Background-Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. Methods and Results-Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr 1 )apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all PϽ0.0001). Vasodilatation to acetylcholine (Pϭ0.01) but not apelin (Pϭ0.3) or sodium nitroprusside (Pϭ0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all PϽ0.05). Systemic infusions of (Pyr 1 )apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all PϽ0.01) but increased heart rate only in control subjects (PϽ0.01). Conclusions-Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure. (Circulation.
The diuretic and natriuretic response to an intravenous dose of frusemide 40 mg was assessed in the erect and supine positions in 10 patients with cardiac failure who were being treated with enalapril 10 mg twice daily in addition to diuretics (Enalapril group) and in 10 patients with cardiac failure taking diuretics alone (Control group). Total 4 h diuresis in the erect position was 728 ml and in the supine position was 824 ml in the patients taking enalapril compared to 655 ml in the erect position and 1166 ml in the supine position in those patients taking diuretics alone. Total 4 h natriuresis in the erect positions was 78 mmol and in the supine position was 85 mmol in patients taking enalapril 10 mg twice daily but in those patients taking diuretics alone total 4 h natriuresis in the erect position was 67 mmol increasing to 120 mmol in the supine position. Measurements of plasma renin activity and plasma angiotensin II concentration confirmed effective converting enzyme inhibition, in the group of patients taking enalapril, but in those patients taking diuretics alone the erect position was associated with an increase in plasma renin activity, and plasma concentrations of angiotensin II and aldosterone. We conclude that the renin angiotensin system is a major factor in mediating the effect of posture on loop diuretic drugs.
We report the results and one-year follow-up of 20 elderly patients (age range 70-82 years) with severe rheumatic mitral stenosis treated by mitral balloon valvuloplasty (MBV). All 20 were breathless at rest despite treatment with diuretics and digoxin. At cardiac catheterization, successful dilatation was achieved in 17 patients: mean transvalvular mitral gradient fell by 45%, mean cardiac output rose by 24% and mean valve area increased by 76%. There was no procedure-related mortality. At one month, 15 patients had experienced an improvement in symptoms of at least one New York Heart Association class and, at one year, ten had maintained this improvement. Three patients proceeded to mitral valve replacement because of a suboptimal symptomatic result. Mitral balloon valvuloplasty can be successfully performed with significant symptomatic benefit in frail elderly patients unfit for surgery and may also be offered to other selected elderly patients as an alternative to surgical treatment.
Objective-To assess the effects on haemodynamic function and symptoms of percutaneous balloon dilatation of mitral stenosis in patients unable to undergo surgical treatment because of associated medical/cardiac problems.
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