Combination of hypertonic saline and low-dose furosemide is an effective treatment for refractory congestive heart failure with hyponatremia

AbstractHyponatremia often associates with heart failure. Although severe salt restriction is generally recommended in heart failure treatment, it may promote hyponatremia which is a risk factor for increased morbidity and mortality in heart failure patients. Therefore, it is not yet clear whether correction of hyponatremia is an effective treatment in congestive heart failure with hyponatremia. We experienced a successful case of refractory congestive heart failure with hyponatremia treated with hypertonic saline and furosemide. A 45-year-old man, suffering from dilated cardiomyopathy, was admitted to our hospital for heart failure worsening with hyponatremia. We started diuretics therapy without correction of hyponatremia, but his clinical status of heart failure was not improved. Therefore, we additionally started to correct hyponatremia by continuous injection of hypertonic saline. The correction of hyponatremia increased urinary volume dramatically, and improved cardiac output and clinical status of heart failure. This case strongly suggests that combination of hypertonic saline and furosemide could enhance diuretic effect, and improve the clinical status of heart failure in congestive heart failure patients with hyponatremia.<Learning objective: Hyponatremia is a major problem associated with heart failure, but it is not yet clear whether correction of hyponatremia is an effective treatment in patients with congestive heart failure. We experienced a successful case of refractory congestive heart failure with hyponatremia treated with hypertonic saline and low dose furosemide. This case strongly suggests that aggressive correction of hyponatremia can be an effective treatment for refractory congestive heart failure with hyponatremia.

Increased renal iron accumulation in hypertensive nephropathy of salt-loaded hypertensive rats.

Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2'-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis

Temporary dietary iron restriction affects the process of thrombus resolution in a rat model of deep vein thrombosis.

Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT.We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation.The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet.These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT

Physiological parameters, hematologic parameters, and relative hepatic hepcidin gene expression levels in all groups at 12 weeks of age.

*<p>p<0.05 versus Control group,</p>†<p>p<0.05 versus HS+IR group. n = 6 per group. Control, SHRSP fed a normal salt diet; HS, SHRSP fed a high-salt diet; HS+IR, SHRSP fed a high-salt with iron-restricted diet; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin.</p