Therapeutic Mechanism of Yuxingeng Liquid(愈心梗液)on Early Ventricular Remodeling with Acute Myocardial Infarction in Rats

Objective:To examine the therapeutic mechanism of Yuxingeng liquid (愈心梗液,YXGL) on early ventricular remodeling in Wistar rats with acute myocardial infarction(AMI). Methods: Measuring the cardiac index (CI), left ventricular weight (LVW) and cardiac myocyte dimension and observing the concentration of endothelin (ET) and angiotensin E (Ang n ) in the plasma and myocardium. AMI models were established by ligature of left anterior descending coronary artery and the rats with AMI were randomly divided into 6 groups: the model group, sham-operation group, captopril group, high dosage YXGL group, middle dosage YXGL group and low dosage YXGL group. From the next day after modeling, the rats had been given YXGL through the gastric tube, which lasted for 4 weeks. And then, CI, LVW and concentration of ET and Ang II in the plasma and myocardium were tested. Results: Comparing with model control group, high dosage YXGL, middle dosage YXGL and captopril can all significantly reduce CI, LVW, cardiac cell dimension and content of ET and AngII in both plasma and myocardium (P< 0. 05 or P<0. 01). Conclusion: YXGL can remarkably reduce LVW, CI and concentration of ET and Ang II,and lowering the concentration of ET and Ang II is possibly one of the mechanisms intervening the pathological course of the early ventricular remodeling in rats with AMI.

Increasing angiotensin-converting enzyme(ACE)2/ACE axes ratio alleviates early pulmonary vascular remodeling in a porcine model of acute pulmonary embolism with cardiac arrest

BACKGROUND:Acute pulmonary embolism(APE)with cardiac arrest(CA)is characterized by high mortality in emergency due to pulmonary arterial hypertension(PAH).This study aims to determine whether early pulmonary artery remodeling occurs in PAH caused by massive APE with CA and the protective effects of increasing angiotensin-converting enzyme(ACE)2-angiotensin(Ang)(1-7)-Mas receptor axis and ACE-Ang II-Ang II type 1 receptor(AT1)axis(ACE2/ACE axes)ratio on pulmonary artery lesion after return of spontaneous circulation(ROSC).METHODS:To establish a porcine massive APE with CA model,autologous thrombus was injected into the external jugular vein until mean arterial pressure dropped below 30 mmHg(1 mmHg=0.133 kPa).Cardiopulmonary resuscitation and thrombolysis were delivered to regain spontaneous circulation.Pigs were divided into four groups of five pigs each:control group,APE-CA group,ROSC-saline group,and ROSC-captopril group,to examine the endothelial pathological changes and expression of ACE2/ACE axes in pulmonary artery with or without captopril.RESULTS:Histological analysis of samples from the APE-CA and ROSC-saline groups showed that pulmonary arterioles were almost completely occluded by accumulated endothelial cells.Western blotting analysis revealed a decrease in the pulmonary arterial ACE2/ACE axes ratio and increases in angiopoietin-2/angiopoietin-1 ratio and expression of vascular endothelial growth factor(VEGF)in the APE-CA group compared with the control group.Captopril significantly suppressed the activation of angiopoietin-2/angiopoietin-1 and VEGF in plexiform lesions formed by proliferative endothelial cells after ROSC.Captopril also alleviated endothelial cell apoptosis by increasing the B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X(Bax)ratio and decreasing cleaved caspase-3 expression.CONCLUSION:Increasing the ACE2/ACE axes ratio may ameliorate pulmonary arterial remodeling by inhibiting the apoptosis and proliferation of endothelial cells after ROSC induced by APE.