Hemodynamic and neuroendocrine effects for candoxatril and frusemide in mild stable chronic heart failure.

OBJECTIVES: The study aimed to assess the hemodynamic and neuroendocrine effects of candoxatril and frusemide compared with placebo in patients with mild chronic heart failure. BACKGROUND: Candoxatril is an atriopeptidase inhibitor. It increases circulating levels of atrial natriuretic peptide leading to natriuresis and diuresis, which alleviate the symptoms of a failing heart. METHODS: This was a multicenter, randomized, double-blind study. Forty-seven patients with mild stable chronic heart failure received candoxatril 400 mg/day, frusemide 40 mg/day or placebo for up to six weeks. Cardiac indices were determined at rest and during exercise, and blood samples were taken for laboratory analysis. Assessments were performed at baseline (day 0) and after six weeks (day 42). RESULTS: In comparison with placebo, both drugs significantly reduced mean pulmonary capillary wedge pressure following the first dose administration. Only candoxatril significantly reduced pulmonary capillary wedge pressure during exercise on day 0, while both drugs significantly reduced this parameter on day 42. Changes in the remaining hemodynamic parameters were comparable for both drugs relative to placebo. Frusemide significantly increased mean plasma renin activity (days 0 and 42), and the mean aldosterone concentration (day 42) in comparison with placebo, whereas candoxatril caused no significant changes in any of the hormonal parameters assessed. CONCLUSIONS: These results show that candoxatril, 400 mg/day, has a similar hemodynamic profile to frusemide, 40 mg/day, but it does not induce adverse neuroendocrine effects. Candoxatril therefore appears to offer a clinically significant advantage over frusemide, providing an alternative therapeutic approach to the treatment of patients with mild stable chronic heart failure.

[Digitalis poisoning treated with a specific antidote]. / Digitalisforgiftning behandlet med spesifikt antidot.

Toxicity by digitalis is a common problem in everyday clinical practice. In this paper three cases of severe poisoning with digitoxin with maximal S-digitoxin levels of 115, 150 and 239 nmol/l are described. All patients received specific digoxin Fab-fragment intravenously. Administration of antidotes resulted in a favourable outcome in all three patients. So far, the use of digoxin-specific antibodies has been limited to a few cases of severe intoxication where life-threatening arrhythmias and hyperkalaemia were present. We discuss whether a more liberal indication should be accepted.

Transdermal nitrate therapy: bioavailability during exercise increases transiently after the daily change of patch.

Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001). The two nitrate-concentration curves differed significantly (P less than 0.0001). Thus, change of patch augmented nitrate availability during exercise.

[Ischemic left ventricular failure. Main stem coronary stenosis treated with angioplasty]. / Ischemisk betinget venstre ventrikkel-svikt. Hovedstammestenose behandlet med angioplastikk.

We describe a patient with stenosis on the left main stem and severe impairment of the left ventricular function. Because of reversible myocardial ischaemia in a patient whose clinical situation prohibited surgery, angioplasty on the left main stem was performed, leading to considerable improvement of the ventricular function. Improvement was slow, however, probably due to "stunning" of the myocardium. We underline the importance of early angiography in patients when it is suspected that a larger part of the myocardium is affected by severe, reversible ischaemia.