Elevated plasma amylase levels in advanced chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy: correlation with circulating interleukin-6 activity.

It has been reported that proinflammatory cytokine activation is associated with both mesenteric venous congestion and peripheral tissue underperfusion in advanced chronic heart failure. The aim of our study was to investigate if plasma amylase (as an easily approached marker of a low-grade peripheral organ injury caused by elevated systemic venous pressure and reduced cardiac output) is elevated in severe heart failure and if this elevation is correlated with cytokine and neurohormonal activation in the plasma of heart failure patients. Plasma levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), norepinephrine, and renin activity were measured in 43 severe heart failure patients (ischemic, 28; dilated, 15; left ventricular ejection fraction [LVEF] 27 +/- 3%; New York Heart Association [NYHA] classes III-IV), in 37 mild heart failure patients (ischemic, 26; dilated, 11; LVEF, 33 +/- 5%; NYHA classes I-II), and in 20 age-matched and gender-matched healthy controls. NYHA III-IV heart failure patients exhibited significantly higher plasma levels of amylase (342 +/- 19 vs. 174 +/- 13 U/L, p < 0.01), TNF-alpha (6.2 +/- 0.5 vs. 4.2 +/- 0.3 pg/ml, p < 0.01), IL-6 (5.9 +/- 0.3 vs. 4.4 +/- 0.3 pg/ml, p < 0.05), GM-CSF (21.2 +/- 2.7 vs. 4.1 +/- 0.9 pg/ml, p < 0.001), and neurohormones (both p < 0.001) compared with NYHA I-II heart failure patients and healthy controls (amylase, 165 +/- 11 U/L, p < 0.01; TNF-alpha, 2.7 +/- 0.3 pg/ml, p < 0.001; IL-6, 3.2 +/- 0.2 pg/ml, p < 0.01; GM-CSF, 3.1 +/- 0.7 pg/ml, p < 0.001). Only in NYHA III-IV heart failure patients, plasma amylase levels were significantly correlated with plasma IL-6 activity (r = 0.86, p < 0.001), plasma norepinephrine levels (r = 0.82, p < 0.001) and right atrial pressure (r = 0.52, p < 0.05). Additionally, circulating IL-6 was also significantly correlated with plasma norepinephrine (r = 0.86, p < 0.001) and right atrial pressure (r = 0.57, p < 0.01). In conclusion, plasma amylase levels were elevated in severe heart failure patients and correlated well with circulating IL-6 activation, possibly as a result of both mesenteric venous congestion and impaired peripheral tissue perfusion observed in advanced chronic heart failure. However, the lack of association between plasma IL-6 and amylase levels in mild heart failure patients indicates an independent correlation of each variable with the functional status of the disease.

Serum profiles of C-C chemokines in acute myocardial infarction: possible implication in postinfarction left ventricular remodeling.

C-C chemokines are essential factors in the recruitment and activation of leukocytes from the circulation into inflamed tissue and may play a role in ischemia-induced myocardial injury and left ventricular remodeling after acute myocardial infarction (AMI). We investigated the kinetics of three major C-C chemokines, macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1 alpha), and regulated on activation normally T cell expressed and secreted (RANTES), in the sera of AMI patients and correlated the findings with the severity of the disease. Serum levels of C-C chemokines were determined in 35 AMI patients by ELISA assays serially during the first week of hospitalization and 1 month after hospital admission. Patients (n = 18) with uncomplicated AMI (Killip class I) were classified as group A, patients (n = 17) with AMI complicated by heart failure manifestations (Killip classes II and III) were classified as group B, and 15 age-matched and sex-matched volunteers were used as healthy controls. A sustained increase in serum C-C chemokines was observed in both AMI groups during the 7-day hospitalization period. Peaks of these inflammatory factors were significantly higher in group B than in group A (MCP-1, 295 +/- 11 vs. 203 +/- 9 pg/ml, p < 0.01; MIP-1 alpha, 30 +/- 1 vs. 24 +/- 2 pg/ml, p < 0.05; RANTES, 32 +/- 2 vs. 16 +/- 1 ng/ml, p < 0.01) and healthy controls (MCP-1, 125 +/- 7 pg/ml, p < 0.001; MIP-1 alpha, 14 +/- 1 pg/ml, p < 0.001; RANTES, 12 +/- 1 ng/ml, p < 0.001). In group B, significant correlations were found between the peak of MCP-1 and the peak of C-reactive protein levels (r = 0.55, p < 0.02) as well as wedge pressure (r = 0.40, p < 0.05). In the same group, the peak of MIP-1 alpha levels was also significantly correlated with the peak of serum creatine kinase-myocardial band (MB) (r = 0.51, p < 0.04) and left ventricular ejection fraction (LVEF) (r = -0.45, p < 0.05). After 1 month, AMI patients (n = 14) with severe left ventricular dysfunction (LVEF < or = 35%) exhibited significantly higher levels of C-C chemokines (all p < 0.05) than the other AMI patients (n = 21) (LVEF > 35%). A significant correlation was found between MIP-1 alpha levels and left ventricular end-diastolic diameter (r = 0.47, p < 0.03) in this patient population. In conclusion, we have detected a significant elevation of major C-C chemokines during the course of AMI, with the highest levels in patients with AMI complicated by heart failure manifestations and severe left ventricular dysfunction. The elevation of these chemotactic inflammatory factors may actively contribute to the pathophysiology of the disease and the subsequent left ventricular remodeling.