The Effect of Aprotinin on Brain Ischemic-Reperfusion Injury After Hemorrhagic Shock in Rats: An Experimental Study

Eser, Olcay; Kalkan, Erdal; Çoşar, Murat; Büyükbaş, Sadık; Avunduk, Mustafa Cihat; Aslan, Adem; Kocabaş, Volkan

doi:10.1097/01.ta.0000236054.42254.b7

Cited by 11 publications

(16 citation statements)

References 30 publications

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“…It is known that aprotinin reduces apoptosis. For example Eser reported that aprotinin decreased apoptotic cell death after brain ischemia [28 Eser]. We also have confirmed that aprotinin reduces apoptotic cell death caused by serum deprivation at the concentration of 100 KIU/mL using a cell culture model (data not shown).…”

Section: Discussionsupporting

confidence: 78%

Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model

Iwata

Okamura

Ishibashi

et al. 2009

The Journal of Thoracic and Cardiovascular Surgery

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Objective The efficacy of aprotinin in reducing blood loss after CPB is well established although its neuroprotective potential is less well known. Furthermore, there is controversy regarding optimal dosing and possible renal complications. Methods 54 piglets were randomized to one of three CPB groups designed to carry risk of post-op cerebral and renal dysfunction: circulatory arrest at 25°C, ultra-low flow (10 ml/kg/min) at either 25°C or 34°C. Animals were randomized to: control (no aprotinin), low dose (30,000 KIU/kg into prime only), standard full dose (30,000 KIU/kg bolus IV into prime plus 10,000 KIU/kg infusion), and double full dose. Tissue oxygenation index (TOI) was monitored by near-infrared spectroscopy (NIRS). Neurologic functional and histological scores, creatinine and blood urea nitrogen (BUN) were outcomes of interest. Results Aprotinin significantly improved neurological scores on postoperative day 1 after ultra-low flow bypass at 25°C or 34°C (P<.01), but not after HCA (P=.57). Linear regression indicated a strong dose-response relationship with higher aprotinin doses having the best neurological scores. During LF, a higher TOI was correlated with a higher aprotinin dose (P<.05). Aprotinin dose had no significant effect on creatinine or BUN on day 1. Low body weight was the only predictor of high BUN (r = −0.39, P<.01). Conclusion Aprotinin significantly improves neurologic recovery without compromising renal function in the young piglet.

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Section: Discussionsupporting

confidence: 78%

Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model

Iwata

Okamura

Ishibashi

et al. 2009

The Journal of Thoracic and Cardiovascular Surgery

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“…Cell death is considered one of the mechanisms by which hemorrhagic shock may lead to organ dysfunction or failure [1,29]. When cell death was inhibited, both organ function and survival rates were significantly improved after prolonged hemorrhage and resuscitation [30].…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiology is a situation where all tissues cannot receive enough blood and oxygen for their normal metabolic activities, and following reperfusion often exacerbates the injury [1]. Despite improvements in intensive care medicine, the mortality of massive surgical blood loss and its complications remain very high [2].…”

Section: Introductionmentioning

confidence: 99%

Emulsified Isoflurane Preconditioning Protects Against Liver and Lung Injury in Rat Model of Hemorrhagic Shock

Zhang

Luo

Liu

et al. 2011

Journal of Surgical Research

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“…A desirable outcome would be to combine thrombolytic properties without hemorrhage or compromise of BBB permeability; however, this outcome remains elusive. However, plasmin inhibitors are neuroprotective, and the plasmin/PAR1 axis identified here may be explored further as a therapeutic target [17, 49–51]. …”

Section: Discussionmentioning

confidence: 99%

Plasmin Activation of Glial Cells through Protease-Activated Receptor 1

Greenidge

Hall

Hambleton

et al. 2013

Pathology Research International

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The objective of this study was to determine whether plasmin could induce morphological changes in human glial cells via PAR1. Human glioblastoma A172 cells were cultured in the presence of plasmin or the PAR1 specific activating hexapeptide, SFLLRN. Cells were monitored by flow cytometry to detect proteolytic activation of PAR1 receptor. Morphological changes were recorded by photomicroscopy and apoptosis was measured by annexinV staining. Plasmin cleaved the PAR1 receptor on glial cells at 5 minutes (P = 0.02). After 30 minutes, cellular processes had begun to retract from the basal substratum and by 4 hours glial cells had become detached. Similar results were obtained by generating plasmin de novo from plasminogen. Morphological transformation was blocked by plasmin inhibitors aprotinin or epsilon-aminocaproic acid (P = 0.03). Cell viability was unimpaired during early morphological changes, but by 24 hours following plasmin treatment 22% of glial cells were apoptotic. PAR1 activating peptide SFLLRN (but not inactive isomer FSLLRN) promoted analogous glial cell detachment (P = 0.03), proving the role for PAR1 in this process. This study has identified a plasmin/PAR1 axis of glial cell activation, linked to changes in glial cell morophology. This adds to our understanding of pathophysiological disease mechanisms of plasmin and the plasminogen system in neuroinjury.

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The Effect of Aprotinin on Brain Ischemic-Reperfusion Injury After Hemorrhagic Shock in Rats: An Experimental Study

Abstract: The results suggest that the systemic use of aprotinin in ischemic neural tissue prevents reperfusion injury and also protects the morphologic, functional, and biochemical integrity of the neural tissue.

Cited by 11 publications

References 30 publications

Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model

Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model

Emulsified Isoflurane Preconditioning Protects Against Liver and Lung Injury in Rat Model of Hemorrhagic Shock

Plasmin Activation of Glial Cells through Protease-Activated Receptor 1

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