Glucocorticoids ameliorate cardiorenal syndrome through the NPR1/SGK1 pathway in natriuretic peptide receptor A­heterozygous mice.

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome.

Relationship between lipids levels and right ventricular volume overload in congestive heart failure.

BACKGROUND: The relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechanisms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels. METHODS: We collected data of clinical characteristics, echocardiograph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels [including total cholesterol (TCL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area. RESULTS: There was a significantly inverse correlation between TCL levels and RVEDD (r = -0.34, P < 0.001) and RA (r = -0.36, P < 0.001). Other lipids such as LDL-C, HDL-C, and TG had a similar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use. CONCLUSIONS: Lipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as well as identify a causal relationship, if any.

Serum uric acid as an index of impaired renal function in congestive heart failure.

BACKGROUND: Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid (UA) metabolism. This study was to assess their potential relations to UA metabolism in heart failure. METHODS: We retrospectively assessed clinical characteristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure (n = 553). By clustering of indices, those variables were explored using factor analysis. RESULTS: In factor analysis, serum uric acid (SUA) formed part of a principal cluster of renal functional variables which included serum creatinine (SCr) and blood urea nitrogen (BUN). Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN (r = 0.48, P < 0.001) and SCr (r = 0.47, P < 0.001). CONCLUSIONS: There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

[Effect of spironolactone on left ventricular remodeling in patients with acute myocardial infarction].

OBJECTIVE: To investigate the effect of spironolactone on left ventricular remodeling (LVRM) in patients with acute myocardial infarction. METHODS: In this multicentric, randomized, controlled study, spironolactone 40 mg/d was randomly administered in addition to the routine treatment for patients with AMI. During the 6 months the serum PIIINP, BNP and echocardiography were examined in all patients to assess myocardial fibrosis, LV function and volume. RESULTS: A total of 88 AMI patients entered the study came from 4 hospitals in Shijiazhuang. There were 43 patients with anterior MI and 45 with inferior MI. In anterior MI group 23 patients received spironolactone and 20 accepted the routine treatment. In inferior MI group 23 received spironolactone and 22 accepted the routine treatment. In anterior MI group: (1) At 3rd, 6th month PIIINP and BNP serum levels were significantly lower in the spironolactone group compared with those in control group [PIIINP (260.2 +/- 59.9) vs (328.0 +/- 70.3) ng/L, P = 0.001, (197.1 +/- 46.3) vs (266.7 +/- 52.4) ng/L, P < 0.001], [BNP (347.4 +/- 84.0) vs (430.1 +/- 62.9) ng/L, P < 0.001, (243.7 +/- 79.7) vs (334.6 +/- 62.8) ng/L, P < 0.001]; (2) There were smaller LVEDD and LVESD in spironolactone group compared with those in control group after 6 months intervention [(51.0 +/- 5.5) vs (55.6 +/- 4.5) mm, P = 0.005, (35.7 +/- 4.6) vs (39.1 +/- 5.6) mm, P = 0.046]. However, in inferior MI group: (1) There were no significant differences in PIIINP and BNP values between the two groups after 6 months intervention; (2) There were no significant differences in the LVEDD, LVESD, LVEF after 6 months treatment. CONCLUSION: (1) In patients with anterior MI, spironolactone combined with the routine treatment could inhibit myocardial fibrosis and left ventricular dilation and prevent LVRM. (2) In patients with inferior MI, no significant difference in prevention of LVRM was found between the spironolactone combined with the routine treatment and the routine treatment alone.

Permanent cardiac pacing through the right supraclavicular subclavian vein approach.

BACKGROUND: The infraclavicular subclavian route is commonly used for insertion of permanent pacing leads. However, the subclavian vein route may at times be a very difficult way to gain access to the heart. OBJECTIVE: To explore a new route to reliably and safely insert pacing leads. METHODS: The right supraclavicular subclavian vein route was selected to implant permanent leads in patients with critical illness or in situations where access through the infraclavicular approach was difficult. Access was achieved by Yoffa's venipuncture technique. A subcutaneous arc tunnel was made to pull the leads over the clavicle, which first arched close to the sternoclavicular joint and then curved to the inlet of the leads. The pacemaker was implanted in a right infraclavicular surgical pocket. RESULTS: This technique was used in 44 patients. The venipuncture time of 4.4+/-1.2 min was faster with the supraclavicular route than with the infraclavicular route. However, there was slightly more blood loss with the supraclavicular route. Total duration of implantation was similar for both routes (supraclavicular route 72+/-16 min and infraclavicular route 75+/-20 min). Lead dislodgement, lead fracture and skin erosion did not occur. CONCLUSION: Pacing through the right supraclavicular subclavian vein route is a safe and reliable alternative in cases where access through the infraclavicular route is difficult.