RESUMEN
PURPOSE: The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3ß/NF-kB signaling pathway. METHODS: Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3ß, p-GSK-3ß (Ser9) and nuclear factor-κB (NF-κB) were measured in heart homogenates. RESULTS: Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3ß/GSK-3ß and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3ß/GSK-3ß and expression of p- NF-kB. CONCLUSIONS: Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3ß signaling.
Asunto(s)
Lesiones Cardíacas , Sepsis , Animales , Glucógeno Sintasa Quinasa 3 beta , Lesiones Cardíacas/tratamiento farmacológico , Glucósidos Iridoides , Iridoides , FN-kappa B , Ratas , Sepsis/complicaciones , Sepsis/tratamiento farmacológicoRESUMEN
Cardiac fibroblasts (CFs) have a key role in the inflammatory response after cardiac injury and are necessary for wound healing. Resolvins are potent agonists that control the duration and magnitude of inflammation. They decrease mediators of pro-inflammatory expression, reduce neutrophil migration to inflammation sites, promote the removal of microbes and apoptotic cells, and reduce exudate. However, whether resolvins can prevent pro-inflammatory-dependent effects in CFs is unknown. Thus, the present work was addressed to study whether resolvin D1 and E1 (RvD1 and RvE1) can prevent pro-inflammatory effects on CFs after lipopolysaccharide (LPS) challenge. For this, CFs were stimulated with LPS, in the presence or absence of RvD1 or RvE1, to analyze its effects on intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), monocyte adhesion and the cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), interleukin-1beta (IL-1ß), monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10). Our results showed that CFs are expressing ALX/FPR2 and ChemR23, RvD1 and RvE1 receptors, respectively. RvD1 and RvE1 prevent the increase of ICAM-1 and VCAM-1 protein levels and the adhesion of spleen mononuclear cells to CFs induced by LPS. Finally, RvD1, but not RvE1, prevents the LPS-induced increase of IL-6, MCP-1, TNF-α, and IL-10. In conclusion, our findings provide evidence that in CFs, RvD1 and RvE1 might actively participate in the prevention of inflammatory response triggered by LPS.
Asunto(s)
Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/análogos & derivados , Lesiones Cardíacas/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Animales , Movimiento Celular/efectos de los fármacos , Citocinas/genética , Ácido Eicosapentaenoico/farmacología , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Lesiones Cardíacas/inducido químicamente , Lesiones Cardíacas/patología , Humanos , Inflamación/inducido químicamente , Inflamación/patología , Interleucina-1beta/genética , Lipopolisacáridos/toxicidad , Neutrófilos/efectos de los fármacos , Ratas , Factor de Necrosis Tumoral alfa/genética , Molécula 1 de Adhesión Celular Vascular/genética , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Purpose The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3beta/NF-kB signaling pathway. Methods Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3beta, p-GSK-3beta (Ser9) and nuclear factor-B (NF-B) were measured in heart homogenates. Results Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3beta/GSK-3beta and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3beta/GSK-3beta and expression of p- NF-kB. Conclusions Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3beta signaling.(AU)
Asunto(s)
Animales , Ratas , Lesiones Cardíacas/tratamiento farmacológico , Lesiones Cardíacas/veterinaria , Sepsis/complicaciones , Sepsis/veterinariaRESUMEN
ABSTRACT Purpose The present study explored the potential therapeutic role of oleuropein in sepsis-induced heart injury along with the role of GSK-3β/NF-kB signaling pathway. Methods Sepsis-induced myocardial injury was induced by cecal ligation and puncture (CLP) in rats. The cardiac injury was assessed by measuring the levels of cTnI and creatine kinase-MB (CK-MB). Sepsis-induced inflammation was assessed by measuring interleukin-6 (IL-6), IL-10 and HMGB1 levels. The different doses of oleuropein (5, 10, and 20 mg/kg) were given prior to CLP. Oleuropein (20 mg/kg) was administered after 6 hof CLP. The expressions of GSK-3β, p-GSK-3β (Ser9) and nuclear factor-κB (NF-κB) were measured in heart homogenates. Results Cecal ligation and puncture was associated with myocardial injury, an increase in IL-6, a decrease in IL-10 and an increase in HMGB1. Moreover, it decreased the ratio of p-GSK-3β/GSK-3β and increased the expression of p-NF-kB. Pretreatment with oleuropein attenuated CLP-induced myocardial injury and systemic inflammation in a dose-dependent manner. Administration of oleuropein after the onset of CLP also attenuated cardiac injury and inflammation. It also restored CLP-induced changes in the HMGB1 levels, the ratio of p-GSK-3β/GSK-3β and expression of p- NF-kB. Conclusions Oleuropein attenuates sepsis-induced systemic inflammation and myocardial injury by inhibiting NF-kB and GSK-3β signaling.
Asunto(s)
Animales , Ratas , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Lesiones Cardíacas/tratamiento farmacológico , FN-kappa B , Iridoides , Glucósidos Iridoides , Glucógeno Sintasa Quinasa 3 betaRESUMEN
Purpose: To investigate the protective effect of L-carnitine on myocardial injury in rats with heatstroke. Methods: orty-eight rats were randomly divided into control, heatstroke and 25, 50 and 100 mg/kg L-carnitine groups. The last three groups were treated with 25, 50 and 100 mg/kg L-carnitine, respectively, for seven successive days. Then, except for the control group, the other four groups were transferred into the environment with ambient temperature of (39.5 ± 0.4 °C) and relative humidity of (13.5 ± 2.1%) for 2 h. The core temperature (Tc), mean arterial pressure (MAP), heart rate (HR) and serum and myocardial indexes were detected. Results: Compared with the heatstroke group, in the 100 mg/kg L-carnitine group, the Tc was significantly decreased, the MAP and HR were significantly increased, the serum creatine kinase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, tumor necrosis factor and interleukin 1 levels were significantly decreased, the myocardial superoxide dismutase and glutathione peroxidase levels were significantly increased, the myocardial malondialdehyde level was significantly decreased and the cardiomyocyte apoptosis index and myocardial caspase-3 protein expression level were remarkably decreased (p 0.05). Conclusions: The L-carnitine pretreatment can alleviate the myocardial injury in heatstroke rats through reducing the inflammatory response, oxidative stress and cardiomyocyte apoptosis.(AU)
Asunto(s)
Animales , Ratas , Carnitina/uso terapéutico , Lesiones Cardíacas/tratamiento farmacológico , Lesiones Cardíacas/veterinaria , Insolación/tratamiento farmacológico , Insolación/veterinaria , Reperfusión Miocárdica/veterinariaRESUMEN
Purpose: To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. Methods: Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. Results: The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. Conclusion: Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.(AU)
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Animales , Masculino , Adulto , Ratas , Atenolol/administración & dosificación , Atenolol/farmacología , Isquemia Mesentérica/inducido químicamente , Daño por Reperfusión/inducido químicamente , Lesiones Cardíacas/tratamiento farmacológico , Modelos Animales de Enfermedad , Ratas WistarRESUMEN
Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg−1·day−1), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.
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Animales , Femenino , Contusiones/tratamiento farmacológico , Lesiones Cardíacas/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Miocardio/patología , Quercetina/uso terapéutico , Heridas no Penetrantes/complicaciones , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Contusiones/etiología , Quimioterapia Combinada , Lesiones Cardíacas/etiología , Inmunohistoquímica , Necrosis , Óxido Nítrico Sintasa de Tipo II/aislamiento & purificación , Ratas Sprague-Dawley , Traumatismos Torácicos/complicaciones , Troponina I/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg(-1)·day(-1)), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.
Asunto(s)
Contusiones/tratamiento farmacológico , Lesiones Cardíacas/tratamiento farmacológico , Metilprednisolona/uso terapéutico , Miocardio/patología , Quercetina/uso terapéutico , Heridas no Penetrantes/complicaciones , Animales , Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Contusiones/etiología , Quimioterapia Combinada , Femenino , Lesiones Cardíacas/etiología , Inmunohistoquímica , Necrosis , Óxido Nítrico Sintasa de Tipo II/aislamiento & purificación , Ratas Sprague-Dawley , Traumatismos Torácicos/complicaciones , Troponina I/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Las primeras descripciones de una lesión cardiaca se remontan al papiro de Edwin Smith alrededor del 3000 AC. Hasta el siglo IX, las heridas penetrantes cardiacas eran consideradas intratables y mortales. Fue en 1896, cuando se reportó la primera reparación cardiaca exitosa. Aunque la mortalidad ha disminuido con el paso del tiempo, una herida penetrante al corazón sigue teniendo un grave pronóstico y es causa importante de morbilidad y mortalidad en pacientes de trauma. En la actualidad, cada vez se ven con más frecuencia las heridas penetrantes cardiacas por arma de fuego, lo que indudablemente ensombrece aún más el pronóstico de estas lesiones, por lo que se torna de vital importancia para el cirujano que trabaja en una Unidad de Emergencia, conocer con exactitud los mecanismos fisiopatológicos que se ven involucrados en este tipo de situaciones, además de todas las complicaciones que pueden ocurrir al intentar reparar una herida penetrante cardiaca. Este artículo pretende dar una visión precisa, clara y actual del manejo de un paciente con una herida penetrante cardiaca.
Asunto(s)
Humanos , Heridas Penetrantes/cirugía , Lesiones Cardíacas/cirugía , Lesiones Cardíacas/etiología , Adenosina/administración & dosificación , Antiarrítmicos/administración & dosificación , Urgencias Médicas , Heridas Penetrantes/fisiopatología , Heridas Penetrantes/tratamiento farmacológico , Lesiones Cardíacas/fisiopatología , Lesiones Cardíacas/tratamiento farmacológico , Complicaciones Posoperatorias , Resucitación , Toracotomía , Taponamiento Cardíaco/cirugía , Taponamiento Cardíaco/etiologíaRESUMEN
Although thoracic trauma is frequently accompanied by myocardial injury; this later is often oversighted at early stages of trauma and misdiagnosed by the time complications are present. Myocardial abnormalities have been attributed to a reduction of cardiac flow. Nitroglycerin and isosorbide dinitrate, both agents with a known vasodilator effect on coronary arteries, might improve myocardial ischemic resulting from traumatic contusion. In order to compare safety and efficacy between two nitrates and placebo on myocardial contusion resulting from thoracic trauma, we carried out a comparative, prospective, single blind study. Subjects were randomly allocated to one of the following 3 groups: a) transdermal nitroglycerin, b) isosorbide dinitrate and c) placebo. Medication was dispensed for five days. Major endpoint were electrocardiographic abnormalities at entry and their final modifications. Other were severity injury score and myocardial enzyme levels. Twelve patients were included in each group. Four measured enzymes were high at entry, but MB fraction in the nitroglycerin group showed the most rapid normalization. Creatine phosphokinase and lactic dehydrogenase significantly correlated with severity injury index, but not MB fraction. Electrocardiographic normalization was mainly observed in the nitroglycerin group. Transdermal nitroglycerin systems demonstrated to be effective on recovering from electrocardiographic abnormalities resulting of myocardial contusion.
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Contusiones/tratamiento farmacológico , Lesiones Cardíacas/tratamiento farmacológico , Nitratos/administración & dosificación , Administración Cutánea , Administración Oral , Adulto , Distribución de Chi-Cuadrado , Contusiones/diagnóstico , Femenino , Lesiones Cardíacas/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Nitratos/efectos adversos , Estudios Prospectivos , Método Simple Ciego , Estadísticas no ParamétricasRESUMEN
Incomplete ventricular septal tears are uncommon or probably underreported cardiac lesions caused by blunt chest trauma. This report describes two cases of incomplete ventricular septal tears that were not suspected clinically. Transthoracic and transesophageal echocardiography provided the diagnostic information in both of these cases. Despite associated valvular lesions, the patients' stable in-hospital course lead to the decision to treat them medically with no specific treatment to the incomplete ventricular septal tears. Accordingly, these two cases were observed for a mean period of 1.5 years with serial echocardiographic studies to track the natural history of these lesions. During the follow-up period, both of these cases did not manifest any changes in the extent of ventricular septal tear, septal structure, or any left-to-right shunting through the tear. There were no significant changes in left ventricular size, shape, or systolic function. Thus echocardiographic imaging proved to be useful both in initial diagnosis and follow-up.