Continuous Pulmonary Artery Perfusion With Oxygenated Cold Blood And Ulinastatin Reduces Lung Injury After Cardiopulmonary Bypass

Background:Although the technical refinement of cardiopulmonary bypass (CPB) has progressively improved, but it inevitably leads to systemic inflammatory response syndrome (SIRS). The SIRS is the main cause of post-CPB lung injury. The post-CPB lung injury may be manifested as conditions ranging from subclinical functional changes in most patients to postoperative lung complication in 15～30%, even progressive to acute respiratory distress syndrome (ARDS) in 2% of cases. This study was to evaluate the protective effect of continuous pulmonary artery perfusion with oxygenated cold blood and ulinastatin on lung function after CPB. Objective:1) To establish the continuous pulmorary artery perfusion system, and evaluate the safty and feasibility.2) To evaluate the protective effect of continuous pulmonary artery perfusion with oxygenated cold blood on lung function after CPB.3) To evaluate the protective effect of continuous pulmonary artery perfusion with oxygenated cold blood and ulinastatin on lung function after CPB. Method:1) Thirty paitents diagnosed with mitral stenosis undergoing mitral valve replacement were divided randomly into two groups:control group (C group, n=15) and perfusion group (P group, n=15). Patients received mitral valve replacement and continuous pulmonary artery perfusion with oxygenated cold blood (28-30℃) in 15ml·kg-1·min perfusion speed and 10～20mmHg perfusion pressure in P group, while patients only received mitral valve replacement in C group. Compare the perioperative data between the two groups.2) Thirty paitents diagnosed with mitral stenosis undergoing mitral valve replacement were divided randomly into two groups:control group (C group, n=15) and perfusion group (P group, n=15). Patients received mitral valve replacement and continuous pulmonary artery perfusion with oxygenated cold blood (28～30℃) in 10ml·kg-1·min-1 perfusion speed and 10～20mmHg perfusion pressure in P group, while patients only received mitral valve replacement in C group. Compare the perioperative data between the two groups. Blood samples were drawn from the radial artery at several time points respectively. The plasma levels of tumor necrosis factor-a(TNFa), interleukin-6 (IL-6), Interleukin-8(IL-8), Interteukin-10(IL-10) were measured. Blood samples were drawn from left and right atrium at several time points respectively, and the white blood cell count were taken. lung biopsies were obtained from right middle lobe of lung for light microscopy.3) Sixty paitents diagnosed with mitral stenosis undergoing mitral valve replacement were divided randomly into three groups:control group (Ⅰgroup,n=20), ulinastatin intravenous group (Ⅱgroup, n=20) and ulinastatin perfusion group (Ⅲgroup, n=20). InⅢgroup, patients received mitral valve replacement and continuous pulmonary artery perfusion with oxygenated cold blood (28～30℃) and ulinastatin (20000U·kg-1) in 15ml·g-1·min perfusion speed and 10～20mmHg perfusion pressure. InⅡgroup, patients received mitral valve replacement and ulinastatin intravenous administration (20000U·kg-1) before CPB. Patients only received mitral valve replacement inⅠgroup. Compare the perioperative data between the three groups. Blood samples were drawn from the radial artery at several time points respectively. The plasma levels of tumor necrosis factor-a(TNFa), interleukin-6 (IL-6), Interleukin-8(IL-8), Interteukin-10(IL-10), malonaldehyde (MDA), myeloperoxidase (MPO), soluble P-selectin (sP-selectin), soluble intercellular adhesion molecule-1(sICAM-1) were measured. Blood samples were drawn from left and right atrium at several time points respectively, and the white blood cell count were taken. lung biopsies were obtained from right middle lobe of lung for light microscopy, electron microscopy and immunohistochemical examines for matrix metalloproteinases-9 (MMP-9). Results:1) The operative difficulty and operative duration have no difference between the P group and the C group.2) The ratio between right atrium and leftwhite blood cell countat (RWBC/LWBC) were increased after CPB in the both P and C group(P=0.0011). But the increased degree of RWBC/LWBC was lower in the P group (P=0.0214). The level of TNF-α,IL-6,IL-8,IL-10were increased after CPB in the both P and C group(P=0.0000, P=0.0000,P=0.0021, P=0.0000). But the increased degree of TNF-α,IL-6,IL-8 was lower and the increased degree of IL-10 was higher in the P group (P=0.0032,P=0.0132, P=0.0284, P=0.0139). The value of oxygenation index (01) and static compliance (Cst) were decreased after CPB in the both P and C group (P=0.0001, P=0.0082). But the decreased degree of 01 and Cst was lower in the P group (P=0.0083, P=0.0104). The value of alveolar-arterial oxygen partial pressure difference (PA-aO2) were increased after CPB in the both P and C group (P=0.0000). But the increased degree of PA-a02 was lower in the P group (P=0.0024).3) The ratio between right atrium and leftwhite blood cell countat (RWBC/LWBC) were increased after CPB in all theⅢ,Ⅱand group(P=0.0164). But the increased degree of RWBC/LWBC was lower in the III group compared with theⅡandⅠgroup, simultaneouly, the increased degree of RWBC/LWBC was lower in theⅡ group compared with the I group (P=0.0253). The level of TNF-α,IL-6,IL-8,IL-10were increased after CPB in all theⅢ,ⅡandⅠgroup(P=0.0000, P=0.0000, P=0.0037, P=0.0000). But the increased degree of TNF-α,IL-6,IL-8 was lower and the increased degree of IL-10 was higher in theⅢgroup compared with theⅡandⅠgroup, simultaneouly, the increased degree of TNF-α,IL-6,IL-8 was lower in theⅡgroup compared with theⅠgroup (P=0.0021, P=0.0183, P=0.0134, P=0.0004). The value of OI and Cst were decreased after CPB in all theⅢ,ⅡandⅠgroup (P=0.0002, P=0.0011). But the decreased degree of OI and Cst was lower in theⅢgroup compared with theⅡandⅠgroup, simultaneouly, the decreased degree of 01 and Cst was lower in theⅡgroup compared with theⅠgroup (P=0.0052, P=0.0115). The value of PA-aO2 were increased after CPB in all theⅢ,ⅡandⅠgroup (P=0.0000). But the increased degree of PA-aO2 was lower in theⅢgroup compared with theⅡandⅠgroup, simultaneouly, the increased degree of PA-aO2 was lower in theⅡgroup compared with theⅠgroup (P=0.0024). The leveal of MDA were increased after CPB in all theⅢ,ⅡandⅠgroup (P=0.0000). But the increased degree of MDA was lower in theⅢgroup compared with theⅡandⅠgroup, simultaneouly, the increased degree of MDA was lower in theⅡgroup compared with theⅠgroup (P=0.0001). The level of sPselectin, sICAM-1 were increased after CPB in all theⅢ,ⅡandⅠgroup(P=0.0003, P=0.0000). But the increased degree of sPselectin, sICAM-1 was lower in theⅢgroup compared with theⅡandⅠgroup (P=0.0035, P=0.0017). The level of MPO were increased after CPB in all theⅢ,ⅡandⅠgroup(P=0.0000). But the increased degree of MPO was lower in theⅢgroup compared with theⅡandⅠgroup.lung pathologic studies with a light microscope disclosed capillary hyperemia, hemorrhage and leukocytes accumulation in theⅠgroup, Electron microscopic studies revealed intra-alveolar edema, gas-blood barrier broadening, and Lung epithelium mitochondria swelling and vacuolation in theⅠgroup, whereas there were moderate changes in theⅡgroup and no significant changes inⅢgroup. Conclusion:1) the technique for establish the continuous pulmorary artery perfusion system is safty and feasibility.2) Continuous pulmonary artery perfusion with oxygenated cold blood during CPB can reduce lung injury induced by cardiopulmonary bypass.3) Continuous pulmonary artery perfusion with oxygenated cold blood and ulinastatin during CPB can reduce lung injury, the effects of which is better than ulinastatin intravenous administration.