Abstract 074: Endothelial Caveolin-1 Mediates The Effects Of Dietary Sodium On Cardiovascular And Metabolic Function

Hypertension and insulin resistance (IR) are often associated with endothelial dysfunction; however, the underpinnings of their association are not well understood. Caveolin-1 (cav1) is a transmembrane protein identified in many cell types including cardiovascular (CV) and adipose cells. Our recent findings in mice and humans consistently suggest a role of cav1 in IR, dyslipidemia, CV dysfunction and hypertension in response to sodium loading. While adipose cav1 has been established as a critical mediator of glucose and lipid homeostasis, the role of endothelial cav1 in cardiometabolic dysfunction , and its relationship with dietary sodium is unclear. To test whether the cav1 in the endothelium mediates the effect of dietary sodium on CV and metabolic function, we used the Cre- loxP technology to generate a novel, endothelium-specific cav1 KO mouse model (Ecav1 KO). Glucose tolerance, BP, fasting insulin, lipids and the state of circulating RAAS were measured in Ecav1 KO and WT mice studied on low- and high-sodium diets (0.03 vs 1.6% Na) for 7 days. Ecav1 KO and WT mice had similar BW, food and water intake and urinary output on either diet. Compared to the WT, Ecav1 KO animals had significantly higher fasting blood glucose levels on a LS diet (103±4 vs 87±3 mg/dl, p&lt;0.01) but not on a HS diet. Ecav1 KO mice also had impaired glucose tolerance vs the WT, especially on a HS diet; however, the glucose intolerance was not as pronounced in the Ecav1 KO as in the full cav1 KO. There were no differences in fasting insulin or lipid levels between the genotypes. On a HS diet, Ecav1 KO vs WT mice had significantly higher SBP levels (117±2 vs 109±3 mmHg, p&lt;0.05). In addition, they had significantly higher pulse pressure (38±2 vs 29±1 mmHg, p&lt;0.01), heart rates (802±11 vs 725±12 bpm, p&lt;0.01) and rate pressure products, consistent with increased arterial stiffness and myocardial workload. These changes could not be explained by differences in kidney function; however, aldosterone levels were increased in Ecav1 KO vs WT animals (74±11 vs 48±5 ng/dl) despite no changes in PRA. Our findings are consistent with a direct role of endothelial cav1 in the development of IR and CV dysfunction, and highlight the importance of endothelial function in cardiometabolic homeostasis. </jats:p

Venous Excess Doppler ultrasound assessment and loop diuretic efficiency in acute cardiorenal syndrome

Abstract Background Cardiorenal syndrome poses significant diagnostic and therapeutic challenges. The Venous Excess Ultrasound (VExUS) grading system based on the combination of venous Doppler assessments has shown potential in predicting acute kidney injury and cardiovascular outcomes, but its relevance regarding the management of acutely decompensated heart failure (ADHF) remains to be fully understood. Methods In this prospective study, patients with ADHF and acute kidney injury (AKI) were enrolled from a medical intensive care unit over 20 months. The study involved echocardiography and VExUS grading at admission and 72 h later. Data collection included clinical parameters, diuretic dosages, urine output, and fluid balance. Statistical analyses focused on exploring the relationships between VExUS grades and its components, including the renal venous stasis index (RVSI), diuretic efficiency, and renal function improvement. Results The cohort of 43 patients showed varied VExUS grades at admission. Higher VExUS grades were significantly associated with lower diuretic efficiency. Specifically, the mean urine output per 40 mg of furosemide was 368 ± 213 mL, with patients having VExUS grade 2 or 3 exhibiting reduced diuretic efficiency compared to those with grade 0–1 (Grade 2 vs. Grade 0–1: 333 ± 214 mL vs. 507 ± 189 mL, p = 0.02; Grade 3 vs. Grade 0–1: 270 ± 167 mL vs. 507 ± 189 mL, p = 0.004). The relationship between VExUS grade and diuretic efficiency was independent of admission creatinine and prior use of loop-diuretics (β = -106 CI: -180; -32 p = 0.006). Among the components of venous congestion assessment, the RVSI had the best ability to predict low diuretic efficiency (AUROC: 0.76 (0.60; 091) p = 0.001). Improvement in VExUS grade at 72 h was correlated with significant renal function improvement (84.6% vs. 47.1% for improved vs. non-improved VExUS grades, p = 0.03). Conclusion High VExUS and RVSI grades at admission are independently associated with reduced diuretic efficiency in ADHF patients with AKI. The findings emphasize the clinical value of venous congestion assessment in cardiorenal syndrome management including the selection of an initial diuretic dose