Coronary microembolization induced myocardial contractile dysfunction through a p38 mapk pathway

Background Cathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis,especially in the plaque destabilization and rupture leading to acute coronary syndrome.However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet. Methods Sprague-Dawley rats were randomly divided into three groups;Sham group,CME group and SB203580 group (n=10 per group).CME rats were produced by injection of 42μm microspheres into the left ventricle with occlusion of the ascending aorta.SB203580,a p38 MAPK inhibitor,was injected into femoral vein after finishing the injection of microspheres in SB203580 group.Left ventricular Ejection Fraction was determined by echocardiography.The level of phosphorylated and total P38 MAPK in myocardium was assessed by Western Blot.Results Left ventricular(LV) Ejection Fraction was depressed at 3 hours and until up to 12 hours in CME group.The increased p38 MAPK activation was observed in CME group.The administration of SB203580 partly inhibited the p38 MAPK activity and preserved cardiac contractile function.Conclusions p38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly preserve cardiac contractile function.

Sheng-Mai-San attenuates contractile dysfunction and structural damage induced by chronic intermittent hypoxia in mice

Sheng-Mai-San(SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia(CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days(nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle(LV) dysfunction and structure abnormalities. After administration of SMS(0.55, 1.1, and 5.5 g·kg-1·d-1) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors(Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.

Synchronous electrogastrographic and manometric study of the stomach as an esophageal substitute

AIM: To investigate the electric and contractile mechanisms involved in the deranged function of the transposed stomach in relation to the course of the symptoms and the changes in contractile and electrical parameters over time.METHODS: Twenty-one patients after subtotal esophagectomy and 18 healthy volunteers were studied.Complaints were compiled by using a questionnaire, and a symptom score was formed. Synchronous electrogastrography and gastric manometry were performed in the fasting state and postprandially.RESULTS: Eight of the operated patients were symptomfree and 13 had symptoms. The durations of the postoperative periods for the symptomatic (9.1±6.5 mo)and the asymptomatic (28.3±8.8 mo) patients were significantly different. The symptom score correlated negatively with the time that had elapsed since the operation. The percentages of the dominant frequency in the normogastric, bradygastric and tachygastric ranges differed significantly between the controls and the patients.A significant difference was detected between the power ratio of the controls and that of the patients. The occurrence of tachygastria in the symptomatic and the symptom-free patients correlated negatively both with the time that had elapsed and with the symptom score. There was a significant increase in motility index after feeding in the controls, but not in the patients. The contractile activity of the stomach increased both in the controls and in the symptom-free patients. In contrast, in the group of symptomatic patients, the contractile activity decreased postprandially as compared with the fasting state.CONCLUSION: The patients' post-operative complaints and symptoms change during the post-operative period and correlate with the parameters of the myoelectric and contractile activities of the stomach. Tachygastria seems to be the major pathogenetic factor involved in the contractile dysfunction.