Nitric oxide, when administered as a gas at low concentration, is able to blunt the release of markers of myocardial injury and to antagonize the left ventricular subclinical dysfunction during and immediately after cardiopulmonary bypass. The organ protection could be mediated, at least in part, by its anti-inflammatory properties.

Results: Cardiac surgery with CPB induced down-modulation of surface molecules expression on peripheral monocytes, especially at 24 h after CPB, for CD18, CD11a, and CD11b (P < 0.003) and for the CD15 adhesive cluster (P ‫؍‬ 0.0028) and HLA-DR (P < 0.001). At 4 h after CPB, downregulation was observed for CD14 (P ‫؍‬ 0.004), CD45 (P ‫؍‬ 0.014), and CD15 (P ‫؍‬ 0.0056). A loss of MPO was detected in venous peripheral (at 24 h after CPB, P ‫؍‬ 0.01) or coronary (at reperfusion, P < 0.02) blood. The CD15 cluster complex exhibited a down-modulation in coronary blood (at reperfusion, P ‫؍‬ 0.0003). Spontaneous intracellular production of IL-1␤, IL-6, and IL-8 decreased at 24 h after CPB (P < 0.05).Conclusions: The down-modulation of integrins and adhesive receptor expression and the loss of MPO suggest a strong activation and shedding reaction of circulating monocyte after CPB, further exacerbated by contact with coronary ischemic vessels. The changes of differentiation antigens may reflect the appearance of a partially immature population immediately after CPB. The reduced proinflammatory cytokine production, observed at 24 h after CPB, suggests a functional polarization of circulating monocytes.

No abstract

Background: Platelet response to activating agents is used to monitor the efficacy of anti-aggregation therapies. The aim of our study has been to demonstrate the existence of relationships between early events of ADP-induced platelet activation, measured by flow cytometry and platelet-rich plasma aggregation, quantified by optical aggregometry.Methods: We evaluated peripheral blood of 12 donors. The following parameters were quantified by cytometry after stimulation with adenosine diphosphate (ADP) (0.5, 1, 2, 5, 10, 20 lM): CD62P (P-selectin) and PAC-1 expression, and cytosolic Ca 21 mobilization. Aggregation was measured by optical aggregometry. We also studied 13 patients, undergoing coronary stenting, treated with aspirin (before procedure) or with aspirin plus clopidogrel (after procedure). We evaluated CD62P and PAC-1 expression, aggregation, and vasodilator-stimulated phopshoprotein phosphorylation (platelet reactivity index, PRI).Results: Flow procedures were more sensitive than aggregometry, with a lowest interindividual variability. Linear relationships existed in donors between CD62P expression and Ca 21 mobilization (P < 0.0001), and between aggregation and Ca 21 mobilization (P < 0.0001). Linear relationships existed between aggregation and CD62P expression, as percentage (P < 0.0001), or relative fluorescence intensity (RFI) (P < 0.0001). Exponential equations related aggregation and PAC-1 expression, as percentage (P < 0.0001), or RFI (P < 0.0001). Linear relationships between aggregation and CD62P expression (as percentage) existed in the patients before (P 5 0.0022) and after procedure (P 5 0.0020). Exponential relationships between aggregation and PAC-1 expression (as percentage) existed before (P 5 0.0012) and after procedure (P 5 0.0024). Linear correlations related aggregation response predicted on CD62P expression, and measured aggregation inhibition after clopidogrel (P 5 0.0013) as well as predicted aggregation and PRI inhibition (P 5 0.0031).Conclusions: Tight relationships between aggregation and cytometric quantification of platelet markers

Background: Neutrophil-granulocyte and mononuclear-cell functional changes occur during cardiopulmonary bypass and cardiovascular surgery. In particular, leukocyte-platelet interaction, leading to generation of heterotypic coaggregates, represents an amplification mechanism of the local inflammatory response and tissue damage.Methods: Samples of 20 patients were drawn from venous coronary sinus before cardioplegic arrest and immediately after reperfusion, as well as from peripheral blood at 5 and 24 h postoperatively. The granulocyte and monocyte surface expression of CD162, CD15s, CD18, and CD11b were quantified by flow cytometry at the different times. Parallel variations of circulating leukocyte-platelet conjugates (percentages) and a derived (cell number-normalized) leukocyte-platelet adhesion index were measured using a combination of antibodies against CD45, CD14, and CD41a. The evaluation of platelet functional state was carried out using antibodies against CD62P (P-selectin) and PAC-1.Results: Monocyte and granulocyte cell number increased markedly in coronary blood at reperfusion and in peripheral blood postoperatively when compared with measurements done before cardioplegia. A very different course characterized the changes of the leukocyte-platelet adhesion index with respect to the variations of circulating leukocyte-platelet coaggregates (percentages). Leukocyte molecules expression showed no significant variations for CD15s on both the leukocyte subsets, while a significant up-modulation for CD162 was observed on monocytes at 24 h after extracorporeal circulation (P 5 0.0002), and for CD11b on granulocytes at 5 h postoperatively (P 5 0.033). A loss of CD162 expression was observed in coronary blood at reperfusion (P 5 0.0038) on granulocytes, associated to a down-modulation of CD18 (P 5 0.0033) and CD11b (P 5 0.0184) in peripheral blood at 24 h postoperatively. No significant up-regulation of platelet activatory molecules expression was found at coronary reperfusion, as well as postoperatively in the peripheral blood, when compared with the before-cardioplegia derived data.Conclusions: The over time variations of a normalized leukocyte-platelet adhesion index seem to reflect the cumulative leukocyte-platelet functional interaction more accurately than the parallel measurements of cellular conjugates. The absence of platelet activation suggests that the leukocyte membrane modifications play a main role in controlling the formation and stability of heterotypic leukocyte-platelet coaggregates after cardiac surgery with extracorporeal circulation. q