Clinical Study Of Influence Of Prostaglandin E₁ In Vascular Endothelia Cells Injury And Lung Leucocyte Sequestration During Open Heart Operation

PGE₁ has lots of biological activities including dilating vessels, inhibiting the aggregation and activation of leukocyte and platelet and stabilizing biological membrane and is extensively used in treatment of many kinds of diseases. Cardiopulmonary bypass (CPB) is applied in open heart operation but can bring about systemic inflammation response (SIR) and even cause systemic inflammation response syndrome (SIRS) that may result in damage to important organs like the heart, the lung and the kidneys. CPB causes vessel endothelial cells injury that plays an important role in damaging all of organs; therefore, protection of vessel endothelial cells alleviates organ damage caused by SIR. Pulmonary function is damaged at different extent during open heart operation, while leukocytes are critical for lung injury. During and after CPB, many factors beget lung leukocyte sequestration, arousing or aggravating lung injury. The factors include cell adhesion, capillary stricture due to vessel endothelial cells swelling and vessel hyperkinesias, which prevents leukocytes from passing by the capillaries. Because of its excellent dilating vessel bioactivities, in previous cardiovascular surgery, PGE₁ was mainly applied in treatment of congenital heart diseases. As for its use in the field of clinical research, reports about its anti-inflammation activity are rare. Twenty-eight patients with rheumatic heart diseases undergoing valve replacement are involved in this experiment for discussing protective effect of PGE₁ on vessel endothelial cells and lung leukocyte sequestration as well as possible mechanism of protective effect. Anti-inflammation role of PGE₁ was determined through investigating protective effect of vessel endothelial cells and alleviation of lung leucocyte sequestration. Methods, results and main conclusions of the study are as follows: 1. Twenty-eight patients with rheumatic heart diseases undergoing valve replacement were involved and divided randomly into two groups, ie, PGE1 treatment group and control group. PGE1 treatment group was extra-administered with PGE1 from 5min-10min before CPB to 1 h after operation at the speed of 20mg.kg-1.min-1. Samples were taken at the different set time respectively: Blood samples were from ancom veins at the time of the very morning of the operation, vena cava opening, 1 h after vena cava opening, 3 h,7 h,24 h,48 h,72 h and 7 d for examination fo level of circulation endothelial cell(CEC) and level of plasma of soluble intercellular adhesion molecule-1(sICAM-1)and thrombomodulin (TM), and the level of them in blood samples taken at the very moring of operation looked as the baselines before operation. During operation, at the time before CPB, the time of vena cava openging, 1 h after vena cava opening, blood samples from the left atrium and the right atrium were taken, and level of CEC and leucocytye was examined. During operation, before and after CPB, lung tissue samples for regular biopsy and ultra-structural examination were taken. Level of plasma sICAM-1 and TM in peripheral blood was examined by ELISA; CECs in the peripheral blood, the left atrium and the right atrium were isolated by PVP-silica density gradients and then counted under microscope,and were identified by immunohistochemistry SABC. Count of PMN in both the left atrium and the right atrium was detected in the blood cell auto-analyzing system. A comparison between indices of both groups showed statistical difference. 2. Compared with preoperation, levels of sICAM-1, TM and CEC increased during and after CPB, and ultrastructure of vessel endothelial cells showed injury at different extents. Posterior to resume of lung circulation, there appeared difference upon level of PMN in the left atrium and the right atrium (P<0.05), with lower level in the left atrium. In the atria, there were lots of CECs, some of which existed in mass. Regular biopsy showed different extent leukocyte aggregation in the lung after CPB. At 1 h after vena cava opening and 3 h after operation, there showed significant difference in level of plasma TM between two groups (P<0.01), lower in PGE 1 treatment group. From the time of vena cava opening to 48 h after operation, there was difference in level of CEC in peripheral blood (P<0.05), lower in PGE 1 treatment group. Compared with control group, from the time of vena cava opening to 48 h after operation, level of sICAM-1in PGE 1 treatment group was lower (P<0.05). The value difference of PMN (PMN value in the right atrium subtracts that in the leftatrium) between PGE 1 treatment group and control group was very significant at time of vena cava opening (P<0.01) and significant at 1 h after vena cava opening (P<0.05). If total time of CPB was similar, regular biopsy lung slides showed a little lighter leukocyte aggregation in the tissue sample of PGE1 treatment group. 3. Administration of PGE1 induces injury of vessel endothelial cells and lung leukocyte sequestration and inhibits expression of sICAM-1 that may be one of the key mechanisms of protective effect on vessel endothelia cells.