ABSTRACT
Remote Ischemic Preconditioning (RIPC) induced by brief episodes of ischemia of the limb protects against multi-organ damage by ischemia-reperfusion (IR). Although it has been demonstrated that RIPC affects gene expression, the proteomic response to RIPC has not been determined. This study aimed to examine RIPC induced changes in the plasma proteome. Five healthy adult volunteers had 4 cycles of 5 min ischemia alternating with 5 min reperfusion of the forearm. Blood samples were taken from the ipsilateral arm prior to first ischaemia, immediately after each episode of ischemia as well as, at 15 min and 24 h after the last episode of ischemia. Plasma samples from five individuals were analysed using two complementary techniques. Individual samples were analysed using 2Dimensional Difference in gel electrophoresis (2D DIGE) and mass spectrometry (MS). Pooled samples for each of the time-points underwent trypsin digestion and peptides generated were analysed in triplicate using Liquid Chromatography and MS (LC-MS). Six proteins changed in response to RIPC using 2D DIGE analysis, while 48 proteins were found to be differentially regulated using LC-MS. The proteins of interest were involved in acute phase response signalling, and physiological molecular and cellular functions. The RIPC stimulus modifies the plasma protein content in blood taken from the ischemic arm in a cumulative fashion and evokes a proteomic response in peripheral blood.
Subject(s)
Blood Proteins/metabolism , Ischemic Preconditioning , Proteome/metabolism , Adult , Blood Proteins/chemistry , Chromatography, Liquid , Down-Regulation , Electrophoresis, Gel, Two-Dimensional , Humans , Male , Mass Spectrometry , Peptides/blood , Proteome/chemistry , Proteomics , Up-RegulationABSTRACT
BACKGROUND: Repair of total anomalous pulmonary venous drainage (TAPVD) in neonates remains a challenge. It is associated with a high mortality. We aimed at determining a method for risk stratification of this group of patients. METHODS: From 1994 to 2008, 54 patients underwent simple TAPVD operations during the first month of life. Mean pulmonary arterial pressure (PAP), mean systemic arterial pressure (MAP), systolic blood pressure, diastolic blood pressure, central venous pressure, and left atrial pressure were recorded in 44 of the 54 patients for the first 36 hours postoperatively. The remaining 10 patients were excluded because data from invasive pressure monitoring were not available. RESULTS: There were overall 8 deaths (18.2%, 8/44), including 4 (9%, 4/44) early deaths, and 5 reoperations (11.4%, 5/44). The mean PAP was 23.1 ± 6.4 mm Hg, the mean MAP was 50.3 ± 5 mm Hg, and the PAP-to MAP-ratio (PAP/MAP) was 0.80 ± 0.36. By multivariable logistic analysis, the risk factors for mortality were a higher PAP/MAP (p = 0.037) and lower operative weight (p = 0.02). All deaths had either a PAP/MAP of greater than 0.80 or an operative weight of less than 2.5 kg. Hemodynamic index (PAP/MAP divided by operative weight) was predictive of mortality (p = 0.007). Furthermore, the hemodynamic index (p = 0.003) predicted prolonged length of stay in the intensive care unit by regression analysis. CONCLUSIONS: The hemodynamic index (PAP/MAP/weight) ≥0.25 in the first 36 hours after TAPVD repair in neonates is predictive of mortality. A higher index predicted longer stay in the intensive care unit. This hemodynamic index may be a useful adjunct for risk stratification in neonates undergoing TAPVD repair.
