Williamson, Eric E.

Abstract—Endothelin-1 (ET-1) is a cardiovascular peptide that binds to two distinct receptors, ETAand ETB, resulting in systemic and regional vasoconstriction, alteration in sodium excretion, mitogenesis, and release of other vasoactive peptides such as atrial natriuretic peptide (ANP). A role for ET-1 has been proposed in congestive heart failure (CHF) based on the increase in circulating ET-1 in this cardiovascular disease state. The present study determined the cardiorenal and endocrine responses to chronic selective oral ETAantagonism in experimental CHF. Two groups of conscious dogs underwent 21 days of pacing-induced CHF. These groups included a control untreated group (n=6) and a group that received an orally active ETAreceptor antagonist (A-127722, Abbott Pharmaceuticals, 5mg/kg PO bid, n=6). Each group was studied at baseline before the onset of CHF and after 14 and 21 days of CHF. Compared with the CHF control group, the ETAreceptor antagonism group at 14 days of CHF showed lower mean arterial pressure and systemic vascular resistance. Similarly, ETAreceptor antagonism markedly attenuated the increase in circulating ANP despite similar atrial pressures. At 21 days of CHF, ETAreceptor antagonism lowered pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance in association with a higher cardiac output. Plasma ANP remained suppressed. Despite the lower mean arterial pressure and circulating ANP in the ETAreceptor antagonist group, the absolute decrease in sodium excretion from baseline was less compared with the untreated CHF control group. The present investigation supports the conclusion that endogenous ET-1 participates in the systemic and pulmonary vasoconstriction, the elevation of ANP, and the sodium retention that characterize this model of experimental CHF, suggesting a potential therapeutic role for ETAreceptor antagonism in CHF.

Abstract We compared the clinical concordance of estimated glomerular filtration rate (eGFR) based on 3 whole blood creatinine assays with the eGFR calculated from a reference plasma creatinine assay. Whole blood creatinine on the Radiometer ABL800 FLEX (Radiometer A/S, Bronshoj, Denmark) demonstrated the best correlation and concordance to plasma creatinine/eGFR compared with the i-STAT (i-STAT, East Windsor, NJ) and StatSensor (Nova Biomedical, Waltham, MA). The i-STAT had better sensitivity (compared with Radiometer) but poorer specificity for prediction of plasma eGFR less than 60 mL/min/1.73 m2. The StatSensor demonstrated lower concordance of whole blood to plasma eGFR but offered a slope and an intercept offset feature that partially compensates for this effect. The optimal device for use in rapid determination of eGFR from whole blood creatinine may depend on whether it is more important in a given practice to optimize sensitivity, specificity, or overall concordance for determining plasma eGFR less than 60 mL/min/1.73 m2.