Search

Background Acute lung injury is common during sepsis. Whereas gaseous exchange often can be supported adequately, death results frequently from cardio-circulatory depression, the mechanisms of which remain unclear. The aim of this study was to determine whether cardio-circulatory dysfunction during sepsis results from release of macrophage migration inhibitory factor (MIF) by the lung.Methods Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in adult Sprague-Dawley rats. Macrophage MIF was measured in the plasma sampled from the right ventricle (pre-lung) and left atrium (post-lung).Results The concentration of macrophage MIF in each of the post-lung samples was higher than in the corresponding pre-lung sample at 6 h (p 0.015; paired t-test), 20 h (p 0.008), and 30 h (p 0.026) after the induction of sepsis. Next, rats that underwent CLP were treated with either saline (control) or our specific MIF inhibitor, (S, R)-3-(4-hydroxyphenyl)-4,5-dehydro-5-isoxazole acetic acid methyl ester (ISO-1). Echocardiography revealed that ISO-1 significantly improved the left ventricular end-diastolic volume index (p 0.02), stroke volume index (p 0.01), and cardiac index (p 0.02) at 30 h after the induction of sepsis.Conclusions The lung appears to release significant amounts of macrophage MIF into the systemic circulation during late sepsis. Inhibition of MIF in a clinically relevant time frame blocked polymicrobial peritonitis-induced cardio-circulatory dysfunction. Inhibition of MIF may be a useful strategy to prevent cardio-circulatory deterioration associated with late sepsis. [ABSTRACT FROM AUTHOR]

Background. Increased levels of oxidized proteins have been reported in the serum of patients with end-stage renal disease, though little is known regarding the oxidized protein content of the dialysate in patients on peritoneal dialysis (PD) and no information is available as to how this may correlate with important clinical and laboratory variables, including abnormal peritoneal membrane function. In this study we attempted to identify oxidized proteins in the dialysate of patients on PD using western blot analysis, and examined the relationship between these proteins and the function of the peritoneal membrane and other clinical and laboratory variables. Methods. Peritoneal dialysate and serum samples were obtained from 18 patients on PD, and western blot analysis using an antibody to oxidized protein was carried out with reprobing for albumin. Oxidized protein/albumin ratios were determined and compared with various clinical and laboratory variables including peritoneal equilibration test results. Results. Oxidized protein/albumin ratios were higher in the dialysate of patients who were high/high average transporters compared to low/low average transporters. Oxidized protein ratios were also found to be higher in the dialysate of patients who had diminished urine output as a reflection of loss of residual renal function. Negative correlations were noted between oxidized protein ratios in the dialysate and serum albumin levels and creatinine clearance. Conclusions. Higher levels of oxidized protein in the dialysate appear to be correlated with high/high average peritoneal membrane transport characteristics and may be related to loss of residual renal function. These preliminary findings suggest that it is plausible that oxidized proteins in the dialysate might play a contributory role in complications including membrane damage and ultrafiltration failure in patients on PD. [ABSTRACT FROM AUTHOR]