RESUMO
Background Prevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well-being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well-being was associated with less progression of coronary artery calcium (CAC). Methods and Results Participants were 312 women (mean age 50.8) from the SWAN (Study of Women's Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well-being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well-being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well-being was associated with less progression (RR, 0.909; 95% CI, 0.843-0.979; P=0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871-1.020; P=0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852-0.995; P=0.037). Conclusions Optimum early prevention of CVD in women may result from including the mind side of the mind-heart-body continuum.
Assuntos
Doença da Artéria Coronariana , Calcificação Vascular , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Vasos Coronários/diagnóstico por imagem , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X , Calcificação Vascular/complicações , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Saúde da MulherRESUMO
Patients with serious COVID infections develop shock frequently. To characterize the hemodynamic profile of this cohort, 156 patients with COVID pneumonia and shock requiring vasopressors had interpretable echocardiography with measurement of ejection fraction (EF) by Simpson's rule and stroke volume (SV) by Doppler. RV systolic pressure (RVSP) was estimated from the tricuspid regurgitation peak velocity. Patients were divided into groups with low or preserved EF (EFL or EFP, cutoff ≤45%), and low or normal cardiac index (CIL or CIN, cutoff ≤2.2 L/min/m2). Mean age was 67 ± 12.0, EF 59.5 ± 12.9, and CI 2.40 ± 0.86. A minority of patients had depressed EF (EFLCIL, n = 15, EFLCIN, n = 8); of those with preserved EF, less than half had low CI (EFPCIL, n = 55, EFPCIN, n = 73). Overall hospital mortality was 73%. Mortality was highest in the EFLCIL group (87%), but the difference between groups was not significant (p = 0.68 by ANOVA). High PEEP correlated with low CI in the EFPCIL group (r = 0.44, p = 0.04). In conclusion, this study reports the prevalence of shock characterized by EF and CI in patients with COVID-19. COVID-induced shock had a cardiogenic profile (EFLCIL) in 9.6% of patients, reflecting the impact of COVID-19 on myocardial function. Low CI despite preservation of EF and the correlation with PEEP suggests underfilling of the LV in this subset; these patients might benefit from additional volume. Hemodynamic assessment of COVID patients with shock with definition of subgroups may allow therapy to be tailored to the underlying causes of the hemodynamic abnormalities.
Assuntos
COVID-19/epidemiologia , Hemodinâmica/fisiologia , Choque/fisiopatologia , Idoso , Comorbidade , Ecocardiografia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Choque/diagnóstico , Choque/epidemiologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: This study sought to define the 2-dimensional and Doppler echocardiographic hemodynamics associated with each Society for Cardiovascular Angiography and Interventions (SCAI) stage, and to determine their association with mortality. BACKGROUND: The SCAI shock stages classification stratifies mortality risk in cardiac intensive care unit (CICU) patients, but the echocardiographic and hemodynamic parameters that define these SCAI shock stages are unknown. METHODS: Unique CICU patients admitted from 2007 to 2015 who had a transthoracic echocardiogram within 1 day of CICU admission were included. Echocardiographic variables were evaluated as a function of SCAI shock stage. Multivariable logistic regression determined the association between echocardiographic parameters with adjusted hospital mortality. RESULTS: We included 5,453 patients with a median age of 69.3 years (interquartile range: 58.2 to 79.0 years) (37% women), and a median left ventricular ejection fraction (LVEF) of 50% (interquartile range: 35% to 61%). Higher SCAI shock stages were associated with lower LVEF and worse systemic hemodynamics. Hospital mortality was higher in patients with LVEF <40%, cardiac index <1.8 l/min/m2, stroke volume index <35 ml/m2, cardiac power output <0.6 W, or medial early mitral valve inflow velocity to early diastolic annular velocity (E/e') ratio >15 (particularly in SCAI shock Stages A to C). After multivariable adjustment, only stroke volume index <35 ml/m2 (adjusted odds ratio: 2.0; 95% confidence interval: 1.4 to 3.0; p < 0.001) and E/e' ratio >15 (adjusted odds ratio: 1.52; 95% confidence interval: 1.04 to 2.23; p = 0.03) remained associated with higher hospital mortality. CONCLUSIONS: Noninvasive 2-dimensional and Doppler echocardiographic parameters correlate with the SCAI shock stages and improve risk stratification for hospital mortality in CICU patients. Low stroke volume index and high E/e' ratio demonstrated the strongest association with hospital mortality.
Assuntos
Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Idoso , Feminino , Hemodinâmica , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Choque Cardiogênico , Volume SistólicoAssuntos
Cardiologia/organização & administração , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Medição de Risco/métodos , Cardiologia/métodos , Comorbidade , Consenso , Continuidade da Assistência ao Paciente , Tomada de Decisões , Diuréticos/uso terapêutico , Hospitalização , Humanos , Cuidados Paliativos , Alta do Paciente , Guias de Prática Clínica como Assunto , Sociedades Médicas , Estados UnidosRESUMO
Patients undergoing cardiac valve replacement may receive mechanical or bioprosthetic valves. Mechanical valves require lifelong anticoagulation but are durable and the need for a second surgery is up to eightfold times less than with bioprosthetic valves. Bioprosthetic valves do not require lifelong anticoagulation and thus are associated with fewer bleeding complications but they are less durable and associated with higher morbidity and mortality rates, particularly in younger patients. Anticoagulation with mechanical valves is achieved using warfarin; use of direct-acting oral anticoagulants is not indicated. Concomitant low-dose aspirin is recommended for patients with mechanical valves and as sole thromboembolism prophylaxis for patients receiving aortic or mitral bioprosthetic valves. If a patient taking warfarin is to undergo a surgical procedure that requires interruption of anticoagulation, bridging therapy with heparin is indicated if the patient has a mechanical aortic valve and any risk of thromboembolism, an older-generation mechanical aortic valve, or a mechanical mitral valve. Warfarin is teratogenic; pregnant women should take heparin. Patients with mechanical or bioprosthetic valves should receive antibiotic prophylaxis before some dental and surgical procedures to prevent endocarditis. Thrombolytic therapy should be considered in patients who develop a thrombus on a valve that does not resolve with heparin.
Assuntos
Anticoagulantes/uso terapêutico , Endocardite/prevenção & controle , Doenças das Valvas Cardíacas/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Tromboembolia/prevenção & controle , Varfarina/uso terapêutico , Antibioticoprofilaxia/métodos , Bioprótese , Feminino , Heparina/uso terapêutico , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Gravidez , Complicações Cardiovasculares na Gravidez/prevenção & controle , Desenho de PróteseRESUMO
A variety of microorganisms can cause infective endocarditis (IE) in patients with native valves. Staphylococci and streptococci are most common in community-acquired IE; staphylococci are most common in nosocomial IE. Microbiology of prosthetic valve endocarditis (PVE) depends on timing. Early-onset PVE (ie, 60 days or fewer postsurgery) typically is nosocomial, with Staphylococcus aureus infection being most common. Intermediate-onset PVE (ie, 60 to 365 days postsurgery) typically involves a mix of nosocomial and non-nosocomial organisms. PVE that develops more than 1 year after surgery has microbiology similar to that of native valve endocarditis. Fever is the most common symptom; others include dyspnea, pleuritic pain, anorexia, and myalgias. The Modified Duke Criteria is the standard for diagnosis, with blood cultures being the most important test. If patients are in stable condition, three sets of blood cultures should be obtained more than 6 hours apart and from separate sites before starting antibiotics. Echocardiography aids in diagnosis and can identify conditions best managed with surgery. For empiric therapy for native valve IE, most patients should receive vancomycin. For PVE, vancomycin and gentamicin should be prescribed, plus cefepime or an antipseudomonal carbapenem. Treatment typically continues for 6 weeks after blood culture results are negative.
Assuntos
Endocardite Bacteriana/diagnóstico , Próteses Valvulares Cardíacas , Infecções Relacionadas à Prótese/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estreptocócicas/diagnóstico , Antibacterianos/uso terapêutico , Hemocultura , Carbapenêmicos/uso terapêutico , Cefepima , Cefalosporinas/uso terapêutico , Infecção Hospitalar , Ecocardiografia , Endocardite/diagnóstico , Endocardite/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Gentamicinas/uso terapêutico , Humanos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus , Infecções Estreptocócicas/tratamento farmacológico , Vancomicina/uso terapêuticoRESUMO
Depressive disorders have been associated with cardiovascular disease (CVD), but the impact of depression on early atherogenesis has not been well described, particularly in women and minorities. The relation between repeated episodes of high depressive symptoms and coronary calcium (CAC) is unknown in women at midlife when depression is common. Participants in the Study of Women's Health Across the Nation Heart study were assessed annually for depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D scale]) over 5 years before CAC assessment and classified as high (CES-D ≥16) or not. CAC, measured by computed tomography, was analyzed as a categorical variable using cumulative logit partial proportional odds models. In these middle-aged women free of CVD and diabetes (194 black, 334 white), high depressive symptoms over 5 years were common; 19% had 1, 9% had 2, and 11% experienced ≥3 episodes. CAC was low; 54% had no CAC, 25% had scores from 0 to 10, and 21% had CAC ≥10 Agatston score. After adjusting for CVD risk factors, women with ≥3 episodes were twice as likely to have significant CAC (≥10 Agatston units) than women with no depressive episodes (odds ratio 2.20, 95% confidence interval 1.13 to 4.28, p = 0.020) with no difference by race. Women with 1 or 2 episodes did not differ from women with no episodes. In conclusion, in healthy women aged 46 to 59 years without clinical CVD or diabetes, persistent depressive symptoms were significantly associated with elevated CAC scores, suggesting that they are more likely to have pathophysiological and behavioral effects on the development of subclinical CVD than does a single episode of elevated depressive symptoms.
Assuntos
Calcinose/complicações , Doença da Artéria Coronariana/complicações , Vasos Coronários/diagnóstico por imagem , Depressão/etiologia , Saúde da Mulher , Fatores Etários , Calcinose/diagnóstico , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Depressão/epidemiologia , Progressão da Doença , Eletrocardiografia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Razão de Chances , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Estados Unidos/epidemiologiaRESUMO
Emergency departments and hospitals are being urged to implement onsite interventions to promote smoking cessation, yet little is known about the theoretical underpinnings of behavior change after a healthcare visit. This observational pilot study evaluated three factors that may predict smoking cessation after an acute health emergency: perceived illness severity, event-related emotions, and causal attribution. Fifty smokers who presented to a hospital because of suspected cardiac symptoms were interviewed, either in the emergency department (ED) or, for those who were admitted, on the cardiac inpatient units. Their data were analyzed using both qualitative and quantitative methodologies to capture the individual, first-hand experience and to evaluate trends over the illness chronology. Reported perceptions of the event during semistructured interview varied widely and related to the individual's intentions regarding smoking cessation. No significant differences were found between those interviewed in the ED versus the inpatient unit. Although the typical profile was characterized by a peak in perceived illness severity and negative emotions at the time the patient presented in the ED, considerable pattern variation occurred. Our results suggest that future studies of event-related perceptions and emotional reactions should consider using multi-item and multidimensional assessment methods rated serially over the event chronology.
RESUMO
BACKGROUND: Black women experience higher rates of cardiovascular disease (CVD) than white women, though evidence for racial differences in subclinical CVD is mixed. Few studies have examined multiple roles (number, perceived stress, and/or reward) in relation to subclinical CVD, or whether those effects differ by race. PURPOSE: The aim of this study was to investigate the effects of multiple roles on 2-year progression of coronary artery calcium. METHODS: Subjects were 104 black and 232 white women (mean age 50.8 years). Stress and reward from four roles (spouse, parent, employee, caregiver) were assessed on five-point scales. Coronary artery calcium progression was defined as an increase of ≥10 Agatston units. RESULTS: White women reported higher rewards from their multiple roles than black women, yet black women showed cardiovascular benefits from role rewards. Among black women only, higher role rewards were related significantly to lower progression of coronary artery calcium, adjusting for body mass index, blood pressure, and other known CVD risk factors. Blacks reported fewer roles but similar role stress as whites; role number and stress were unrelated to coronary artery calcium progression. CONCLUSION: Rewarding roles may be a novel protective psychosocial factor for progression of coronary calcium among black women.
Assuntos
Calcinose/patologia , Doença da Artéria Coronariana/patologia , Progressão da Doença , Papel (figurativo) , Estresse Psicológico/fisiopatologia , Negro ou Afro-Americano , Calcinose/etnologia , Calcinose/psicologia , Cálcio/análise , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/psicologia , Vasos Coronários/química , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Risco , Estresse Psicológico/etnologia , População BrancaRESUMO
OBJECTIVE: The aim of this study was to examine whether obesity modifies the effects of endogenous steroid sex hormones on arterial calcification in women at midlife. METHODS: Associations between estradiol, testosterone, sex hormone-binding globulin, and free androgen index and the presence and extent of coronary and aortic calcification were evaluated in 187 obese (body mass index, ≥30 kg/m) and 281 nonobese (body mass index, <30 kg/m) women from the Study of Women's Health Across the Nation. Logistic and linear regressions were used as appropriate. RESULTS: Prevalence rates of coronary and aortic calcification were significantly higher among obese compared with nonobese women (P < 0.001, for both). In multivariable analyses, steroid sex hormones were not associated with the presence of coronary calcification. However, for the extent of coronary calcification, significant interactions were found between obesity and both sex hormone-binding globulin (P < 0.0001) and free androgen index (P = 0.008). In nonobese women, higher sex hormone-binding globulin (P = 0.0006) and lower free androgen index (P = 0.01) were associated with a greater extent of coronary calcification, whereas lower sex hormone-binding globulin was associated with greater extent of coronary calcification in obese women (P = 0.05). For aortic calcification outcomes, higher sex hormone-binding globulin was associated with the presence of aortic calcification among nonobese women (odds ratio, 1.64; 95% CI, 1.16-2.32, for each 1-SD greater sex hormone-binding globulin). CONCLUSIONS: Associations between endogenous steroid sex hormones and arterial calcification vary by obesity status among perimenopausal women. Further research is needed to better understand the possible mechanisms of these associations.
Assuntos
Calcinose/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Hormônios Esteroides Gonadais/sangue , Obesidade/epidemiologia , Placa Aterosclerótica/epidemiologia , Pós-Menopausa/sangue , Calcificação Vascular/epidemiologia , Calcinose/sangue , Calcinose/patologia , Comorbidade , Doença da Artéria Coronariana/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônios Esteroides Gonadais/metabolismo , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Placa Aterosclerótica/sangue , Calcificação Vascular/sangueRESUMO
The syndrome of cardiogenic shock (CS) comprises a constellation of symptoms and signs that define a subset of patients with inadequate tissue perfusion secondary to myocardial dysfunction. Careful attention to and rapid identification of patients at risk for the development of CS and those with impending CS by both hospitalists and subspecialists will help to implement the time-sensitive therapy that it requires. Physicians should gain a familiarity with the underlying pathophysiology of CS and available diagnostic tools as well as the importance of vasopressor therapy, inotropic therapy, rapid reperfusion therapy, and mechanical support.
Assuntos
Choque Cardiogênico/diagnóstico , Choque Cardiogênico/terapia , Algoritmos , Angioplastia Coronária com Balão , Cateterismo Cardíaco , Cardiotônicos/uso terapêutico , Causalidade , Ponte de Artéria Coronária , Árvores de Decisões , Diagnóstico Diferencial , Diuréticos/uso terapêutico , Ecocardiografia , Eletrocardiografia , Fibrinolíticos/uso terapêutico , Coração Auxiliar , Mortalidade Hospitalar , Humanos , Balão Intra-Aórtico , Prognóstico , Choque Cardiogênico/epidemiologia , Choque Cardiogênico/etiologia , Choque Cardiogênico/fisiopatologia , Vasoconstritores/uso terapêuticoRESUMO
INTRODUCTION: Continuous cardiac index (CCI) monitoring can provide information to assist in hemodynamic support. However, pulmonary artery catheters (PAC) pose logistic challenges in acute care settings. We hypothesized that CCI measured with a calibrated minimally invasive technique (LiDCO/PulseCO, UK) would have good agreement with the PAC. METHODS: We performed a prospective observational study in post-operative cardiac surgery patients. All patients had a PAC with CCI monitoring capability. We connected the LiDCO apparatus to a radial artery line and performed a one-time calibration with a lithium dilution indicator. In order to test the least invasive method possible, we used a peripheral intravenous (IV) line for indicator delivery rather than the conventional central line technique. We recorded paired PAC/LiDCO-PulseCO CCI measurements every minute for 3h. We blinded investigators and clinicians to minimally invasive data with an opaque shield over the monitor. We assessed agreement with Bland-Altman analysis. RESULTS: We obtained 1485 paired measurements in 8 subjects. The mean CI was 2.9L/min/m(2). By Bland-Altman plot, PAC and LiDCO measurements showed minimal bias (-0.01), but the 95% limits of agreement (+/-2SD) of+/-1.3L/min/m(2) were relatively wide with respect to the mean. CONCLUSIONS: This calibrated minimally invasive (i.e. radial arterial line and peripheral IV) technique demonstrated low bias compared with CCI measured by PAC. However, the relatively wide confidence limits indicate that differences in the two measurements could still be clinically significant.
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Débito Cardíaco/fisiologia , Reanimação Cardiopulmonar/métodos , Cateterismo de Swan-Ganz/instrumentação , Cuidados Críticos/métodos , Técnicas de Diagnóstico Cardiovascular/normas , Monitorização Fisiológica/métodos , Calibragem , Pressão Venosa Central/fisiologia , Técnicas de Diagnóstico Cardiovascular/instrumentação , Desenho de Equipamento , Seguimentos , Humanos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
This article reviews current concepts about the diagnosis and acute management of postoperative arrhythmias. A systematic approach to diagnosis of arrhythmias and evaluation of predisposing factors is presented, followed by consideration of common bradyarrhythmias and tachyarrhythmias in the postoperative setting. Postoperative arrhythmias are common and represent a major source of morbidity after surgical procedures, both cardiac and noncardiac. Postoperative dysrhythmias are most likely to occur in patients with structural heart disease. The initiating factor for an arrhythmia following surgery is usually a transient insult such as hypoxemia, cardiac ischemia, catecholamine excess, or electrolyte abnormality. Management includes correction of these imbalances and, if clinically indicated, medical therapy directed at the arrhythmia itself.
Assuntos
Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/diagnóstico , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Bradicardia/diagnóstico , Bradicardia/tratamento farmacológico , Bradicardia/mortalidade , Eletrocardiografia , Feminino , Bloqueio Cardíaco/tratamento farmacológico , Bloqueio Cardíaco/mortalidade , Humanos , Masculino , Complicações Pós-Operatórias/mortalidade , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Procedimentos Cirúrgicos Operatórios/métodos , Taxa de Sobrevida , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/tratamento farmacológico , Taquicardia Supraventricular/mortalidade , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/mortalidadeRESUMO
OBJECTIVE: Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. We used serial studies to evaluate changes in coronary endothelial function in patients with and without clinically evident CAV. BACKGROUND: In serial studies with intravascular ultrasound (IVUS) and Doppler flow wire measurements, we previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. METHODS: We studied 45 patients annually, beginning at transplantation until pre-specified end-points (angiographic CAV or cardiac death) were reached. At each study, we measured coronary endothelial function using intracoronary infusions of adenosine, acetylcholine, and nitroglycerin. We simultaneously recorded IVUS images and Doppler velocities. RESULTS: Of the 45 patients studied, 9 reached end-points during the study (6 had CAV and 3 died). The mean annual change in area response to acetylcholine was -4.5% +/- 3.0% in patients who reached end-points and -0.9% +/- 1.5% in those who did not (p = 0.04). The mean annual decrement in flow response to acetylcholine was greater in patients who reached end-points (-31% +/- 11% vs -5% +/- 5%, p = 0.08). Responses to adenosine and nitroglycerin did not differ. CONCLUSIONS: When serial responses were evaluated, patients with end-points had more rapid decreases in endothelial function. The rate of disease progression may be more important than the absolute degree of intimal thickening in early CAV. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function may provide important prognostic information about the development of CAV after heart transplantation.
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Doença das Coronárias/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Endotélio Vascular/fisiopatologia , Transplante de Coração , Complicações Pós-Operatórias/fisiopatologia , Velocidade do Fluxo Sanguíneo , Circulação Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/etiologia , Vasos Coronários/fisiopatologia , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Ultrassonografia de IntervençãoAssuntos
Endotélio Vascular/citologia , Endotélio Vascular/fisiopatologia , Inflamação/fisiopatologia , Doença Aguda , Permeabilidade Capilar/efeitos dos fármacos , Permeabilidade Capilar/fisiologia , Moléculas de Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/fisiologia , Medicina Baseada em Evidências , Humanos , Selectina L/farmacologia , Selectina L/fisiologia , Sepse/metabolismo , Sepse/fisiopatologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacocinéticaRESUMO
The ability of increased endogenous adenosine to mitigate microvascular derangements in sepsis was studied. Pentostatin (2'-deoxycoformycin), an inhibitor of adenosine deaminase, was administered to mice immediately after induction of sepsis by cecal ligation and puncture. Intravital video microscopy of cremasteric postcapillary venules was performed. Leukocyte rolling and adhesion were significantly increased in septic mice compared with control mice. Treatment of septic mice with pentostatin significantly decreased leukocyte rolling and adhesion (6.02 +/- 0.09 versus 1.72 +/- 0.12 rolling cells/min, 2.07 +/- 0.04 versus 0.62 +/- 0.05 adherent cells/100 microm per minute; p < 0.001). Albumin leakage (ratio) was significantly attenuated in septic animals treated with pentostatin (0.42 +/- 0.05 versus 0.21 +/- 0.04; p < 0.01). Circulating levels of interleukin-6, tumor necrosis factor-alpha, and soluble tumor necrosis factor type II receptor were decreased in septic mice treated with pentostatin. Survival was significantly improved at 48 hours in mice treated with pentostatin. These results suggest an important role for adenosine in modulating both leukocyte-dependent and -independent mechanisms of endothelial injury in sepsis. Exploiting the advantageous action of endogenous adenosine represents a potentially useful and novel therapeutic approach for the treatment of sepsis.