title: Cardiovascular effects of canrenone in patients with preascitic cirrhosis.
abstract: In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (PNE) when on a 150-mmol/d-sodium diet (baseline), after 1 month on canrenone (100 mg/d) plus a 40-mmol/d-sodium diet and after 1 month on canrenone plus a 150-mmol/d-sodium diet. Echocardiographic evaluation was performed with the patient in the supine position and during active standing. At baseline, patients had high plasma volume and normal renal function, PRA, PAC, and PNE. CI, LVEF, and stroke volume index were also normal. Standing caused a significant reduction in CI and LVEF. After canrenone and either sodium diet, CI significantly decreased, and PRA and PNE increased in the supine position. On standing, LVEF and CI did not decrease further. Plasma volume significantly decreased only after low-sodium diet plus canrenone. In conclusion, canrenone normalizes the cardiac response to the postural challenge in patients with preascitic cirrhosis.
authors.affiliation: Department of Internal Medicine, University of Florence School of Medicine, Azienda Ospedaliera Careggi, Florence, Italy. g.lavilla@dmi.unifi.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: La Villa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barletta
authors.forename: Roberto Giulio
authors.initials: RG
authors.lastname: Romanelli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Laffi
authors.forename: Riccarda
authors.initials: R
authors.lastname: Del Bene
authors.forename: Francesco
authors.initials: F
authors.lastname: Vizzutti
authors.forename: Pietro
authors.initials: P
authors.lastname: Pantaleo
authors.forename: Valeria
authors.initials: V
authors.lastname: Mazzocchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Gentilini
mesh_terms: D000368:Aged; D001201:Ascites; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002192:Canrenone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007668:Kidney / Q000502:physiology; D008103:Liver Cirrhosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D010953:Plasma Volume / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D002192:Canrenone; D012964:Sodium