Modulation of chemokine gradients by apheresis redirects leukocyte trafficking to different compartments during sepsis, studies in a rat model.

INTRODUCTION: Prior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues. METHODS: In total, 76 male adult Sprague-Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann-Whitney U test. RESULTS: Apheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals. CONCLUSIONS: Our results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung.

Comparison of inflammatory response during on-pump and off-pump coronary artery bypass surgery.

PURPOSE: On-pump coronary artery bypass graft (CABG) surgery has been traditionally associated with a higher magnitude of inflammatory response than off-pump CABG. However with the development of polymer-coated biocompatible extracorporeal circuits, we wanted to see if cardiopulmonary bypass still played an important role in triggering this inflammatory response. METHODS: In this prospective observational study, 33 patients undergoing CABG surgeries (25 on-pump and 8 off-pump patients) were studied. Serial plasma cytokine (TNF IL-6, IL-10) and procalcitonin concentrations were measured at different time-points during and after the surgery. Demographic and baseline clinical data, intra-operative management details and post-operative complications were also collected from the patients' charts. RESULTS: Plasma levels of all 4 mediators increased during surgery and returned towards normal postoperatively. There were no differences between groups for any mediator at any time-point. CONCLUSIONS: We conclude that with the use of recent polymer-coated biocompatible extracorporeal circuits, the inflammatory response triggered by on-pump CABG becomes very similar in magnitude and pattern to that triggered by off-pump CABG. Thus, the surgical procedure contributes to most of the inflammatory response, with the extra-corporeal circuit having minimal to no effect on this response.