic function in MI rats.In this study, we first explored that the effect of STVNa in myocardial infarction, and provide theoretical basis for further research. And then, we first compare the difference of drug efficacy to MI and decompensate hypertrophy, providing evidence to clinical research.