Furosemide and spironolactone doses and hyponatremia in patients with heart failure.

BACKGROUND: Hyponatremia, a marker of disease severity and prognosis, has been associated with various clinical factors and drug use, especially diuretics. METHODS: This observational prospective cohort study enrolled patients hospitalized at the University Hospital Center Split because of heart failure (HF). We investigated the association of clinical variables and cardiovascular drugs, including furosemide, hydrochlorothiazide, spironolactone, and their doses, with the presence of hyponatremia at admission. RESULTS: Of the 565 included patients, 32.4% were hyponatremic, 62.6% were males, and the mean age was 73.1 ± 10.6 years. In the univariate analysis, hyponatremic patients were more often current smokers (p = 0.01), alcohol consumers (p = 0.01), receiving spironolactone (p = 0.004) or combination of furosemide and spironolactone (p = 0.003). Patients who received 50 and 100 mg of spironolactone, compared to those receiving 25 mg (p < 0.0001), as well as patients who received 250 to 500 mg of furosemide compared to ≤240 mg (p = 0.001), were significantly more often hyponatremic. In the multivariate analysis, when diuretic doses were accounted for, furosemide doses of 250 to 500 mg (p = 0.009), spironolactone doses of 50 to 100 mg (p = 0.0003), increasing age (p = 0.03), diabetes mellitus (p = 0.02) and alcohol consumption (p = 0.04) were independently associated with hyponatremia. CONCLUSION: High doses of furosemide and spironolactone, or concomitant use of these diuretics, seem to be an important cause of hyponatremia in HF patients, particularly in combination with advanced age, diabetes and alcohol consumption. Diuretic dose reduction may help avoid hyponatremia and improve clinical status and prognosis in such patients.

Changes in cardiac innervation during maturation in long-term diabetes.

Diabetic autonomic neuropathy being a common complication of diabetes mellitus (DM) is related to an increased risk of cardiovascular mortality. However, mechanisms underlying changes of innervation density in affected hearts remain insufficiently understood. Hence, the aim of this study was to describe quantitative changes of intra-myocardial nerve terminals in hearts of diabetic rats of various ages. Male Sprague-Dawley rats were injected with 55mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control). After 2weeks, 2months, 6months and 12months, sections of their hearts were analyzed in five areas-left ventricle, interventricular septum, right ventricle, anterior and posterior wall. Nerve fibers were visualized immunohistochemically, using antibody against a general neuronal marker, protein gene product 9.5 (PGP 9.5). Significant increase in total nerve fibers from all heart areas was observed 2weeks and 2months after diabetes induction, followed by a decrease at 6months and again increase at 12months was observed in both control and diabetic rats. Significant difference between control and diabetic rats was visible after 2weeks and 2months, with diabetic rats exhibiting significantly more nerve fibers. There were no consistent differences in quantity of nerve fibers in different areas of the heart within a particular age-related group of animals. In conclusion, cardiac innervation undergoes dynamic changes both in control and in diabetic rats, with a time-dependent significant increase in neuronal fiber density in diabetic animals. This novel information may contribute to our understanding of pathophysiological changes associated with diabetic cardiac neuropathy.