RESUMEN
BACKGROUND: On the one hand, the primary coronary slow flow phenomenon (CSFP) can cause recurrence of chest pain, prompting medical examinations and further healthcare costs, while on the other hand, it can lead to myocardial infarction, ventricular arrhythmia and sudden cardiac death. Nevertheless, there is not any agreement on the optimal treatment for primary CSFP, so we decided to examine the effectiveness of sildenafil in this context. METHODS: This pilot study is a 12-week, triple-blind, randomised, placebo-controlled trial for receiving either 50 mg daily oral sildenafil or placebo. Twenty eligible patients aged 30-70 years from a tertiary hospital in Yazd were randomly allocated in a 1:1 ratio to two groups. The primary outcomes were the alterations in functional capacity (metabolic equivalents, METs), Duke treadmill score (DTS) and angina severity (Canadian Cardiovascular Society (CCS) class). The study protocol registration code is IRCT20220223054103N1. RESULTS: The angina severity in the Sildenafil group improved, with all receivers achieving a state of being asymptomatic during regular physical activity (CCS I). Whereas just 40% of the recipients in the placebo group achieved the same level of improvement (p=0.011). Mean METs at baseline were 9.9 (SD: 3.1) and at week 12 were 13.1 (SD: 3.3) for sildenafil and 9.56 (SD: 2.1) and 9.63 (SD: 2.4) for placebo (difference favouring sildenafil with a median increase of 3.1 (IQR: 1.1 to 4.1, p=0.008)). Median DTS scores at baseline were 3 (IQR: 0 to 9) and at week 12 were 9.5 (IQR: 7.75 to 15) for sildenafil and 7 (IQR: -1.5 to 9.25) and 8 (IQR: 1.5 to 11.25) for placebo (difference favouring sildenafil with a median increase of 5.5 (IQR: 1 to 9.2, p=0.01)). CONCLUSIONS: We suggest that a daily low dose of sildenafil could be a valuable therapeutic option for primary CSFP. TRIAL REGISTRATION NUMBER: IRCT20220223054103N1.
Asunto(s)
Circulación Coronaria , Citrato de Sildenafil , Vasodilatadores , Humanos , Citrato de Sildenafil/administración & dosificación , Citrato de Sildenafil/uso terapéutico , Persona de Mediana Edad , Masculino , Proyectos Piloto , Femenino , Anciano , Resultado del Tratamiento , Adulto , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéutico , Circulación Coronaria/efectos de los fármacos , Método Doble Ciego , Factores de Tiempo , Administración Oral , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Inhibidores de Fosfodiesterasa 5/administración & dosificación , Angiografía CoronariaRESUMEN
BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.
Asunto(s)
Cardiomiopatías , Modelos Animales de Enfermedad , Epinefrina , Microcirculación , Choque Séptico , Animales , Perros , Choque Séptico/fisiopatología , Choque Séptico/complicaciones , Choque Séptico/sangre , Epinefrina/sangre , Microcirculación/efectos de los fármacos , Cardiomiopatías/fisiopatología , Cardiomiopatías/sangre , Cardiomiopatías/etiología , Volumen Sistólico/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/sangre , Isquemia Miocárdica/complicaciones , Función Ventricular Izquierda/efectos de los fármacos , Catecolaminas/sangre , Troponina/sangre , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/fisiopatología , Factores de Tiempo , Imagen de Perfusión Miocárdica/métodos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. METHODS: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. RESULTS: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). CONCLUSIONS: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.
Asunto(s)
Nitroglicerina , Diálisis Renal , Vasodilatación , Vasodilatadores , Humanos , Femenino , Masculino , Diálisis Renal/métodos , Persona de Mediana Edad , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Nitroglicerina/farmacología , Nitroglicerina/administración & dosificación , Anciano , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Acetilcolina/farmacología , Acetilcolina/administración & dosificación , Fallo Renal Crónico/terapia , Fallo Renal Crónico/fisiopatología , Arteria Braquial/efectos de los fármacos , Arteria Braquial/fisiopatología , Adenosina/administración & dosificación , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Vasos Coronarios/efectos de los fármacos , Angiografía CoronariaRESUMEN
OBJECTIVE: To test the efficacy of metformin (MET) during the induction of coronary ischemia on myocardial performance in a large animal model of coronary artery disease (CAD) and metabolic syndrome (MS), with or without concomitant extracellular vesicular (EV) therapy. BACKGROUND: Although surgical and endovascular revascularization are durably efficacious for many patients with CAD, up to one-third are poor candidates for standard therapies. For these patients, many of whom have comorbid MS, adjunctive strategies are needed. EV therapy has shown promise in this context, but its efficacy is attenuated by MS. We investigated whether MET pretreatment could ameliorate therapeutic decrements associated with MS. METHODS: Yorkshire swine (n = 29) were provided a high-fat diet to induce MS, whereupon an ameroid constrictor was placed to induce CAD. Animals were initiated on 1000 mg oral MET or placebo; all then underwent repeat thoracotomy for intramyocardial injection of EVs or saline. Swine were maintained for 5 weeks before the acquisition of functional and perfusion data immediately before terminal myocardial harvest. Immunoblotting and immunofluorescence were performed on the most ischemic tissue from all groups. RESULTS: Regardless of EV administration, animals that received MET exhibited significantly improved ejection fraction, cardiac index, and contractility at rest and during rapid myocardial pacing, improved perfusion to the most ischemic myocardial region at rest and during pacing, and markedly reduced apoptosis. CONCLUSIONS: MET administration reduced apoptotic cell death, improved perfusion, and augmented both intrinsic and load-dependent myocardial performance in a highly translatable large animal model of chronic myocardial ischemia and MS.
Asunto(s)
Enfermedad de la Arteria Coronaria , Modelos Animales de Enfermedad , Metformina , Animales , Metformina/farmacología , Metformina/uso terapéutico , Porcinos , Enfermedad de la Arteria Coronaria/cirugía , Síndrome Metabólico , Precondicionamiento Isquémico Miocárdico/métodos , Enfermedad Crónica , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Circulación Coronaria/efectos de los fármacosRESUMEN
Studies assessing the treatment of refractory no-reflow in patients with ST-elevation myocardial infarction (STEMI) are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary adrenaline administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after the initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in Group 1 received adrenaline, and 45 patients in Group 2 (control) received conventional treatments alone. After intracoronary drug administration, the adrenaline group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction grade 3 (56% vs 29% [p = 0.01]) and resolution of STEMI >50% after PCI (78% vs 36% [p <0.001]). Additionally, the adrenaline group showed a lower indexed microvascular obstruction (MVO) volume compared with the control group (0.9 [0.3; 3.1] % vs 1.9 [0.6; 7.9] % [p = 0.048]). A significant improvement in ejection fraction (EF) was observed in the adrenaline group (p = 0.025). Intracoronary adrenaline administration during PCI in patients with STEMI with refractory no-reflow is more effective compared with conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of STEMI, enhances EF, and reduces MVO volume. Intracoronary adrenaline administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary adrenaline administration during PCI could be an effective treatment strategy for patients with STEMI with refractory no-reflow.
Asunto(s)
Angiografía Coronaria , Circulación Coronaria , Epinefrina , Fenómeno de no Reflujo , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Femenino , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/fisiopatología , Epinefrina/administración & dosificación , Persona de Mediana Edad , Fenómeno de no Reflujo/etiología , Resultado del Tratamiento , Estudios Prospectivos , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Vasos Coronarios , Anciano , Inyecciones IntraarterialesRESUMEN
Understanding of the mechanisms contributing to the increased maternal susceptibility for major adverse cardiovascular events in the postpartum period remains poor. Accordingly, this study tested the hypothesis that the balance between coronary blood flow and myocardial metabolism is compromised during the puerperium period (35-45 days post-delivery) in swine. Systemic and coronary hemodynamic responses were assessed in anesthetized, open-chest control (nonpregnant) and puerperium/postpartum swine at baseline and in response to intravenous infusion of dobutamine (1-30 µg/kg/min). Blood pressure and heart rate were lower in postpartum swine at baseline and in response to dobutamine (P < 0.05). Coronary blood flow and myocardial oxygen delivery were significantly diminished at baseline in postpartum swine (P < 0.001), which corresponded with â¼35% reduction in myocardial oxygen consumption (MVO2) (P < 0.001). Postpartum swine displayed enhanced retrograde coronary flow, larger cardiomyocyte area (P < 0.01) and marked capillary rarefaction (P < 0.01). The relationship between coronary blood flow and heart rate (P < 0.05) or MVO2 (P < 0.001) was significantly diminished in postpartum swine as dobutamine increased MVO2 up to â¼135% in both groups. This reduction in myocardial perfusion was associated with decreases in myocardial lactate uptake (P < 0.001), increases in coronary venous PCO2 (P < 0.01) and decreased coronary venous pH (P < 0.01). These findings suggest an impaired balance between coronary blood flow and myocardial metabolism could contribute to the increased incidence of maternal myocardial ischemia and premature death in the postpartum period.
Asunto(s)
Circulación Coronaria , Miocardio , Periodo Posparto , Animales , Femenino , Porcinos , Miocardio/metabolismo , Circulación Coronaria/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Dobutamina/farmacología , Consumo de Oxígeno/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , EmbarazoRESUMEN
BACKGROUND: Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR. OBJECTIVES: This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial. METHODS: Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m2) [95% CI: 26.1-29.5 kg/m2)]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments. RESULTS: Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; P = 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; P = 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; P = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; P = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; P = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; P =0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; P = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; P = 0.009). CONCLUSIONS: Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; NCT04657939).
Asunto(s)
Estudios Cruzados , Diabetes Mellitus Tipo 2 , Tolerancia al Ejercicio , Hipoglucemiantes , Liraglutida , Pioglitazona , Humanos , Masculino , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/metabolismo , Persona de Mediana Edad , Liraglutida/uso terapéutico , Liraglutida/farmacología , Femenino , Anciano , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Tolerancia al Ejercicio/efectos de los fármacos , Tolerancia al Ejercicio/fisiología , Pioglitazona/uso terapéutico , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Resistencia a la Insulina/fisiologíaRESUMEN
BACKGROUND: Extensive evidence has suggested the cardio-protective properties of the polyphenol curcumin. The aim of this study was to investigate the effects of a highly bioavailable curcumin supplement on cardiometabolic risk factors, health-related quality of life, and depression in patients with coronary slow flow phenomenon (CSFP). METHODS: This randomized double-blind placebo-controlled clinical trial was conducted in 42 patients with CSFP (age 35-70 years, 25 ≤ body mass index < 40 kg/m2). Patients received either 80 mg/day nano-curcumin or placebo for 12 weeks. Serum levels of visfatin, high-sensitivity C-reactive protein (hs-CRP), and glycemic indices were measured before and after the intervention. The short form 36-item quality of life (SF-36) and Beck's Depression Inventory-II (BDI-II) questionnaires were assessed, as well. RESULTS: No significant improvements were observed in circulating hs-CRP and visfatin following the intervention. A significant increase was observed in pre- to post-fasting blood glucose (- 0.9 ± 12.2 vs. 7.7 ± 12.4 mg/dl, p = 0.02) and hemoglobin A1C (- 0.1 ± 0.8 vs. 0.5 ± 0.8%, p = 0.04) levels, in the placebo compared with the intervention group. Physical (8.2 ± 8.1 vs. - 1.2 ± 6.5, p < 0.001) and mental (6.8 ± 11.8 vs. - 1.1 ± 10.4, p = 0.02) component summary scores were significantly improved in the nano-curcumin than the placebo group. Additionally, the number of patients with lower degrees of depression was significantly better in the intervention than the placebo group following the supplementation (p = 0.046). CONCLUSION: Curcumin supplementation prevented deterioration of glycemic control and improved physical and psychological quality of life and depression in patients with CSFP. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT20131125015536N8), June 19, 2019.
Asunto(s)
Factores de Riesgo Cardiometabólico , Curcumina , Depresión , Suplementos Dietéticos , Calidad de Vida , Humanos , Curcumina/administración & dosificación , Método Doble Ciego , Persona de Mediana Edad , Masculino , Depresión/psicología , Depresión/tratamiento farmacológico , Depresión/prevención & control , Femenino , Anciano , Adulto , Resultado del Tratamiento , Circulación Coronaria/efectos de los fármacos , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisisRESUMEN
BACKROUND: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) has been associated with increased cardiovascular risk. The aim of this Randomized Double-blind clinical Trial was to evaluate the effects of coenzyme-Q10 supplementation in patients with MASLD in terms of endothelial, vascular and myocardial function. METHODS: Sixty patients with MASLD were randomized to receive daily 240 mg of coenzyme-Q10 or placebo. At baseline and at 6-months, the a)Perfused boundary region of sublingual vessels using the Sideview Darkfield imaging technique, b)pulse-wave-velocity, c)flow-mediated dilation of the brachial artery, d)left ventricular global longitudinal strain, e)coronary flow reserve of the left anterior descending coronary artery and f)controlled attenuation parameter for the quantification of liver steatosis were evaluated. RESULTS: Six months post-treatment, patients under coenzyme-Q10 showed reduced Perfused boundary region (2.18 ± 0.23vs.2.29 ± 0.18 µm), pulse-wave-velocity (9.5 ± 2vs.10.2 ± 2.3 m/s), controlled attenuation parameter (280.9 ± 33.4vs.304.8 ± 37.4dB/m), and increased flow-mediated dilation (6.1 ± 3.8vs.4.3 ± 2.8%), global longitudinal strain (-19.6 ± 1.6vs.-18.8 ± 1.9%) and coronary flow reserve (3.1 ± 0.4vs.2.8 ± 0.4) compared to baseline (p < 0.05). The placebo group exhibited no improvement during the 6-month follow-up period (p > 0.05). In patients under coenzyme-Q10, the reduction in controlled attenuation parameter score was positively related to the reduction in Perfused boundary region and pulse wave velocity and reversely related to the increase in coronary flow reserve and flow-mediated dilation (p < 0.05 for all relations). CONCLUSIONS: Six-month treatment with high-dose coenzyme-Q10 reduces liver steatosis and improves endothelial, vascular and left ventricle myocardial function in patients with MASLD, demonstrating significant improvements in micro- and macro-vasculature function. TRIAL REGISTRATION: NCT05941910.
Asunto(s)
Endotelio Vascular , Ubiquinona , Función Ventricular Izquierda , Humanos , Método Doble Ciego , Ubiquinona/análogos & derivados , Ubiquinona/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Función Ventricular Izquierda/efectos de los fármacos , Endotelio Vascular/fisiopatología , Endotelio Vascular/efectos de los fármacos , Factores de Tiempo , Suplementos Dietéticos , Anciano , Vasodilatación/efectos de los fármacos , Adulto , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Circulación Coronaria/efectos de los fármacos , Análisis de la Onda del Pulso , Hígado Graso/fisiopatología , Hígado Graso/tratamiento farmacológico , Hígado Graso/diagnósticoRESUMEN
BACKGROUND: Despite restoration of epicardial blood flow in acute ST-elevation myocardial infarction (STEMI), inadequate microcirculatory perfusion is common and portends a poor prognosis. Intracoronary (IC) thrombolytic therapy can reduce microvascular thrombotic burden; however, contemporary studies have produced conflicting outcomes. OBJECTIVES: This meta-analysis aims to evaluate the efficacy and safety of adjunctive IC thrombolytic therapy at the time of primary percutaneous coronary intervention (PCI) among patients with STEMI. METHODS: Comprehensive literature search of six electronic databases identified relevant randomised controlled trials. The primary outcome was major adverse cardiac events (MACE). The pooled risk ratio (RR) and weighted mean difference (WMD) with a 95% CI were calculated. RESULTS: 12 studies with 1915 patients were included. IC thrombolysis was associated with a significantly lower incidence of MACE (RR=0.65, 95% CI 0.51 to 0.82, I2=0%, p<0.0004) and improved left ventricular ejection fraction (WMD=1.87; 95% CI 1.07 to 2.67; I2=25%; p<0.0001). Subgroup analysis demonstrated a significant reduction in MACE for trials using non-fibrin (RR=0.39, 95% CI 0.20 to 0.78, I2=0%, p=0.007) and moderately fibrin-specific thrombolytic agents (RR=0.62, 95% CI 0.47 to 0.83, I2=0%, p=0.001). No significant reduction was observed in studies using highly fibrin-specific thrombolytic agents (RR=1.10, 95% CI 0.62 to 1.96, I2=0%, p=0.75). Furthermore, there were no significant differences in mortality (RR=0.91; 95% CI 0.48 to 1.71; I2=0%; p=0.77) or bleeding events (major bleeding, RR=1.24; 95% CI 0.47 to 3.28; I2=0%; p=0.67; minor bleeding, RR=1.47; 95% CI 0.90 to 2.40; I2=0%; p=0.12). CONCLUSION: Adjunctive IC thrombolysis at the time of primary PCI in patients with STEMI improves clinical and myocardial perfusion parameters without an increased rate of bleeding. Further research is needed to optimise the selection of thrombolytic agents and treatment protocols.
Asunto(s)
Fibrinolíticos , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Terapia Trombolítica , Humanos , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/fisiopatología , Terapia Trombolítica/métodos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Intervención Coronaria Percutánea/métodos , Resultado del Tratamiento , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Microcirculación/efectos de los fármacosRESUMEN
BACKGROUND: Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion. METHOD: Consecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n = 102 for dipyridamole, n = 29 for dobutamine). RESULTS: Prevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,P < 0.001). CFR was higher during dipyridamole stress without-caffeine versus with-caffeine (2.22 ± 0.80 vs 1.55 ± 0.37,P = 0.048) but lower than dobutamine stress (2.22 ± 0.80 vs 2.82 ± 1.02,P = 0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group. CONCLUSION: We demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.
Asunto(s)
Cafeína , Dipiridamol , Dobutamina , Trasplante de Hígado , Imagen de Perfusión Miocárdica , Vasodilatadores , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cafeína/sangre , Imagen de Perfusión Miocárdica/métodos , Circulación Coronaria/efectos de los fármacos , Tomografía de Emisión de Positrones , Anciano , Adulto , Vasodilatación/efectos de los fármacosRESUMEN
Myocardial perfusion imaging (MPI) is a powerful tool for the functional assessment of ischemia in patients with suspected or known coronary artery disease (CAD). Given that the diagnostic accuracy and prognostic value of MPI and post-test management are highly dependent on achieving an adequate stress vasodilatory response, it is critical to identify those who may not have adequately responded to vasodilator pharmacological stress agents such as adenosine, dipyridamole, and regadenoson. Caffeine, a potent inhibitor of the adenosine receptor, is a compound that can affect vasodilatory hemodynamics, result in false negative studies, and potentially alter management in cases of inaccurate test results. Vasodilator non-responsiveness can be suspected by examining hemodynamics, quantitative positron emission tomography (PET) metrics such as myocardial flow reserve (MFR), and splenic response to stress. Quantitative MFR values of 1-1.2 should raise suspicion for nonresponsiveness in the setting of normal perfusion, along with the absence of a splenic switch off. Newer metrics, such as splenic response ratio, can be used to aid in the identification of potential nonresponders to pharmacologic vasodilators.
Asunto(s)
Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Vasodilatadores , Humanos , Imagen de Perfusión Miocárdica/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Prueba de Esfuerzo , Tomografía de Emisión de Positrones/métodos , Dipiridamol/farmacología , Circulación Coronaria/efectos de los fármacos , Adenosina , Purinas , PirazolesRESUMEN
The no-reflow phenomenon induced by ischemia-reperfusion (I/R) injury seriously limits the therapeutic value of coronary recanalization and leads to a poor prognosis. Previous studies have shown that luteolin (LUT) is a vasoprotective factor. However, whether LUT can be used to prevent the no-reflow phenomenon remains unknown. Positron emission tomography perfusion imaging, performed to detect the effects of LUT on the no-reflow phenomenon in vivo, revealed that LUT treatment was able to reduce the no-reflow area in rat I/R models. In vitro, LUT was shown to reduce the hypoxia-reoxygenation injury-induced endothelial permeability and apoptosis. The levels of malondialdehyde, reactive oxygen species and NADPH were also measured and the results indicated that LUT could inhibit the oxidative stress. Western blot analysis revealed that LUT protected endothelial cells from I/R injury by regulating the Wnt/ß-catenin pathway. Overall, we concluded that the use of LUT to minimize I/R induced microvascular damage is a feasible strategy to prevent the no-reflow phenomenon.
Asunto(s)
Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Luteolina/farmacología , Daño por Reperfusión Miocárdica/prevención & control , Fenómeno de no Reflujo/prevención & control , Vía de Señalización Wnt/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Células Cultivadas , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/metabolismo , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Humanos , Imagen de Perfusión Miocárdica , Daño por Reperfusión Miocárdica/diagnóstico por imagen , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Fenómeno de no Reflujo/diagnóstico por imagen , Fenómeno de no Reflujo/metabolismo , Fenómeno de no Reflujo/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Tomografía de Emisión de Positrones , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
It is well established that the vasculature plays a crucial role in maintaining oxygen and nutrients supply to the heart. Increasing evidence further suggests that the microcirculation has additional roles in supporting a healthy microenvironment. Heart failure is well known to be associated with changes and functional impairment of the microvasculature. The specific ablation of protective signals in endothelial cells in experimental models is sufficient to induce heart failure. Therefore, restoring a healthy endothelium and microcirculation may be a valuable therapeutic strategy to treat heart failure. This review article will summarize the current understanding of the vascular contribution to heart failure with reduced or preserved ejection fraction. Novel therapeutic approaches including next generation pro-angiogenic therapies and non-coding RNA therapeutics, as well as the targeting of metabolites or metabolic signalling, vascular inflammation and senescence will be discussed.
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Inductores de la Angiogénesis/uso terapéutico , Vasos Coronarios/efectos de los fármacos , Terapia Genética , Insuficiencia Cardíaca Diastólica/terapia , Insuficiencia Cardíaca Sistólica/terapia , Microvasos/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Vacunas/uso terapéutico , Inductores de la Angiogénesis/efectos adversos , Animales , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/fisiopatología , Terapia Genética/efectos adversos , Insuficiencia Cardíaca Diastólica/genética , Insuficiencia Cardíaca Diastólica/metabolismo , Insuficiencia Cardíaca Diastólica/fisiopatología , Insuficiencia Cardíaca Sistólica/genética , Insuficiencia Cardíaca Sistólica/metabolismo , Insuficiencia Cardíaca Sistólica/fisiopatología , Humanos , Microcirculación/efectos de los fármacos , Microvasos/metabolismo , Microvasos/fisiopatología , ARN no Traducido/genética , ARN no Traducido/metabolismo , Recuperación de la Función , Vacunas/efectos adversos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
The "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction (AMI) but tissue perfusion is not restored, is associated with worse outcome. The mechanism of no reflow is unknown. We hypothesized that pericytes contraction, in an attempt to maintain a constant capillary hydrostatic pressure during reduced coronary perfusion pressure, causes capillary constriction leading to no reflow and that this effect is mediated through the orphan receptor, GPR39, present in pericytes. We created AMI (coronary occlusion followed by reperfusion) in GPR39 knock out mice and littermate controls. In a separate set of experiments, we treated wild-type mice undergoing coronary occlusion with vehicle or VC43, a specific inhibitor of GPR39, before reperfusion. We found that no reflow zones were significantly smaller in the GPR39 knockouts compared with controls. Both no reflow and infarct size were also markedly smaller in animals treated with VC43 compared with vehicle. Immunohistochemistry revealed greater capillary density and larger capillary diameter at pericyte locations in the GPR39-knockout and VC43-treated mice compared with controls. We conclude that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow during AMI and that smaller no reflow zones in GPR39-knockout and VC43-treated animals are associated with smaller infarct sizes. These results elucidate the mechanism of no reflow in AMI, as well as providing a therapeutic pathway for the condition.NEW & NOTEWORTHY The mechanism of "no reflow" phenomenon, where the coronary artery is patent after treatment of acute myocardial infarction but tissue perfusion is not restored, is unknown. This condition is associated with worse outcome. Here, we show that GPR39-mediated pericyte contraction during reduced coronary perfusion pressure causes capillary constriction resulting in no reflow. Smaller no-reflow zones in GPR39-knockout animals and those treated with a GPR39 inhibitor are associated with smaller infarct size. These results could have important therapeutic implications.
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Fármacos Cardiovasculares/farmacología , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Fenómeno de no Reflujo/prevención & control , Pericitos/efectos de los fármacos , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Vasoconstricción/efectos de los fármacos , Animales , Señalización del Calcio/efectos de los fármacos , Células Cultivadas , Vasos Coronarios/metabolismo , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Femenino , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Fenómeno de no Reflujo/metabolismo , Fenómeno de no Reflujo/fisiopatología , Pericitos/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismoRESUMEN
BACKGROUND: Primary percutaneous coronary intervention is the treatment of choice in ST-segment elevation myocardial infarction and no-reflow phenomenon is still an unsolved problem. METHODS: We searched PubMed, EmBase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials. The primary endpoint was the incidence of major adverse cardiac events and the secondary endpoint was the incidences of no-reflow phenomenon and complete resolution of ST-segment elevation. RESULTS: Eighteen randomized controlled trials were enrolled. Nicorandil significantly reduced the incidence of no-reflow phenomenon (OR, 0.46; 95% CI, 0.36-0.59; P < 0.001; I2 = 0%) and major adverse cardiac events (OR, 0.42; 95% CI, 0.27-0.64; P < 0.001; I2 = 52%). For every single outcome of major adverse cardiac events, only heart failure and ventricular arrhythmia were significantly improved with no heterogeneity (OR, 0.36; 95% CI, 0.23-0.57, P < 0.001; OR, 0.43; 95% CI, 0.31-0.60, P < 0.001 respectively). A combination of intracoronary and intravenous nicorandil administration significantly reduced the incidence of major adverse cardiac events with no heterogeneity (OR, 0.24; 95% CI, 0.13-0.43, P < 0.001; I2 = 0%), while a single intravenous administration could not (OR, 0.66; 95% CI, 0.40-1.06, P = 0.09; I2 = 52%). CONCLUSIONS: Nicorandil can significantly improve no-reflow phenomenon and major adverse cardiac events in patients undergoing primary percutaneous coronary intervention. The beneficial effects on major adverse cardiac events might be driven by the improvements of heart failure and ventricular arrhythmia. A combination of intracoronary and intravenous administration might be an optimal usage of nicorandil.
Asunto(s)
Circulación Coronaria/efectos de los fármacos , Nicorandil/administración & dosificación , Fenómeno de no Reflujo/prevención & control , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST/terapia , Vasodilatadores/administración & dosificación , Administración Intravenosa , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nicorandil/efectos adversos , Fenómeno de no Reflujo/diagnóstico , Fenómeno de no Reflujo/etiología , Intervención Coronaria Percutánea/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/fisiopatología , Resultado del Tratamiento , Vasodilatadores/efectos adversosRESUMEN
Inducible hypercapnia is an alternative for increasing the coronary blood flow necessary to facilitate the quantification of myocardial blood flow during hyperemia. The current study aimed to quantify the pharmacokinetic effect of a CO2 gas challenge on myocardial perfusion in rats using high-resolution, first-pass perfusion CMR and compared it with pharmacologically induced hyperemia using regadenoson. A dual-contrast, saturation-recovery, gradient-echo sequence with a Cartesian readout was used on a small-animal 9.4-T scanner; additional cine images during hyperemia/rest were recorded with an ultrashort echo time sequence. The mean myocardial blood flow value at rest was 6.1 ± 1.4 versus 13.9 ± 3.7 and 14.3 ± 4 mL/g/min during vasodilation with hypercapnia and regadenoson, respectively. Accordingly, the myocardial flow reserve value was 2.6 ± 1.1 for the gas challenge and 2.5 ± 1.4 for regadenoson. During hyperemia with both protocols, a significantly increased cardiac output was found. It was concluded that hypercapnia leads to significantly increased coronary flow and yields similar myocardial flow reserves in healthy rats as compared with pharmacological stimulation. Accordingly, inducible hypercapnia can be selected as an alternative stressor in CMR studies of myocardial blood flow in small animals.
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Dióxido de Carbono/sangre , Circulación Coronaria/efectos de los fármacos , Imagen de Perfusión Miocárdica/métodos , Animales , Dióxido de Carbono/farmacología , Femenino , Reserva del Flujo Fraccional Miocárdico , Hipercapnia/fisiopatología , Contracción Miocárdica , Ratas , Ratas Wistar , Vasodilatación/efectos de los fármacosRESUMEN
We investigated the impact of pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade (pre-TIMI) on 3-month (3-mo) and 12-mo of dual antiplatelet therapy (DAPT) in patients with acute myocardial infarction (AMI). This was a post hoc analysis of the TICO trial. A total of 2083 patients with AMI (pre-TIMI 0/1: n = 1143; pre-TIMI 2/3: n = 940) were evaluated. The primary outcome was the occurrence of net adverse clinical events (NACE), defined as a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events (MACCE) within 12-mo following PCI. The secondary outcomes were the occurrence of the individual components of TIMI bleedings and MACCE. In the pre-TIMI 0/1 group, the primary and second outcomes were not significantly different between the 3-mo and 12-mo DAPT groups. However, in the pre-TIMI 2/3 group, the occurrences of TIMI minor (adjusted hazard ratio [aHR]: 0.294; p = 0.016) and major or minor bleeding (aHR: 0.483; p = 0.014) on intention-to-treat analysis were significantly higher in the 12-mo than in the 3-mo DAPT group. The occurrence of MACCE was similar between the two groups. A higher bleeding tendency in 12-mo DAPT compared with 3-mo DAPT was more obvious in the pre-TIMI 2/3 group than in the pre-TIMI 0/1 group.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02494895.
Asunto(s)
Circulación Coronaria/efectos de los fármacos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/fisiopatología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Biomarcadores , Duración de la Terapia , Femenino , Pruebas de Función Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Evaluación del Resultado de la Atención al Paciente , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Periodo PreoperatorioRESUMEN
BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) disease. In patients with T2D and established CV disease, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2) have been shown to decrease CV and all-cause mortality, and heart failure (HF) admissions. Utilising CV magnetic resonance imaging (CMR) and continuous glucose monitoring (CGM) by FreeStyle Libre Pro Sensor, we aim to explore the mechanisms of action which give Empagliflozin, an SGLT2 inhibitor, its beneficial CV effects and compare these to the effects of dipeptidyl peptidase-4 inhibitor Sitagliptin. METHODS: This is a single centre, open-label, cross-over trial conducted at the Leeds Teaching Hospitals NHS Trust. Participants are randomised for the order of treatment and receive 3 months therapy with Empagliflozin, and 3 months therapy with Sitagliptin sequentially. Twenty-eight eligible T2D patients with established ischaemic heart disease will be recruited. Patients undergo serial CMR scans on three visits. DISCUSSION: The primary outcome measure is the myocardial perfusion reserve in remote myocardium. We hypothesise that Empaglifozin treatment is associated with improvements in myocardial blood flow and reductions in myocardial interstitial fibrosis, independent of CGM measured glycemic control in patients with T2D and established CV disease. TRIAL REGISTRATION: This study has full research ethics committee approval (REC: 18/YH/0190) and data collection is anticipated to finish in December 2021. This study was retrospectively registered at https://doi.org/10.1186/ISRCTN82391603 and monitored by the University of Leeds. The study results will be submitted for publication within 6 months of completion.
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Compuestos de Bencidrilo/uso terapéutico , Circulación Coronaria/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Glucósidos/uso terapéutico , Control Glucémico , Isquemia Miocárdica/tratamiento farmacológico , Fosfato de Sitagliptina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos de Bencidrilo/efectos adversos , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inglaterra , Fibrosis , Glucósidos/efectos adversos , Control Glucémico/efectos adversos , Humanos , Isquemia Miocárdica/diagnóstico por imagen , Isquemia Miocárdica/fisiopatología , Miocardio/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Fosfato de Sitagliptina/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Impaired coronary microvascular function (e.g., reduced dilation and coronary flow reserve) predicts cardiac mortality in obesity, yet underlying mechanisms and potential therapeutic strategies remain poorly understood. Mineralocorticoid receptor (MR) antagonism improves coronary microvascular function in obese humans and animals. Whether MR blockade improves in vivo regulation of coronary flow, a process involving voltage-dependent K+ (Kv) channel activation, or reduces coronary structural remodeling in obesity is unclear. Thus, the goals of this investigation were to determine the effects of obesity on coronary responsiveness to reductions in arterial PO2 and potential involvement of Kv channels and whether the benefit of MR blockade involves improved coronary Kv function or altered passive structural properties of the coronary microcirculation. Hypoxemia increased coronary blood flow similarly in lean and obese swine; however, baseline coronary vascular resistance was significantly higher in obese swine. Inhibition of Kv channels reduced coronary blood flow and augmented coronary resistance under baseline conditions in lean but not obese swine and had no impact on hypoxemic coronary vasodilation. Chronic MR inhibition in obese swine normalized baseline coronary resistance, did not influence hypoxemic coronary vasodilation, and did not restore coronary Kv function (assessed in vivo, ex vivo, and via patch clamping). Lastly, MR blockade prevented obesity-associated coronary arteriolar stiffening independent of cardiac capillary density and changes in cardiac function. These data indicate that chronic MR inhibition prevents increased coronary resistance in obesity independent of Kv channel function and is associated with mitigation of obesity-mediated coronary arteriolar stiffening.