RESUMO
BACKGROUND: Arterial blood pressure-induced shear stress causes endothelial cell apoptosis and inflammation in vein grafts after coronary artery bypass grafting. As the inflammatory protein type IIA secretory phospholipase A2 (sPLA2-IIA) has been shown to progress atherosclerosis, we hypothesized a role for sPLA2-IIA herein. METHODS: The effects of PX-18, an inhibitor of both sPLA2-IIA and apoptosis, on residual endothelium and the presence of sPLA2-IIA were studied in human saphenous vein segments (n = 6) perfused at arterial blood pressure with autologous blood for 6 hrs. RESULTS: The presence of PX-18 in the perfusion blood induced a significant 20% reduction in endothelial cell loss compared to veins perfused without PX18, coinciding with significantly reduced sPLA2-IIA levels in the media of the vein graft wall. In addition, PX-18 significantly attenuated caspase-3 activation in human umbilical vein endothelial cells subjected to shear stress via mechanical stretch independent of sPLA2-IIA. CONCLUSIONS: In conclusion, PX-18 protects saphenous vein endothelial cells from arterial blood pressure-induced death, possibly also independent of sPLA2-IIA inhibition.
Assuntos
Ácidos Alcanossulfônicos/farmacologia , Pressão Arterial , Células Endoteliais/efeitos dos fármacos , Fosfolipases A2 do Grupo II/antagonistas & inibidores , Mecanotransdução Celular/efeitos dos fármacos , Ácidos Oleicos/farmacologia , Inibidores de Fosfolipase A2/farmacologia , Veia Safena/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/enzimologia , Células Endoteliais/patologia , Fosfolipases A2 do Grupo II/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/enzimologia , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Veia Safena/enzimologia , Veia Safena/patologia , Fatores de TempoRESUMO
BACKGROUND: Complement is an important mediator in arterial blood pressure-induced vein graft failure. Previously, we noted activation of cell protective mechanisms in human saphenous veins too. Here we have analyzed whether C4b-binding protein (C4bp), an endogenous complement inhibitor, is present in the vein wall. METHODS: Human saphenous vein segments obtained from patients undergoing coronary artery bypass grafting (n = 55) were perfused in vitro at arterial blood pressure with either autologous blood for 1, 2, 4, or 6 hr or with autologous blood supplemented with reactive oxygen species scavenger N-acetylcysteine. The segments were subsequently analyzed quantitatively for presence of C4bp and complement activation product C3d using immunohistochemistry. RESULTS: Perfusion induced deposition of C3d and C4bp within the media of the vessel wall, which increased reproducibly and significantly over a period of 4 hr up to 3.8% for C3d and 81% for C4bp of the total vessel area. Remarkably after 6 hr of perfusion, the C3d-positive area decreased significantly to 1.3% and the C4bp-positive area to 19% of the total area of the vein. The areas positive for both C4bp and C3d were increased in the presence of N-acetylcysteine. CONCLUSIONS: Exposure to arterial blood pressure leads to a transient presence of C4bp in the vein wall. This may be part of a cell-protective mechanism to counteract arterial blood pressure-induced cellular stress and inflammation in grafted veins.
Assuntos
Pressão Arterial , Proteína de Ligação ao Complemento C4b/metabolismo , Ponte de Artéria Coronária , Veia Safena/metabolismo , Veia Safena/transplante , Antioxidantes/farmacologia , Complemento C3d/metabolismo , Humanos , Técnicas In Vitro , Veia Safena/efeitos dos fármacos , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: This retrospective analysis describes blood conservation strategies and overall consumption of red blood cells (RBCs), fresh-frozen plasma (FFP), and platelet (PLT) concentrates during nonaortic cardiac surgery with cardiopulmonary bypass (CPB) in a tertiary hospital over a 10-year period. STUDY DESIGN AND METHODS: Study variables of 6026 patients that underwent cardiac surgery between 2002 and 2011 were incorporated in the database and included hemoglobin (Hb), lowest temperature, CPB duration, 24-hour blood loss, fluid balance, and overall transfusion requirements. RESULTS: Between 2002 and 2011, the lowest intraoperative Hb levels and temperature increased from 8.5 ± 1.2 to 10.4 ± 1.4 g/dL and from 32 ± 2 to 34 ± 1°C, respectively. In addition to the steep decrease in the postoperative fluid balance over time, a reduction in 24-hour blood loss from 815 ± 588 mL (2002) to 590 ± 438 mL (2011) was observed. These changes were paralleled by a 28% reduction in overall RBC transfusion from 1443 units in 2002 to 1038 in 2011. While RBC transfusion decreased over time, there was no significant change in the use of FFP or PLT concentrate transfusion. The probability to receive RBC transfusion increased after cessation of aprotinin, but reduced after routine cell salvage in all operations. CONCLUSION: This institutional report shows a large reduction in blood loss and transfusion requirements in cardiac surgery over a 10-year period. This reduction is most probably attributed to structural cell salvage, reduced intraoperative fluid volumes, and the increase in the lowest intraoperative body temperature.
Assuntos
Ponte Cardiopulmonar/estatística & dados numéricos , Ponte de Artéria Coronária/estatística & dados numéricos , Transfusão de Eritrócitos/estatística & dados numéricos , Plasma , Transfusão de Plaquetas/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Algoritmos , Perda Sanguínea Cirúrgica/prevenção & controle , Volume Sanguíneo , Temperatura Corporal , Bases de Dados Factuais/estatística & dados numéricos , Hemoglobinas , Humanos , Período Intraoperatório , Recuperação de Sangue Operatório , Valor Preditivo dos Testes , Prática Profissional , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
OBJECTIVES: Arterial pressure induced vein graft injury can result in endothelial loss, accelerated atherosclerosis and vein graft failure. Inflammation, including complement activation, is assumed to play a pivotal role herein. Here, we analyzed the effects of C1-esterase inhibitor (C1inh) on early vein graft remodeling. METHODS: Human saphenous vein graft segments (n=8) were perfused in vitro with autologous blood either supplemented or not with purified human C1inh at arterial pressure for 6h. The vein segments and perfusion blood were analyzed for cell damage and complement activation. In addition, the effect of purified C1inh on vein graft remodeling was analyzed in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. RESULTS: Application of C1inh in the in vitro perfusion model resulted in significantly higher blood levels and significantly more depositions of C1inh in the vein wall. This coincided with a significant reduction in endothelial loss and deposition of C3d and C4d in the vein wall, especially in the circular layer, compared to vein segments perfused without supplemented C1inh. Administration of purified C1inh significantly inhibited vein graft intimal thickening in vivo in atherosclerotic C57Bl6/ApoE3 Leiden mice, wherein donor caval veins were interpositioned in the common carotid artery. CONCLUSION: C1inh significantly protects against early vein graft remodeling, including loss of endothelium and intimal thickening. These data suggest that it may be worth considering its use in patients undergoing coronary artery bypass grafting.
Assuntos
Aterosclerose/complicações , Pressão Sanguínea , Proteínas Inativadoras do Complemento 1/farmacologia , Ponte de Artéria Coronária/efeitos adversos , Veia Safena/efeitos dos fármacos , Enxerto Vascular/efeitos adversos , Veias Cavas/efeitos dos fármacos , Animais , Apolipoproteína E3 , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Proteína Inibidora do Complemento C1 , Complemento C3d/metabolismo , Complemento C4b/metabolismo , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Infiltração de Neutrófilos , Fragmentos de Peptídeos/metabolismo , Perfusão , Veia Safena/imunologia , Veia Safena/patologia , Veia Safena/transplante , Fatores de Tempo , Veias Cavas/imunologia , Veias Cavas/patologia , Veias Cavas/transplanteRESUMO
BACKGROUND: Elderly patients and patients with a poor cardiac function have increased morbidity rates when undergoing cardiac surgery. The aim of this study was to determine whether addition of glycine to a standard preoperative oral immune-enhancing nutrition supplement (OIENS) improves outcome. Glycine-enriched OIENS was compared with 2 formulas: standard OIENS and control. METHODS: In this double-blind, 3-armed study, patients scheduled to undergo cardiac surgery with the use of extracorporeal circulation received either the glycine-enriched OIENS (OIENS + glyc, n = 24), standard OIENS (OIENS, n = 25), or control formula (Control, n = 25) for minimally 5 preoperative days. Patients were included if they were aged 70 years or older, had a compromised left ventricular function, or were planned for mitral valve surgery. Main outcome measures were postoperative infectious morbidity, organ function, and postoperative recovery. RESULTS: Infectious morbidity was significantly lower in both treatment groups compared with the control group (p = .02). An infection was diagnosed in 5 and 4 patients in the OIENS + glyc and OIENS groups, respectively, and in 12 control patients. Less supportive therapy was necessary to stabilize circulation in both treatment groups compared with the control group. Median length of hospital stay was 7.0, 6.5, and 8.0 days in the OIENS + glyc, OIENS, and control groups, respectively. Inflammatory responses, as measured by systemic levels of proinflammatory cytokines and surface markers on polymorphonuclear cells, were comparable for all groups. CONCLUSIONS: Preoperative OIENS reduces postoperative infectious morbidity and results in a more stable circulation; the addition of glycine does not result in any beneficial effect over standard OIENS.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Nutrição Enteral , Glicina/administração & dosagem , Cuidados Pré-Operatórios/métodos , Infecção da Ferida Cirúrgica/mortalidade , Idoso , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação , Masculino , Estudos Prospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: During cardiopulmonary bypass (CPB), systemic coagulation is believed to become activated by blood contact with the extracorporeal circuit and by retransfusion of pericardial blood. To which extent retransfusion activates systemic coagulation, however, is unknown. We investigated to which extent retransfusion of pericardial blood triggers systemic coagulation during CPB. METHODS: Thirteen patients undergoing elective coronary artery bypass grafting surgery were included. Pericardial blood was retransfused into nine patients and retained in four patients. Systemic samples were collected before, during and after CPB, and pericardial samples before retransfusion. Levels of prothrombin fragment F(1+2) (ELISA), microparticles (flow cytometry) and non-cell bound (soluble) tissue factor (sTF; ELISA) were determined. RESULTS: Compared to systemic blood, pericardial blood contained elevated levels of F(1+2), microparticles and sTF. During CPB, systemic levels of F(1+2) increased from 0.28 (0.25-0.37; median, interquartile range) to 1.10 (0.49-1.55) nmol/l (p=0.001). This observed increase was similar to the estimated (calculated) increase (p=0.424), and differed significantly between retransfused and non-retransfused patients (1.12 nmol/l vs 0.02 nmol/l, p=0.001). Also, the observed systemic increases of platelet- and erythrocyte-derived microparticles and sTF were in line with predicted increases (p=0.868, p=0.778 and p=0.205, respectively). Before neutralization of heparin, microparticles and other coagulant phospholipids decreased from 464 microg/ml (287-701) to 163 microg/ml (121-389) in retransfused patients (p=0.001), indicating rapid clearance after retransfusion. CONCLUSION: Retransfusion of pericardial blood does not activate systemic coagulation under heparinization. The observed increases in systemic levels of F(1+2), microparticles and sTF during CPB are explained by dilution of retransfused pericardial blood.
Assuntos
Coagulação Sanguínea/fisiologia , Transfusão de Sangue Autóloga/efeitos adversos , Ponte Cardiopulmonar/métodos , Circulação Coronária/fisiologia , Pericárdio/fisiopatologia , Idoso , Plaquetas/química , Transfusão de Sangue Autóloga/métodos , Eritrócitos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Fosfolipídeos/sangue , Estudos Prospectivos , Protrombina , Solubilidade , Tromboplastina/análiseRESUMO
The Trillium coating is designed to minimize adsorption of protein and the attachment of cells and other particles. The present study was undertaken to investigate the effect of surface coating on the adhesion of thrombotic components (activated platelets, white blood cells and fibrin) to the surface of a clinically used oxygenator. Twenty patients undergoing elective coronary artery bypass grafting (CABG) were randomized to one of the two oxygenator groups: non-coated (NC, n = 10) or Trillium-coated (TC, n = 10). Platelet and white blood cell counts and factor XIIa concentrations were determined prior to the induction of anesthesia and at the end of cardiopulmonary bypass (CPB). Binding of activated platelets, white blood cells and fibrin to the artificial surfaces was quantified by means of antibody binding and histological validation was achieved by scanning electron microscopy. Patient demographic and CPB data were similar for the two groups. No significant differences between the groups were found for any of the tested thrombotic components. However, observations from our scanning electron microscopy suggested a release of formed particles from the Trillium-coated surface. Primary adhesion of activated platelets, white blood cells and fibrin to the artificial surface of the venous blood inlet from an oxygenator is not affected by the Trillium surface coating under conditions of full systemic heparinization.
Assuntos
Plaquetas , Materiais Revestidos Biocompatíveis , Ponte de Artéria Coronária , Fator XIIa/análise , Fibrina/análise , Leucócitos , Oxigenadores , Adesividade Plaquetária , Idoso , Plaquetas/ultraestrutura , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Contagem de Leucócitos , Leucócitos/ultraestrutura , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Contagem de Plaquetas , Propriedades de SuperfícieRESUMO
Recent studies indicate a role of atherosclerosis-like changes involved in the pathogenesis of aortic valve stenosis. Interestingly, one of the major advanced glycation end products (AGEs), N(omega)-(carboxymethyl)lysine (CML) has been related to the process of atherosclerosis in blood vessels. In the present study, we have analyzed the presence of CML in degenerative altered aortic valves with atherosclerosis-like changes, and in degenerated mitral valves without atherosclerosis-like changes, derived from patients suffering from acute rheumatism during childhood. Degenerated and non-degenerated valves were derived from autopsy or obtained during cardiac surgery. The presence of CML was examined by immunohistochemistry. CML was found on the endothelium and fibroblasts in control aortic and mitral valves. Minor differences in CML staining were observed between control and degeneratively affected mitral valves. In contrast, in degenerated aortic valves, CML accumulation was found in macrophages and on calcification sites, comparable to that in atherosclerotic arteries, while the presence of CML staining on the endothelium and fibroblasts was significantly less as compared with control aortic valves. Our data support the hypothesis that the process of degeneration of aortic valves resembles that of atherosclerosis in blood vessels. They suggest that CML also plays a role in the process of atherosclerosis in aortic valves.
Assuntos
Valva Aórtica/patologia , Arteriosclerose/patologia , Produtos Finais de Glicação Avançada/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Valva Mitral/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/metabolismo , Arteriosclerose/fisiopatologia , Biomarcadores , Vasos Sanguíneos/patologia , Cadáver , Técnicas de Cultura , Endotélio Vascular/patologia , Feminino , Fibroblastos/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Valva Mitral/metabolismo , Probabilidade , Valores de ReferênciaRESUMO
Dutch cardiac surgery centers lack consistency in management with respect to the prevention of postoperative constipation. Although not based on any evidence, the administration of lactulose syrup is widely used. Because it often causes intestinal discomfort such as abdominal pain, bowel cramps, and feelings of distention, a study was performed in postoperative cardiac surgery patients who were given either standard care (routine administration of lactulose syrup twice daily) or laxative on indication. Postoperative constipation appeared equally frequent in both groups, and patients who received lactulose had more symptoms of intestinal discomfort. Based on these findings, it is safe to abolish the routine management of postoperative laxatives on a cardiac surgery ward.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Constipação Intestinal/prevenção & controle , Fármacos Gastrointestinais/uso terapêutico , Lactulose/uso terapêutico , Dor Abdominal/induzido quimicamente , Centros Médicos Acadêmicos , Protocolos Clínicos , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Defecação , Medicina Baseada em Evidências , Seguimentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Lactulose/efeitos adversos , Cãibra Muscular/induzido quimicamente , Países Baixos , Avaliação em Enfermagem/métodos , Pesquisa em Avaliação de Enfermagem , Projetos Piloto , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/enfermagem , Cuidados Pós-Operatórios/normas , Guias de Prática Clínica como Assunto , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Compliance of artificial and autologous vascular grafts is related to future patency. We investigated whether differences in compliance exist between saphenous vein grafts derived from the upper or lower leg, which might indicate upper or lower leg saphenous vein preference in coronary artery bypass surgery. Furthermore, the effect of perivenous application of fibrin glue on mechanical vein wall properties was studied to evaluate its possible use as perivenous graft support. METHODS: Vein segments (N = 10) from upper or lower leg saphenous vein grafts were collected for histopathologic examination and smooth muscle cell/extracellular matrix (SMC/ECM) ratio was calculated. This ratio is suggested to be related with vascular elastic compliance. In a second group vein graft segments (N = 6) from upper and lower leg were placed in an in vitro model generating stepwise increasing static pressure up to 150 cm H(2)O. Outer diameter was measured continuously with a video micrometer system. Distensibility was calculated from the pressure-diameter curves. A third group of vein graft segments (N = 7) was pressurized after fibrin glue application to prevent overdistension, and studied in the same setup. RESULTS: Vein segments from the lower leg demonstrated a consistent higher relative response compared with the upper leg saphenous vein graft (0.9176 +/- 0.03993 vs 0.5245 +/- 0.02512). Both reach a plateau in the high-pressure range (> 100 cm H(2)O). A significant difference in in vitro distensibility between upper and lower leg saphenous vein was only found at a pressure of 50 cm H(2)O (p < 0.05). With fibrin glue, support overdistension is prevented as revealed by the maximum relative response between fibrin glue supported upper and lower leg saphenous vein segments (0.4080 +/- 0.02464 vs 0.582 +/- 0.051), and no plateau is reached in the pressure range up to 150 cm H(2)O. CONCLUSIONS: No upper or lower leg saphenous vein preference could be deduced from the differences in pressure-diameter response due to loss of distensibility (and thus of compliance) in the high-pressure range. Fibrin glue effectively prevents overdistension and preserves some distensibility in the high-pressure range in both the upper and lower leg saphenous vein. This might provide a basis for clinical application of perivenous support.
Assuntos
Ponte de Artéria Coronária/métodos , Rejeição de Enxerto/prevenção & controle , Veia Safena/patologia , Veia Safena/transplante , Biópsia por Agulha , Doença das Coronárias/cirurgia , Endotélio Vascular/patologia , Feminino , Adesivo Tecidual de Fibrina/uso terapêutico , Humanos , Imuno-Histoquímica , Perna (Membro)/irrigação sanguínea , Masculino , Cuidados Pré-Operatórios/métodos , Pressão , Sensibilidade e Especificidade , Grau de Desobstrução VascularRESUMO
OBJECTIVE: The mechanisms causing the presence of platelet-derived microparticles in the circulation are unknown. In vitro platelets release platelet-derived microparticles in response to complement activation. This study evaluates the relationship between complement activation and levels of circulating platelet-derived microparticles in patients undergoing cardiac surgery. METHODS: Prospectively, 71 patients were included who underwent elective coronary artery bypass grafting with cardiopulmonary bypass. The patients were randomly allocated to one of the 3 groups: uncoated oxygenator, UnModified Surface (n = 25) or oxygenator coated with either BioPassive Surface (n = 25) or BioActive Surface (n = 21). Platelet-derived microparticles and terminal complement complexes were determined before bypass and after induction of anesthesia, 15 minutes after the start of cardiopulmonary bypass, at the end of cardiopulmonary bypass, and 30 minutes after administration of protamine sulfate. RESULTS: Demographic and cardiopulmonary bypass data were similar for the 3 groups. At the end of cardiopulmonary bypass, platelet-derived microparticle numbers were decreased in all 3 groups. No significant differences were observed among the groups at any sampling point. At the end of cardiopulmonary bypass, terminal complement complex concentrations were increased in all groups (P <.001), and significant differences among the groups were present (P =.002). CONCLUSIONS: Despite significant complement activation, no increase in numbers of circulating platelet-derived microparticles was found in the systemic blood of patients undergoing cardiac surgery with cardiopulmonary bypass. Thus complement activation in vivo does not necessarily affect generation of platelet-derived microparticles.