ABSTRACT
【Objective】 To explore the effect of bisoprolol on ICa，Lin volume overload combined with pressure overload heart failure in rabbits. 【Methods】 Totally 82 male New Zealand rabbits （2.5-3.0 kg） were randomly divided into three groups： SO （sham group）， HF （heart failure group）， and BF （heart failure with bisoprolol treatment group）. HF rabbits were duplicated by aortic valve insufficiency procedure combined with abdominal aorta constriction procedure. Real-time PCR and Western blot analysis were performed to detect the expression of ICa，L in left ventricular myocytes. Left ventricular myocytes were isolated； then the cell membrane capacitance， the current density， activation and inactivation of ICa，L were recorded by whole cell patch clamp. 【Results】 ① Bisoprolol could improve the heart function of heart failure rabbits according to the measurement of echocardiography and BNP. ② The expressions of ICa，L mRNA and protein decreased significantly in heart failing rabbits （P<0.01）， but remained unaltered after chronic bisoprolol treatment （P>0.05）. ③ Membrane capacitance was larger in heart failing groups than in sham group （P<0.01）. ICa，L current density decreased greatly in HF group （P<0.01）. Bisoprolol treatment could not change Cm or ICa，L density （P>0.05）. V1/2 of activation curve negative shift enlarged window currents in heart failure groups. Bisoprolol treatment caused window currents to decrease. 【Conclusion】 Bisoprolol could reverse the heart function of heart failure rabbits and also affect the function of ICa，L.
ABSTRACT
OBJECTIVE: To investigate the diagnostic value of plasma growth and differentiation factor-15 (GDF-15) level, GDF-15 mRNA expression in circulating mononuclear cells (MNCs), and plasma pro-B-type natriuretic peptide (NT-proBNP) level for heart failure in patients with different underlying cardiac diseases, namely dilated cardiomyopathy (DCM) and coronary artery heart disease (CAD), and assess their value in predicting the severity of heart failure and long-term cardiovascular disease (CVD) events. METHODS: Fasting venous blood samples were collected from 261 patients with DCM and 251 patients with CAD admitted in our hospital between January, 2018 and January, 2019, with 132 healthy individuals serving as the control group. The plasma level of GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA), and the expression of GDF-15 mRNA in the MNCs was measured by real-time PCR. We also analyzed the expression of GDF-15 in patients with different NYHA classes, and the ROC curve was used to evaluate the predictive power of GDF-15 mRNA for CVD events. RESULTS: The plasma levels of GDF-15 and GDF-15 mRNA in the MNCs were significantly higher in patients with DCM and CAD than in the control group (P < 0.01). Plasma GDF-15 levels were significantly higher in NYHA class â £ patients than in class â ¡ and â ¢ patients, and GDF-15 mRNA expressions in the MNCs were much higher in class â ¢ and â £ patients than class â ¡ patients (P < 0.01). ROC curve analysis showed that for predicting CVD events, the area under the curve (AUC) was 0.73 (95% CI: 0.69-0.77, P < 0.001) for NT-proBNP alone, as compared with 0.83 (95% CI: 0.79-0.86, P < 0.001) for GDF-15 mRNA in the MNCs combined with NT-proBNP. CONCLUSIONS: Plasma GDF-15 level and GDF-15 mRNA expression level in the MNSc can both be used as biomarkers for heart failure. Plasma level of GDF-15 is more sensitive for predicting NYHA class â £ patients with heart failure, while GDF-15 mRNA level in the MNCs better predicts class â ¡ patients. The combination of NT-proBNP with GDF-15 mRNAlevel in the MNCs can more accurately predict the risk of long-term CVD events.
Subject(s)
Growth Differentiation Factor 15/blood , Heart Failure , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Biomarkers , Cardiovascular Diseases , Heart Failure/diagnosis , Humans , Predictive Value of Tests , PrognosisABSTRACT
Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.
