Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

Background The arterial in line application of the leukocyte inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting leukocyte activity during cardiac surgery. We now studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion)without (group I; n=6) or with LIM (group II; n=6). The cardiac indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 +/- 0.31; pre: 4.05 +/- 0.45 l/min/m2; p<0.01). In group II, the CI was only slightly reduced (post: 3.86 +/- 0.49; pre 4.21 +/- 1.32 l/min/m2; p=0.23). Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p<0.05) which was in conjunction with higher pre-load independent endsystolic pressure volume relationship (ESPVR) values (group I: 1.57 +/- 0.18; group II: 1.93 +/- 0.16; p<0.001). Moreover, the systemic vascular resistance and pulmonary vascular resistance were lower in the LIM group. LIM appeared to accelerate the sequestration of hyperactivated neutrophils in the spleen and to reduce neutrophil infiltration of heart and lung. Conclusions Our data provide strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen

Extracorporeal immune therapy with immobilized agonistic anti-Fas antibodies leads to transient reduction of circulating neutrophil numbers and limits tissue damage after hemorrhagic shock/resuscitation in a porcine model

Background: Hemorrhagic shock/resuscitation is associated with aberrant neutrophil activation and organ failure. This experimental porcine study was done to evaluate the effects of Fas-directed extracorporeal immune therapy with a leukocyte inhibition module (LIM) on hemodynamics, neutrophil tissue infiltration, and tissue damage after hemorrhagic shock/resuscitation. Methods: In a prospective controlled double-armed animal trial 24 Munich Mini Pigs (30.3 +/- 3.3 kg) were rapidly haemorrhaged to reach a mean arterial pressure (MAP) of 35 +/- 5 mmHg, maintained hypotensive for 45 minutes, and then were resuscitated with Ringer's solution to baseline MAP. With beginning of resuscitation 12 pigs underwent extracorporeal immune therapy for 3 hours (LIM group) and 12 pigs were resuscitated according to standard medical care (SMC). Haemodynamics, haematologic, metabolic, and organ specific damage parameters were monitored. Neutrophil infiltration was analyzed histologically after 48 and 72 hours. Lipid peroxidation, and apoptosis were specifically determined in lung, bowel, and liver. Results: In the LIM group, neutrophil counts were reduced versus SMC during extracorporeal immune therapy. After 72 hours, the haemodynamic parameters MAP and cardiac output (CO) were significantly better in the LIM group. Histological analyses showed reduction of shock-related neutrophil tissue infiltration in the LIM group, especially in the lungs. Lower amounts of apoptotic cells and lipid peroxidation were found in organs after LIM treatment. Conclusions: Transient Fas-directed extracorporeal immune therapy may protect from posthemorrhagic neutrophil tissue infiltration and tissue damage

Os leucócitos e a resposta inflamatória na lesão de isquemia-reperfusão

Os eventos de isquemia-reperfusão desencadeiam uma resposta inflamatória sistêmica que pode levar a lesões celulares e até falência de órgãos. Tais repercussões são notadas no pós-operatório de cirurgias, em especial, com o uso de circulação extracorpórea. Sabe-se, atualmente, que os leucócitos exercem importante papel neste processo. Assim, este estudo aborda o papel dos leucócitos na fisiopatologia das lesões de isquemia-reperfusão e a ativação das cascatas inflamatórias por esse processo e procura auxiliar na compreensão destes mecanismos assim como trazer contribuições acerca das abordagens terapêuticas que possam atenuá-los. Esta revisão bibliográfica retrospectiva foi realizada a partir de documentos científicos publicados nos últimos dez anos, em português e inglês, indexados em bases de dados internacionais Medline e SciELO e de textos clássicos relacionados. Os descritores pesquisados foram: isquemia-reperfusão, leucócitos, resposta inflamatória, circulação extracorpórea, efeitos adversos e apoptose.The events of ischemia-reperfusion injury triggers a systemic inflammatory response and can lead to cellular injury and organ failure. Such effects are noted in the postoperative recovery, especially with the use of cardiopulmonary bypass. Nowadays, it is known that leukocytes play an important role in this process. Therefore, this study addresses the role of leukocytes in the physiopathology of ischemia-reperfusion injuries and activation of inflammatory cascades through this process and seek to help in the understanding of these mechanisms as well as to bring contributions on the therapeutic approaches that can mitigate them. This retrospective review was performed from indexed scientific papers published over the last ten years in Portuguese and English in international databases MEDLINE and SciELO and related classic texts. The descriptors investigated were: ischemia-reperfusion, leukocytes, inflammatory response, cardiopulmonary bypass, adverse effects and apoptosis

Efeitos do alfa-tocoferol nas lesões de isquemia-reperfusão induzidas em pata direita de ratos

Recentes estudos demonstraram que os radicais livres de oxigênio parecem desempenhar papel importante nas lesões de isquemia-reperfusão. O alfa-tocoferol(AT) age in vivo como um anti-oxidante. Nosso objetivo foi o de verificar se o AT atenuava as lesões de isquemia-reperfusão em pata direita de ratos. Os animais, randomizados, foram divididos nos seguintes grupos(G): G1-controle sem isquemia; G2 e G3 - quatro horas isquemia e duas reperfusão. Os animais do G2 foram tratados com salina e os do G3 com AT, 50mg/kg. Como parâmetros examinamos as alterações de volume e circunferência do pé direito ao longo do experimento, assim como a captação de 99mTc-pirofosfato e a microscopia eletrônica de transmissão do músculo soleus direito. Os aumentos de volume e circunferência do pé dos animais do G2 foram estatisticamente maiores quando comparados com o G1. As medidas do G3 não diferiram do G1. A captação de 99mTc-pirofosfato foi bem aumentada nos G2 e G3, quando comparados ao G1, porém sem diferenças entre os grupos isquêmicos. As lesões ao MET foram menos intensas em três animais do G3, quando comparados ao G2. Conclusão: O tratamento com AT diminuiu a formação do edema mas só protegeu parcialmente as células musculares contra as lesões de isquemia-reperfusão

Clinical and nutritional status in the late postoperative of pancreaticoduodenectomy: influence of pylorus preservation procedure Estado clínico e nutricional no pós-operatório tardio de pancreaticoduodenectomia: influência da preservação do piloro

PURPOSE: To evaluate the nutritional status of patients in the late postoperative period of pancreaticoduodenectomy (PD) and compare the long-term outcome according to pylorus-preserving (PPPD) or the standard technique (SPD) in which the pylorus is resected. METHODS: This prospective study was conducted twelve months prior or more in patients who had underwent PD (PD Group, n=15) and health volunteers (Control Group, n=15). At a post hoc analysis, the PD Group was divided in PPPD Subgroup (n=9) and SPD Subgroup (n=6), according to the PD techniques. Gastrointestinal complaints and nutritional status were evaluated, apart from a biochemical assessment; Student t-test or Mann-Whitney test were used. RESULTS: The patients recovered their body weight and the gastrointestinal complaints were uncommon. The PD Group showed higher energy and protein intake even though BMI was lower than in Control Group. There were no differences in laboratorial data, except for higher glycemia, serum alkaline phosfatase and C-reactive protein in PD Group. There was no difference in the various parameters evaluated when the Subgroups (PPPD and SPD) were compared. CONCLUSION: For long-term pancreaticoduodenectomy, the gastrointestinal symptoms are minimal and the patients had the clinical and nutritional status preserved, regardless of pylorus preservation.<br>OBJETIVO: Avaliar o estado nutricional de pacientes em pós-operatório tardio de pancreaticoduodenectomia (PD) e comparar a evolução de acordo com a preservação de piloro (PPPD) ou pela técnica padrão com ressecção do piloro (SPD). MÉTODOS: O estudo prospectivo foi conduzido com pacientes submetidos à PD após período mínimo de 12 meses (Grupo PD, n=15) e voluntários saudáveis (Grupo Controle, n=15). Numa análise posterior, o Grupo PD foi dividido em Subgrupo PPPD (n=9) e Subgrupo SPD (n=6), de acordo com a técnica de PD. Foram avaliadas as queixas digestivas, o estado nutricional e dados bioquímicos; a análise estatística foi realizada por meio do teste t-Student ou Mann-Whitney. RESULTADOS: Os pacientes recuperaram o estado nutricional e as queixas gastrointestinais foram incomuns. A ingestão protéica e energética foi maior no Grupo PD, apesar do menor IMC. Não houve diferenças em relação aos exames laboratoriais, exceto pelos maiores níveis de glicemia, fosfatase alcalina sérica e proteína C-reativa no Grupo PD. Quando os Subgrupos PPPD e SPD foram comparados, não houve diferenças nos diversos parâmetros analisados. CONCLUSÃO: No pós-operatório tardio de pancreaticoduodenectomia, os sintomas gastrointestinais são mínimos e o estado clínico e nutricional é adequado, independente da preservação do piloro