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      Managing the inflammatory response after cardiopulmonary bypass: review of the studies in animal models Translated title: Manejo da resposta inflamatória pós-circulação extracorpórea: revisão dos estudos em modelos animais

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          Abstract

          Objective

          To review studies performed in animal models that evaluated therapeutic interventions to inflammatory response and microcirculatory changes after cardiopulmonary bypass.

          Methods

          It was used the search strategy ("Cardiopulmonary Bypass" (MeSH)) and ("Microcirculation" (MeSH) or "Inflammation" (MeSH) or "Inflammation Mediators" (MeSH)). Repeated results, human studies, non-English language articles, reviews and studies without control were excluded.

          Results

          Blood filters, system miniaturization, specific primers regional perfusion, adequate flow and temperature and pharmacological therapies with anticoagulants, vasoactive drugs and anti-inflammatories reduced changes in microcirculation and inflammatory response.

          Conclusion

          Demonstrated efficacy in animal models establishes a perspective for evaluating these interventions in clinical practice.

          Translated abstract

          Objetivo

          Revisar estudos realizados em modelos animais avaliando intervenções terapêuticas e resposta inflamatória e alterações da microcirculação após instalação de circulação extracorpórea.

          Métodos

          Utilizada a estratégia de busca ("Cardiopulmonary Bypass" (MeSH)) AND ("Microcirculation" (MeSH) OR "Inflammation" (MeSH) OR "Inflammation Mediators" (MeSH)). Resultados repetidos, estudos humanos, artigos em língua não inglesa, revisões e estudos sem controle foram excluídos.

          Resultados

          Filtros sanguíneos, miniaturização do sistema, perfusatos específicos, perfusão regional, fluxo e temperatura adequados e terapias farmacológicas com fármacos anticoagulantes, vasoativos e anti-inflamatórios reduziram alterações em microcirculação e resposta inflamatória.

          Conclusão

          A eficácia demonstrada em modelos animais estabelece uma perspectiva para avaliação dessas intervenções na prática clínica.

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          Most cited references146

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          Application of a mechanical heart and lung apparatus to cardiac surgery.

          J H GIBBON (1954)
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            Inhaled but not intravenous milrinone prevents pulmonary endothelial dysfunction after cardiopulmonary bypass.

            Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. Milrinone is a type III phosphodiesterase inhibitor. The objective of this study was to compare the effects of inhaled and intravenous milrinone on the pulmonary endothelium-dependent relaxations and hemodynamic and oxygenation parameters after cardiopulmonary bypass in a porcine model. Five groups of Landrace swine were compared: (1) control group, no cardiopulmonary bypass; (2) bypass group, 90 minutes of normothermic bypass and 60 minutes of reperfusion; (3) inhaled milrinone group, bypass preceded by a 1.8-mg bolus of inhaled milrinone followed by a continuous milrinone nebulization; (4) intravenous milrinone group, bypass preceded by 2 mg of intravenous milrinone; and (5) inhaled NaCl group, bypass preceded by inhaled saline solution. After sacrifice, pulmonary arterial endothelium-dependent relaxations to acetylcholine and bradykinin were studied in organ chambers. Inhaled milrinone caused less hypotension ( P < .05), a lesser decrease in peripheral vascular resistances ( P < .01), and a lower heart rate ( P < .05) than intravenous milrinone. Inhaled milrinone prevented the alterations in relaxations of pulmonary arteries to acetylcholine caused by cardiopulmonary bypass, and relaxations to bradykinin were improved in the inhaled milrinone group ( P < .05) compared with the cardiopulmonary bypass and control groups. Inhaled milrinone prevents the occurrence of the pulmonary endothelial dysfunction seen after cardiopulmonary bypass. The hemodynamic and oxygenation profiles obtained with inhaled milrinone are safer than with intravenous milrinone. These strategies might be useful in preventing pulmonary hypertension after cardiac surgery.
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              Effect of hydrogen sulfide on myocardial protection in the setting of cardioplegia and cardiopulmonary bypass.

              We investigated the impact of hydrogen sulfide (H(2)S) on myocardium in the setting of cold crystalloid cardioplegia and cardiopulmonary bypass (CP/CPB). Eighteen male Yorkshire pigs underwent 1 h CP/CPB followed by 2 h of reperfusion. Pigs received either: placebo (control, n=9), or H(2)S (as NaHS) as a bolus/infusion (bolus/infusion, n=6), or as an infusion (infusion, n=6). The expression pattern of various myocardial effector pathways was investigated. Coronary microvascular relaxation to endothelium-dependent and -independent agonists was assessed. No differences in cardiac function were observed among groups. Endothelium-dependent microvascular relaxation to adenosine diphosphate was improved in the H(2)S bolus/infusion group only (P<0.05). The expression of hemeoxygenase-1, phospho-heat shock proteins27 and phospho-p44/42 MAPK extracellular signal-regulated kinase were higher in H(2)S-treated groups (P<0.05). Phospho-endothelial nitric oxide synthase (P=0.08), phospho-B-cell lymphoma 2 (P=0.09), and phospho-Bad (P=0.06) all displayed a trend to be higher with H(2)S treatment. The expressions of apoptosis inducing factor and Bcl 2/adenovirus E1B 19 kDa-interacting protein were lower in H(2)S treated groups (P<0.05). The microtubule-associated protein 1 light chain 3 ratio was lower in the infusion group vs. control animals (P<0.05). There was a trend for lower phospho-mammalian target of rapamycin expression in the infusion group (P=0.07), whereas phosphorylation of p70S6K1 was higher with H(2)S-treatment (P=0.09). This study demonstrates that H(2)S-treatment may offer biochemical myocardial protection via attenuation of caspase-independent apoptosis and autophagy in the setting of CP/CPB.
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                Author and article information

                Journal
                Rev Bras Cir Cardiovasc
                Rev Bras Cir Cardiovasc
                Revista Brasileira de Cirurgia Cardiovascular : órgão oficial da Sociedade Brasileira de Cirurgia Cardiovascular
                Sociedade Brasileira de Cirurgia Cardiovascular
                0102-7638
                1678-9741
                Jan-Mar 2014
                Jan-Mar 2014
                : 29
                : 1
                : 93-102
                Affiliations
                Heart Institute at the Clinics Hospital of the Faculty of Medicine, University of São Paulo (InCor -FMUSP), São Paulo, SP, Brazil.
                Author notes
                Correspondence address: Gabriel Romero Liguori, Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar, 44 - 2º andar - bloco II - sala 13 - Cerqueira César, São Paulo, SP, Brazil - Zip code: 05403-000. E-mail: gabriel.liguori@ 123456usp.br
                Article
                10.5935/1678-9741.20140017
                4389477
                24896169
                e561b83d-02ae-4069-ac01-a56868c0e238

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 April 2013
                : 24 September 2013
                Categories
                Review Article

                extracorporeal circulation,inflammation,models, animal,microcirculation

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