A intervenção precoce do paciente com síndrome coronariana aguda e sua implicação na redução da morbimortalidade cardiovascular / The early intervention of acute coronary disease and its implication in the reduction of cardiovascular morbimortality

Introdução. O infarto agudo do miocárdio apresenta significativas taxas de morbimortalidade. A reperfusão precoce por angioplastia primária é a intervenção que reduz a mortalidade e as complicações, e deve ser iniciada em até 12 horas, a fim de impedir a perda muscular irreversível. O tempo entre chegada do paciente ao hospital e a abertura da artéria acometida, tempo porta-balão, determina a morbimortalidade do paciente. Objetivo. Esse estudo busca analisar o potencial benefício do tratamento da reperfusão coronariana precoce, os fatores de risco, as possíveis complicações e o Killip em pacientes que sofreram infarto agudo do miocárdio relacionando-os a sua morbimortalidade. Materiais e métodos. Estudo observacional transversal realizado por meio de coleta de dados dos prontuários dos pacientes submetidos a angioplastia primária de um hospital privado. Resultados. A hipertensão arterial sistêmica foi a variável mais prevalente (75%), e que houve predomínio no sexo masculino (71%) e associação com a progressão da idade. 61% dos pacientes apresentaram um tempo porta balão menor que 90 minutos. Houve significância estatística entre o tempo porta balão e a evolução do Killip, evidenciando um tempo porta-balão maior que 90 minutos na maioria dos pacientes que obtiveram aumento da pontuação do Killip. Conclusão. A precocidade da intervenção no paciente com IAM impacta na morbimortalidade, visto que o tempo porta balão está diretamente associado a evolução da do Killip. Logo, deve-se identificar os fatores que interferem no atendimento, a fim de proporcionar uma intervenção otimizada. (AU)

Introduction. Acute myocardial infarction has significant rates of morbidity and mortality. Early reperfusion by primary angioplasty is the intervention that reduces mortality and complications, and should be started within 12 hours in order to prevent irreversible muscle loss. The time between the patient's arrival at the hospital and the opening of the affected artery, door-to-balloon time, determines the patient's morbidity and mortality. Objective. The proposition of this study is to analyze the potential benefits of early coronary reperfusion, associated with the risk factors, possible complications, and the Killip score in patients whit acute myocardial infarction (AMI) and the relation of those factors with the morbidity and mortality. Materials and methods. This is a transversal observational study and uses data collected of medical records of patients subjected to primary angioplasty in a private hospital. Results. Systemic arterial hypertension was the most prevalent one (75%), it was more common in males (71%) and associated with a higher age. In 61% of the patients port-balloon time was less than 90 minutes. There was statistical significance between port-balloon time and Killip score evaluation, that showed a higher score in patient with a port-balloon time that exceeded 90 minutes. Conclusion. Early intervention in patients with AMI impacts morbimortality, once that the port-balloon time is directly associated with the Killip score results. Therefore, all factors that can lead to a delay in their care of those patients should be identified with the objective of optimize the intervention. (AU)

Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction.

OBJECTIVES: This study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size. BACKGROUND: Ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemia-reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1α is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3ß. METHODS: AMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1° Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1° Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified. RESULTS: Compared with 1° Reperfusion, 1° Unloading reduced LV wall stress and increased myocardial levels of SDF-1α, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3ß in the infarct zone. 1° Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1° Reperfusion (73 ± 13% vs. 42 ± 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01). CONCLUSIONS: Compared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up-regulates SDF-1α/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI.

An experimental model of myocardial infarction and controlled reperfusion using a miniaturized cardiopulmonary bypass in rats.

OBJECTIVES: Different revascularization strategies for patients with acute myocardial infarction (AMI) exist. It remains unclear whether ventricular unloading using cardiopulmonary bypass (CPB) or extracorporeal life support (ECLS) has an impact on early postischaemic ventricular function. Here, we report on the results of an approach using a miniaturized CPB in a well-established animal model of AMI. METHODS: In a randomized fashion, 30 male Wistar rats were assigned to temporary left anterior descending (LAD) ligation (30 min) followed by 180 min of reperfusion either with or without 60 min of CPB (70 ml/min, 36°C). The CPB circuit consisted of a venous reservoir, a peristaltic roller pump and a membrane oxygenator with heat exchanger. Cardiac function was measured at 60 and 120 min after reperfusion (F60, F120) using a conductance catheter. RESULTS: The mortality rate was 37% (11/30). Thus, 19 animals could be included into the analysis (8 CPB). The mean cardiac output did not differ between the groups at F60 [63 ± 29 vs 54 ± 25 ml/min (CPB), P = 0.56] and F120 [73 ± 27 vs 53 ± 24 ml/min (CPB), P = 0.21]. During reperfusion, the mean left ventricular ejection fraction (LVEF) was stable in both the control (F60 37 ± 5% vs F120 33 ± 8%, P = 0.42) and the CPB groups (F60 52 ± 11% vs F120 51 ± 13%, P = 0.71). CPB animals had a significantly better LVEF after reperfusion (F60 P = 0.007, F120 P = 0.01). CONCLUSIONS: In this animal model of AMI, the establishment of CPB resulted in a significantly better LVEF in comparison with conventional reperfusion only. This beneficial effect may have an impact on revascularization strategies and timing in patients presenting with AMI in the future.

Development of a new selective coronary perfusion cannula.

The two most common types of coronary perfusion cannulae currently being used are the "balloon type", with a balloon at the tip, and the "fenestrated type", which has holes along the side near the tip. However, on occasion an unusually high perfusion pressure or a considerable amount of leakage is encountered during infusion of the cardioplegic solution. We have examined the properties of a newly developed Kochi Medical School (KMS)-type cannula and compared these to the properties of the balloon-type and fenestrated-type cannulae in an ex vivo experimental model that contains ostia of 4, 3, or 2 mm in diameter. Ejected flow velocity, circuit pressure, and the amount of leakage were measured at an infusion rate of 100 and 200 mL/min, with the latter two parameters measured under the counterpressure of 0 and 50 cmH2O to examine the influence of coronary vascular resistance. Without counterpressure, the balloon type presented with the highest flow velocity (263 cm/s at 200 mL/min) and perfusion pressure (64 mmHg at 200 mL/min) but without leakage. The fenestrated type yielded a considerable amount of leakage (40 % at an ostium size of 2 mm). The KMS type showed a lower flow velocity and circuit pressure with less leakage. Under 50 cmH2O counterpressure, however, only the KMS-type cannula could inject the water to any ostium size at both flow rates. These results suggest that the concept of the KMS-type cannula may be advantageous to achieving a secure infusion to a diseased coronary ostium.

Novel F-18-labeled PET myocardial perfusion tracers: bench to bedside.

Myocardial perfusion imaging is a widely used approach to noninvasively identify myocardial ischemia and guide therapies. It is typically performed using single photon emission computed tomography. The competing technology positron emission tomography (PET) offers higher diagnostic accuracies but suffers from logistical limitations due to the use of short-lived radioisotopes. New (18)F-labeled perfusion markers were introduced in the past years and offer simplified supply approaches, as known from oncologic PET imaging. This review summarizes the available literature especially from preclinical studies, but also very recent findings from early clinical trials. We discuss the consequences of long-lived radioisotopes in myocardial PET and the potential role of absolute blood flow quantification to establish efficient clinical protocols.

Estudo comparativo entre o protocolo convencional de estresse com dobutamina e um novo protocolo mais rápido e com menos efeitos adversos / Comparative study between the conventional dobutamine stress protocol and new faster protocol with fewer adverse effects

Fundamentos: a cintilografia de perfusão miocárdica (CPM) após estresse com dobutamina (Dob) tem o seu valor diagnóstico comprovado, sendo principalmente utilizada em pacientes com contra-indicação para emprego de vasodilatadores, como dipiridamol ou adenosina.No entanto, o protocolo convencional recomendado para estresse com Dob é demorado e com efeitos adversos frequentes.Objetivos:comparar dois protocolos de estresse com Dob em pacientes encaminhados para a realização de CPM.Métodos: Foram estudados consecutivamente 110 pacientes encaminhados para a realização de CPM após estresse com Dob. Todos apresentavam contra-indicação para a realização de estresse com vasodilatador...

Evolução temporal do perfil de gravidade clínico e das intervenções invasivas e farmacológicas no infarto agudo do miocárdio em unidade coronariana no período de 1994-2003 / Trends in outcomes of severe clinical profile and management of invasive and pharmacological interventions of acute myocardial infarction in the coronary care unit from 1994 to 2003

Objetivo: analisar o comportamento do perfil de gravidade clínico, as intervenções invasivas e farmacológicas em pacientes acometidos de Infarto Agudo do Miocárdio (IAM), ao longo de 9 anos.Métodos: Estudo de coorte, em que foram avaliados 1055 pacientes, não selecionados e consecutivos, internados com diagnóstico de IAM, no período de 1994-2003, em unidade coronariana (UC). Foram analisadas variáveis relacionadas ao perfil clínico, procedimentos invasivos e farmacológicos. A análise estatística utilizou o qui-quadrado para tendência linear.Resultados: Entre os 1055 pacientes incluídos, 67,4 por cento eram homens e 32,4 por cento mulheres, com idade média de 60,93 anos e 64,84 anos, respectivamente. Não se observou variação significativa no conjunto do perfil de grvidade dos pacientes...

Long-term preservation using a new apparatus combined with suppression of pro-inflammatory cytokines improves donor heart function after transplantation in a canine model.

OBJECTIVE: We developed a new apparatus for long-term heart preservation that combines simple immersion with coronary perfusion. In a previous study, we reported that suppression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta), improved results after transplantation. In this study, we evaluated whether long-term preservation using our apparatus for continuous coronary perfusion, combined with suppression of pro-inflammatory cytokines, improves donor heart function after transplantation in a canine model. METHODS: We used adult mongrel dogs in this study. Coronary vascular beds were washed with University of Wisconsin (UW) solution after arresting hearts with glucose-insulin-potassium solution. The heart was then excised and preserved for 12 hours with a combination of immersion and coronary perfusion using a preservation apparatus. Adult mongrel dogs were divided into 2 groups: the coronary perfusion (CP) group (n = 7) and the FR167653 (FR-CP) group (n = 6). In the CP group, we used a 4 degrees C UW solution for immersion and coronary perfusion. In the FR-CP group, we used a 4 degrees C UW solution supplemented with 20 mg/liter of the anti-inflammatory agent FR167653 for immersion and coronary perfusion. At 2 and at 3 hours after orthotopic transplantation, we compared hemodynamic parameters with pre-operative values in donor animals, with right atrial pressure at 10 mm Hg and with 5 microg/kg/min dopamine infusion. We compared serum concentrations of TNF-alpha from the coronary sinus and compared electron microscopic studies between the 2 groups. RESULTS: Three hours after transplantation, cardiac output (CO), left ventricular pressure (LVP), and -LVdp/dt were significantly greater (p < 0.05) in the FR-CP group than in the CP group (CO, 178% +/- 65% vs 93% +/- 40%; LVP, 115% +/- 22% vs 73% +/-26%; -LVdp/dt, 168% +/- 13% vs 61% +/- 17%, respectively). Electron microscopic studies showed that glycogen was well preserved in the FR-CP group compared with the CP group. Serum concentrations of TNF-alpha were decreased significantly in the FR-CP group compared with the CP group at 3 hours after reperfusion (161 +/- 54 pg/dl vs 642 +/- 636 pg/dl, respectively). CONCLUSION: Hemodynamics after transplantation were significantly better in the FR-CP group than in the CP group. The combined preservation method of continuous perfusion and immersion using our apparatus in conjunction with suppression of pro-inflammatory cytokines improves donor heart function after transplantation.

Changes in P-selectin expression on cardiac microvessels in blood-perfused rat hearts subjected to ischemia-reperfusion.

BACKGROUND: During cardiac surgery involving cardiopulmonary bypass, activation of polymorphonuclear cells is believed to contribute to ischemia-reperfusion injury and subsequent myocardial impairment of function. The early tethering of polymorphonuclear cells to blood vessel walls depends upon recognition of the adhesion molecule P-selectin on endothelium. The purpose of this study was to define the kinetic changes in expression of P-selectin on myocardial vessels in a model of global ischemia-reperfusion injury. METHODS: In a novel recirculating blood-based perfusion system, rat hearts were subjected to 30 minutes of aerobic perfusion, 60 minutes of global ischemia, and 60 minutes of reperfusion, or to 120 minutes of continuous aerobic blood perfusion (with or without leukocyte/platelet depletion). Heart function (left ventricular developed pressure), heart rate, and perfusion pressure were monitored throughout. Hearts were sampled at defined periods for microvascular expression of P-selectin, identified by immunohistochemistry. RESULTS: In control (nonperfused) hearts and in hearts subjected to perfusion and ischemia, few cardiac vessels (8% to 16%) expressed P-selectin. After 15 minutes of reperfusion, P-selectin was present on the majority of vessels (77%; p < 0.05) but expression decreased subsequently throughout the remaining duration of reperfusion. Interestingly, upregulation of P-selectin also occurred when hearts were subjected to continuous perfusion alone (no ischemia), but this upregulation was less rapid. Depletion of leukocytes/platelets from the blood perfusate did not modify P-selectin expression. CONCLUSIONS: The augmented expression of P-selectin on myocardial vessels during reperfusion of ischemic hearts probably reflects changes induced during global ischemia and by the duration of perfusion through the nonbiological tubing of the circuit. That is likely to mimic the effects initiated during cardiopulmonary bypass.

Extended support with the Terumo Baby-RX oxygenator.

The Terumo Baby-RX, a new-generation low prime oxygenator, recently has entered the perfusion market in North America. This oxygenator is designed exclusively for neonates and infants and has the smallest priming volume of any clinically available oxygenator. The BABY-RX also is treated with X Coating, Terumo's biocompatible, hydrophilic polymer surface coating that reduces platelet adhesion and protein denaturation. The oxygenator has a blood flow range of 0.1 to 1500 mL/min and operates with a minimum reservoir volume of 15 mL. A 3.2-kg patient, status post-Stage 1 Norwood, Palliation was placed on cardiopulmonary support after thrombus formation within the modified Blalock-Taussig shunt during a general surgery procedure. The extended support circuit incorporated the Baby-RX oxygenator for 17.5 hours. The oxygenator performed well over this time period at flows of 600-800 mL/min, sweep rates of 100-300 mL/min, FiO2 of 30-40%, and ACTs of 140-200 seconds. There were no indices of oxygenator failure noted within the time frame of support. After placement of a new systemic to pulmonary shunt, the patient was removed from support and the oxygenator drained of residual blood. No evidence of fiber damage or clot formation was noted. The patient had a successful support run without complications related to cardiopulmonary support.

A non-heart-beating donor model to evaluate functional and morphologic outcomes in resuscitated pig hearts.

A non-heart-beating donor model was considered to examine whether pig hearts from the abattoir could be resuscitated by whole blood reperfusion. For preservation, machine perfusion using University of Wisconsin (UW) solution was compared with storage on ice. Nineteen hearts from abattoir pigs, harvested 25 +/- 3 min after exsanguination, were harvested and transported to the laboratory. Controls (n = 7) were immediately reperfused with homologous whole pig blood in an isolated heart model for 60 min with monitoring of left ventricular developed pressure (LVDP), contractility, and coronary flow. UW solution hearts (UW, n = 6) were perfused for 4 h with 10 degrees C cold UW solution before blood reperfusion. In the cold storage group (CS, n = 6), the organs were stored for an additional 4 h on ice before blood reperfusion. In all hearts, histology was performed after 60 min of blood reperfusion to evaluate myocardial reperfusion injury. All three groups showed significant increases in LVDP (p <.001), although this functional recovery was earliest in the control group and latest in the UW group. Significant declines were observed for both LVDP and contractility from the peak values in each group to the end of blood reperfusion. Coronary flow increased steadily over the time course for the UW group, whereas in the control and CS groups flow increased during the first 15 min of blood reperfusion and then decreased. In the UW and CS groups, there were significant positive correlations between coronary flow and LVDP (p <.001). Microscopic examination revealed no differences between the three groups. Thus, hearts from an abattoir with 25 min of warm ischemic time can be resuscitated. For storage of these organs, continuous machine perfusion with UW solution is superior to cold storage on ice.

Resposta contrátil de miócitos cardíacos isolados a níveis fisiológicos de pressão hidrostática / Contractile response of isolated cardiac myocytes to physiological levels of hydrostatic pressure

Com o advento da técnica de isolamento de células cardíacas por digestão enzimática, tornaram-se possíveis inúmeros estudos sobre a atividade contrátil cardíaca. Muito se tem progredido no estudo do acoplamento excitação-contração no coração sadio e doente. Contudo, na situação fisiológica, as células do coração estão submetidas a pressões da ordem de 100 mmHg durante parte do cliclo cardíaco, condição na qual se desconhece o comportamento dos miócitos, provavelmente pela dificuldade de montagem de preparação adequada. Com a possibilidade de medição de encurtamento celular por meio da detecção de borda de sinal de vídeo, realizamos um estudo do efeito de níveis diferentes de pressão, na faixa fisiológica, sobre a atividade contrátil de miócitos ventriculares isolados de ratos adultos, usando para isto uma câmara de perfusão desenvolvida no nosso laboratório. Os resultados indicaram que, para pressões supra-atmosféricas de até 140 mm-Hg, o limiar estimulatório, amplitude do encurtamento, tempo para encurtamento máximo e duração total da contração não foram afetados significativamente. Concluímos que a pressão hidrostática aplicada não deve submeter os miócitos a qualquer tensão, indicando que estes aparentemente comportam-se como recipientes homogeneamente preenchidos de fluido incompressível.

Caracteristicas operativas de la perfusion miocardica de reposo en la evaluacion del dolor toracico en urgencias / Myocardial perfusion at rest in chest pain

Objetivo: evaluar las características operativas de la perfusión miocárdica de reposo con sestamibi-Tc99m, en pacientes que consultan a urgencias con dolor torácico y electrocardiograma normal o no diagnóstico. Métodos: se condujo un estudio de pruebas diagnósticas para establecer la sensibilidad, la especificidad, el valor predictivo negativo, el valor predictivo positivo y la razón de verosimilitud de la perfusión miocárdica de reposo. Se utilizó la arteriografía coronaria como patrón de oro. Se midió la variabilidad entre los observadores con un coeficiente kappa. Los evaluadores del resultado de la perfusión miocárdica no conocían los hallazgos de la arteriografía coronaria. Resultados: se incluyeron 52 pacientes entre mayo de 1996 y mayo de 1997. Todos ellos se sometieron a estudio de perfusión miocárdica de reposo. Se utilizó la arteriografía como patrón de oro y el seguimiento a seis meses. La perfusión miocárdica de reposo mostró una sensibilidad de 96 por ciento con especificidad de 92.5 por ciento. El valor predictivo negativo encontrado fue de 97.3 por ciento para el diagnóstico de síndrome coronario agudo. La razón de verosimilitud negativa indica que el resultado negativo identificó en forma correcta, como sanos, al 92 por ciento de los pacientes. Conclusión: debido al alto valor predictivo negativo de la perfusión miocárdica de reposo y a su adecuada capacidad para clasificar correctamente los pacientes sanos como tales, se podría considerar su uso como una estrategia razonable en el tamízale de pacientes que consultan a urgencias con dolor torácico y electrocardiograma normal o no diagnóstico. La perfusión miocárdica de reposo es adecuada para definir cuáles de los pacientes con dolor precordial deben hospitalizarse y cuáles son susceptibles de ser estudiados en forma ambulatoria.

LV-powered coronary sinus retroperfusion reduces infarct size in acutely ischemic pigs.

BACKGROUND: We developed a prosthetic left ventricle (LV) to coronary sinus (CS) shunt (LVCSS) that is autoregulating and provides LV-powered retrograde perfusion of the coronary sinus. METHODS: Each of 20 Yorkshire pigs underwent 1 hour of left anterior descending diagonal artery occlusion followed by 3 hours of reperfusion. The controls (n = 5) did not have shunt treatment. The LVCSS group (n = 9) underwent shunt treatment during the ischemic period. The LVCSS with partial coronary sinus occlusion (PCSO) group (LVCSS+PCSO, n = 6) underwent shunt treatment and PCSO during the ischemic period. Vital staining and planimetry techniques were used to determine the area at risk for infarction and the area of necrosis. RESULTS: The area at risk was not significantly different among groups. The area of necrosis was decreased by 53% in the LVCSS group and by 73% in the LVCSS+PCSO group when compared to controls (p<0.01 among all groups). CONCLUSIONS: The LVCSS reduces infarct size in pigs after acute coronary artery occlusion. The addition of PCSO to LVCSS further improves myocardial salvage.