Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLPreduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection.
The cytokine network and its association with complement activation during cardiac surgery with cardiopulmonary bypass (CPB) is complex. Extracorporeal membrane oxygenation (ECMO) differs from CPB in duration of days to weeks rather than hours. However, few studies have analyzed the levels of inflammatory mediators during ECMO treatment. Plasma samples from 22 patients [nine neonates, one infant, four children and eight adults (14 males and eight female)] who underwent ECMO treatment were collected prior to, during and after treatment, and analyzed for concentrations of inflammatory and anti-inflammatory cytokines and parameters of complement activation. Seven children were treated for cardiac and seven for pulmonary failure and, in the adult group, four were treated for cardiac and four for pulmonary failure. ECMO was performed with veno-arterial (VA) bypass in all children and five adults, and with veno-venous (VV) bypass in three adults. Fourteen patients survived (64%) and eight (36%) patients died during follow-up. A marked (approximately 99%) and rapid (i.e., within two days) decrease in IL-6 was seen in survivors. The non-survivors were characterized by persistently high IL-6 levels throughout the observation period (i.e., until death). C-reactive protein (CRP) levels showed a similar pattern as the IL-6, with higher levels in non-survivors throughout the observation period. However, in contrast to IL-6, the differences between survivors and non-survivors reached statistical significance, but only at the end of the observation period. It is possible that early measurements of IL-6 in ECMO patients could give prognostic information beyond that of CRP.
Mediastinitis is treated with either vacuum-assisted closure (VAC) or traditional closed drainage (TCD) with irrigation. The aim of the study was to determine the effect of the two treatments on mortality and re-infection rate in a source population, using 21 314 consecutive patients undergoing isolated coronary artery bypass grafting (CABG) from January 1997 to October 2010. Median observation time was 2·9 years in the VAC group and 8·0 years in the TCD group. The epidemiological design was of an exposed (VAC, n = 64) versus non-exposed (TCD, n = 66) cohort with two endpoints: (1) mortality and (2) failure of sternal wound healing or re-infection. The crude effect of treatment technique versus endpoint was estimated by univariate analysis. Stratification analysis by the Mantel-Haenszel method was performed to quantify confounders and to pinpoint effect modifiers. Adjustment for confounders was performed using Cox regression analysis. Mediastinitis was diagnosed 6-105 (median 14) days after primary operation in the VAC group and 13 (5-29) days in the TCD group. There was no difference between groups in long-term survival. Failure of sternal wound healing or re-infection occurred less frequently in the VAC group (6%) than in the TCD group (21%; relative risk = 0·29, 95% CI = 0·06-0·88, P = 0·01). There are concerns for increase in right ventricle rupture in VAC compared with TCD. There was no difference in survival after VAC therapy and TCD therapy of post-CABG mediastinitis. Failure of sternal wound healing or re-infection was more common after TCD therapy.
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