RESUMEN

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Aterosclerosis , Infarto del Miocardio , Prevención Primaria , Receptores de Interleucina-1 , Prevención Secundaria , Factor de Necrosis Tumoral alfa , Humanos , Angina Inestable/prevención & control , Angina Inestable/mortalidad , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Aterosclerosis/prevención & control , Aterosclerosis/mortalidad , Sesgo , Causas de Muerte , Infarto del Miocardio/prevención & control , Infarto del Miocardio/mortalidad , Prevención Primaria/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria/métodos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Receptores de Interleucina-1/antagonistas & inhibidores

RESUMEN

BACKGROUND: Postoperative myocardial infarction (POMI) is associated with major surgeries and remains the leading cause of mortality and morbidity in people undergoing vascular surgery, with an incidence rate ranging from 5% to 20%. Preoperative coronary interventions, such as coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCI), may help prevent acute myocardial infarction in the perioperative period of major vascular surgery when used in addition to routine perioperative drugs (e.g. statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents), CABG by creating new blood circulation routes that bypass the blockages in the coronary vessels, and PCI by opening up blocked blood vessels. There is currently uncertainty around the benefits and harms of preoperative coronary interventions. OBJECTIVES: To assess the effects of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, and CINAHL EBSCO on 13 March 2023. We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs that compared the use of preoperative coronary interventions plus usual care versus usual care for preventing acute myocardial infarction during major open vascular or endovascular surgery. We included participants of any sex or any age undergoing major open vascular surgery, major endovascular surgery, or hybrid vascular surgery. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were acute myocardial infarction, all-cause mortality, and adverse events resulting from preoperative coronary interventions. Our secondary outcomes were cardiovascular mortality, quality of life, vessel or graft secondary patency, and length of hospital stay. We reported perioperative and long-term outcomes (more than 30 days after intervention). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included three RCTs (1144 participants). Participants were randomised to receive either preoperative coronary revascularisation with PCI or CABG plus usual care or only usual care before major vascular surgery. One trial enrolled participants if they had no apparent evidence of coronary artery disease. Another trial selected participants classified as high risk for coronary disease through preoperative clinical and laboratorial testing. We excluded one trial from the meta-analysis because participants from both the control and the intervention groups were eligible to undergo preoperative coronary revascularisation. We identified a high risk of performance bias in all included trials, with one trial displaying a high risk of other bias. However, the risk of bias was either low or unclear in other domains. We observed no difference between groups for perioperative acute myocardial infarction, but the evidence is very uncertain (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.02 to 4.57; 2 trials, 888 participants; very low-certainty evidence). One trial showed a reduction in incidence of long-term (> 30 days) acute myocardial infarction in participants allocated to the preoperative coronary interventions plus usual care group, but the evidence was very uncertain (RR 0.09, 95% CI 0.03 to 0.28; 1 trial, 426 participants; very low-certainty evidence). There was little to no effect on all-cause mortality in the perioperative period when comparing the preoperative coronary intervention plus usual care group to usual care alone, but the evidence is very uncertain (RR 0.79, 95% CI 0.31 to 2.04; 2 trials, 888 participants; very low-certainty evidence). The evidence is very uncertain about the effect of preoperative coronary interventions on long-term (follow up: 2.7 to 6.2 years) all-cause mortality (RR 0.74, 95% CI 0.30 to 1.80; 2 trials, 888 participants; very low-certainty evidence). One study reported no adverse effects related to coronary angiography, whereas the other two studies reported five deaths due to revascularisations. There may be no effect on cardiovascular mortality when comparing preoperative coronary revascularisation plus usual care to usual care in the short term (RR 0.07, 95% CI 0.00 to 1.32; 1 trial, 426 participants; low-certainty evidence). Preoperative coronary interventions plus usual care in the short term may reduce length of hospital stay slightly when compared to usual care alone (mean difference -1.17 days, 95% CI -2.05 to -0.28; 1 trial, 462 participants; low-certainty evidence). We downgraded the certainty of the evidence due to concerns about risk of bias, imprecision, and inconsistency. None of the included trials reported on quality of life or vessel graft patency at either time point, and no study reported on adverse effects, cardiovascular mortality, or length of hospital stay at long-term follow-up. AUTHORS' CONCLUSIONS: Preoperative coronary interventions plus usual care may have little or no effect on preventing perioperative acute myocardial infarction and reducing perioperative all-cause mortality compared to usual care, but the evidence is very uncertain. Similarly, limited, very low-certainty evidence shows that preoperative coronary interventions may have little or no effect on reducing long-term all-cause mortality. There is very low-certainty evidence that preoperative coronary interventions plus usual care may prevent long-term myocardial infarction, and low-certainty evidence that they may reduce length of hospital stay slightly, but not cardiovascular mortality in the short term, when compared to usual care alone. Adverse effects of preoperative coronary interventions were poorly reported in trials. Quality of life and vessel or graft patency were not reported. We downgraded the certainty of the evidence most frequently for high risk of bias, inconsistency, or imprecision. None of the analysed trials provided significant data on subgroups of patients who could potentially experience more substantial benefits from preoperative coronary intervention (e.g. altered ventricular ejection fraction). There is a need for evidence from larger and homogeneous RCTs to provide adequate statistical power to assess the role of preoperative coronary interventions for preventing acute myocardial infarction in the perioperative period of major open vascular or endovascular surgery.

Asunto(s)

Puente de Arteria Coronaria , Procedimientos Endovasculares , Infarto del Miocardio , Intervención Coronaria Percutánea , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Puente de Arteria Coronaria/métodos , Complicaciones Posoperatorias/prevención & control , Procedimientos Endovasculares/métodos , Procedimientos Endovasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad , Cuidados Preoperatorios/métodos , Sesgo , Periodo Perioperatorio , Tiempo de Internación

RESUMEN

INTRODUCTION: The harmful effects of first and secondhand smoking are well-established. Smoke-free laws aim at protecting nonsmokers. This study aimed to assess the impact of the 2013 total ban on indoor smoking in Chile on hospitalizations and deaths of major cardiovascular events. AIMS AND METHODS: The logarithm of the monthly hospitalization and death rates, standardized by age for every 100 000 inhabitants, were estimated for ischemic heart disease, acute myocardial infarction, strokes, and a composite outcome of ischemic heart diseases (which includes acute myocardial infarction) and strokes. In addition, interrupted time series with synthetic control groups were used to assess changes in levels and trends after the intervention. RESULTS: The total ban on indoor smoking caused significant reductions in death rates for the three diseases studied for age groups above 20 years old. In addition, there were substantial decreases in the post-intervention hospitalization rates for ischemic heart disease: for the 20-44 age group, the decrease was 8.7% compared to the pre-intervention period (p < .01). In comparison, such a reduction was 4% (p < .01) for the ≥65 age group. For acute myocardial infarction, the decrease was 11.5% (p < .01) for the 20-44 age group, while for stroke, it was a 1.2% (p < .01) decrease for the total population. It is estimated that the smoking ban averted 15.6% of the deaths compared with the synthetic control groups. CONCLUSIONS: The implementation of total smoke-free environments in Chile contributed to the reduction of mortality for main cardiovascular diseases. This study provides additional evidence of causality linking the policy to health outcomes. IMPLICATIONS: The total indoor smoking ban significantly affected age-standardized hospitalization and deaths. The number of deaths averted by this policy is estimated at approximately 4758 and 5256 for IHD and stroke, respectively, during the 2013-2017 period (15.6% fewer deaths than predicted by the synthetic control groups). The study contributes to the body of evidence that supports total indoor smoking bans.

Asunto(s)

Enfermedades Cardiovasculares , Hospitalización , Contaminación por Humo de Tabaco , Humanos , Chile/epidemiología , Hospitalización/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Contaminación por Humo de Tabaco/prevención & control , Contaminación por Humo de Tabaco/legislación & jurisprudencia , Contaminación por Humo de Tabaco/efectos adversos , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Anciano , Masculino , Femenino , Adulto Joven , Política para Fumadores/legislación & jurisprudencia , Infarto del Miocardio/mortalidad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Fumar/legislación & jurisprudencia , Fumar/epidemiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control

RESUMEN

BACKGROUND: Glucocorticoid (GR) and mineralocorticoid (MR) receptors are highly expressed in cardiac tissue, and both can be activated by corticosteroids. MR activation, in acute myocardial infarction (AMI), worsens cardiac function, and increase NHE activity contributing to the deleterious process. In contrast, effects of GR activation are not fully understood, probably because of the controversial scenario generated by using different doses or potencies of corticosteroids. AIMS: We tested the hypothesis that an acute dose of hydrocortisone (HC), a low-potency glucocorticoid, in a murine model of AMI could be cardioprotective by regulating NHE1 activity, leading to a decrease in oxidative stress. MATERIALS AND METHODS: Isolated hearts from Wistar rats were subjected to regional ischemic protocol. HC (10 nmol/L) was added to the perfusate during early reperfusion. Infarct size and oxidative stress were determined. Isolated papillary muscles from non-infarcted hearts were used to evaluate HC effect on sodium-proton exchanger 1 (NHE1) by analysing intracellular pH recovery from acute transient acidosis. RESULTS: HC treatment decreased infarct size, improved cardiac mechanics, reduced oxidative stress after AMI, while restoring the decreased level of the pro-fusion mitochondrial protein MFN-2. Co-treatment with the GR-blocker Mifepristone avoided these effects. HC reduced NHE1 activity by increasing the NHE1 pro-inhibiting Ser648 phosphorylation site and its upstream kinase AKT. HC restored the decreased AKT phosphorylation and anti-apoptotic BCL-2 protein expression detected after AMI. CONCLUSIONS: Our results provide the first evidence that acute HC treatment during early reperfusion induces cardioprotection against AMI, associated with a non-genomic HC-triggered NHE1 inhibition by AKT and antioxidant action that might involves mitochondrial dynamics improvement.

Asunto(s)

Infarto del Miocardio , Daño por Reperfusión , Ratas , Ratones , Animales , Miocardio/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Hidrocortisona/farmacología , Hidrocortisona/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucocorticoides/farmacología , Glucocorticoides/metabolismo , Ratas Wistar , Intercambiadores de Sodio-Hidrógeno , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismo , Daño por Reperfusión/metabolismo

RESUMEN

Antecedentes. El valor pronóstico de una ergometría positiva en el contexto de imágenes tomográficas de perfusión miocárdica de estrés y reposo (SPECT) normales no está bien establecido. Objetivos. Documentar la incidencia de infarto, muerte y revascularización coronaria en pacientes con una ergometría positiva de riesgo intermedio e imágenes de perfusión SPECT normales, y explorar el potencial valor del puntaje de riesgo de Framingham en la estratificación pronóstica de estos pacientes. Métodos. Cohorte retrospectiva integrada por pacientes que habían presentado síntomas o hallazgos electrocardiográficos compatibles con enfermedad arterial coronaria durante la prueba de esfuerzo, con criterios de riesgo intermedio en la puntuación de Duke y perfusión miocárdica SPECT normal. Fueron identificados a partir de la base de datos del laboratorio de cardiología nuclear del Instituto de Cardiología y Cirugía Cardiovascular de la ciudad de Posadas, Argentina. Resultados. Fueron elegibles 217 pacientes. El seguimiento fue de 3 1,5 años. La sobrevida libre de eventos (muerte,infarto de miocardio no fatal, angioplastia coronaria o cirugía de bypass de arteria coronaria) a uno, tres y cinco años fue significativamente menor (Log-rank test, p= 0,001) en el grupo con puntaje de Framingham alto o muy alto (77, 71y 59 %, respectivamente) que en el grupo de puntaje bajo o intermedio (89, 87 y 83 %). Tomando como referencia a los pacientes con riesgo bajo en el puntaje de Framingham, luego de ajustar por edad, sexo y puntaje de Duke, los pacientes categorizados en los estratos alto y muy alto riesgo del puntaje de Framingham presentaron una incidencia del evento combinado cercana al triple (hazard ratio [HR] 2,81; intervalo de confianza [IC] del 95 % 0,91 a 8,72; p= 0,07 y HR 3,61;IC 95 % 1,23 a 10,56; p= 0,019 respectivamente). Conclusiones. La estimación de riesgo con el puntaje de Framingham sería de ayuda en la estratificación pronóstica de los pacientes con ergometría positiva y SPECT normal. (AU)

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Background. The prognostic value of positive exercise testing with normal SPECT myocardial perfusion imaging is not well established. Objectives. To document the incidence of infarction, death, and coronary revascularization in patients with a positive intermediate-risk exercise test and normal SPECT perfusion images and to explore the potential value of the Framingham Risk Score in the prognostic stratification of these patients. Methods. A retrospective cohort comprised patients who presented symptoms or electrocardiographic findings compatible with coronary artery disease during the stress test, with intermediate risk criteria in the Duke score and normal SPECT myocardial perfusion. They were identified from the database of the nuclear cardiology laboratory of the Instituto de Cardiología y Cirugía Cardiovascular of Posadas, Argentina. Results. 217 patients were eligible. Follow-up was 3 1.5 years. Event-free survival (death, non-fatal myocardial infarction, coronary angioplasty, or coronary artery bypass surgery) at one, three, and five years was significantly lower (Log-ranktest, p: 0.001) in the group with a score of Framingham high or very high (77, 71 and 59 %, respectively) than in the lowor intermediate score group (89, 87 and 83 %). Taking as reference the low-risk patients in the Framingham score, after adjusting for age, sex, and Duke score, the patients categorized in the high-risk and very high-risk strata showed about three times higher incidence of the combined event (hazard ratio [HR] 2.81; 95 % confidence interval [CI] 0.91 to 8.72;p=0.07 and HR 3.61; 95 % CI 1.23 to 10.56; p=0.019 respectively). Conclusions. Risk estimation with the Framingham score would be helpful in the prognostic stratification of patients with positive exercise testing and normal SPECT. (AU)

Asunto(s)

Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Infarto del Miocardio/prevención & control , Infarto del Miocardio/diagnóstico por imagen , Análisis de Supervivencia , Tomografía Computarizada de Emisión de Fotón Único , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Ergometría , Medición de Riesgo/métodos , Prueba de Esfuerzo , Imagen de Perfusión Miocárdica , Intervención Coronaria Percutánea , Infarto del Miocardio/mortalidad

RESUMEN

La evaluación de la perfusión miocárdica con SPECT combina una prueba de esfuerzo (ergometría o estrés farmacológico) junto a imágenes de perfusión con radioisótopos. Este estudio es útil para establecer el diagnóstico de enfermedad arterial coronaria, estratificar el riesgo de infarto y tomar decisiones terapéuticas. Un resultado normal aporta un alto valor predictivo negativo, es decir, una muy baja probabilidad de que el paciente presente eventos cardiovasculares. El hallazgo de signos de isquemia en la ergometría podría poner en jaque el valor predictivo negativo de una perfusión normal. En presencia de este resultado, el paso siguiente es evaluar los predictores de riesgo en la ergometría, el riesgo propio del paciente en función de los antecedentes clínicos y el puntaje cálcico coronario, cuando este se encuentra disponible. Ante la presencia concomitante de otros marcadores de riesgo se sugiere completar la evaluación con un estudio anatómico.El uso de nuevas tecnologías podría mejorar la precisión en la predicción de eventos. (AU)

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Assessment of myocardial perfusion with SPECT combines a stress test (ergometry or pharmacological stress) with radioisotope perfusion imaging. This test is helpful to diagnose coronary artery disease, stratify the risk of heart attack, and make therapeutic decisions. A normal result provides a high negative predictive value; therefore, the probability of cardiovascular events is very low. Signs of ischemia on an ergometry could jeopardize the negative predictive value of normal perfusion. In this clinical setting, the next step is to evaluate the risk predictors in the stress test, the individual risk based on the clinical history, and the coronary calcium score when available. Given the simultaneous presence of other risk markers,completing the evaluation with an anatomical study is suggested. The use of new technologies could improve the accuracy of event prediction. (AU)

Asunto(s)

Humanos , Tomografía Computarizada de Emisión de Fotón Único , Ergometría , Isquemia Miocárdica/diagnóstico por imagen , Medición de Riesgo/métodos , Imagen de Perfusión Miocárdica , Infarto del Miocardio/prevención & control , Pronóstico , Sobrevida , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Sensibilidad y Especificidad , Prueba de Esfuerzo , Toma de Decisiones Clínicas

RESUMEN

BACKGROUND: Dexmedetomidine (DEX), a specific α2-adrenergic receptor agonist, is protective against myocardial ischemia/reperfusion injury (MIRI). However, the association between DEX preconditioning-induced cardioprotection and mitophagy suppression remains unclear. OBJECTIVE: Hence, we aimed to investigate whether DEX preconditioning alleviates MIRI by suppressing mitophagy via α2-adrenergic receptor activation. METHOD: Sixty isolated rat hearts were treated with or without DEX before inducing ischemia and reperfusion; an α2-adrenergic receptor antagonist, yohimbine (YOH), was also administered before ischemia, alone or with DEX. The heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal and minimal rate of left ventricular pressure development (±dp/dtmax), and myocardial infarction size were measured. The mitochondrial ultrastructure and autophagosomes were assessed using transmission electron microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using JC-1 and dichloride hydrofluorescein diacetate assays, respectively. The expression levels of the mitophagy-associated proteins Beclin1, LC3II/I ratio, p62, PINK1, and Parkin were detected by western blotting. RESULTS: Compared with the control group, in the ischemia/reperfusion group, the HR, LVDP, and ±dp/dtmax were remarkably decreased (p< 0.05), whereas LVEDP and infarct sizes were significantly increased (p< 0.05). DEX preconditioning significantly improved cardiac dysfunction reduced myocardial infarction size, maintained mitochondrial structural integrity, increased mitochondrial membrane potential, inhibited autophagosomes formation, and decreased ROS production and Beclin1, LC3II/I ratio, PINK1, Parkin, and p62 expression(p< 0.05). When DEX and YOH were combined, YOH canceled the effect of DEX, whereas the use of YOH alone had no effect. CONCLUSION: Therefore, DEX preconditioning was cardioprotective against MIRI in rats by suppressing mitophagy via α2-adrenergic receptor activation.

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FUNDAMENTO: A dexmedetomidina (DEX), um agonista específico do receptor α2-adrenérgico, é protetora contra lesão de isquemia/reperfusão miocárdica (I/R). No entanto, a associação entre a cardioproteção induzida pelo pré-condicionamento DEX e a supressão da mitofagia permanece pouco clara. OBJETIVO: Portanto, nosso objetivo foi investigar se o pré-condicionamento com DEX alivia a I/R, suprimindo a mitofagia via ativação do receptor α2-adrenérgico. MÉTODO: Sessenta corações de ratos isolados foram tratados com ou sem DEX antes de induzir isquemia e reperfusão; um antagonista do receptor α2-adrenérgico, a ioimbina (YOH), também foi administrado antes da isquemia, isoladamente ou com DEX. A frequência cardíaca (FC), pressão diastólica do ventrículo esquerdo (PDVE), pressão diastólica final do ventrículo esquerdo (PDFVE), taxa máxima e mínima de desenvolvimento da pressão ventricular esquerda (±dp/dtmax) e tamanho do infarto do miocárdio foram medidos. A ultraestrutura mitocondrial e as autofagossomas foram avaliadas por microscopia eletrônica de transmissão. O potencial de membrana mitocondrial e os níveis de espécies reativas de oxigênio (ROS) foram medidos usando os ensaios JC-1 e diacetato de diclorodi hidrofluoresceína, respectivamente. Os níveis de expressão das proteínas associadas à mitofagia Beclin1, relação LC3II/I, p62, PINK1 e Parkin foram detectados por western blotting. RESULTADOS: Em comparação com o grupo controle, no grupo isquemia/reperfusão, a FC, PDVE e ±dp/dtmax foram notavelmente diminuídas (p<0,05), enquanto os tamanhos da PDFVE e do infarto aumentaram significativamente (p<0,05). O pré-condicionamento com DEX melhorou significativamente a disfunção cardíaca, reduziu o tamanho do infarto do miocárdio, manteve a integridade estrutural mitocondrial, aumentou o potencial de membrana mitocondrial, inibiu a formação de autofagossomas e diminuiu a produção de ROS e a relação Beclin1, relação LC3II/I, expressão PINK1, Parkin e p62(p<0,05). Quando DEX e YOH foram combinados, o YOH cancelou o efeito da DEX, enquanto o uso de YOH sozinha não teve efeito. CONCLUSÃO: Portanto, o pré-condicionamento DEX foi cardioprotetor contra I/R em ratos, suprimindo a mitofagia por meio da ativação do receptor α2-adrenérgico.

Asunto(s)

Dexmedetomidina , Infarto del Miocardio , Daño por Reperfusión Miocárdica , Daño por Reperfusión , Ratas , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Beclina-1 , Mitofagia , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas , Receptores Adrenérgicos

RESUMEN

SUMMARY: The main cause of mortality and disability globally is myocardial infarction (MI). Isoproterenol (ISO), a β-adrenoceptor agonist, has been used to induce rat myocardial necrosis. Whereas interleukin-37 (IL-37) has anti-inflammatory and cytoprotective properties. The study aimed to investigate the potential protective effects of IL-37 administration on cardiac architecture, oxidative stress, and inflammatory markers during ISO-induced MI in rats. Three groups of adult male rats were used in this study, the normal control group (n=8), ISO-induced MI group (n=8) that received isoproterenol hydrochloride (ISO) (100 mg/kg/day, SC, for the first 2 consecutive days), and IL-37-treated group (ISO+IL-37) (n=8) that received recombinant human IL-37 (40 µg/kg /day, intraperitoneally, for 2 weeks during and after ISO injections. Heart rate (HR.) and ECG changes were monitored. Some oxidative stress markers such as superoxide dismutase (SOD), nitric oxide (NOx), malondialdehyde (MDA), and glutathione (GSH) tissue levels in the tissue homogenate were assayed. Interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), caspase-8, P53, and C- reactive protein (CRP) were among the inflammatory markers examined. In addition, serum levels of creatinine kinase (CK-MB) and lactate dehydrogenase (LDH) were analyzed to evaluate the myocardial injury. For histological analysis, tissues were sectioned, fixed in paraffin, and stained with hematoxylin and eosin (H&E), Masson Trichrome and, immunohistochemical against NF-kB, TNF-α, and Caspase-9. IL-37 improved ECG changes, cardiac enzyme markers, and some inflammatory markers of oxidative stress in ISO-induced MI. It also improved the histopathological and immunohistochemical changes in MI. In conclusion: IL-37 might be a promising therapeutic modality in myocardial infarction.

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La principal causa de mortalidad y discapacidad a nivel mundial es el infarto de miocardio (IM). El isoproterenol (ISO), un agonista de los receptores adrenérgicos β, se ha utilizado para inducir necrosis miocárdica en ratas. Mientras que la interleucina-37 (IL-37) tiene propiedades antiinflamatorias y citoprotectoras. El estudio tuvo como objetivo investigar los posibles efectos protectores de la administración de IL-37 en la arquitectura cardíaca, el estrés oxidativo y los marcadores inflamatorios durante el infarto de miocardio inducido por ISO en ratas. En este estudio se utilizaron tres grupos de ratas macho adultas, el grupo control normal (n=8), el grupo con IM inducido por ISO (n=8) que recibió clorhidrato de isoproterenol (ISO) (100 mg/kg/día, SC, durante los primeros 2 días consecutivos) y el grupo tratado con IL-37 (ISO+IL- 37) (n=8) que recibió IL-37 humana recombinante (40 µg/kg/día, por vía intraperitoneal, durante 2 semanas durante y después de las inyecciones de ISO. Se monitorearon la frecuencia cardíaca (FC) y los cambios en el ECG. Se analizaron algunos marcadores de estrés oxidativo como la superóxido dismutasa (SOD), el óxido nítrico (NOx), el malondialdehído (MDA) y los niveles tisulares de glutatión (GSH) en el homogeneizado de tejido. La interleucina-6 (IL-6), el factor de necrosis tumoral-α (TNF-α), la caspasa-8, la P53 y la proteína C reactiva (CRP) se encontraban entre los marcadores inflamatorios examinados. Se analizaron los niveles de creatinoquinasa (CK-MB) y lactato deshidrogenasa (LDH) para evaluar la lesión miocárdica; para el análisis histológico se seccionaron los tejidos, se fijaron en parafina y se tiñeron con hematoxilina y eosina (H&E), Tricromo de Masson e inmunohistoquímica contra NF-kB, TNF-α y Caspasa-9. IL-37 mejoró los cambios de ECG, los marcadores de enzimas cardíacas y algunos marcadores inflamatorios de estrés oxidativo en el IM inducido por ISO. Además mejoró los cambios histopatológicos e inmunohistoquímicos en MI. En conclusión: la IL-37 podría ser una modalidad terapéutica prometedora en el infarto de miocardio.

Asunto(s)

Animales , Masculino , Ratas , Interleucinas/administración & dosificación , Corazón/efectos de los fármacos , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/prevención & control , Inmunohistoquímica , Ratas Wistar , Estrés Oxidativo/efectos de los fármacos , Inflamación , Isoproterenol/efectos adversos

RESUMEN

PURPOSE: Myocardial ischemia/reperfusion injury (MIRI) leads to myocardial tissue necrosis, which will increase the size of myocardial infarction. The study examined the protective effect and mechanism of the Guanxin Danshen formula (GXDSF) on MIRI in rats. METHODS: MIRI model was performed in rats; rat H9C2 cardiomyocytes were hypoxia-reoxygenated to establish a cell injury model. RESULTS: The GXDSF significantly reduced myocardial ischemia area, reduced myocardial structural injury, decreased the levels of interleukin (IL-1ß, IL-6) in serum, decreased the activity of myocardial enzymes, increased the activity of superoxide dismutase (SOD), and reduced glutathione in rats with MIRI. The GXDSF can reduce the expression of nucleotide- binding oligomerization domain, leucine-rich repeat and pyrin domain containing nod-like receptor family protein 3 (NLRP3), IL-1ß, caspase-1, and gasdermin D (GSDMD) in myocardial tissue cells. Salvianolic acid B and notoginsenoside R1 protected H9C2 cardiomyocytes from hypoxia and reoxygenation injury and reduced the levels of tumor necrosis factor α (TNF-α) and IL-6 in the cell supernatant, decreasing the NLRP3, IL-18, IL-1ß, caspase-1, and GSDMD expression in H9C2 cardiomyocytes. GXDSF can reduce the myocardial infarction area and alleviate the damage to myocardial structure in rats with MIRI, which may be related to the regulation of the NLRP3. CONCLUSIONS: GXDSF reduces MIRI in rat myocardial infarction injury, improves structural damage in myocardial ischemia injury, and reduces myocardial tissue inflammation and oxidative stress by lowering inflammatory factors and controlling focal cell death signaling pathways.

Asunto(s)

Infarto del Miocardio , Isquemia Miocárdica , Daño por Reperfusión Miocárdica , Salvia miltiorrhiza , Ratas , Animales , Ratas Sprague-Dawley , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-6/metabolismo , Salvia miltiorrhiza/metabolismo , Miocitos Cardíacos/patología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/metabolismo , Caspasa 1 , Hipoxia/metabolismo

RESUMEN

Dentre as Doenças Cardiovasculares, o infarto agudo do miocárdio (IAM) é a principal causa de hospitalizações no Brasil. A educação do paciente é fundamental para uma alta segura por meio do envolvimento do paciente, da família e do cuidador e as tecnologias educacionais são as estratégias para mediar esses processos de ensino e aprendizado para troca de experiências e desenvolvimento de habilidades. Percebe-se uma lacuna relacionada a estudos que avaliam o efeito de intervenções validadas no Brasil que orientem pacientes para a alta hospitalar após o IAM. Assim, esse estudo teve por objetivo avaliar efeito de uma intervenção por cenário simulado no conhecimento de pacientes acometidos por IAM sobre cuidados após alta hospitalar. Trata-se de um estudo composto por duas etapas: estudo metodológico de elaboração e validação de conteúdo de cenário simulado para pacientes acometidos por IAM e estudo quase experimental, do tipo antes e depois de avaliação do efeito da intervenção por cenário simulado no conhecimento sobre cuidados após alta hospitalar em pacientes acometidos por IAM desenvolvido em um hospital de cuidado terciário, público e de grande porte, referência em Cardiologia da cidade de Belo Horizonte, Minas Gerais. A amostra foi composta por 58 pacientes com idade maior ou igual a 18 anos, acometidos por IAM, com ou sem supradesnivelamento do segmento ST submetidos a tratamento clínico ou Intervenção Coronária Percutânea com quadro clínico estável, orientados no tempo e espaço, e em condições de responder ao instrumento de coleta. O estudo foi desenvolvido em três fases, sendo: 1­Avaliação do conhecimento do paciente antes da intervenção; 2­Intervenção com cenário simulado e 3­Avaliação do conhecimento do paciente após a intervenção. Os dados foram submetidos a análise estatística quantitativa com os testes teste t-student e Teste de Shapiro- Wilk. Para validação de conteúdo do cenário simulado foram avaliados itens relacionados à: clareza de linguagem, pertinência prática e relevância teórica. O índice de validação de conteúdo global foi satisfatório para a análise geral do cenário pelos especialistas apresentando o valor de 100%. Em relação aos pacientes, predominou o sexo masculino (60,3%), com mediana de idade de 60 anos. O principal diagnóstico foi IAM sem supra de ST ou IAM de localização não especificada (75%) e hipertensão (70,7%) e diabetes (32,8%) como comorbidades mais prevalentes. Quanto à avaliação do conhecimento após aplicação do cenário simulado, observou- se que os domínios com melhores desempenhos foram 'Clínico', 'Exercícios', 'Dieta' e "Psicossocial" apresentando diferença significativa com valor de p=0,012; 0,028;<0,001 e 0,026, respectivamente. Na análise da média global observou-se diferença significativa (p<0,001), ou seja, houve melhora do conhecimento dos pacientes em relação aos cuidados após alta para prevenção de novos eventos coronarianos. A intervenção por cenário simulado para orientação de alta hospitalar de pacientes pós-IAM mostrou-se efetiva e modificou o conhecimento dos pacientes participantes. Ressalta-se que o planejamento da alta deve fornecer informações claras, oportunas e pautadas em evidências científicas para a garantia de uma transição suave do ambiente hospitalar para o cuidado em casa.

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Among Cardiovascular Diseases, acute myocardial infarction (AMI) is the leading cause of hospitalizations in Brazil. Patient education is crucial for a safe discharge through the involvement of the patient, family, and caregiver, and educational technologies are the strategies to mediate these teaching and learning processes for the exchange of experiences and skills development. There is a gap in studies evaluating the effect of validated interventions in Brazil guiding patients for hospital discharge after AMI. Thus, this study aimed to evaluate the effect of an intervention through simulated scenarios on the knowledge of patients affected by AMI regarding post-hospital discharge care. This study consists of two stages: a methodological study for the development and validation of content in a simulated scenario for patients affected by AMI, and a quasi-experimental study, before and after the assessment of the effect of the simulated scenario intervention on knowledge about post-hospital discharge care in patients affected by AMI. The study was conducted at a large, public, tertiary care hospital, a reference in Cardiology in the city of Belo Horizonte, Minas Gerais.The sample included 58 patients aged 18 or older, affected by AMI, with or without ST-segment elevation, undergoing clinical treatment or Percutaneous Coronary Intervention with a stable clinical condition, oriented in time and space, and able to respond to the data collection instrument. The study was developed in three phases: 1 ­ Evaluation of patient knowledge before the intervention; 2 ­ Intervention with simulated scenarios; and 3 ­ Evaluation of patient knowledge after the intervention. Data were subjected to quantitative statistical analysis using the t-student test and Shapiro-Wilk test. For content validation of the simulated scenario, items related to language clarity, practical relevance, and theoretical significance were evaluated. The overall content validation index was satisfactory for the overall scenario analysis by experts, with a value of 100%. Regarding patients, males predominated (60.3%), with a median age of 60 years. The main diagnosis was AMI without ST elevation or AMI of unspecified location (75%), with hypertension (70.7%) and diabetes (32.8%) as the most prevalent comorbidities. Concerning the evaluation of knowledge after the application of the simulated scenario, it was observed that the domains with the best performances were 'Clinical,' 'Exercise,' 'Diet,' and 'Psychosocial,' showing a significant difference with values of p=0.012, 0.028, <0.001, and 0.026, respectively. In the analysis of the overall mean, a significant difference was observed (p<0.001), indicating an improvement in patients' knowledge regarding post-discharge care to prevent new coronary events. The intervention through simulated scenarios for post-AMI hospital discharge guidance proved to be effective and modified the knowledge of participating patients. It is emphasized that discharge planning should provide clear, timely information based on scientific evidence to ensure a smooth transition from the hospital environment to home care.

Asunto(s)

Alta del Paciente , Enfermedad de la Arteria Coronaria , Tecnología Educacional , Infarto del Miocardio/prevención & control , Educación en Salud , Enfermería

RESUMEN

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

Asunto(s)

Síndrome Coronario Agudo , Gripe Humana , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Síndrome Coronario Agudo/terapia , Gripe Humana/prevención & control , Infarto del Miocardio/prevención & control , Vacunación , Accidente Cerebrovascular/prevención & control , Vacunas de Productos Inactivados , Resultado del Tratamiento

RESUMEN

BACKGROUND: Myocardial infarction (MI) is associated with high mortality rates, despite the fact that there are therapies available. Importantly, excessive oxidative stress may contribute to ischemia/reperfusion injury leading to death related to MI. In this scenario, naturally occurring antioxidant compounds are an important source of possible therapeutic intervention. Thus, this study sought to elucidate the mechanisms of cardioprotection of s-limonene in an isoproterenol-induced MI animal model. METHODS: Wistar rats were treated with 1 mg/kg s-limonene (SL) or 100 mg/kg N-acetylcysteine (NAC, positive control) once, 30 min after isoproterenol-induced MI (applied in two doses with a 24 h interval). The protective effects of SL in the heart were examined via the serum level of creatine kinase myocardial band (CK-MB), electrocardiographic profile, infarct size and histological parameters. Using isolated cardiomyocytes, we also assessed calcium transient amplitude, cytosolic and mitochondrial oxidative stress and the expression of proteins related to oxidative stress. RESULTS: SL at a concentration of 1 mg/kg attenuated isoproterenol-induced MI injury, by preventing ST-segment elevation and QTc prolongation in the ECG. SL reduced the infarct size and collagen content in cardiac tissue. At the cellular level, SL prevented increased Ca2+, associated with attenuation of cytosolic and mitochondrial oxidative stress. These changes resulted in a reduction of the oxidized form of Ca2+ Calmodulin-Dependent Kinase II (CaMKII) and restored superoxide dismutase and glutathione peroxidase activity. CONCLUSION: Our data show that s-limonene promotes cardioprotection against MI injury, probably through inhibition of increased Ca2+ and attenuation of oxidative stress via CaMKII.

Asunto(s)

Lesiones Cardíacas , Infarto del Miocardio , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Lesiones Cardíacas/metabolismo , Isoproterenol/toxicidad , Limoneno/metabolismo , Limoneno/farmacología , Limoneno/uso terapéutico , Modelos Teóricos , Infarto del Miocardio/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/prevención & control , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

CONTEXT: C-Phycocyanin is a protein with anti-scavenger, antioxidant and anti-inflammatory actions against agents that cause cellular damage. The cardioprotective action of C-phycocyanin against acute myocardial infarction (AMI) has not been studied in animal models. OBJECTIVE: To investigate C-phycocyanin's effect on oxidative stress, inflammation and cardiac damage in a model of isoproterenol-induced AMI. MATERIALS AND METHODS: Wistar rats were divided into four groups: (1) sham + vehicle (0.9% saline solution by oral gavage, OG); (2) sham + C-phycocyanin (50 mg/kg/d, OG); (3) AMI + vehicle, and (4) AMI + C-phycocyanin. AMI was induced by administering isoproterenol (20, 10, 5 and 3 mg/kg each dose per day), and serum cardiac enzymes were quantified. After five days, the animals were euthanized; the heart was dissected to determine oxidative stress, redox environment, inflammation and cardiac damage markers. RESULTS: We observed that C-phycocyanin reduced AMI-increased cardiac enzymes (CK by about 53%, CKMB by about 60%, AST by about 16% and ALT by about 21%), lipid peroxidation (57%), reactive oxygen species (50%), nitrites (46%), oxidized glutathione (41%), IL1ß (3%), INFγ (5%), TNFα 3%), Bcl2 (37%), Bax (43%), COX2 (21%) and caspase 9 (61%). Finally, C-phycocyanin reduced AMI-induced aberrant histological changes related to myonecrosis, interstitial oedema and inflammatory infiltration in the heart muscle. CONCLUSIONS: C-Phycocyanin prevents AMI-induced oxidative stress, inflammation and heart damage. This study is the first report that employed C-phycocyanin in an animal model of AMI and supports the potential use of C-phycocyanin in the management of AMI.

Asunto(s)

Infarto del Miocardio , Ficocianina , Animales , Inflamación/tratamiento farmacológico , Inflamación/prevención & control , Infarto del Miocardio/patología , Infarto del Miocardio/prevención & control , Estrés Oxidativo , Ficocianina/efectos adversos , Ficocianina/metabolismo , Ratas , Ratas Wistar

Asunto(s)

Ingestión de Alimentos , Grasa Subcutánea Abdominal , Factores de Riesgo de Enfermedad Cardiaca , Síndrome Metabólico , Dieta , Síndrome Coronario Agudo , Obesidad Abdominal/etiología , Infarto del Miocardio/prevención & control

RESUMEN

Cardiovascular diseases have high morbidity and mortality rates, and their treatment is not effective in reducing the damage caused by myocardial infarction (MI). This study aimed to investigate whether nerolidol (NRD), a sesquiterpene alcohol, could attenuate MI in an isoproterenol-treated rat model. MI was induced by the administration of two doses of isoproterenol (ISO, 100 mg/kg, i.p.) with an interval of 24 h between doses.The animals were divided into four groups: control (CTR) (vehicle - NaCl 0.9% + Tween 80 0.2%), MI (ISO + vehicle), MI + NRD (50 mg/kg) and MI + NRD (100 mg/kg). An electrocardiogram was performed, and contractile parameters, cardiac enzymes, infarction size, and antioxidant parameters in the heart were measured to evaluate the effects of NRD. The ISO group showed a significant rise in ST segment, QTc, and heart rate associated with a reduction in left ventricular developed pressure (LVDP), + dP/dt, and -dP/dt. In addition, there were increases in levels of creatine kinase (CK), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and thiobarbituric acid (TBARS); reductions in superoxide dismutase (SOD) and catalase (CAT) activities; and an increase in the infarction size. Interestingly, NRD significantly attenuated almost all the parameters of ISO-induced MI mentioned above. Our results suggest that nerolidol attenuates MI caused by ISO by a marked reduction in myocardial infarct size and suppression of oxidative stress. CK total, creatine kinase total; CK-MB, creatine kinase myocardial band; LDH, lactate dehydrogenase; SOD, superoxide dismutase; CAT, catalase. CTR (vehicle group), MI (100 mg/kg of isoproterenol), ISO + NRD 50 (50 mg/kg of nerolidol), and ISO + NRD 100 (100 mg/kg of nerolidol).

Asunto(s)

Cardiotónicos/farmacología , Infarto del Miocardio/prevención & control , Sesquiterpenos/farmacología , Animales , Antioxidantes/metabolismo , Cardiotónicos/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Isoproterenol , L-Lactato Deshidrogenasa/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Sesquiterpenos/administración & dosificación , Superóxido Dismutasa/metabolismo

RESUMEN

CONTEXT: Infarction leads to a decrease in NO bioavailability in the erythrocytes. Thyroid hormones (TH) present positive effects after infarction. However, there are no studies evaluating the effects of cardioprotective doses of TH in the erythrocytes after infarction. OBJECTIVE: This study aimed to evaluate the effects of TH in NO bioavailability and oxidative stress parameters in the erythrocytes of infarcted rats. MATERIAL AND METHODS: Wistar rats were allocated into the three groups: Sham-operated (SHAM), infarcted (AMI) and infarcted + TH (AMIT). AMIT rats received T4 and T3 for 12 days by gavage. Subsequently, the animals were evaluated by echocardiography and the LV and erythrocytes were collected. RESULTS: TH improved NO bioavailability and increased catalase activity in the erythrocytes. Besides that, TH increased HIF-1α in the heart. CONCLUSION: TH seems to be positive for erythrocytes preventing a decrease in NO bioavailability and increasing antioxidant enzymatic defense after infarction.

Asunto(s)

Antioxidantes , Infarto del Miocardio , Animales , Ratas , Catalasa , Eritrocitos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/metabolismo , Ratas Wistar , Hormonas Tiroideas/farmacología , Óxido Nítrico

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Enfermedades Cardiovasculares/inducido químicamente , Accidente Cerebrovascular/inducido químicamente , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Insuficiencia Cardíaca , Metformina/efectos adversos , Infarto del Miocardio/inducido químicamente , Sodio/uso terapéutico , Estados Unidos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/epidemiología , Medicare , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Glucosa/uso terapéutico , Hipoglucemiantes/efectos adversos , Infarto del Miocardio/prevención & control , Infarto del Miocardio/epidemiología

Asunto(s)

Humanos , Embarazo , Niño , Marcapaso Artificial , Bradicardia/complicaciones , Bradicardia/prevención & control , Bradicardia/terapia , Síndromes de la Apnea del Sueño/complicaciones , Cardiomiopatía Hipertrófica/complicaciones , Electrocardiografía Ambulatoria/métodos , Trasplante de Corazón/efectos adversos , Infarto del Miocardio/prevención & control

RESUMEN

Resumo Fundamento A cardiopatia isquêmica atraiu muito atenção devido às altas taxas de mortalidade, custos do tratamento e a crescente morbidade na população jovem. Estratégias de reperfusão reduziram a mortalidade. Porém, a reperfusão pode levar à morte do cardiomiócito e subsequente dano irreversível ao miocárdio. No momento, não há um tratamento eficiente e direcionado para a lesão de isquemia-reperfusão (I/R). Objetivos Avaliar se a dexmedetomidina (DEX) tem efeito protetivo na I/R do miocárdio e explorar os possíveis mecanismos por trás dela. Métodos Corações de ratos foram perfundidos com o sistema de perfusão de Langendorff e aleatoriamente distribuídos em cinco grupos: grupo controle, perfundido com solução de Krebs-Henseleit (K-H) por 205 minutos sem isquemia; e quatro grupos de teste que foram submetidos a 40 minutos de isquemia global e 120 minutos de reperfusão. O Grupo DEX, o grupo ioimbina (IO) e o grupo DEX + IO foram perfundidos com DEX (10 nM), IO (1 μM) ou a combinação de DEX e IO antes da reperfusão, respectivamente. A hemodinâmica cardíaca, o tamanho do infarto do miocárdio e a histologia do miocárdio foram avaliados. A expressão da proteína-78 regulada pela glicose (GRP78), a proteína quinase do retículo endoplasmático (PERK), a PERK fosforilada, o fator de iniciação eucariótico 2α (eIF2α), eIF2α fosforilado, o fator de transcrição 4 (TCF-4) e a proteína homóloga à proteína ligadora do acentuador CCAAT (CHOP) foram avaliados. P< 0,05 foi considerado para indicar a diferença estatisticamente significativa. Resultados O pré-condicionamento com DEX melhorou a função cardíaca nos corações com I/R, reduziu o infarto do miocárdio, a apoptose do miocárdio e a expressão de GRP78, p-PERK, eIF2α, p-eIF2α, TCF-4 e CHOP. Conclusões O pré-tratamento com DEX reduziu a lesão de I/R no miocárdio ao suprimir a apoptose, o que foi induzido pela via PERK.

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Abstract Background Ischemic heart disease has attracted much attention due to its high mortality rates, treatment costs and the increasing morbidity in the young population. Strategies for reperfusion have reduced mortality. However, reperfusion can lead to cardiomyocyte death and subsequent irreversible myocardial damage. At present, the timely and targeted treatment of ischemia-reperfusion (I/R) injury is often lacking. Objectives To evaluate if dexmedetomidine (DEX) has a protective effect in myocardiual I/R and explore the possible mechanism behind it. Methods Rat hearts were perfused with a Langendorff perfusion system, and randomly assigned to five groups: control group, perfused with Krebs-Henseleit (K-H) solution for 205 minutes without ischemia; and four test groups that underwent 40 minutes of global ischemia and 120 min of reperfusion. The DEX group, the yohimbine (YOH) group and the DEX + YOH group were perfused with DEX (10 nM), YOH (1 μM) or the combination of DEX and YOH prior to reperfusion, respectively. Cardiac hemodynamics, myocardial infarct size, and myocardial histology were evaluated. The expression of glucose-related protein 78 (GRP78), protein kinase R-like ER kinase (PERK), phosphorylated PERK, eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α, activating transcription factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) were assessed. P<0.05 was considered to indicate a statistically significant difference. Results DEX preconditioning improved the cardiac function of I/R hearts, reduced myocardial infarction, myocardial apoptosis, and the expression of GRP78, p-PERK, eIF2α, p-eIF2α, ATF4 and CHOP. Conclusions DEX pretreatment reduced myocardial I/R injury by suppressing apoptosis, which was induced by the PERK pathway.

Asunto(s)

Animales , Ratas , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión , Isquemia Miocárdica , Dexmedetomidina/farmacología , Infarto del Miocardio/prevención & control , Infarto del Miocardio/tratamiento farmacológico , Transducción de Señal

RESUMEN

Abstract Background Stroke and acute myocardial infarction (AMI) are cardiovascular diseases commonly characterized by the development of atheromatous plaques associated with major complications and high mortality rates. Objective To identify an epidemiological trend in hospitalizations due to stroke and AMI and to analyze the relationship between health programs applied in Primary Health Care, gender and the Federative Unit. Methods Ecological study with a time series design between 1998 and 2018, collecting data from all federal units in Brazil stratified by, gender and place of residence. There were analyzed Hospitalization Authorizations (AIH) for stroke and MI, consulting the Hospital Admissions System (SIH) of the Informatics Department of the National Health Service with p <0.05. Results From 1998 to 2018, the rate of hospitalization for AMI increased in Brazil approximately 42.58 events per 100 thousand inhabitants annually (p<0.001), while hospitalizations for stroke declined 32.17 cases (p=0.03). This pattern was observed in both sexes in AMI and stroke. There is also evidence of the effect of the Hiperdia (p<0.001) and Mais Médicos (p=0.001) program in reducing stroke and Hiperdia cases in mitigating the evolution of AMI cases (p = 0.0001). Conclusion Although these diseases remain as an important cause of death, stroke hospitalization has reduced significantly in the period evaluated. National programs as the Hiperdia and Mais Médicos showed an impact in the acute cases of strokes and AMI.

Asunto(s)

Atención Primaria de Salud , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Consorcios de Salud , Hospitalización , Infarto del Miocardio/prevención & control , Infarto del Miocardio/epidemiología , Factores de Tiempo , Brasil/epidemiología , Estudios Ecológicos , Placa Aterosclerótica , Programas Nacionales de Salud