Long-term control of hypertension in dialysis patients by low dose atenolol.

Hypertension in dialysis patients is considered a major factor in cardiovascular mortality. We investigated long-term efficacy of intermittent atenolol (AT) administration in 10 (7M/3F) hypertensive dialysis patients, age 60.5 (38-72), on dialysis for 56.5 months (8-156) thrice per week (10.5-13.5 h/w) (A). A similar group of 11 normotensive patients served as controls (B). Hypertension was defined as BP> 140/90 (day) and >120/80 mmHg (night) by a 44-h ambulatory BP monitoring (ABPM) after the mid-week session. Dialysis ultrafiltration, hematology, biochemistry were similar in A and B. Atenolol was started on an alternate day, 37.5 mg/w and increased as needed. After 34 days (6-80) and a dose of 68.75 (37.5-450) mg/w, BP dropped (ABPM: MAP 104+/-11.5 to 95.6+/-10.4 mmHg, P=0.0025) similar to controls and daytime HR dropped: 84.6+/-9.2 to 69.3+/-8.2, P=0.0008 and at night: 79.5+/-7.6 to 68.6+/-8.6 b/1' becoming lower than in B: 83+/-10.8/69.3+/-8.2, P=0.009 and 80.5+/-11.7/68.6+/-8.6 b/1' (P=0. 02). Six months later ABPM in A as well as echocardiography in A and B remained unchanged. Moderate, volume independent hypertension in stable dialysis patients is easily controlled during the interdialytic period by small intermittent atenolol doses.

Plasma levels of soluble cellular adhesion molecules in patients with arterial hypertension. Correlations with plasma endothelin-1.

Background: Several reports have shown that circulating, soluble cellular adhesion molecules and endothelin-1 (ET-1) are implicated in the pathophysiological events of atherosclerosis and may reflect the endothelial dysfunction characterizing this disorder. Methods: To evaluate the expression of these factors in arterial hypertension (AH), we measured plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble P-selectin (sP-selectin), and ET-1 in 60 untreated patients with mild to moderate AH (hypercholesterolemic: n=31, normocholesterolemic: n=29) and 30 sex- and age-matched normocholesterolemic normotensive controls. Results: Hypertensive patients exhibited significantly higher levels of sICAM-1 (234+/-21 vs. 187+/-12 ng/ml, P<0.005), sVCAM-1 (681+/-42 vs. 589+/-23 ng/ml, P<0.005), sP-selectin (89+/-17 vs. 55+/-11 ng/ml, P<0.01) and ET-1 (6.2+/-0.7 vs. 2.4+/-0.3 pg/ml, P<0.01) than did normotensive controls. The normocholesterolemic hypertensives had lower levels of sICAM-1, sVCAM-1 (P<0.01), sP-selectin and ET-1 (P<0.05) than hypercholesterolemic hypertensives, but higher levels than normotensive controls (P<0.05). In hypertensives, plasma ET-1 was significantly correlated with mean arterial pressure (r=0.51, P<0.03) and sICAM-1 levels (r=0.64, P<0.01). In hypercholesterolemic hypertensives, LDL cholesterol was also significantly correlated with plasma levels of sICAM-1 (r=0.53, P<0.04) and sP-selectin (r=0.41, P<0.05). Conclusions: Plasma levels of soluble cellular adhesion molecules are elevated in hypertensive patients in comparison to normotensive controls and may be related to plasma ET-1 activity. The coexistence of hypercholesterolemia may enhance the plasma soluble adhesion molecule activity induced by AH.

Clinical and neurohormonal correlates of circulating granulocyte-macrophage colony-stimulating factor in severe heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

In this report, we showed for the first time that granulocyte-macrophage colony-stimulating factor plasma levels are elevated in patients with severe heart failure, and these levels are correlated well with neurohormonal activation and hemodynamic deterioration characterizing this syndrome.

Serum profiles of granulocyte-macrophage colony-stimulating factor and C-C chemokines in hypertensive patients with or without significant hyperlipidemia.

The present study investigates the differences in serum activity of granulocyte-macrophage colony-stimulating factor, macrophage chemoattractant protein-1, and macrophage inflammatory protein-1alpha between hypertensive patients with and without significant hyperlipidemia before receiving any medical treatment. The serum activity of the studied inflammatory factors is more elevated in hypertensive patients with significant hyperlipidemia and may be associated with atherosclerotic inflammatory process induced by the coexistence of 2 major cardiovascular risk factors.

Tumor necrosis factor-alpha serum activity during treatment of acute decompensation of cachectic and non-cachectic patients with advanced congestive heart failure.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces left ventricular dysfunction and a negative inotropic effect in cardiac tissue when overexpressed in human subjects. Previous studies have shown that levels of circulating TNF-alpha are elevated in patients with advanced congestive heart failure (CHF) and especially in those with cardiac cachexia. To clarify the potential role of TNF-alpha in the unstable state of decompensated advanced CHF, we investigated the TNF-alpha serum activity in 25 cachectic and 22 non-cachectic CHF patients (New York Heart Association, NYHA functional classes III or IV), who were treated with intravenous diuretics and positive inotropic agents for acute decompensation of the disease, during a 5-day hospitalization period, as well as in 15 age-matched healthy control subjects. Cachectic CHF patients needed higher dosages of inotropic agents than non-cachectic patients and the determination of TNF-alpha serum concentrations in this patient group showed high levels of TNF-alpha at hospital admission (18.3 +/- 3.2 pg/ml) and a transient increase in circulating TNF-alpha during the treatment period with the highest levels on the 2nd day of hospitalization (32.5 +/- 7.1 pg/ml). The TNF-alpha serum levels were low in non-cachectic CHF patients and healthy controls on the 1st day (4.0 +/- 0.9 and 3.7 +/- 0.6 pg/ml, respectively) and did not change substantially during the course of the study. The present results show that TNF-alpha serum activity is transiently increased during the treatment of decompensated cachectic CHF patients only and may be related to the clinical instability and the consequent therapeutic interventions in this category of CHF patients.

Correlation of interleukin-6 gene expression to immunologic features in patients with cardiac myxomas.

Cardiac myxomas, the most common primary heart tumors in adults, show a variety of clinical manifestations and laboratory findings correlated with elevated interleukin-6 (IL-6) serum concentration. The aim of this study was to determine the expression of IL-6 mRNA in myxoma tissue as a cause to frequent immunologic abnormalities in patients with such tumors. In our centers, we analyzed 17 surgically resected myxomas using the polymerase chain reaction (PCR) and found increased IL-6 mRNA expression in 14 of 17 cases. The serum IL-6 levels of the 14 patients, detected by enzyme-linked immunosorbent assay (ELISA) with mouse antihuman monoclonal antibody (mAb), were high preoperatively (> 6 pg/ml) and decreased to normal postoperatively (< or = 6 pg/ml). These same 14 patients exhibited significant autoimmune disorders preoperatively. The other 3 patients had normal serum levels of IL-6 (< or = 6 pg/ml) and did not present any serious signs and symptoms, and molecular analysis did not show overexpression of IL-6 mRNA in neoplasmic tissue. These results suggest that IL-6 is overproduced in myxoma tissue and secreted into the systemic circulation as a stimulator of the immunoregulatory system. Furthermore, this study indicates the promising role of molecular biology techniques in the research of pathophysiologic mechanisms of cardiac myxomas.