RESUMO
CONTEXT: Perioperative blood transfusions are costly and have safety concerns. As a result, there have been multiple initiatives to reduce transfusion use. However, the degree to which perioperative transfusion rates vary among hospitals is unknown. OBJECTIVE: To assess hospital-level variation in use of allogeneic red blood cell (RBC), fresh-frozen plasma, and platelet transfusions in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN, SETTING, AND PATIENTS: An observational cohort of 102,470 patients undergoing primary isolated CABG surgery with cardiopulmonary bypass during calendar year 2008 at 798 sites in the United States, contributing data to the Society of Thoracic Surgeons Adult Cardiac Surgery Database. MAIN OUTCOME MEASURES: Perioperative (intraoperative and postoperative) transfusion of RBCs, fresh-frozen plasma, and platelets. RESULTS: At hospitals performing at least 100 on-pump CABG operations (82,446 cases at 408 sites), the rates of blood transfusion ranged from 7.8% to 92.8% for RBCs, 0% to 97.5% for fresh-frozen plasma, and 0.4% to 90.4% for platelets. Multivariable analysis including data from all 798 sites (102,470 cases) revealed that after adjustment for patient-level risk factors, hospital transfusion rates varied by geographic location (P = .007), academic status (P = .03), and hospital volume (P < .001). However, these 3 hospital characteristics combined only explained 11.1% of the variation in hospital risk-adjusted RBC usage. Case mix explained 20.1% of the variation between hospitals in RBC usage. CONCLUSION: Wide variability occurred in the rates of transfusion of RBCs and other blood products, independent of case mix, among patients undergoing CABG surgery with cardiopulmonary bypass in US hospitals in an adult cardiac surgical database.
Assuntos
Ponte de Artéria Coronária , Transfusão de Eritrócitos/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Plasma , Transfusão de Plaquetas/estatística & dados numéricos , Idoso , Estudos de Coortes , Grupos Diagnósticos Relacionados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Estados UnidosAssuntos
Substitutos Sanguíneos/uso terapêutico , Ponte de Artéria Coronária/tendências , Bases de Dados Factuais/tendências , Sociedades Médicas/tendências , Idoso , Ponte de Artéria Coronária/normas , Bases de Dados Factuais/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Sociedades Médicas/normas , Procedimentos Cirúrgicos Torácicos/normas , Procedimentos Cirúrgicos Torácicos/tendências , Fatores de TempoRESUMO
A number of previous studies have indirectly (electron paramagnetic resonance, nitrite/nitrate, ribonuclease protection assay for inducible nitric oxide synthase (iNOS) mRNA, l-citrulline assay) demonstrated the production of nitrogen monoxide (NO) during early cardiac allograft rejection. This study reports the first direct, quantitative measurement using an electrochemical method of NO produced from rejecting allograft tissue studied in vitro. A rat heterotopic abdominal transplant preparation was utilized. Day 7 isograft (ACI to ACI) or allograft (Lewis to ACI) transplanted hearts were atraumatically harvested and suspended at 4 degrees C in Ringers-Hepes solution. An electrochemical system highly sensitive and specific for NO consisting of a Nafion-coated platinum disk electrode (lower limit, 50 nM NO) coupled to an analysis system measured ongoing oxidation of NO. Measurements were carried out after inserting the electrode in the tissue block and warming the block to 25 degrees C. Additional measurements were also made after incubation of tissue with aminoguanidine (AG), a relatively selective iNOS inhibitor. Direct measurements (mean +/- SEM) from allograft tissue indicated a fourfold increase in NO as compared with isografts (13.41 +/- 4.40 microM NO vs. 3.43 +/- 2.04 microM NO). Incubation of allograft tissue with AG reduced NO levels to isograft levels (13.41 +/- 4.40 microM NO vs. 5.94 +/- 3.14 microM NO); AG had no effect on measured isograft NO levels. Direct, quantitative measurement of NO from tissue is feasible and reproducible, and discrimination between different levels of NO production can be made. These results confirm the imputed results from the previous studies using this experimental model. This technology promises to be a valuable tool for evaluating specific modulators of NO production studied under a variety of physiologic and pathophysiologic conditions.
Assuntos
Eletroquímica/métodos , Rejeição de Enxerto , Transplante de Coração , Óxido Nítrico/biossíntese , Animais , Inibidores Enzimáticos/farmacologia , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II , Ratos , Ratos Endogâmicos Lew , Ratos Sprague-Dawley , Transplante HomólogoRESUMO
OBJECTIVE: To review the Department of Veteran Affairs (VA) and the Society of Thoracic Surgeons (STS) national databases over the past 10 years to evaluate their relative similarities and differences, to appraise their use as quality improvement tools, and to assess their potential to facilitate improvements in quality of cardiac surgical care. SUMMARY BACKGROUND DATA: The VA developed a mandatory risk-adjusted database in 1987 to monitor outcomes of cardiac surgery at all VA medical centers. In 1989 the STS developed a voluntary risk-adjusted database to help members assess quality and outcomes in their individual programs and to facilitate improvements in quality of care. METHODS: A short data form on every veteran operated on at each VA medical center is completed and transmitted electronically for analysis of unadjusted and risk-adjusted death and complications, as well as length of stay. Masked, confidential semiannual reports are then distributed to each program's clinical team and the associated administrator. These reports are also reviewed by a national quality oversight committee. Thus, VA data are used both locally for quality improvement and at the national level with quality surveillance. The STS dataset (217 core fields and 255 extended fields) is transmitted for each patient semiannually to the Duke Clinical Research Institute (DCRI) for warehousing, analysis, and distribution. Site-specific reports are produced with regional and national aggregate comparisons for unadjusted and adjusted surgical deaths and complications, as well as length of stay for coronary artery bypass grafting (CABG), valvular procedures, and valvular/CABG procedures. Both databases use the logistic regression modeling approach. Data for key processes of care are also captured in both databases. Research projects are frequently carried out using each database. RESULTS: More than 74,000 and 1.6 million cardiac surgical patients have been entered into the VA and STS databases, respectively. Risk factors that predict surgical death for CABG are very similar in the two databases, as are the odds ratios for most of the risk factors. One major difference is that the VA is 99% male, the STS 71% male. Both databases have shown a significant reduction in the risk-adjusted surgical death rate during the past decade despite the fact that patients have presented with an increased risk factor profile. The ratio of observed to expected deaths decreased from 1.05 to 0.9 for the VA and from 1.5 to 0.9 for the STS. CONCLUSION: It appears that the routine feedback of risk-adjusted data on local performance provided by these programs heightens awareness and leads to self-examination and self-assessment, which in turn improves quality and outcomes. This general quality improvement template should be considered for application in other settings beyond cardiac surgery.
Assuntos
Procedimentos Cirúrgicos Cardíacos/mortalidade , Procedimentos Cirúrgicos Cardíacos/normas , Cardiopatias/mortalidade , Cardiopatias/cirurgia , Garantia da Qualidade dos Cuidados de Saúde , Cirurgia Torácica/normas , Bases de Dados Factuais , Feminino , Cardiopatias/diagnóstico , Hospitais de Veteranos , Humanos , Masculino , Razão de Chances , Sistema de Registros , Medição de Risco , Sensibilidade e Especificidade , Sociedades Médicas , Análise de Sobrevida , Cirurgia Torácica/tendências , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVES: Postoperative low cardiac output may persist after repair of total anomalous pulmonary venous drainage (TAPVD) because of a relatively small and non-compliant left atrium and left ventricle. We examined the effects of selective vertical vein patency on postoperative hemodynamics. METHODS: Thirty-four patients less than 3 months of age with TAPVD were operated from July 1993 to June 2000. The mean age at operation was 21+/-8 days (range, 3-62 days) and the mean weight was 3+/-0.2 kg (range, 2-4.1 kg). Supracardiac type drainage was found in 12 (35%), cardiac in three (9%), mixed in one (3%), and infracardiac in 18 (53%) patients. Twenty-two patients (65%) had obstructed venous drainage. All operations were performed with deep hypothermic circulatory arrest. Supracardiac, mixed and infracardiac types were repaired through a posterior approach, whereas, in the cardiac type, the coronary sinus was unroofed and the atrial septal defect was patched. The decision whether to keep the vertical vein open was made at the end of the operation and was based on the hemodynamic state of the patient. RESULTS: There were no operative deaths. The suture on the vertical vein was released in 22 patients who had obstructed pulmonary venous drainage (infracardiac type, n=18; supracardiac type, n=3; and mixed type, n=1), resulting in a significant drop in the left atrial pressure from 19+/-2 to 12+/-2 mmHg (P<0.05), and in the mean pulmonary artery pressure from 42+/-6 to 35+/-3 mmHg (P<0.05), associated with an immediate increase in the mean arterial blood pressure from a mean of 46+/-3 to 60+/-4 mmHg (P<0.05). During a mean follow-up of 38+/-6 months (range, 8-71 months), there were no late deaths. Follow-up, two-dimensional echocardiography with Doppler studies demonstrated good left ventricular function and trivial or no left to right shunt through the vertical vein in those patients in whom the snare was released. CONCLUSIONS: Maintaining the vertical vein patent in a selective group of patients with infracardiac total anomalous venous drainage contributes to a favorable outcome following surgery.
Assuntos
Baixo Débito Cardíaco/fisiopatologia , Cardiopatias Congênitas/cirurgia , Hemodinâmica/fisiologia , Hipertensão Pulmonar/congênito , Complicações Pós-Operatórias/fisiopatologia , Veias Pulmonares/anormalidades , Feminino , Seguimentos , Cardiopatias Congênitas/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/cirurgia , Lactente , Recém-Nascido , Masculino , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
BACKGROUND: The Society of Thoracic Surgeons (STS) established the National Database (NDB) for Cardiac Surgery in 1989. Since then it has grown to be the largest database of its kind in medicine. The NDB has been one of the pioneers in the analysis and reporting of risk-adjusted outcomes in cardiothoracic surgery. METHODS AND RESULTS: This report explains the numerous changes in the NDB and its structure that have occurred over the past 2 years. It highlights the benefits of these changes, both to the individual member participants and to the STS overall. Additionally, the vision changes to the NDB and reporting structure are identified. The individuals who have participated in this effort since 1989 are acknowledged, and the STS owes an enormous debt of gratitude to each of them. CONCLUSIONS: Because of their collective efforts, the goal to establish the STS NDB as a "gold standard" worldwide for process and outcomes analysis related to cardiothoracic surgery is becoming a reality.
Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Cirurgia Torácica , Custos e Análise de Custo , Bases de Dados Factuais/economia , Humanos , Sociedades Médicas , Software , Estados UnidosRESUMO
BACKGROUND: The surgical approach to tetralogy of Fallot (TOF) continues to evolve and now many centers favor early repair for TOF. METHODS: Our experience includes 82 consecutive patients less than 1 year old with TOF (n = 74) and TOF with pulmonary atresia (n = 8) who were operated on between January 1992 and March 1998. Mean age at repair was 5.2 +/- 1.2 months and mean weight was 4.5 +/- 0.4 kg. Seven patients (anomalous left anterior descending artery [n = 1], pulmonary atresia with hypoplastic pulmonary arteries [n = 6]), underwent palliative procedures in the neonatal period followed by complete repair. Forty-nine patients (59%) were symptomatic (severe cyanosis or hypoxic spells), and 33 patients (41%) were asymptomatic. A combined transatrial-transpulmonary approach was employed in 28 patients (34%), and transannular patch or conduit for reconstruction of the right ventricular outflow tract (RVOT) was required in 54 patients (66%). The mean Nakata index was 160 +/- 25 mm2/m2. RESULTS: There were no hospital deaths. Mean post-repair peak right ventricular/systemic pressure ratio was 0.48 +/- 0.1. There were no late deaths or reoperations during a mean follow-up of 23 +/- 5 months. All patients are currently asymptomatic and in New York Heart Association class 1. Postoperative evaluation by two-dimensional and Doppler echocardiography or cardiac catheterization showed minimal pulmonary artery stenosis with a mean pressure gradient of 15 +/- 6 mm Hg across the RVOT. CONCLUSIONS: Our experience suggests that early repair of TOF can yield excellent results and initial palliation does not preclude early complete repair.
Assuntos
Tetralogia de Fallot/cirurgia , Pressão Sanguínea/fisiologia , Ecocardiografia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Cuidados Paliativos , Atresia Pulmonar/fisiopatologia , Atresia Pulmonar/cirurgia , Estudos Retrospectivos , Tetralogia de Fallot/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: We have demonstrated that inhibition of inducible nitric oxide synthase (NOS) ameliorated acute cardiac allograft rejection. This study determined the time course and cellular localization of inducible NOS expression during the histologic progression of unmodified acute rat cardiac allograft rejection. METHODS: Tissue from syngeneic (ACI to ACI) and allogeneic (Lewis to ACI) transplants were harvested on postoperative days 3 through 10 and analyzed for inducible NOS mRNA expression (ribonuclease protection assay), inducible NOS enzyme activity (conversion of L-[3H]arginine to nitric oxide and L-[3H]citrulline), and nitric oxide production (serum nitrite/nitrate levels). Inducible NOS mRNA and protein expression were localized using in situ hybridization and immunohistochemistry. RESULTS: Inducible NOS mRNA and enzyme activity were expressed in allografts during mild, moderate, and severe acute rejection (postoperative days 4 through 10), but were not detected in normals, isografts, or allografts before histologic changes of mild acute rejection (postoperative day 3). Inducible NOS expression resulted in increased serum nitrite/nitrate levels during mild and moderate rejection (postoperative days 4 through 6). Inducible NOS mRNA and protein expression localized to infiltrating mononuclear inflammatory cells in allograft tissue sections during all stages of rejection but were not detected in allograft parenchymal cells or in normals or isografts. CONCLUSIONS: Inducible NOS expression and increased nitric oxide production occurred during the early stages of acute rejection, persisted throughout the unmodified rejection process, and localized to infiltrating inflammatory cells but not allograft parenchymal cells during all stages of acute rejection.
Assuntos
Rejeição de Enxerto/enzimologia , Transplante de Coração , Miocárdio/enzimologia , Óxido Nítrico Sintase/metabolismo , Doença Aguda , Animais , Rejeição de Enxerto/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , Nitratos/sangue , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Nitritos/sangue , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos Lew , Transplante IsogênicoRESUMO
We previously demonstrated that inhibition of inducible nitric oxide (NO) synthase (iNOS) ameliorated acute cardiac allograft rejection. This study used a rat cardiac transplant model to characterize contractile and electrophysiological dysfunction during early acute rejection, further examine the role of NO and iNOS in this process, and determine which cells expressed iNOS during early rejection. During early acute rejection, before significant myocyte necrosis, allograft papillary muscles had reduced tension development and rates of tension development and decline during beta-adrenergic, adenylate cyclase, and calcium stimulation compared with isograft and normals [e.g., tension of 36 (allograft) vs. 73 (isograft) mN/mm2 during calcium stimulation, P < 0.001]. Allografts had resting membrane potential depolarization and reduced action potential amplitude and upstroke velocity. iNOS mRNA was expressed in infiltrating inflammatory cells but not in allograft myocytes, endothelial cells, or isografts. Corticosteroids attenuated allograft contractile and electrophysiological dysfunction and inhibited iNOS enzyme activity. Direct iNOS inhibition with aminoguanidine inhibited NO production and prevented allograft contractile and electrophysiological dysfunction (e.g., tension of 64 mN/mm2 during calcium stimulation, P < 0.001). We conclude that 1) early allograft rejection caused contractile and electrophysiological dysfunction that was largely mediated by iNOS expression in infiltrating inflammatory cells, 2) corticosteroid-mediated amelioration of allograft contractile and electrophysiological dysfunction may reflect inhibition of iNOS, and 3) iNOS inhibition may offer an alternative in management of immune-mediated myocardial dysfunction.
Assuntos
Transplante de Coração/fisiologia , Contração Miocárdica , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico/fisiologia , Músculos Papilares/fisiologia , Potenciais de Ação/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Corticosteroides/farmacologia , Animais , Cálcio/farmacologia , Células Cultivadas , Eletrofisiologia/métodos , Guanidinas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Metilprednisolona/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Músculos Papilares/efeitos dos fármacos , Sondas RNA , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos ACI , Ratos Endogâmicos Lew , Transcrição Gênica , Transplante Heterotópico , Transplante Homólogo/fisiologia , Transplante Isogênico/fisiologiaRESUMO
BACKGROUND: We recently demonstrated that inhibition of inducible nitric oxide synthase (iNOS) ameliorated severe acute lung allograft rejection. This study used a rat lung transplant model to determine (1) the time course and cellular localization of iNOS expression during the histological progression of unmodified acute rejection and (2) whether inhibition of iNOS prevented impaired gas exchange function of the allograft lung and/or ameliorated the histological changes of acute rejection. METHODS AND RESULTS: iNOS mRNA and enzyme activity were expressed in allograft lungs during mild, moderate, and severe acute rejection, but not in normal, isograft, or allograft lungs before histological changes of mild acute rejection. iNOS expression in allografts resulted in elevated serum nitrite/nitrate levels, indicative of increased in vivo nitric oxide (NO) production. In situ hybridization demonstrated iNOS mRNA expression in infiltrating inflammatory cells, but not in allograft parenchymal cells. Allografts had significantly impaired gas exchange, which was prevented with the selective iNOS inhibitor aminoguanidine (PaO2 of 566+/-19, 76+/-22, and 504+/-105 mmHg for isograft, allograft, and aminoguanidine-treated allograft, respectively; P<0.0002). Aminoguanidine also significantly improved the histological rejection scores. CONCLUSIONS: (1) iNOS expression and increased NO production occurred during the early stages of acute rejection, persisted throughout the unmodified rejection process, and localized to infiltrating inflammatory cells, but not allograft parenchymal cells; (2) aminoguanidine ameliorated the histological and functional changes of acute rejection; and (3) increased NO production, detected by the presence of iNOS mRNA, protein, or noninvasively by measuring serum nitrite/nitrate levels, may serve as an early marker of acute allograft rejection.
Assuntos
Transplante de Pulmão/imunologia , Óxido Nítrico Sintase/antagonistas & inibidores , Doença Aguda , Animais , Expressão Gênica , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Hibridização In Situ , Masculino , Óxido Nítrico Sintase/genética , Sondas RNA , RNA Antissenso/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344 , Transplante Homólogo/imunologia , Transplante Homólogo/patologiaRESUMO
BACKGROUND: We recently demonstrated that inhibition of nitric oxide (NO) production ameliorated acute pulmonary allograft rejection. This study examined whether inducible NO synthase (iNOS) was expressed in the transplanted lung during acute rejection. METHODS: With a rat left lung transplant model, tissue from syngeneic (Fischer 344 to Fischer 344) and allogeneic (Brown Norway to Fischer 344) transplants were harvested on postoperative day 4 and analyzed for iNOS mRNA expression (ribonuclease protection assay), iNOS enzyme activity (conversion of L-[3H]-arginine to NO and L-[3H]-citrulline), and serum nitrite/nitrate levels. RESULTS: The iNOS mRNA was expressed in allograft lungs but was not detected in isografts or controls. The iNOS protein was present in allograft lungs, as demonstrated by high levels of L-[3H]-citrulline production compared with minimal iNOS enzyme activity in isograft and control lungs (10.1 +/- 2.4 vs 0.6 +/- 0.2 and 0.7 +/- 0.2 pmol L-[3H]-citrulline.mg-1.min-1, respectively; n = 6, p < 0.001). Allografts had significantly elevated systemic serum nitrite/nitrate levels compared with isografts and controls (38 +/- 6 vs 18 +/- 2 and 16 +/- 1 mumol/L, respectively; n = 6; p < 0.005). CONCLUSIONS: These results, together with our previous demonstration that iNOS inhibition ameliorated lung allograft rejection, suggest that (1) iNOS expression and increased NO production contributed to acute rejection of the transplanted lung, (2) iNOS inhibition may offer an alternative in management of acute lung allograft rejection, and (3) increased NO production, detected by the presence of iNOS mRNA or protein or noninvasively by measuring serum nitrite/nitrate levels, may serve as an early marker of acute allograft rejection.
Assuntos
Rejeição de Enxerto/genética , Transplante de Pulmão/imunologia , Óxido Nítrico Sintase/genética , Animais , Indução Enzimática/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Rejeição de Enxerto/enzimologia , Pulmão/imunologia , Masculino , Óxido Nítrico/fisiologia , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344 , Transplante HomólogoRESUMO
Rapid advances in pacing technology will continue to affect the quality of life of many patients with cardiovascular disease. A truly "smart" device that seemed fanciful 30 years ago now seems to be a virtual certainty by early in the next century. The surgical contributions and expertise of individuals trained in cardiothoracic surgery in these bradypacing developments is highly desirable to minimize morbidity to the greatest possible degree, to optimize the outcome of the procedure for the individual patient, and to conserve health care costs as much as possible. To maintain this cardiothoracic presence in cardiac pacing, acquisition of knowledge and expertise in the basic electrophysiology and technology of cardiac pacing, to go along with surgical expertise, is necessary on the part of individuals with the interest and opportunity to do so.
Assuntos
Estimulação Cardíaca Artificial , Marca-Passo Artificial , Arritmias Cardíacas/terapia , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/métodos , Estimulação Cardíaca Artificial/normas , Eletrodos , Eletrofisiologia , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Tumor necrosis factor (TNF-alpha) and nitric oxide (NO) are important vasoactive mediators of septic shock. This study used a well-characterized quantitative permeation method to examine the effect of TNF-alpha and NO on systemic vascular barrier function in vivo, without confounding endotoxemia, hypotension, or organ damage. Our results showed 1) TNF-alpha reversibly increased albumin permeation in the systemic vasculature (e.g., lung, liver, brain, etc.); 2) TNF-alpha did not affect hemodynamics or blood flow or cause significant tissue injury; 3) pulmonary vascular barrier dysfunction was associated with increased lung water content and impaired oxygenation; 4) TNF-alpha caused inducible nitric oxide synthase (iNOS) mRNA expression in the lung and increased in vivo NO production; 5) selective inhibition of iNOS with aminoguanidine prevented TNF-alpha-induced lung and liver vascular barrier dysfunction; 6) aminoguanidine prevented increased tissue water content in TNF-alpha-treated lungs and improved oxygenation; and 7) nonselective inhibition of NOS with NG-monomethly-L-arginine increased vascular permeation in control lungs and caused severe lung injury in TNF-alpha-treated animals. We conclude that 1) TNF-alpha reversibly impairs vascular barrier integrity through NO-dependent and -independent mechanisms; 2) nonselective NOS inhibition increased vascular barrier dysfunction and caused severe lung injury, whereas selective inhibition of iNOS prevented impaired endothelial barrier integrity and pulmonary dysfunction; and 3) selective inhibition of iNOS may be beneficial in treating increased vascular permeability that complicates endotoxemia and cytokine immunotherapy.
Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Endotélio Vascular/fisiologia , Hemodinâmica/fisiologia , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico/fisiologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Encéfalo/irrigação sanguínea , Permeabilidade Capilar/fisiologia , Endotélio Vascular/efeitos dos fármacos , Guanidinas/farmacologia , Hemodinâmica/efeitos dos fármacos , Intestinos/irrigação sanguínea , Fígado/irrigação sanguínea , Pulmão/enzimologia , Pulmão/patologia , Masculino , Músculo Esquelético/irrigação sanguínea , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos ACI , Proteínas Recombinantes/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Soroalbumina Bovina/farmacocinética , Pele/irrigação sanguínea , Transcrição Gênica/efeitos dos fármacos , ômega-N-Metilarginina/farmacologiaRESUMO
In summary, the National Database Committee's Audit and Validation Subcommittee is working to maximize the data completeness and quality of the STS National Database. Toward this end, we welcome your suggestions for improvement.
Assuntos
Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Bases de Dados Factuais/normas , Adulto , Coleta de Dados/normas , Humanos , Estados UnidosRESUMO
BACKGROUND: We previously demonstrated that continuous treatment with aminoguanidine, a selective inhibitor of nitric oxide production by inducible nitric oxide synthase, attenuated acute cardiac allograft rejection. METHODS: A rat transplant model was used to determine (1) when inducible nitric oxide synthase was expressed in the allograft heart during unmodified acute rejection and (2) whether pulse therapy with aminoguanidine attenuated the histologic changes of established acute rejection, in comparison with the effects of pulse therapy with corticosteroids. RESULTS: Inducible nitric oxide synthase messenger RNA and protein were expressed during early and late acute rejection. Pulse therapy with aminoguanidine inhibited nitric oxide production and attenuated the histologic changes of acute rejection, but not as effectively as corticosteroid therapy (rejection scores of 4.1 +/- 0.4, 2.5 +/- 0.9, and 1.4 +/- 0.6 on postoperative day 8, for untreated, aminoguanidine-, and dexamethasone-treated allografts, respectively (scale, 0 to 5; p < 0.05). CONCLUSIONS: (1) Inducible nitric oxide synthase expression first occurs during early acute allograft rejection and persists throughout rejection and (2) nitric oxide is an important effector molecule in acute rejection. Inducible nitric oxide synthase inhibition may offer a therapeutic adjunct in the management of acute rejection.