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      Decrease in serum alkaline phosphatase and prognostic relevance in adult cardiopulmonary bypass

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          Abstract

          OBJECTIVES

          Cardiopulmonary bypass (CPB) induces inflammatory responses, which may lead to the loss of alkaline phosphatase (AP) that is consumed in the process of dephosphorylating detrimental extracellular nucleotides in this proinflammatory state. It has been reported that low postoperative AP levels correlate with increased postoperative support requirement and organ dysfunction after paediatric cardiac surgery. However, little is known about the perioperative development and clinical relevance of AP depletion in adults undergoing CPB.

          METHODS

          A total of 183 patients with a preoperative left ventricular ejection fraction ≤50% undergoing mitral valve surgery ± concomitant related procedures at the Department of Cardiac Surgery, Medical University of Vienna, between 2013 and 2016 were included in this retrospective analysis. Serum AP measurements at baseline and on postoperative days 1–15 were collected. Absolute and relative drop of AP on postoperative day 1 from baseline was correlated with perioperative and early postoperative parameters. Receiver operating characteristics were used to define suitable predictors and cut-offs for postoperative outcome variables.

          RESULTS

          Receiver operating characteristics showed a reduction of >50% of baseline AP to predict in-hospital mortality [area under the curve (AUC) 0.807], prolonged intensive care unit stay (>72 h, AUC 0.707), prolonged mechanical ventilation (>24 h, AUC 0.712) and surgery-related dialysis requirement (AUC 0.736). Patients with a perioperative reduction in circulating AP to levels below 50% of baseline had a significantly decreased survival. Patients with high perioperative AP loss had higher preoperative AP levels (P < 0.001), longer CPB duration (P < 0.001) and higher incidence of extracorporeal membrane oxygenation support (P < 0.001).

          CONCLUSIONS

          Increased perioperative AP loss is associated with adverse early outcome. Prospective trials are needed to determine whether this effect can be counteracted by perioperative AP supplementation.

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          Most cited references28

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          Ischemia and reperfusion--from mechanism to translation.

          Ischemia and reperfusion-elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies, including myocardial infarction, ischemic stroke, acute kidney injury, trauma, circulatory arrest, sickle cell disease and sleep apnea. Ischemia-reperfusion injury is also a major challenge during organ transplantation and cardiothoracic, vascular and general surgery. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion-associated tissue inflammation and organ dysfunction.
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            Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update.

            Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications. Recent data indicate that a complex sequence of events leads to the final activation of leukocytes and endothelial cells (EC), which is responsible for cell dysfunction in different organs. Activation of the contact system, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. Different pro- and anti-inflammatory mediators (cytokines, adhesion molecules) are involved and their release is mediated by intracellular transcription factors (nuclear factor-kappa B, NF-kappa B). In this review, we examine recent advances in the understanding of the pathophysiology of the CPB-induced acute phase reaction and evaluate the different pharmacological, technical and surgical strategies used to reduce its effects. Emphasis is given to the central role of transcription factor NF-kappa B in the complex mechanism of the inflammatory reaction and to the effects of compounds such as heparin and glycosaminoglycans, phosphodiesterase inhibitors and protease inhibitors whose role as anti-inflammatory agent has only recently been recognized.
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              Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury

              Sepsis-associated acute kidney injury (AKI) adversely affects long-term kidney outcomes and survival. Administration of the detoxifying enzyme alkaline phosphatase may improve kidney function and survival.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Interactive CardioVascular and Thoracic Surgery
                Oxford University Press (OUP)
                1569-9285
                September 2020
                September 01 2020
                August 04 2020
                September 2020
                September 01 2020
                August 04 2020
                : 31
                : 3
                : 383-390
                Affiliations
                [1 ]Division of Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria
                [2 ]Division of Cardiac Thoracic Vascular Anaesthesia and Intensive Care Medicine, Medical University of Vienna, Vienna, Austria
                [3 ]Alloksys Life Sciences BV, Wageningen, Netherlands
                [4 ]University of Utrecht, Utrecht, Netherlands
                Article
                10.1093/icvts/ivaa103
                0ca4b719-199a-4dde-b80b-b567d887c038
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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