Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration

Defraigne, Jean-Olivier; Pincemaïl, Joël; Larbuisson, Robert; Blaffart, Francine; Limet, Raymond

doi:10.1016/s0003-4975(00)01093-6

Cited by 70 publications

(43 citation statements)

References 26 publications

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“…Statistically signifi cant differences were found neither clinically nor biochemically, and they concluded that none of these agents was successfull. Same results have been demonstrated by Defraigne et al (10).…”

Section: Discussionsupporting

confidence: 88%

Does preoperative administration of allopurinol protect the lungs from ischemia–reperfusion injury occuring during cardiopulmonary bypass?

Görmüş¹,

Çelik²,

Ergene³

et al. 2013

BLL

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Abstract:Background: It is investigated whether preoperative allopurinol administration protects lung injury induced by cardiopulmonary bypass (CPB). Methods: Sixty patients with coronary artery disease who need elective coronary artery bypass grafting operations by using CPB were taken into this study. They were divided into two groups; control and allopurinol. Allopurinol (300 mg/day) was administered to the latter group during the preoperative period of 5 days. Standard CPB procedures were used in all cases. Blood was sampled for TNF-alpha, IL-6, IL-8, IL-10 before anesthesia (T0), after anesthesia and before skin incision (T1), before CPB (T2), after aortic declamping (T3), at the end of CPB (T4), 6 hours after operation (T5), 12 hours after operation (T6), and 24 hours after operation (T7). Pulmonary function test (PFT) was performed before and following the 6th day of operation. Results: TNF-alpha, IL-6, IL-8 increased in both groups at T3, T4, T5 and T6 compared to control (p<0.05). TNF-alpha, IL-6, and IL-8 levels were lower in group A at T3, T4, T5 and T6 (p<0.05). Creatinin phosphokinase (CK) levels were lower in group A at T6 (p<0.05). CK-MB levels were lower in group A than in group C (p<0.05). Pulmonary function test (PFT) did not yield any differences between the groups. Conclusions: Preoperative allopurinol administration decreases the infl ammation and myocardial injury according to biochemical markers of ischemia reperfusion injury. However, this biochemical success does not rebound to PFT (Tab. 5, Ref. 15). Full Text in PDF www.elis.sk.

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Section: Discussionsupporting

confidence: 88%

Does preoperative administration of allopurinol protect the lungs from ischemia–reperfusion injury occuring during cardiopulmonary bypass?

Görmüş¹,

Çelik²,

Ergene³

et al. 2013

BLL

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“…Other data 8 supports a reduction of TNF␣ by aprotinin although this effect has not been borne out consistently, particularly in human studies. 24 Our study shows cardioprotection by aprotinin occurs not only through an antinecrotic but also through an antiapoptotic mechanism. In the present study, we illustrate a potential genetic mechanism by which aprotinin may influence apoptosis.…”

Section: Discussionmentioning

confidence: 61%

Effects of Aprotinin on Gene Expression and Protein Synthesis After Ischemia and Reperfusion in Rats

Buerke

Pruefer²,

Sankat³

et al. 2007

Circulation

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Background-Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown. Methods and Results-We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20 000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (PϽ0.01), myocardial injury (determined by CK depletion, PϽ0.01) and myocyte apoptosis (PϽ0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E-selectin, intercellular adhesion molecule, tumor necrosis factor-␣, tumor necrosis factor-␣ receptor, interleukin-6, monocyte chemoattractant protein-1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor-␣, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin. Conclusions-We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion.

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“…Horton et al [18] suggested that a heparin-coated CPB circuit did not attenuate the inflammatory response component attributable to the concentration of IL-6 and IL-8. Also Defraigne et al [19] have shown that cytokine release [tumor necrosis factor-α (TNF-α), IL-6, and IL-8] and neutrophil activation were not prevented by heparincoated circuits.…”

Section: Discussionmentioning

confidence: 99%

Soluble interleukin-2 receptor and interleukin-8 plasma levels during and after cardiopulmonary bypass: correlations with creatine kinase and creatine kinase MB

Alataş

Çolak

Büyükkidan

et al. 2001

Clinical and Experimental Medicine

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In this study, soluble receptor of interleukin-2, interleukin-8, creatine kinase, and creatine kinase MB isoenzyme levels were determined serially before, during, and after cardiopulmonary bypass in blood samples of 24 patients. Interleukin-2 receptor levels were 683+/-80 U/ml in the preoperative period and 640+/-60 U/ml during hypothermia. Subsequently, these levels increased significantly at the end of the procedure (791+/-70 U/ml, P<0.01), remaining elevated 1 h after (882+/-92 U/ml, P<0.001) and reaching peak values 24 h postoperatively (1,752+/-200 U/ml, P<0.001). Preoperative plasma values of interleukin-8 were 230+/-43 pg/ml. Interleukin-8 concentrations were 185+/-25 pg/ml during hypothermia. The peak interleukin-8 levels were observed at the end of cardiopulmonary bypass (754+/-94 pg/ml, P<0.001) and tended to decrease 1 h after the procedure (643+/-76 pg/ml, P<0.001), declining to preoperative values, 24 h postoperatively (273+/-41 pg/ml). Interleukin-2 receptor levels correlated well with creatine kinase levels during the procedure. Furthermore, creatine kinase MB levels were correlated with interleukin-2 receptor values only at the end and 1 h after completion of cardiopulmonary bypass. We concluded that interleukin-8 and Interleukin-2 receptor levels are elevated after cardiopulmonary bypass and may contribute to myocardial injury as reflected by increased levels of creatine kinase and creatine kinase MB and correlations between interleukin-2 receptor and both creatine kinase and creatine kinase MB levels.

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Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration

Cited by 70 publications

References 26 publications

Does preoperative administration of allopurinol protect the lungs from ischemia–reperfusion injury occuring during cardiopulmonary bypass?

Does preoperative administration of allopurinol protect the lungs from ischemia–reperfusion injury occuring during cardiopulmonary bypass?

Effects of Aprotinin on Gene Expression and Protein Synthesis After Ischemia and Reperfusion in Rats

Soluble interleukin-2 receptor and interleukin-8 plasma levels during and after cardiopulmonary bypass: correlations with creatine kinase and creatine kinase MB

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