ABSTRACT
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Subject(s)
Male , Female , Humans , Aged , Natriuretic Peptide, Brain , Simendan/therapeutic use , Non-ST Elevated Myocardial Infarction , Heart Failure/drug therapy , Peptide Fragments , Arrhythmias, Cardiac , Biomarkers , PrognosisABSTRACT
BACKGROUND@#We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling. @*METHODS@#Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague–Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs. @*RESULTS@#The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis. @*CONCLUSION@#The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.
ABSTRACT
BACKGROUND@#We previously found that atorvastatin (ATV) enhanced mesenchymal stem cells (MSCs) migration, by a yet unknown mechanism. CXC chemokine receptor 4 (CXCR4) is critical to cell migration and regulated by microRNA-146a (miR-146a). Therefore, this study aimed to assess whether ATV ameliorates MSCs migration through miR-146a/CXCR4 signaling. @*METHODS@#Expression of CXCR4 was evaluated by flow cytometry. Expression of miR-146a was examined by reverse transcription-quantitative polymerase chain reaction. A transwell system was used to assess the migration ability of MSCs. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague–Dawley rats with acute myocardial infarction (AMI). Mimics of miR-146a were used in vitro, and miR-146a overexpression lentivirus was used in vivo, to assess the role of miR-146a in the migration ability of MSCs. @*RESULTS@#The results showed that ATV pretreatment in vitro upregulated CXCR4 and induced MSCs migration. In addition, flow cytometry demonstrated that miR-146a mimics suppressed CXCR4, and ATV pretreatment no longer ameliorated MSCs migration because of decreased CXCR4. In the AMI model, miR-146a-overexpressing MSCs increased infarct size and fibrosis. @*CONCLUSION@#The miR-146a/CXCR4 signaling pathway contributes to MSCs migration and homing induced by ATV pretreatment. miR-146a may be a novel therapeutic target for stimulating MSCs migration to the ischemic tissue for improved repair.
ABSTRACT
There is a strong timeliness for the rescue of cardiac arrest and the prognosis is associated with many factors. The final status of patients depends on the recovery of neurologic function. The establishment of a multidisciplinary cardiopulmonary-cerebral resuscitation center based on emergency medicine is imminent. The center relies on multidisciplinary rescue,emphasizing the effectiveness of rescue, that is,the recovery of neurologic function. The scientific and clinical research on this platform will surely make a great contribution to human health.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of fasudil on in vitro cultured cardiomyocytes (CMs) exposed to omethoate and its possible mechanism.</p><p><b>METHODS</b>Cardiomyocytes were isolated from male SD rats and were then cultured in DMEM conventionally. The CMs were divided into different groups based on the doses of omethoate and fasudil in culture media. After 3, 6, 12, and 24 h of culture, the survival rate of CMs in each group was measured, the CMs in the medium-dose omethoate and medium-dose fasudil groups were subject to shortening amplitude measurement , and the content of lactate dehydrogenase (LDH) in culture media and expression of Bcl-2 and Bax in CMs were measured.</p><p><b>RESULTS</b>Compared with the normal control group, each omethoate group showed significantly lower survival rate of CMs, which was negatively correlated with the dose of omethoate (P < 0.01). Compared with the normal control group, the medium-dose omethoate and medium-dose fasudil groups showed significantly decreased shortening amplitudes of CMs at all time points (P < 0.01), and the shortening amplitudes of CMs were significantly higher in the medium-dose fasudil group than in the medium-dose omethoate group after 12 h and 24 h of culture (P < 0.01). The LDH level was significantly higher in the medium-dose omethoate and medium-dose fasudil groups than in the normal control group, and the medium-dose fasudil group showed significantly lower LDH level than the medium-dose omethoate group (P < 0.01). Compared with those in the normal control group, the Bcl-2 expression in the medium-dose omethoate and medium-dose fasudil groups was decreased significantly, and the Bax expression in the medium-dose omethoate group was increased significantly (P < 0.01). Compared with the medium-dose omethoate group, the medium-dose fasudil group had significantly increased Bcl-2 expression and significantly decreased Bax expression (P < 0.01).</p><p><b>CONCLUSION</b>Fasudil can inhibit the abnormal expression of apoptosis regulatory proteins (Bcl-2 and Bax) induced by omethoate, which might be one of the factors that reduce the toxic effect of omethoate on CMs.</p>
Subject(s)
Animals , Male , Rats , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine , Pharmacology , Cells, Cultured , Dimethoate , Toxicity , Myocytes, Cardiac , Metabolism , Pesticides , Poisoning , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Rats, Sprague-Dawley , bcl-2-Associated X Protein , MetabolismABSTRACT
Objective To investigate the effect of a selective muscarinic receptor antagonist (penehyclidine hydrochloride) in three vessel occlusion model of acute global cerebral ischemia-reperfusion in rats.Method One hundred and forty-four male SD rats were randomly divided into four groups:sham operated group,vehicle treated group (saline 1 ml,i.p.),scopolamine treated group (0.01 mg/kg,i.p.) and penehyclidine hydrochloride treated group (0.01 mg/kg,i.p.) with drugs injected 40 minutes before ischemia respectively.The ischemic duration was 10 minutes.The animals were subjected to motor activity tests (open field activity test,beam-walking test and grip test) at 24 hours or on the 3rd and 7th day after reperfusion.HE staining,TUNEL staining and immunohistochemical reactions of bax and bel-2 were carried out at the time points of 2,12,24 hours,3 and 7 days after reperfusion.TTC staining was carried out in some rats for assessment of infarction volume on the 4th day after reperfusion.Results As compared with the vehicle treated group,both penehyclidine hydrochloride treatment and scopolamine treatment decreased the numbers of apeptotie neurons (P