RESUMO
The major hemodynamic benefits of intra-aortic balloon pump (IABP) counterpulsation are augmentation in diastolic aortic pressure (Paug ) during inflation, and decrease in end-diastolic aortic pressure (ΔedP) during deflation. When the patient is nursed in the semirecumbent position these benefits are diminished. Attempts to change the shape of the IAB in order to limit or prevent this deterioration have been scarce. The aim of the present study was to investigate the hemodynamic performance of six new IAB shapes, and compare it to that of a traditional cylindrical IAB. A mock circulation system, featuring an artificial left ventricle and an aortic model with 11 branches and physiological resistance and compliance, was used to test one cylindrical and six newly shaped IABs at angles 0, 10, 20, 30, and 40°. Pressure was measured continuously at the aortic root during 1:1 and 1:4 IABP support. Shape 2 was found to consistently achieve, in terms of absolute magnitude, larger ΔedP at angles than the cylindrical IAB. Although ΔedP was gradually diminished with angle, it did so to a lesser degree than the cylindrical IAB; this diminishment was only 53% (with frequency 1:1) and 40% (with frequency 1:4) of that of the cylindrical IAB, when angle increased from 0 to 40°. During inflation Shape 1 displayed a more stable behavior with increasing angle compared to the cylindrical IAB; with an increase in angle from 0 to 40°, diastolic aortic pressure augmentation dropped only by 45% (with frequency 1:1) and by 33% (with frequency 1:4) of the drop reached with the cylindrical IAB. After compensating for differences in nominal IAB volume, Shape 1 generally achieved higher Paug over most angles. Newly shaped IABs could allow for IABP therapy to become more efficient for patients nursed at the semirecumbent position. The findings promote the idea of personalized rather than generalized patient therapy for the achievement of higher IABP therapeutic efficiency, with a choice of IAB shape that prioritizes the recovery of those hemodynamic indices that are more in need of support in the unassisted circulation.
Assuntos
Hemodinâmica , Balão Intra-Aórtico/instrumentação , Posicionamento do Paciente , Pressão Sanguínea , Desenho de Equipamento , Humanos , Modelos Cardiovasculares , Posicionamento do Paciente/métodos , Função VentricularRESUMO
The intra-aortic balloon pump (IABP) is a ventricular assist device that is used with a broad range of pre-, intra-, and postoperative patients undergoing cardiac surgery. Although the clinical efficacy of the IABP is well documented, the question of reduced efficacy when patients are nursed in the semi-recumbent position remains outstanding. The aim of the present work is therefore to investigate the underlying mechanics responsible for the loss of IABP performance when operated at an angle to the horizontal. Simultaneous recordings of balloon wall movement, providing an estimate of its diameter (D), and fluid pressure were taken at three sites along the intra-aortic balloon (IAB) at 0 and 45°. Flow rate, used for the calculation of displaced volume, was also recorded distal to the tip of the balloon. An in vitro experimental setup was used, featuring physiological impedances on either side of the IAB ends. IAB inflation at an angle of 45° showed that D increases at the tip of the IAB first, presenting a resistance to the flow displaced away from the tip of the balloon. The duration of inflation decreased by 15.5%, the inflation pressure pulse decreased by 9.6%, and volume decreased by 2.5%. Similarly, changing the position of the balloon from 0 to 45°, the balloon deflation became slower by 35%, deflation pressure pulse decreased by 14.7%, and volume suctioned was decreased by 15.2%. IAB wall movement showed that operating at 45° results in slower deflation compared with 0°. Slow wall movement, and changes in inflation and deflation onsets, result in a decreased volume displacement and pressure pulse generation. Operating the balloon at an angle to the horizontal, which is the preferred nursing position in intensive care units, results in reduced IAB inflation and deflation performance, possibly compromising its clinical benefits.
Assuntos
Aorta/fisiopatologia , Hemodinâmica , Balão Intra-Aórtico/instrumentação , Posicionamento do Paciente , Pressão Arterial , Velocidade do Fluxo Sanguíneo , Desenho de Equipamento , Humanos , Modelos Anatômicos , Modelos Cardiovasculares , Fluxo Sanguíneo Regional , Fatores de TempoRESUMO
BACKGROUND: The role of mitral valve repair (MVR) during coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation (MR) is uncertain. We conducted a randomized, controlled trial to determine whether repairing the mitral valve during CABG may improve functional capacity and left ventricular reverse remodeling compared with CABG alone. METHODS AND RESULTS: Seventy-three patients referred for CABG with moderate ischemic MR and an ejection fraction >30% were randomized to receive CABG plus MVR (34 patients) or CABG only (39 patients). The study was stopped early after review of interim data. At 1 year, there was a greater improvement in the primary end point of peak oxygen consumption in the CABG plus MVR group compared with the CABG group (3.3 mL/kg/min versus 0.8 mL/kg/min; P<0.001). There was also a greater improvement in the secondary end points in the CABG plus MVR group compared with the CABG group: left ventricular end-systolic volume index, MR volume, and plasma B-type natriuretic peptide reduction of 22.2 mL/m(2), 28.2 mL/beat, and 557.4 pg/mL, respectively versus 4.4 mL/m(2) (P=0.002), 9.2 mL/beat (P=0.001), and 394.7 pg/mL (P=0.003), respectively. Operation duration, blood transfusion, intubation duration, and hospital stay duration were greater in the CABG plus MVR group. Deaths at 30 days and 1 year were similar in both groups: 3% and 9%, respectively in the CABG plus MVR group, versus 3% (P=1.00) and 5% (P=0.66), respectively in the CABG group. CONCLUSIONS: Adding mitral annuloplasty to CABG in patients with moderate ischemic MR may improve functional capacity, left ventricular reverse remodeling, MR severity, and B-type natriuretic peptide levels, compared with CABG alone. The impact of these benefits on longer term clinical outcomes remains to be defined.
Assuntos
Ponte de Artéria Coronária , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral/epidemiologia , Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ponte de Artéria Coronária/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Anuloplastia da Valva Mitral/métodos , Insuficiência da Valva Mitral/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Método Simples-Cego , Resultado do TratamentoRESUMO
A mock circulatory system (MCS) was designed to replicate a physiological environment for in vitro testing and was assessed with the intra-aortic balloon pump (IABP). The MCS was comprised of an artificial left ventricle (LV), connected to a 14-branch polyurethane-compound aortic model. Physiological distribution of terminal resistance and compliance according to published data was implemented with capillary tubes of different sizes and syringes of varying air volume, respectively, fitted at the outlets of the branches. The ends of the aortic branches were connected to a common tube representing the venous system and an overhead reservoir provided atrial pressure. An IABP operating a 40-cc balloon was set to counterpulsate with the LV. Total arterial compliance of the system was 0.94 mL/mm Hg and total arterial resistance was 20.3 ± 3.3 mm Hg/L/min. At control, physiological flow distribution was achieved and both mean and phasic aortic pressure and flow were physiological. With the IABP, aortic pressure exhibited the major features of counterpulsation: diastolic augmentation during inflation, inflection point at onset of deflation, and end-diastolic reduction at the end of deflation. The contribution of balloon inflation and deflation was also evident on the aortic flow pattern. This MCS was verified to be suitable for IABP testing and with further adaptations it could be used for studying other hemodynamic problems and ventricular assist devices.
Assuntos
Balão Intra-Aórtico/instrumentação , Aorta/fisiologia , Desenho de Equipamento , Hemodinâmica , Humanos , Modelos Cardiovasculares , Função Ventricular EsquerdaRESUMO
Over the last half century, surgical aortic valve replacement (SAVR) has evolved to offer a durable and efficient valve haemodynamically, with low procedural complications that allows favourable remodelling of left ventricular (LV) structure and function. The latter has become more challenging among elderly patients, particularly following trans-catheter aortic valve implantation (TAVI). Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss, valvular-vascular impedance to myocardial activation, force-velocity relationship, and myocardial strain. LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour. Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome. Physiological pacing via the His-Purkinje system for conduction abnormalities, further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression, LV coordinate contraction, and global vascular function. TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions. Until comparable long-term durability and the resolution of TAVI related complications become available, SAVR remains the first choice for lower risk younger patients.
Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Catéteres , Humanos , Resultado do Tratamento , Remodelação VentricularRESUMO
BACKGROUND AND OBJECTIVES: In personalised external aortic root support (PEARS), a custom-made, macroporous mesh is used to stabilise a dilated aortic root and prevent dissection, primarily in patients with genetically driven aortopathies. Data are needed on the safety and postoperative incidence of aortic events. METHODS: We present a multicentre cohort study evaluating the first 200 consecutive patients (median age 33 years) undergoing surgery with an intention to perform PEARS for aortic root dilatation in 23 centres between 2004 and 2019. Perioperative outcomes were collected prospectively while clinical follow-up was retrieved retrospectively. Median follow-up was 21.2 months. RESULTS: The main indication was Marfan syndrome (73.5%) and the most frequent concomitant procedure was mitral valve repair (10%). An intervention for myocardial ischaemia or coronary injury was needed in 11 patients, 1 case resulting in perioperative death. No ascending aortic dissections were observed in 596 documented postoperative patient years. Late reoperation was performed in 3 patients for operator failure to achieve complete mesh coverage. Among patients with at least mild aortic regurgitation (AR) preoperatively, 68% had no or trivial AR at follow-up. CONCLUSIONS: This study represents the clinical history of the first 200 patients to undergo PEARS. To date, aortic dissection has not been observed in the restrained part of the aorta, yet long-term follow-up is needed to confirm the potential of PEARS to prevent dissection. While operative mortality is low, the reported coronary complications reflect the learning curve of aortic root surgery in patients with connective tissue disease. PEARS may stabilise or reduce aortic regurgitation.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/prevenção & controle , Procedimentos Cirúrgicos Eletivos/métodos , Implante de Prótese de Valva Cardíaca/métodos , Telas Cirúrgicas , Adolescente , Adulto , Idoso , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/etiologia , Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: The study objective was to investigate the long-term survival of patients undergoing xenograft versus homograft full root aortic valve replacement. METHODS: A total of 166 patients requiring aortic valve surgery were randomized to undergo the Freestyle (Medtronic Inc, Minneapolis, Minn) bioprosthesis (N = 90) or a homograft (N = 76) full root aortic valve replacement between 1997 and 2005 in a single institution. Six patients randomly assigned to the homograft crossed over to the Freestyle bioprosthesis because of the unavailability of suitably sized homografts. All surgeons were required to adhere to the standard surgical technique for homograft root implantation previously described. Follow-up was 98.5% complete. RESULTS: The mean age of the study population was 65 ± 8 years. Coronary artery bypass grafting was associated with root aortic valve replacement in 76 of 166 patients (46%, P = not significant between groups), and overall hospital mortality was 4.8% (8/166, P = not significant between groups). Median follow-up was 13.8 years (range, 0-21.8 years; 2033 patient-years). The Kaplan-Meier survival analysis showed that there was no significant difference in overall survival between the 2 arms at 5, 10, and 15 years. Twenty-year survival was 28.3% ± 5% for the Freestyle group versus 25.1% ± 5.7% for the homograft group (P = .90), which was comparable to the age- and sex-matched UK general population. The freedom from aortic valve reoperation at 20 years was comparable for the Freestyle group versus the homograft group (67.9% ± 8.8% vs 67.2% ± 10.3%, respectively; P = .74). CONCLUSIONS: This is the first study to investigate the long-term survival of xenograft versus homograft full root aortic valve replacement from a prospective randomized trial. The observed 20-year overall survival and freedom from aortic valve reoperation serve as a benchmark for future studies on interventions for aortic valve disease in the elderly.
RESUMO
This study aims to investigate the mechanics of the intra-aortic balloon (IAB) under different aortic pressure (P(ao)) and inclination (0-75 degrees). Pressure and flow were measured in an artificial aorta during IAB pumping with a frequency of 1:3. Volume displaced toward the "coronary arteries" during inflation (V(prox)) and "intra-aortic" pressure reduction during deflation (P(r)) were derived. IAB duration of inflation and deflation was determined with a high-speed camera visualization. When the aorta was horizontal, P(ao) raised from 45 mm Hg to 115 mm Hg, V(prox) reduced by 18% (25.0 +/- 1.0 mL vs. 30.4 +/- 1.9 mL) and P(r) increased by 117% (106.4 +/- 0.3 mm Hg vs. 48.9 +/- 0.6 mm Hg). When the aorta was inclined, at low P(ao) of 45 mm Hg, V(prox) was reduced by 30% from 0 degrees to 45 degrees (19.8 +/- 2.3 mL vs. 28.3 +/- 1.7 mL) and P(r) was reduced by 66% (16.5 +/- 0.1 mm Hg vs. 48.9 +/- 0.6 mm Hg). However, at high P(ao) of 115 mm Hg, V(prox) remained unchanged with increasing angle (20.0 +/- 1.0 mL) and P(r) was reduced by 24% (80.6 +/- 0.8 mm Hg vs. 106.4 +/- 0.3 mm Hg). Increasing P(ao) increased duration of inflation. At low P(ao), increasing angle resulted in increasing duration of inflation, but at high P(ao), increasing angle had the opposite effect. Duration of deflation generally decreased with P(ao) and increased with increasing angle. The IAB pump is affected by both P(ao) and angle, indicating that non-normotensive patients or patients in the semi-recumbent position might not receive the full benefits of IAB counterpulsation.
Assuntos
Aorta/fisiologia , Balão Intra-Aórtico , Fenômenos Biomecânicos , Pressão Sanguínea , HumanosRESUMO
Acute aortic syndrome and in particular aortic dissection (AAD) persists as a cause of significant morbidity and mortality despite improvements in surgical management. This clinical review aims to explore the risks of misdiagnosis, outcomes associated with misdiagnosis and evaluate current diagnostic methods for reducing its incidence.Due to the nature of the pathology, misdiagnosing the condition and delaying management can dramatically worsen patient outcomes. Several diagnostic challenges exist, including low prevalence, rapidly propagating pathology, non-discrete symptomatology, non-specific signs, analogy with other acute conditions and lack of management infrastructure. A similarity to acute coronary syndromes is a specific concern and risks patient maltreatment. AAD with malperfusion syndromes are both a cause of misdiagnosis and marker of disease complication, requiring specifically tailored management plans from the emergency setting.Despite improvements in diagnostic measures, including imaging modalities and biomarkers, misdiagnosis of AAD remains commonplace and current guidelines are relatively limited in preventing its occurrence. This paper recommends the early use of AAD risk scoring, focused echocardiography and most importantly, fast-tracking patients to cross-sectional imaging where the suspicion of AAD is high. This has the potential to improve the diagnostic process for AAD and limit the risk of misdiagnosis. However, our understanding remains limited by the lack of large patient datasets and an adequately audited processes of emergency department practice.
Assuntos
Aneurisma da Aorta Torácica/diagnóstico , Dissecção Aórtica/diagnóstico , Técnicas de Apoio para a Decisão , Doença Aguda , Algoritmos , Dissecção Aórtica/complicações , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/cirurgia , Aortografia , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Erros de Diagnóstico , Ecocardiografia , Serviço Hospitalar de Emergência , Humanos , Incidência , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Tempo para o TratamentoRESUMO
The death rate from thoracic aortic disease is on the rise and represents a growing global health concern as patients are often asymptomatic before acute events, which have devastating effects on health-related quality of life. Biomechanical factors have been found to play a major role in the development of both acquired and congenital aortic diseases. However, much is still unknown and translational benefits of this knowledge are yet to be seen. Phase-contrast cardiovascular magnetic resonance imaging of thoracic aortic blood flow has emerged as an exceptionally powerful non-invasive tool enabling visualization of complex flow patterns, and calculation of variables such as wall shear stress. This has led to multiple new findings in the areas of phenotype-dependent bicuspid valve flow patterns, thoracic aortic aneurysm formation and aortic prosthesis performance assessment. Phase-contrast cardiovascular magnetic resonance imaging has also been used in conjunction with computational fluid modelling techniques to produce even more sophisticated analyses, by allowing the calculation of haemodynamic variables with exceptional temporal and spatial resolution. Translationally, these technologies may potentially play a major role in the emergence of precision medicine and patient-specific treatments in patients with aortic disease. This clinically focused review will provide a systematic overview of key insights from published studies to date.
Assuntos
Aorta Torácica , Hidrodinâmica , Aorta Torácica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Hemodinâmica , Humanos , Imageamento por Ressonância Magnética , Qualidade de VidaRESUMO
Cardiovascular magnetic resonance (CMR) is increasingly used to assess patients with mitral regurgitation. Its advantages include quantitative determination of ventricular volumes and function and the mitral regurgitant fraction, and in ischemic mitral regurgitation, regional myocardial function and viability. In addition to these, identification of leaflet prolapse or restriction is necessary when valve repair is contemplated. We describe a systematic approach to the evaluation of mitral regurgitation using CMR which we have used in 149 patients with varying etiologies and severity of regurgitation over a 15 month period. Following standard ventricular cine acquisitions, including 2, 3 and 4 chamber long axis views and a short axis stack for biventricular function, we image movements of all parts of the mitral leaflets using a contiguous stack of oblique long axis cines aligned orthogonal to the central part of the line of coaptation. The 8-10 slices in the stack, orientated approximately parallel to a 3-chamber view, are acquired sequentially from the superior (antero-lateral) mitral commissure to the inferior (postero-medial) commissure, visualising each apposing pair of anterior and posterior leaflet scallops in turn (A1-P1, A2-P2 and A3-P3). We use balanced steady state free precession imaging at 1.5 Tesla, slice thickness 5 mm, with no inter-slice gaps. Where the para-commissural coaptation lines curve relative to the central region, two further oblique cines are acquired orthogonal to the line of coaptation adjacent to each commissure. To quantify mitral regurgitation, we use phase contrast velocity mapping to measure aortic outflow, subtracting this from the left ventricular stroke volume to calculate the mitral regurgitant volume which, when divided by the left ventricular stroke volume, gives the mitral regurgitant fraction. In patients with ischemic mitral regurgitation, we further assess regional left ventricular function and, with late gadolinium enhancement, myocardial viability. Comprehensive assessment of mitral regurgitation using CMR is feasible and enables determination of mitral regurgitation severity, associated leaflet prolapse or restriction, ventricular function and viability in a single examination and is now routinely performed at our centre. The mitral valve stack of images is particularly useful and easy to acquire.
Assuntos
Imagem Cinética por Ressonância Magnética , Insuficiência da Valva Mitral/patologia , Função Ventricular Esquerda , Humanos , Interpretação de Imagem Assistida por Computador , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
The intra-aortic balloon pump (IABP) is the most widely used cardiac assist device, whose main benefits are augmentation of coronary flow and reduction of left-ventricular afterload. The aim of this study is to investigate the pressure and flow-volume distribution associated with balloon inflation. We hypothesize that in order to displace fluid on both sides of the balloon, a pressure locus must be present along the balloon during inflation. In vitro experiments were performed in two positions, horizontal and angled, using four balloon sizes: 25, 34, 40, and 50 cc. Along and on both sides of each balloon, we measured pressure, flow rate, and calculated flow velocity, volume displacement, wave intensity and energy. A pressure locus was found at the center of each balloon and the average flow volume displaced toward the tip at the horizontal position was about 57% of the balloon volume. In the angled position, the location of the pressure locus was less obvious and average volume displacement toward the top end of the balloon was reduced to 45%. These results confirm the existence of a pressure locus at the center of each of the balloons we tested. Because a clear reduction in flow volume was observed at the angled position, these results may have clinical implications as most patients using IABP in the intensive care units are nursed in semirecumbent position.
Assuntos
Coração Auxiliar , Balão Intra-Aórtico , Humanos , Postura/fisiologia , Pressão , ReologiaRESUMO
BACKGROUND: In patients with ischemic mitral regurgitation requiring mitral valve replacement (MVR), the choice of the prosthesis type is crucial. The exercise hemodynamic and functional capacity performance in patients with contemporary prostheses have never been investigated. To compare exercise hemodynamic and functional capacity between biological (MVRb) and mechanical (MVRm) prostheses. METHODS AND RESULTS: We analyzed 86 consecutive patients with ischemic mitral regurgitation who underwent MVRb (n=41) or MVRm (n=45) and coronary artery bypass grafting. All patients underwent preoperative resting echocardiography and 6-minute walking test. At follow-up, exercise stress echocardiography was performed, and the 6-minute walking test was repeated. Resting and exercise indexed effective orifice areas of MVRm were larger when compared with MVRb (resting: 1.30±0.2 versus 1.19±0.3 cm2/m2; P=0.03; exercise: 1.57±0.2 versus 1.18±0.3 cm2/m2; P=0.0001). The MVRm had lower exercise systolic pulmonary arterial pressure at follow-up compared with MVRb (41±5 versus 59±7 mm Hg; P=0.0001). Six-minute walking test distance was improved in the MVRm (pre-operative: 242±43, post-operative: 290±50 m; P=0.001), whereas it remained similar in the MVRb (pre-operative: 250±40, post-operative: 220±44 m; P=0.13). In multivariable analysis, type of prosthesis, exercise indexed effective orifice area, and systolic pulmonary arterial pressure were joint predictors of change in 6-minute walking test (ie, difference between baseline and follow-up). CONCLUSIONS: In patients with ischemic mitral regurgitation, bioprostheses are associated with worse hemodynamic performance and reduced functional capacity, when compared with MVRm. Randomized studies with longer follow-up including quality of life and survival data are required to confirm these results.
Assuntos
Bioprótese , Exercício Físico/fisiologia , Próteses Valvulares Cardíacas , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/cirurgia , Isquemia Miocárdica/complicações , Idoso , Pressão Sanguínea/fisiologia , Ponte de Artéria Coronária , Ecocardiografia sob Estresse , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/complicações , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/terapia , Desenho de Prótese , Recuperação de Função FisiológicaRESUMO
Recent data have suggested that regular consumption of nonsteroid anti-inflammatory drugs (NSAIDs), particularly selective inhibitors of cyclo-oxygenase-2 (COX-2), is associated with an increased risk of thrombotic events. It has been suggested that this is due to NSAIDs reducing the release from the endothelium of the antithrombotic mediator prostaglandin I2 as a result of inhibition of endothelial COX-2. Here, however, we show that despite normal human vessels and endothelial cells containing cyclo-oxygenase-1 (COX-1) without any detectable COX-2, COX-1 in vessels or endothelial cells is more readily inhibited by NSAIDs and COX-2-selective drugs than COX-1 in platelets (e.g., log IC50+/-SEM values for endothelial cells vs. platelets: naproxen -5.59+/-0.07 vs. -4.81+/-0.04; rofecoxib -4.93+/-0.04 vs. -3.75+/-0.03; n=7). In broken cell preparations, the selectivities of the tested drugs toward endothelial cell over platelet COX-1 were lost. These observations suggest that variations in cellular conditions, such as endogenous peroxide tone and substrate supply, and not the isoform of cyclo-oxygenase present, dictate the effects of NSAIDs on endothelial cells vs. platelets. This may well be because the platelet is not a good representative of COX-1 activity within the body as it produces prostanoids in an explosive burst that does not reflect tonic release from other cells. The results reported here can offer an explanation for the apparent ability of NSAIDs and COX-2-selective inhibitors to increase the risk of myocardial infarction and stroke.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Plaquetas/efeitos dos fármacos , Ciclo-Oxigenase 1/metabolismo , Células Endoteliais/efeitos dos fármacos , Trombose/induzido quimicamente , Aorta/citologia , Plaquetas/enzimologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Células Endoteliais/enzimologia , Epoprostenol/metabolismo , Regulação Enzimológica da Expressão Gênica , Humanos , Tromboxano A2/metabolismo , Veias/citologia , Veias/efeitos dos fármacos , Veias/metabolismoRESUMO
Hibernating myocardium refers to chronically dysfunctional myocardium in patients with coronary artery disease in which cardiac viability is maintained and whose function improves after coronary revascularization. It is our hypothesis that long-term adaptive genomic mechanisms subtend the survival capacity of this ischemic myocardium. Therefore, the goal of this study was to determine whether chronic repetitive ischemia elicits a gene program of survival protecting hibernating myocardium against cell death. Accordingly, we measured the expression of survival genes in hibernating myocardium, both in patients surgically treated for hibernation and in a chronic swine model of repetitive ischemia reproducing the features of hibernation. Human hibernating myocardium was characterized by an upregulation of genes and corresponding proteins involved in anti-apoptosis (IAP), growth (VEGF, H11 kinase), and cytoprotection (HSP70, HIF-1alpha, GLUT1). In the swine model, the same genes and proteins were upregulated after repetitive ischemia, which was accompanied by a concomitant decrease in myocyte apoptosis. These changes characterize viable tissue, because they were not found in irreversibly injured myocardium. Our report demonstrates a novel mechanism by which the activation of an endogenous gene program of cell survival underlies the sustained viability of the hibernating heart. Potentially, promoting such a program offers a novel opportunity to salvage postmitotic tissues in conditions of ischemia.
Assuntos
Regulação da Expressão Gênica , Miocárdio Atordoado/genética , Miócitos Cardíacos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Sobrevivência Celular/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Feminino , Perfilação da Expressão Gênica , Transportador de Glucose Tipo 1 , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Proteínas Inibidoras de Apoptose , Imagem Cinética por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Animais , Chaperonas Moleculares , Proteínas de Transporte de Monossacarídeos/biossíntese , Proteínas de Transporte de Monossacarídeos/genética , Isquemia Miocárdica/genética , Miocárdio Atordoado/diagnóstico por imagem , Miócitos Cardíacos/citologia , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Tomografia por Emissão de Pósitrons , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Proteínas/genética , Proteínas/metabolismo , RNA Mensageiro/biossíntese , Sus scrofa , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND AND AIM OF THE STUDY: Stentless prostheses in the aortic position produce a superior hemodynamic profile in comparison to that with stented valves. To determine whether routine use of stentless valves in an elderly population is justified, a 10-year retrospective review was performed of a consecutive series of patients aged > or =75 years undergoing stentless aortic valve replacement (AVR). METHODS: Demographic, operative and mortality data were obtained retrospectively. Survivors were interviewed by telephone according to a defined protocol. Univariate and multivariate analysis was used to identify independent predictors of 30-day and overall medium-term mortality. Definitions and analyses were in accordance with joint STS/AATS guidelines. RESULTS: A total of 103 patients (57 males, 46 females; mean age 79.8 years; range: 75-91 years) underwent AVR with a either a Toronto stentless porcine valve (size range: 21-29 mm; n = 74) or an aortic homograft (n = 29). Twenty-eight patients (27%) had either urgent/emergency surgery, 12 (11%) underwent redo surgery, and in 54 cases (52%), the preoperative left ventricular function was significantly impaired (ejection fraction <50%). Forty patients (39%) also underwent concomitant coronary artery bypass grafting. The mean cross-clamp and cardiopulmonary bypass times were 105+/-22 min and 144+/-47 min, respectively. The overall 30-day mortality was 11.6% (n = 12). The 30-day mortality for all elective cases was 5.3%, but for isolated elective AVR was only 2.5%. Using a multivariate model, the only independent predictor of 30-day mortality and medium-term overall mortality was increasing age. The mean follow up period was 3.6 years (range: 0.1-9.3 years), and the Kaplan-Meier actuarial five-year survival was 52%. At follow up, 92% of patients were in NYHA functional classes I and II. CONCLUSION: Stentless AVR in elderly patients is associated with excellent functional and survival outcome in the medium term. Furthermore, in elective cases, age alone should not be a deterrent to the routine use of stentless aortic valves.
Assuntos
Valva Aórtica/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bioprótese , Ponte de Artéria Coronária , Feminino , Doenças das Valvas Cardíacas/mortalidade , Humanos , Masculino , Análise Multivariada , Desenho de Prótese , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Disfunção Ventricular Esquerda/cirurgiaRESUMO
PURPOSE: The intra-aortic balloon pump (IABP) provides circulatory support through counterpulsation. The hemodynamic effects of the IABP may vary with assisting frequency and depend on IAB inflation/deflation timing. We aimed to assess in vivo the IABP benefits on coronary, aortic, and left ventricular hemodynamics at different assistance frequencies and trigger timings. METHODS: Six healthy, anesthetized, open-chest sheep received IABP support at 5 timing modes (EC, LC, CC, CE, CL, corresponding to early/late/conventional/conventional/conventional inflation and conventional/conventional/conventional/early/late deflation, respectively) with frequency 1:3 and 1:1. Aortic (Q(ao)) and coronary (Q(cor)) flow, and aortic (P(ao)) and left ventricular (PLV) pressure were recorded simultaneously, with and without IABP support. Integrating systolic Q(ao) yielded stroke volume (SV). RESULTS: EC at 1:1 produced the lowest end-diastolic P(ao) (59.5 ± 7.8 mmHg [EC], 63.4 ± 11.1 mmHg [CC]), CC at 1:1 the lowest systolic PLV (69.1 ± 6.5 mmHg [CC], 76.4 ± 6.5 mmHg [control]), CC at 1:1 the highest SV (88.5 ± 34.4 ml [CC], 76.6 ± 31.9 ml [control]) and CC at 1:3 the highest diastolic Qcor (187.2 ± 25.0 ml/min [CC], 149.9 ± 16.6 ml/min [control]). Diastolic P(ao) augmentation was enhanced by both assistance frequencies alike, and optimal timings were EC for 1:3 (10.4 ± 2.8 mmHg [EC], 6.7 ± 3.8 mmHg [CC]) and CC for 1:1 (10.8 ± 6.7 mmHg [CC], -3.0 ± 3.8 mmHg [control]). CONCLUSIONS: In our experiments, neither a single frequency nor a single inflation/deflation timing, including conventional IAB timing, has shown superiority by uniformly benefiting all studied hemodynamic parameters. A choice of optimal frequency and IAB timing might need to be made based on individual patient hemodynamic needs rather than as a generalized protocol.
Assuntos
Coração Auxiliar , Hemodinâmica , Balão Intra-Aórtico/instrumentação , Animais , Feminino , Masculino , Ovinos , Fatores de TempoRESUMO
BACKGROUND: l Coronary artery bypass grafting for patients with ischemic left ventricular dysfunction (ILVD) remains superior to medical therapy in terms of long-term survival. Recently, off-pump coronary artery bypass surgery has been shown to be very promising in achieving functional improvements with favorable operative mortality in this challenging group of patients. The aim of this study was to assess the risk factors responsible for operative mortality in this group of patients. METHODS: The records of 305 consecutive ILVD patients, who underwent primary isolated coronary artery bypass grafting for multivessel disease at The National Heart and Lung Institute, Imperial College, University of London, between January 1999 and January 2002, were reviewed retrospectively. Patients were considered to have ILVD if they had a left ventricular ejection fraction of 0.30 or less on preoperative coronary angiography. One hundred six patients were operated on using the off-pump coronary artery bypass surgery technique, and 199 patients were operated on using the conventional coronary artery bypass grafting technique with cardiopulmonary bypass. RESU;TS: Seven (6.6%) patients died in the off-pump coronary artery bypass surgery group, whereas 28 (14.1%) patients died in the cardiopulmonary bypass group (p = 0.05). Univariate analysis of all the preoperative characteristics was performed to identify the potential predictors of mortality in the whole group of ILVD patients. Potential predictors of mortality included symptom status (stable/unstable), chronic obstructive airway disease, dyspnea grade III and IV on the New York Heart Association classification, intravenous nitrates, preoperative use of intraaortic balloon pump, ventricular tachycardia or ventricular fibrillation, body surface area less than 2, and cardiopulmonary bypass. Only ventricular tachycardia or ventricular fibrillation was proved to act as an independent predictor of operative mortality in this group of ILVD patients, with an odds ratio of 29.6 (95% confidence interval, 8.9 to 98). CONCLUSIONS: This study showed that using cardiopulmonary bypass for multivessel coronary artery bypass grafting in patients with ILVD was not proved to act as an independent predictor of operative mortality.