ABSTRACT
Objective To evaluate the effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Eighty New York Heart Association (NYHA) class Ⅱ or Ⅲ patients of both sexes,aged 21-59 years,scheduled for cardiac valve replacement with CPB,were randomly divided into four groups (n =20 each):normal saline control group (group C),ulinastatin preconditioning group (group U1),ulinastatin postconditioning group (group U2) and ulinastatin preconditioning plus postconditioning group (group U3).In group U1,uinastatin 20000 U/kg was infused via the central vein at 500-1000 U·kg-1 · min-1 after endotracheal intubation until 10 minutes before blocking the ascending aorta.In group U2,ulinastatin 10000 U/kg was infused via the aortic root at 4000-5000 U· kg-1 · min-1 at 5-7 minutes before opening the aorta.In group U3,ulinastatin preconditioning and postconditioning were performed as described in groups U1 and U2.In group C,the same volume of normal saline was infused instead of ulinastatin.Blood samples were taken from the radial artery at 10 minutes before blocking the ascending aorta,40 minutes after blocking the ascending aorta,45 minutes after opening the aorta and at the end of operation for determination of plasma concentrations of tumor necrosis factor-alpha (TNF-α) and soluble tumor necrosis factor receptor 1 (sTNF-R1).Myocardial tissues were obtained from the right atrial appendage at 45 minutes after opening the aorta for determination of the expression of TNF-α,bcl-2,bax,caspase-3,and apoptosis.The bcl-2/bax ratio and apoptotic index were calculated.Results Plasma concentrations of TNF-α and sTNF-R1 and the expression of TNF-α,bax,caspase-3 and apoptotic index were lower and the expression of bcl-2 and bcl-2/bax ratio were higher in groups U1,U2 and U3 than in group C and they were lower in group U3 than in groups U1 and U2 (P ＜ 0.05).Conclusion Ulinastatin postconditioning can inhibit myocardial apoptosis in patients undergoing cardiac valve replacement with CPB,and the efficacy of combination of ulinastatin preconditioning and postconditioning is stronger than that of ulinastatin postconditioning.The mechanism is involved in balancing the expression of bax and bcl-2 and down-regulating the expression of TNF-α and its receptor.
ABSTRACT
Objective To evaluate the role of Fas/FasL signaling pathway in ulinastatin postconditioning-induced attenuation of apoptosis in the myocardial cells of patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty patients of both sexes,aged 21-59 yr,of ASA physical status Ⅱ or Ⅲ (NYHA class Ⅱ or Ⅲ),scheduled for elective cardiac valve replacement with CPB,were randomly divided into 2 groups (n =20 each):control group (group C),and ulinastatin postconditioning group (group U).In group U,ulinastatin 10 000 U/kg was perfused via the aortic root at 4 000-5 000 U·kg-1 ·min-1 starting from 5 min before aortic unclamping.In group C,the equal volume of normal saline was infused instead of ulinastatin.Myocardial specimens were taken from the right auricle at 45 min after aortic unclamping for determination of Fas,Fas ligand (FasL),caspase-8,Bcl-2 and Bax expression and cell apoptosis.The ratio of Bcl-2 expression to/Bax expression (Bcl-2/Bax) and apoptotic index were calculated.Results Fas,FasL,caspase-8 and Bax expression and apoptotic index were significantly lower,and Bcl-2 expression and Bcl-2/Bax were higher in group U than in group C.Conclusion Ulinastatin postconditioning attenuates apoptosis in the myocardial cells through inhibiting Fas/FasL signaling pathway in the patients undergoing cardiac valve replacement with CPB.
ABSTRACT
Objective To evaluate the effects of ulinastatin on renal ischemia-reperfusion injury in patients undergoing operation on aorta with deep hypothermic circulatory arrest (DHCA ) .Methods Thirty patients ,aged 30-50 yr ,of ASA physical status Ⅲ or Ⅳ (NYHA Ⅱ or Ⅲ) ,scheduled for elective operation on aorta with DHCA ,were randomly divided into 2 groups ( n=15 each) using a random number table :control group (group C ) and ulinastatin group (group U ) .In group U ,ulinastatin 20 000 U/kg was infused via the central vein at 500-1 000 U·kg-1 ·min-1 from the time immediately after tracheal intubation until 10 min before ascending aortic cross-clamping .In group C ,the equal volume of normal saline was infused instead of ulinastatin .At 5 min before the beginning of DHCA (T1 ) and 15 min after the end of DHCA (T2 ) ,blood samples were taken from the extracorporeal circulation for determination of polymorphonuclear leukocyte counts , and plasma levels of intercellular adhesion molecule-1 , tumor necrosis factor-α, iterleukin-6 (IL-6 ) IL-8 , IL-10 , malondialdehyde , myeloperoxidase ,atrial natriuretic peptide ,cystatin C ,and creatinine .Results The polymorphonuclear leukocyte counts and plasma levels of intercellular adhesion molecule-1 , tumor necrosis factor-α, IL-6 , IL-8 , malondialdehyde , myeloperoxidase , cystatin C , and creatinine were significantly lower , and the plasma concentrations of IL-10 and atrial natriuretic peptide were higher in group U than in group C ( P< 0.05 ) . Conclusion Ulinastatin can attenuate renal ischemia-reperfusion injury in patients undergoing operation on aorta with DHCA and inhibition of inflammatory responses is involved in the mechanism .
ABSTRACT
Objective To investigate effects of ulinastatin preconditioning on cerebral ischemia-reperfusion injury in patients undergoing operation on aorta with deep hypothermic circulatory arrest.Methods 30 patients aged 30-50 with national institutes of health stroke scale(NIHSS) ＜ 10 undergoing operation on aorta with deep hypothermic circulatory arrest,were randomly divided into 2 groups(n =15):normal saline control group(group C),ulinastatin preconditioning group(group U).In group U,ulinastatin 20 000U/kg was infused via central vein at 500-1000 U · kg-1 · min-1 from after tracheal intubation,until 10 min before ascending aortic cross-clamping.In group C,same volume normal saline was infused instead of ulinastatin.Blood samples were taken from internal carotid vein at 5 min before the beginning of deep hypothermic circulatory arrest(T1),15 min after the beginning of deep hypothermic circulatory arres(T2)and 15 min after the end of deep hypothermic circulatory arrest(T3)for determination of plasma concentrations of S-100β,CK-BB,Glutamate(Glu) 、TNF-α、IL-1 、IL-10、MDA,SOD and TGF-β1.Cerebral funcition was evaluated and scored using NIHSS at 2 day after operation.Results Plasma concentrations of S-100β,CK-BB,Glu,TNF-o、IL-1 and MDA were lower,the levels of SOD,IL-10 and TGF-β1 were higher,and the NIHSS score was lower in group U (P ＜ 0.05).Conclusion Ulinastatin preconditioning can lighten cerebral ischemia-reperfusion injury in patients undergoing operation on aorta with deep hypothermic circulatory arrest.The mechanism is involved in inhibit the formn of reactive oxygen free radical.
ABSTRACT
Objective To investigate the role of phosphatidylinositol 3-kinase (PI3K)/protein-serine-threonine kinases (Akt) signal pathway in ulinastatin postconditioning-induced attenuation of apoptosis in myocardial cells in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty NYHA class and ASA physical status Ⅱ or Ⅲ patients of both sexes,aged 21-59 yr,scheduled for cardiac valve replacement with CPB,were randomly divided into 2 groups (n =20 each):normal saline control group (group C) and ulinastatin postconditioning group (group U).In group U,ulinastatin 10 000 U/kg was perfused via the aortic root at 4000-5000 U· kg-1 · min-1 starting from 5 min before aortic unclamping.In group C,the equal volume of normal saline was given instead of ulinastatin.Myocardial specimens were taken from the right auricle at 45 min after aortic unclamping for determination of the expression of Akt,phosphorylated Akt (p-Akt),cytochrome c,caspase-9,Bcl-2 and Bax,and cell apoptosis.Bcl-2/Bax ratio and apoptotic index were calculated.Results The expression of p-Akt and Bcl-2 and Bcl-2/Bax ratio were significantly higher,and the expression of cytochrome c,caspase-9 and Bax and apoptotic index were lower in group U than in group C (P ＜ 0.05).Conclusion Ulinastatin postconditioning attenuates apoptosis in myocardial cells in patients undergoing cardiac valve replacement with CPB through activating PI3K/Akt signal pathway.
ABSTRACT
Objective To evaluate the effects of ulinastatin preconditioning on protamine-induced pulmonary injury in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB).Methods Sixty NYHA class Ⅱ or Ⅲ and ASA physical status Ⅱ or Ⅲ patients of sexes,aged 21-59 yr,scheduled for elective cardiac valve replacement under CPB,were randomly divided into 3 groups (n =20 each):group control one protamine given via central vein (group C1) ; group control two protamine given via ascending aorta (group C2) ;group ulinastatin preconditioning (group U).Heparin was neutralized with protamine after termination of CPB.Ulinastatin 20 000 U/kg was infused via the central vein at a rate of 500-1000 U· kg-1 · min-1 starting from the time point after tracheal intubation until 10 min before cross-clamping of superior vena cava and inferior vena cava in group U.At 10 min after termination of CPB,protamine 4 mg/kg was infused over 8 min via the right internal jugular vein in groups C1 and U,or via the aortic root in group C2.Blood samples were obtained from the left atrium and right atrium at 5 min before neutralization of heparin with protamine (T1) and 15 min after neutralization of heparin with protamine (T2) for determination of polymorphonuclear leukocyte (PMN) and platelet (Plt) counts,and plasma concentrations of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α).Blood samples were obtained from the left atrium at T1 and T2 for determination of the levels of TNF-α,IL-1,IL-8,CD11b/CD18,C3a,C5a,and malondialdehyde (MDA) and superoxide dismutase (SOD) activity and for blood gas analysis.Alveolar-arterial oxygen gradiant (A-aDO2),respiratory index (RI) and oxygenation index (OI) were calculated.Pulmonary arterial pressure (PAP) was recorded.Results Plt and PMN counts in the blood obtained from the left atrium were significantly lower,and plasma TXB2 concentrations in the blood obtained from the left atrium were higher at T2 in group C1,and the plasma 6-keto-PGF1α concentrations and SOD activity in the blood obtained from the left atrium were higher at T2 in groups C2 and U than those in the blood obtained from the right atrium (P ＜0.05).Compared with group C1,Plt and PMN counts and plasma 6-keto-PGF1α concentrations were significantly increased,the levels of plasma TXB2,TXB2/6-keto-PGF1α,TNF-α,IL-1,IL-8,C3a,C5a and MDA were decreased,CD11b/CD18 expression was down-regulated,PAP,A-aDO2 and RI were decreased,and OI was increased at T2 in C2 and U groups (P ＜ 0.05).There were no significant differences in the parameters mentioned above between groups C2 and U (P ＞ 0.05).Conclusion Ulinastatin preconditioning can inhibit protamine-induced pulmonary injury in patients undergoing cardiac valve replacement under CPB,and the effect is similar to that of protamine administered via the aorta.
ABSTRACT
Objective To evaluate the effects of ulinastatin on cardiac function in heart valve replacement patients with cardio-pulmonary bypass (CPB).Methods 120 patients received valve replacements were divided into 4 groups at random.Group U 1,preconditioning group:ulinastatin parenteral solution (20 000 U/kg) was injected into the central veins for 10 min before the ascending aorta was clamped.Group U2,postconditioning group:ulinastatin ( 10 000 U/kg) was injected into the aortic root for 5 min before the aortic clamp was opened.Group U3,combined the treatments of group U1 and group U2.Group C was served as control without using ulinastatin.The ST-T of ECG at different 8 time points was recorded from preanesthesia to the end of operation.The dosage of vasoactive agents in the 4 groups was recorded after the aortic clamp was opened.Blood samples were taken from the radial artery at 4 time points during 1O min before the ascending aorta was clamed to the end of operation for determining the serum concentration of H-FABP,IMA,CK-MB,MDA and SOD.The changes in myocardium were examined by microscope.Results The automatic reheating rate of heart in group U1,group U2,and group U3 were 70％,73％ and 90％ respectively,which were all higher than group C (33％) after the aortic clamp was opened in 3 -5 min.The scores of reperfusion arrhythmia,change of ST segments in ECG ( elevation or depression),the dosage of vasoactive drugs ( dopamine and adrenaline) and their using time,the concentration of MDA,H-FABP,IMA and CK-MB in group U1 and group U2 were ＜ than those of group C ( P ＜0.05 ),but was ＞ than those of group U3 ( P ＜0.05 ).The activity of SOD in group U1 and group U2 were ＞ than those of group C ( P ＜ 0.05 ),but was ＜ than those of group U3 ( P ＜ 0.05 ).There were no significant differences between group U1 and group U2( P ＞0.05 ).The myocardium in group C had focal coagulative necrosis.The damage of myocardium in group U3 was minor,the cytoplasm and nucleus was homogeneous,and the boundaries were distinct.Conclusion Ulinastatin parenteral solution preconditioning and postconditioning could improve heart function after valves replacement on CPB.The protective effects were not significantly different regarding ulinastati was administered into the central veins before the ascending aorta was clamped vs.it was injected into the aortic root before the aortic clamp opening.Combined these 2 administration methods and dosages could produce collaborative protection.
ABSTRACT
ObjectiveTo investigate the effects of ulinastatin postconditioning and combining ulinastatin postconditioning with pretreatment on myocardial inflammatory response in patients undergoing cardiac valve replacement under CPB.MethodsEighty NYHA class Ⅱ or Ⅲ patients of both sexes aged 21-59 yr undergoing cardiac valve replacement under CPB were randomly divided into 4 groups ( n =20 each): group control (group C) ; group ulinastatin pretreatment ( group U1 ) ; group ulinastatin postconditioning (group U2 ) and group ulinastatin pretreatment and postconditioning combined (group U3 ).Ulinastatin 20 000 U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 after tracheal intubation until 10 min before cross-clamping of ascending aorta in groups U1 and U3.Ulinastatin 10 000 U/kg was infused into root of aorta at 4000-5000 U· kg- 1 · min- 1 at 5-7 min before declamping of aorta in groups U2 and U3.Blood samples were obtained from radial artery before cross clamping of ascending aorta,at 40 min after aortic cross-clamping,at 45 min after declamping of aorta (T3) and at the end of operation for polymorphonuclear leukocyte (PMN) count,routine analysis of blood and determination of plasma concentrations of IL-10,TNF-α,IL-1 and IL-6 (by ELISA).Myocardial specimens were obtained at 45 min after declamping of aorta for determination of IL-1β and IL-6 expression by immune-histochemistry.Results Ulinastatin pretreatment and/or postconditioning significantly increased plasma IL-10 concentration and decreased plasma IL-1,IL-6,TNF-α concentrations and PMN count and myocardial IL-1β and IL-6 expression in groups U1,U2 and U3 as compared with group C.Plasma IL-10 concentration was significantly higher and plasma IL-1,IL-6 and TNF-α concentrations,PMN count and myocardial IL-1β and IL-6 expression were lower in group U3 than in groups U1 and U2.ConclusionUlinastatin postconditioning can inhibit myocardial imflammatory response in patients undergoing valve replacement under CPB.The protective effect can be augmented by combining ulinastatin postconditioning with pretreatment.