Tetrandrine Ameliorates Myocardial Ischemia Reperfusion Injury through miR-202-5p/TRPV2

Objective. This study is aimed at investigating the therapeutic effects of tetrandrine (Tet) on myocardial ischemia reperfusion (I/R) injury and probe into underlying molecular mechanism. Methods. H9C2 cells were divided into hypoxia/oxygenation (H/R) group, H/R+Tet group, H/R+Tet+negative control (NC) group, and H/R+Tet+miR-202-5p inhibitor group. RT-qPCR was utilized to monitor miR-202-5p and TRPV2 expression, and TRPV2 protein expression was detected via western blot and immunohistochemistry in H9C2 cells. Cardiomyocyte apoptosis was evaluated through detection of apoptosis-related markers and flow cytometry. Furthermore, myocardial enzyme levels were detected by ELISA. Rats were randomly separated into sham operation group, I/R group, I/R+Tet group (50 mg/kg), I/R+Tet+NC group, and I/R+Tet+miR-202-5p inhibitor group. miR-202-5p and TRPV2 mRNA expression was assessed by RT-qPCR. TRPV2 protein expression was detected through western blot and immunohistochemistry in myocardial tissues. Apoptotic levels were assessed via apoptosis-related proteins and TUNEL. Pathological changes were observed by H&E staining. Myocardial infarction size was examined by Evans blue-TCC staining. Results. Abnormally expressed miR-202-5p as well as TRPV2 was found in H/R H9C2 cells and myocardial tissues of I/R rats, which was ameliorated following Tet treatment. Tet treatment significantly suppressed H/R- or I/R-induced cardiomyocyte apoptosis. ELISA results showed that CK-MB and LDH levels were lowered by Tet treatment in H/R H9C2 cells and serum of I/R rats. H&E staining indicated that Tet reduced myocardial injury in I/R rats. Also, myocardial infarction size was lowered by Tet treatment. The treatment effects of Tet were altered following cotreatment with miR-202-5p inhibitor. Conclusion. Our findings revealed that Tet may ameliorate myocardial I/R damage via targeting the miR-202-5p/TRPV2 axis.

C-reactive protein increases myocardial damage after STEMI

Background The CAMI-1 study dealt with the depletion of CRP by apheresis in patients with acute myocardial infarction (AMI). CRP, the prototype human acute phase protein, has been known as a marker of poor prognosis in AMI and independently predicts 30-day mortality. Methods 66 STEMI patients were enrolled in the study following complete coronary revascularization (2–12 h after the onset of symptoms). 32 patients received CRP apheresis, whereas 34 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. A specific CRP adsorber removed up to 79% of the original CRP. In each apheresis session, 6000 ml of plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (CMR) 2–9 days after STEMI. Results Aphereses sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 9 to 279 mg/l. The expected peak CRP level after AMI can be calculated precisely with 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.91. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the CRP concentration is significantly associated with the damage (infarct size, LVEF, circumferential strain) in the controls. This association was lost in the aphereses patients: they performed significantly better at all endpoints (infarct size, LVEF, circumferential strain) than the controls. The CRP apheresis significantly reduced myocardial damage. To our surprise, two apheresis patients had an infarct size of 0%. Conclusions For the first time we find an unequivocal association between myocardial infarct size and the CRP concentration. This is in some respects a surprise, since the basic assumption in AMI is that the vascular occlusion leads to primary damage and the reperfusion to secondary damage, which would not have led one to expect such a clear dose-response relationship as that observed here. In addition, our results show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis is now being further evaluated as a therapeutic approach in the treatment of acute myocardial infarction in a registry (CAMI registry). Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Pentracor GmbH

Influence of sodium ferulate on miR-133a and left ventricle remodeling in rats with myocardial infarction

To explore the influence of sodium ferulate (SF) on miR-133a and left ventricle remodeling (LVR) in rats with myocardial infarction (MI). The left coronary artery was ligated to create 36 ischemia-reperfusion (IR) rat models that were randomly divided into mock surgical group (MSG) (not ligated), model group (MG), and sodium ferulate group (SFG). After the successful modeling, SFG was intravenously injected with SF at the dose of 10 mg/kg, and the other two groups were injected with the same volume of normal saline. After 28 days, cardiac hemodynamic indices of all groups were measured; the myocardial infarction size (MIS), left ventricular mass index (LVMI), and collagen volume fraction (CVF) were calculated, the content of serum malondialdehyde (MDA) and activities of catalase (CAT), superoxide dismutase (SOD) and glutathione catalase (GSH-px) were detected by ELISA, and miR-133a expression in myocardial tissues of the left ventricle (LV) was detected by RT-qPCR. SF improved the cardiac hemodynamic indices of rat model and reduced the MIS, LVMI and CVF. SF decreased the serum MDA level and increased the serum CAT, SOD and GSH-px levels in rat model. SF increased the expression of miR-133a in myocardial tissue of rat model. Therefore, SF could effectively reduce the myocardial injury of IR rats and improve the LVR. Its mechanism may be related to the antioxygenation and upregulation of miR-133a.

STAT3 but not STAT5 contributes to the protective effect of electro-acupuncture against myocardial ischemia/reperfusion injury

Late remote ischemia preconditioning (RIPC) and electro-acupuncture (EA) have both been suggested to reduce injury caused by myocardial ischemia/reperfusion (I/R). Our previous study has found that cardioprotection in RIPC is STAT5-dependent. Here, we aim to observe the effects of electro-acupuncture pretreatment (EAP) on I/R in the presence or absence of STAT5 in mice and investigate whether the protection of EAP is in a STAT5-dependent manner. In this study, EAP decreased myocardial infarction size (IS) /total area (TA) and rate of cardiomyocyte apoptosis. STAT5 was activated by EAP in the Stat5fl/fl mice but not in the Stat5-cKO mice, whereas, STAT3 was activated by EAP only in the Stat5-cKO but not in the Stat5fl/fl mice. Differentially expressed genes (DEGs) regulated by EAP in the Stat5fl/fl and the Stat5-cKO mice were quite distinct, indicating that EAP may activate IL-6/STAT3 signal in the absence of Stat5, and that EAP-induced cardioprotection against myocardial I/R injury was correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling. Our results, for the first time, demonstrated that the protective effect of EAP was attributed to, but not dependent on, STAT5.

The myocardial infarction size measuring using modern methods

An accurate quantitative assessment of myocardium necrosis area and the viable zone (stunned and hibernating) in patients with myocardial infarction is crucial for the preoperative patient selection and predicting the cardiac surgery effectiveness. Currently, researchers and clinicians are most interested in the problem of determining the viable myocardium zone. However, only the necrosis zone area directly correlates with the patients prognosis and determines the heart pathological remodeling processes. In the distant period, the data obtained can be used to predict the post-infarction period course or for analysis the relationship of the necrosis zone with arrhythmogenesis, and a number of other indicators. Thus, the necrosis zone and the viable myocardium zone are two parameters that need to be monitored in dynamics in all patients after myocardial infarction. The most accurate and reproducible method for determining the necrosis area is contrast magnetic resonance imaging of the heart, however, this technique is still inaccessible in most hospitals. In this regard, it remains relevant to estimate the necrotic myocardium area by ubiquitous non-invasive methods such as electrocardiography and echocardiography.

Abstract WP232: Association Between Myocardial Infarction Size and Location and Cerebral Infarction

Introduction: Myocardial infarction (MI) is associated with cerebral infarction. We assessed whether MI size and location is related to the risk of cerebral infarction. Methods: We performed a cross-sectional study of patients evaluated between 2014-2017 at New York-Presbyterian Hospital/Weill Cornell Medicine. We included all adults who underwent both brain MRI and delayed-enhancement cardiac MRI (DE-CMR) within 365 days of each other and had evidence of MI on DE-CMR. We evaluated associations between MI size and any cerebral infarction, apical MI and any cerebral infarction, and between MI size/location and cortical versus subcortical cerebral infarction. We used multiple logistic regression models adjusted for age, sex, race, and the total number of vascular risk factors. Results: We identified 234 patients who underwent DE-CMR and brain MRI within 365 days, among whom 76 had evidence of MI on DE-CMR. Of these 76 patients, 51 (67.1%) had evidence of cerebral infarction. There was no association between the size of MI (global MI burden) and any cerebral infarction (OR per 1% increase in MI size, 1.02; 95% CI, 1.0-1.1; P = 0.43), but there was an association between MI size and cortical cerebral infarction (OR per 1% increase in MI size, 1.05; 95% CI, 1.0-1.1; P = 0.047). We found no association between apical MI location and any cerebral infarction (OR 3.2, 95% CI, 0.9-12.2, P = 0.08), but there was an association between apical MI location and cortical cerebral infarction (OR, 3.7; 95% CI, 1.2-11.3; P = 0.02). Conclusion: Among patients with MI on cardiac imaging, MI size and apical MI location were associated with cortical cerebral infarction. Our results may help stratify cardioembolic risk and lead to improved antithrombotic treatment algorithms among patients with MI.

An ultrasound activated oxygen generation nanosystem specifically alleviates myocardial hypoxemia and promotes cell survival following acute myocardial infarction

An ultrasound-activated oxygen generation nanosystem was developed to significantly reduce the myocardial infarction size as well as promote the cell survival and proliferation of cardiac cells after acute myocardial infarction.

2230Results from the CAMI1 Study: selective CRP apheresis as a new treatment option in acute myocardial infarction

Background Inflammation is increasingly recognized as an important pathogenic feature in cardiovascular disease. In patients with STEMI, C-reactive protein (CRP), the prototype human acute phase protein, is a marker of poor prognosis and independently predicts 30-day mortality. In STEMI, CRP may indeed be intimately involved in myocardial damage by activating the complement system in the ischemic tissue. In animal experiments, CRP removal after STEMI reduces infarct size and results in a significantly better left ventricular ejection fraction (LVEF). Recently, in the multi-center matched-control pilot study on CRP apheresis in Acute Myocardial Infarction (CAMI1), a newly designed CRP adsorber has been demonstrated to efficiently and selectively lower CRP plasma levels in humans. Here, we present preliminary data of the ongoing trial. Methods Up to the present day, 67 STEMI patients were enrolled in the study following complete coronary revascularization. 32 patients received CRP apheresis, whereas 35 patients treated by standard protocols served as controls. CRP apheresis started 24±12 h and 48±12 h after onset of symptoms. In case of a rapid increase in CRP plasma levels following the 2nd session, a 3rd session was carried out another 24 h later. In each apheresis session, 6000 ml plasma was treated via peripheral venous access. Primary study endpoint was myocardial infarction size as determined by Cardiac Magnetic Resonance Imaging (MRI) 5±3 days after STEMI. Results Apheresis sessions were well tolerated with no relevant side effects. Peak CRP plasma levels after STEMI ranged from 12 mg/l to 279 mg/l. The peak CRP level after AMI can be calculated precisely with at 2–3 CRP quantifications during the first 24 h after the onset of symptoms. The regression coefficient for this analysis is 0.95. This mathematical step allows for the comparison of the CRP-apheresis group and the controls on the basis of their individual CRP peak levels. The statistical evaluation shows that the apheresis patients no longer correlate with the control with regard to the endpoints infarct size, LVEF, longitudinal strain and circumferential strain. They perform significantly better at all endpoints. The CRP apheresis reduced the development of myocardial damage. Conclusions Here, an unequivocal association between infarct size and CRP is demonstrated for the first time. CRP apheresis following STEMI is feasible and safe. Our preliminary results in a small cohort show a significant beneficial effect of CRP apheresis on myocardial infarction size and wall motion. Selective CRP apheresis may emerge as a new therapeutic approach in the treatment of acute myocardial infarction.