Plasma immunoreactive endothelin-1 concentrations were determined by radioimmunoassay in 11 septic patients during the first 24 hours after the development of the sepsis syndrome in 15 nonseptic postoperative patients studied 24 hours after open heart surgery and in 14 healthy volunteers. Mean endothelin-1 plasma concentrations were significantly (p less than 0.001) increased in septic patients (19.9 +/- 2.2 pg/mL, mean +/- standard error) compared to concentrations found in postoperative cardiac patients (11.9 +/- 0.7 pg/mL) or in healthy volunteers (6.1 +/- 0.3 pg/mL). In septic patients elevated plasma concentrations of endothelin-1 were inversely correlated with cardiac index (r = -0.80, p less than 0.005) and positively correlated the severity of illness as documented by APACHE II score (r = 0.74, p less than 0.01) and plasma creatinine levels (r = 0.80, p less than 0.005). No such correlations were found in postoperative cardiac patients. These results indicate that endothelin-1 concentrations are correlated with the severity of illness and depression of cardiac output in patients with sepsis.
A sensitive and specific radioimmunoassay was developed to determine the occurrence and concentration of neuropeptide Y (NPY) in plasma and tissue extracts. Furthermore, NPY-like immunoreactivity (NPY-Li) was characterized by means of three different chromatographic systems. The NPY antiserum used (NI) did not cross-react with related peptides of the pancreatic polypeptide family except avian pancreatic polypeptide (1% cross-reactivity). Unextracted plasma contained high molecular weight proteins which interfered in the assay. Acid ethanol extraction removed this protein interference allowing a 90% recovery of NPY-Li. The content of NPY-Li in human plasma from healthy subjects was close to or below the detection limit (less than 22 pmol/l). Sympathetic nerve stimulation in the cat increased the output of NPY-Li from the splenic vein suggesting the release of this peptide upon sympathetic activation. The major peak of NPY-Li in spleen extracts and splenic vein plasma co-eluted with synthetic porcine NPY and a minor peak with larger Stokes radius was also present. The present radioimmunoassay enables further studies on the physiological and pathophysiological role of NPY.
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