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ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. AIM OF THE STUDY: To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. MATERIALS AND METHODS: The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. RESULTS: FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and ß-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. CONCLUSIONS: FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.
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Congelación de Extremidades , Microcirculación , Cicatrización de Heridas , Congelación de Extremidades/tratamiento farmacológico , Animales , Microcirculación/efectos de los fármacos , Masculino , Cicatrización de Heridas/efectos de los fármacos , Piel/efectos de los fármacos , Piel/irrigación sanguínea , Piel/patología , Apoptosis/efectos de los fármacos , Ratas , Modelos Animales de Enfermedad , Ratones , Administración Tópica , Ratas Sprague-Dawley , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVE: To observe the effect of Wenyang Baidu Yin on early microcirculation indicators in patients with sepsis (syndrome of Yang deficiency and turbid toxin), analyze the specific therapeutic effect, and provide a new perspective for clinical treatment of microcirculation disorders in sepsis. METHODS: Sixty-four patients with sepsis admitted to the intensive care unit (ICU) of Shanxi Province Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to July 2023 were enrolled. Patients were divided into control group and observation group by randomly number table method, with 32 cases in each group. The control group received conventional Western medicine treatment. On the basis of conventional Western medicine treatment, the observation group was given Wenyang Baidu Yin 200 mL/d (100 mL each time, with an interval of 12 hours) orally or by nasal feeding for 3 consecutive days. The central venous oxygen saturation (ScvO2), difference of central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO2), arterial lactic acid (Lac), pulse perfusion index (PI), capillary refill time (CRT), and skin mottling score (SMS) of two groups were detected before treatment and at 6, 12, 24, and 48 hours of treatment; simultaneously record the traditional Chinese medicine (TCM) syndrome score before treatment and at 72 hours of treatment, as well as the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation (APACHE) before treatment and at 24 hours and 72 hours of treatment. RESULTS: There were no statistically significant differences in gender, age, and various microcirculation indicators before treatment between the two groups, indicating consistent baseline characteristics. Compared with before treatment, the microcirculation indicators ScvO2, Pcv-aCO2, Lac, PI, CRT, and SMS in both groups showed significant improvement after treatment. Moreover, the observation group showed more significant improvements in Lac and PI compared to the control group at 24 hours and 48 hours of treatment [Lac (mmol/L): 2.45±0.92 vs. 3.07±1.07 at 24 hours, 2.06±0.87 vs. 2.59±1.01 at 48 hours; PI: 3.45±0.89 vs. 2.92±0.98 at 24 hours, 3.56±0.99 vs. 3.01±0.87 at 48 hours, all P < 0.05]. CRT and SMS showed more significant improvements compared to the control group at 48 hours of treatment [CRT (s): 2.04±1.08 vs. 2.62±0.99, SMS: 0.5 (0.0, 1.0) vs. 1.0 (1.0, 1.0), both P < 0.05], while there were no statistically significant differences in ScvO2 and Pcv-aCO2 at each time point between the two groups. After treatment, the APACHE score, SOFA score, and TCM syndrome score improved in both groups compared to before treatment, and the improvement degree of each score in the observation group was significantly higher than that in the control group [72 hours APACHE II score: 15.0 (12.2, 16.0) vs. 17.0 (13.5, 20.0), 72 hours SOFA score: 6.0 (6.0, 8.0) vs. 10.0 (8.0, 13.0), 72 hours TCM syndrome score: 10.13±3.73 vs. 14.63±5.55, all P < 0.05]. CONCLUSIONS: On the basis of conventional Western medicine treatment, the combination of Wenyang Baidu Yin can significantly improve microcirculation disorders in patients with sepsis (syndrome of Yang deficiency and turbid toxin) to a certain extent, thereby improving patient prognosis.
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Medicamentos Herbarios Chinos , Microcirculación , Sepsis , Deficiencia Yang , Humanos , Microcirculación/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Medicamentos Herbarios Chinos/uso terapéutico , Deficiencia Yang/tratamiento farmacológico , Masculino , Femenino , Medicina Tradicional China/métodos , Unidades de Cuidados Intensivos , Persona de Mediana EdadRESUMEN
Cocoa flavan-3-ols affect endothelium-dependent responses in resistance vessels and microcirculation has received little attention. We tested the effects of dark chocolate consumption (396 mg total flavanols/day for 3 days) in two Groups of 10 men (18-25 years; non-smokers) each comprising equal numbers of White European (WE) and South Asian (SA) ethnicity. In Group 1, dark chocolate did not affect reactive hyperaemia in forearm muscle, but augmented muscle dilatation evoked by acute mental stress, and reactive hyperaemia and acetylcholine (ACh)-evoked dilatation in cutaneous microcirculation. Conversely, in Group 2, chocolate did not affect cutaneous reactive hyperaemia or ACh-evoked dilatation, but these responses were blunted in Group 1 relative to Group 2. Further, when Groups 1 and 2 were combined, responses were blunted in SAs relative to WEs, augmented by chocolate in SAs only. In Group 2 individuals whose ACh-evoked dilatation was attenuated by nitric oxide synthase (NOS) inhibition, ACh-evoked dilatation was not altered after chocolate, but the attenuating effect of NOS inhibition was lost. Conversely, in Group 2 individuals whose ACh-evoked dilatation was enhanced by NOS inhibition, ACh-evoked dilatation was also augmented by chocolate. We propose that in resistance and microvessels of young men, cocoa flavan-3-ols preferentially augment endothelium-dependent dilator responses whose responses are depressed by familial and lifestyle factors more prevalent in SAs than Wes. Flavan-3-ols may facilitate the NOS pathway but also influence other endothelium-dependent dilators.
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Cacao , Chocolate , Estilo de Vida , Microcirculación , Humanos , Masculino , Adulto Joven , Adulto , Cacao/química , Microcirculación/efectos de los fármacos , Adolescente , Flavonoides/farmacología , Vasodilatación/efectos de los fármacos , Población Blanca , Hiperemia , Endotelio Vascular/efectos de los fármacos , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Piel/metabolismo , Microvasos/efectos de los fármacos , Pueblo Asiatico , Antebrazo/irrigación sanguínea , Acetilcolina/farmacología , Estrés Psicológico , Óxido Nítrico Sintasa/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismoRESUMEN
Systemic vasodilating agents like nitroglycerin (NG) or iloprost (Ilo) show beneficial effects on intestinal microcirculation during sepsis, which could be attenuated by activation of the sympathetic nervous system or systemic side effects of vasodilating agents. This exploratory study aimed to investigate the effects of topically administered vasodilators and the parasympathetic drug carbachol on colonic microcirculatory oxygenation (µHbO2), blood flow (µFlow) and mitochondrial respiration. A total of 120 male Wistar rats were randomly assigned to twelve groups and underwent either colon ascendens stent peritonitis (CASP) or sham surgery. After 24 h, animals received the following therapeutic regimes: (1) balanced full electrolyte solution, (2) carbachol, (3) NG, (4) Ilo, (5) NG + carbachol, and (6) Ilo + carbachol. Mitochondrial respiration was measured in colon homogenates by respirometry. In sham animals, NG (-13.1%*) and Ilo (-10.5%*) led to a decrease in µHbO2. Additional application of carbachol abolished this effect (NG + carbachol: -4.0%, non-significant; Ilo + carbachol: -1.4%, non-significant). In sepsis, carbachol reduced µHbO2 when applied alone (-10.5%*) or in combination with NG (-17.6%*). Thus, the direction and degree of this effect depend on the initial pathophysiologic condition.
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Sistema Nervioso Autónomo , Carbacol , Microcirculación , Mitocondrias , Ratas Wistar , Sepsis , Vasodilatadores , Animales , Microcirculación/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Masculino , Ratas , Vasodilatadores/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Carbacol/farmacología , Colon/efectos de los fármacos , Colon/irrigación sanguínea , Colon/metabolismo , Nitroglicerina/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Microcirculatory dysfunction is one of the main characteristics of sepsis. Shenfu Injection (SFI) as a traditional Chinese medicine is widely applied in clinical severe conditions. Recent studies have shown that SFI has the ability to ameliorate sepsis-induced inflammation and to improve microcirculation perfusion. AIM OF THE STUDY: This study aims to investigate the underlying mechanism of SFI for ameliorating sepsis-associated endothelial dysfunction and organ injury. MATERIALS AND METHODS: Side-stream dark-field (SDF) imaging was used to monitor the sublingual microcirculation of septic patients treated with or without SFI. Septic mouse model was used to evaluate the effects of SFI in vivo. Metabolomics and transcriptomics were performed on endothelial cells to identify the underlying mechanism for SFI-related protective effect on endothelial cells. RESULTS: SFI effectively abolished the disturbance and loss of sublingual microcirculation in septic patients. Twenty septic shock patients with or without SFI administration were enrolled and the data showed that SFI significantly improved the levels of total vessel density (TVD), perfused vessel density (PVD), microvascular flow index (MFI), and the proportion of perfused vessels (PPV). The administration of SFI significantly decreased the elevated plasma levels of Angiopoietin-2 (Ang2) and Syndecan-1, which are biomarkers indicative of endothelial damage in sepsis patients. In the mouse septic model in vivo, SFI inhibited the upregulation of endothelial adhesion molecules and Ly6G + neutrophil infiltration while restored the expression of VE-Cadherin in the vasculature of the lung, kidney, and liver tissue. Additionally, SFI reduced the plasma levels of Ang2, Monocyte Chemoattractant Protein-1(MCP1), and Interleukin-6 (IL6), and alleviated liver and kidney injury in septic mice. Moreover, SFI significantly inhibited the inflammatory activation and increased permeability of endothelial cells induced by endotoxins in vitro. By performing metabolomics and transcriptomics, we identified the activation of PI3K/Akt-mediated glycolysis as the underlying mechanism for SFI-related protective effect on endothelial cells. CONCLUSIONS: Our findings revealed that SFI may improve microcirculation perfusion and endothelial function in sepsis via inhibiting PI3K/Akt-mediated glycolysis, providing theoretical evidence for the clinical application of SFI.
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Medicamentos Herbarios Chinos , Glucólisis , Proteínas Proto-Oncogénicas c-akt , Animales , Medicamentos Herbarios Chinos/farmacología , Humanos , Masculino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Glucólisis/efectos de los fármacos , Microcirculación/efectos de los fármacos , Endotoxemia/tratamiento farmacológico , Ratones Endogámicos C57BL , Femenino , Fosfatidilinositol 3-Quinasas/metabolismo , Persona de Mediana Edad , Sepsis/tratamiento farmacológico , Sepsis/complicaciones , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Anciano , Transducción de Señal/efectos de los fármacosRESUMEN
Energy drinks are nonalcoholic beverages whose main ingredients are sugar, taurine, and caffeine. The consumption of energy drinks is increasing worldwide, but only a few conflicting studies have investigated the vascular effects of energy drinks in young adults. The aim of this study was to evaluate microvascular reactivity before and after energy drinks consumption in young healthy male volunteers. This was a cross-sectional prospective study. Microvascular reactivity signals were evaluated in the skin of the forearm using laser speckle contrast imaging with acetylcholine (ACh) iontophoresis before and 90 and 180 min after the randomized consumption of one ED or the same volume of water (control), followed by a postocclusive reactive hyperemia (PORH) test. Thirty-two volunteers were evaluated (age: 25.4±4.3 years). Energy drink consumption prevented the rest-induced reduction in cutaneous vascular conductance over time that was observed in the control group. In the control group, there were significant reductions in microvascular vasodilation at 90 and 180 min compared to baseline (P=0.004), but this was not the case in the energy drink group (P=0.76). Our results demonstrated that the reduction in microvascular conductance associated with prolonged immobility can be prevented by the consumption of one energy drink, highlighting the vasodilator effects of this beverage in young individuals at rest. The between-study variability in terms of the brand of energy drinks and the ingested volume, as well as the method of vascular evaluation and the inclusion criteria, may explain the discrepancies among previous studies on the vascular effects of energy drinks.
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Bebidas Energéticas , Humanos , Masculino , Adulto , Estudios Prospectivos , Estudios Transversales , Adulto Joven , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Descanso/fisiología , Antebrazo/irrigación sanguínea , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Hiperemia , Microvasos/efectos de los fármacos , Acetilcolina/administración & dosificación , Acetilcolina/farmacologíaRESUMEN
BACKGROUND: Obesity is associated with resistance to the metabolic (glucose uptake) and vascular (nitric-oxide mediated dilation and microvascular recruitment) actions of insulin. These vascular effects contribute to insulin sensitivity by increasing tissue delivery of glucose. Studies by us and others suggest that sympathetic activation contributes to insulin resistance to glucose uptake. Here we tested the hypothesis that sympathetic activation contributes to impaired insulin-mediated vasodilation in adult subjects with obesity. METHODS AND RESULTS: In a randomized crossover study, we used a euglycemic hyperinsulinemic clamp in 12 subjects with obesity to induce forearm arterial vasodilation (forearm blood flow) and microvascular recruitment (contrast-enhanced ultrasonography) during an intrabrachial infusion of saline (control) or phentolamine (sympathetic blockade). Insulin increased forearm blood flow on both study days (from 2.21±1.22 to 4.89±4.21 mL/100 mL per min, P=0.003 and from 2.42±0.89 to 7.19±3.35 mL/100 mL per min, P=0.002 for the intact and blocked day, respectively). Sympathetic blockade with phentolamine resulted in a significantly greater increase in microvascular flow velocity (∆microvascular flow velocity: 0.23±0.65 versus 2.51±3.01 arbitrary intensity units (AIU/s) for saline and phentolamine respectively, P=0.005), microvascular blood volume (∆microvascular blood volume: 1.69±2.45 versus 3.76±2.93 AIU, respectively, P=0.05), and microvascular blood flow (∆microvascular blood flow: 0.28±0.653 versus 2.51±3.01 AIU2/s, respectively, P=0.0161). To evaluate if this effect was not due to nonspecific vasodilation, we replicated the study in 6 subjects with obesity comparing intrabrachial infusion of phentolamine to sodium nitroprusside. At doses that produced similar increases in forearm blood flow, insulin-induced changes in microvascular flow velocity were greater during phentolamine than sodium nitroprusside (%microvascular flow velocity=58% versus 29%, respectively, P=0.031). CONCLUSIONS: We conclude that sympathetic activation impairs insulin-mediated microvascular recruitment in adult subjects with obesity.
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Estudios Cruzados , Antebrazo , Insulina , Microcirculación , Obesidad , Fentolamina , Flujo Sanguíneo Regional , Sistema Nervioso Simpático , Vasodilatación , Humanos , Antebrazo/irrigación sanguínea , Masculino , Fentolamina/farmacología , Femenino , Obesidad/fisiopatología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Adulto , Sistema Nervioso Simpático/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Flujo Sanguíneo Regional/efectos de los fármacos , Microcirculación/efectos de los fármacos , Velocidad del Flujo Sanguíneo , Persona de Mediana Edad , Técnica de Clampeo de la Glucosa , Resistencia a la Insulina , Bloqueo Nervioso Autónomo/métodosRESUMEN
Systemic inflammation and hemodynamic or microvascular alterations are a hallmark of sepsis and play a role in organs hypoperfusion and dysfunction. Pimobendan, an inodilator agent, could be an interesting option for inotropic support and microcirculation preservation during shock. The objectives of this study were to evaluate effect of pimobendan on cytokine and nitric oxide (NO) release and investigate whether changes of macro and microcirculation parameters are associated with the release of cytokines and NO in pigs sepsis model. After circulatory failure, induced by intravenous inoculation of live Pseudomonas aeruginosa, eight animals were treated with pimobendan and eight with placebo. Pimobendan did not affect cytokines secretion (TNF-α, IL-6 and IL-10), but decreased time-dependently NO release. Data of macro and microcirculation parameters, NO and TNF- α recorded at the time of circulatory failure (Thypotension) and the time maximum of production cytokines was used for analyses. A positive correlation was observed between TNF-α and cardiac index (r = 0.55, p = 0.03) and a negative with systemic vascular resistance (r = -0.52, p = 0.04). Positive correlations were seen both between IL-10, 30 min after resuscitation (T30min), and systolic arterial pressure (r = 0.57, p = 0.03) and cardiac index (r = 0.67, p = 0.01), and also between IL-6, taken 2 h after resuscitation and systolic arterial pressure (r = 0.53, p = 0.04). Negative correlations were found between IL-10 and lactate, measured resuscitation time (r = -0.58, p = 0.03). Regarding microcirculation parameters, we observed a positive correlation between IL-6 and IL-10 with the microvascular flow index (r = 0.52, p = 0.05; r = 0.84, p = 0.0003) and a negative correlation with the heterogeneity index with TNF-α and IL-10 (r = -0.51, p = 0.05; r = -0.74, p = 0.003) respectively. NO derivatives showed a positive correlation with temperature gradient (r = 0.54, p = 0.04). Pimobendan did not show anti-inflammatory effects in cytokines release. Our results also, suggest changes of macro- and microcirculation are associated mainly with low levels of IL-10 in sepsis.
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Citocinas , Modelos Animales de Enfermedad , Hemodinámica , Microcirculación , Óxido Nítrico , Sepsis , Animales , Microcirculación/efectos de los fármacos , Óxido Nítrico/metabolismo , Hemodinámica/efectos de los fármacos , Citocinas/metabolismo , Sepsis/fisiopatología , Sepsis/tratamiento farmacológico , Piridazinas/farmacología , Interleucina-10/metabolismo , Factores de Tiempo , Sus scrofa , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Cardiotónicos/farmacología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/fisiopatología , Infecciones por Pseudomonas/inmunología , Pseudomonas aeruginosaRESUMEN
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.
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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: Among the causes of the progression of intervertebral disc (IVD) degeneration (IDD) is the loss of nutrient intake to the IVD through the microcirculation disruption of the subendplate. Also, the vertebral body fracture intervenes in the degeneration the adjacent IVD. This research aimed to create an animal model of IDD using these 2 strategies. METHODS: Thirty male Sprague-Dawley rats were split into 3 groups: a control group, a middle vertebral body injury (MI) associated with ethanol injection (MI + EtOH) group, and an MI associated with phosphate-buffered saline injection group. A vertebral body fracture with or without endplate injection of ethanol was generated by either drilling a hole in the center of a caudal rat vertebral body to form a fracture with an unabated endplate or drilling a hole in the center of a rat coccygeal vertebral body with endplate injection of ethanol to establish a vertebral body fracture with endplate damage. X-ray, macroscopic, histologic, and biochemical evaluations were utilized to assess IDD at weeks 3 and 6. RESULTS: According to X-ray findings, the MI + EtOH group demonstrated a significant decrease in intervertebral space height over time in comparison to the 2 other groups. The water content also was significantly decreased. Macroscopic and histological analysis demonstrated progressive degenerative changes in the IVD of the MI + EtOH group. CONCLUSIONS: The caudal vertebra fracture with ethanol injection is more likely to induce degeneration of adjacent IVD. This model effectively reproduced IDD, which may serve as a theoretical basis for future clinical intervention for IDD.
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Modelos Animales de Enfermedad , Degeneración del Disco Intervertebral , Microcirculación , Ratas Sprague-Dawley , Fracturas de la Columna Vertebral , Animales , Masculino , Degeneración del Disco Intervertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Ratas , Microcirculación/fisiología , Microcirculación/efectos de los fármacos , Cuerpo Vertebral/diagnóstico por imagen , Etanol , Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/patologíaRESUMEN
BACKGROUND: Chronic venous insufficiency (CVI) is the consequence of venous valve reflux and/or venous flow obstruction and resulting venous hypertension in the lower extremities. The aim of this prospective supplement registry study was to evaluate the efficacy of compression stockings or Pycnogenol® in controlling symptoms and edema in CVI and their efficacy on microcirculatory parameters. METHODS: Two comparable groups of 30 subjects with CVI were observed for 4 months. RESULTS: Elastic compression was less tolerated than Pycnogenol® with 12 subjects being unable to follow the compression routine. No side effects due to supplementation were observed; tolerability of the supplementation was optimal. Ambulatory venous pressure (AVP) and refilling time (RT) at inclusion indicated a significant increase in venous pressure and reflux (refilling time <16 seconds). AVP and RT did not change after 4 months. Microcirculatory and clinical measurements were comparable at inclusion between the 2 groups. After 4 months, skin resting flux (RF) and skin PO
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Edema , Flavonoides , Microcirculación , Extractos Vegetales , Medias de Compresión , Insuficiencia Venosa , Humanos , Insuficiencia Venosa/fisiopatología , Insuficiencia Venosa/tratamiento farmacológico , Flavonoides/uso terapéutico , Microcirculación/efectos de los fármacos , Microcirculación/fisiología , Masculino , Femenino , Extractos Vegetales/uso terapéutico , Edema/tratamiento farmacológico , Estudios Prospectivos , Enfermedad Crónica , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Sistema de RegistrosRESUMEN
Wildfire smoke (WFS) is an urgent and rapidly growing threat to global health. Aside from obvious threats to pulmonary function, increases in cardiac abnormalities or myocardial infarction have been documented during WF season, but little is known about the effects of WFS on cardiovascular health. We investigated the effect of nonoccupational WFS exposure on cardiovascular and pulmonary function at rest and during graded handgrip exercise through a case series of young, healthy adults (n = 4, 25 ± 6 years) assessed after ≥3 days of bad or good air quality. Peripheral and estimated central blood pressures, vascular stiffness, and microvascular function (Near infrared spectroscopy, NIRS) were assessed at rest, and during rhythmic handgrip exercise. WFS did not appear to alter resting peripheral, central BP, or vascular stiffness (all, p > 0.05). Slope 1 and slope 2 from the NIRS-vascular occlusion test (NIRS-VOT) were not different between conditions (p > 0.05). The change in SmO2 during exercise was lower (p = 0.02, η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ = 0.62) with bad air quality. These preliminary findings suggest modest effects of environmental WFS exposure on muscle microvascular function during exercise in healthy adults. Future work is needed to elucidate the physiological changes with WFS exposure and the increased risk of cardiovascular events, perhaps exacerbated through physical activity.
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Ejercicio Físico , Fuerza de la Mano , Humo , Incendios Forestales , Humanos , Fuerza de la Mano/fisiología , Adulto , Masculino , Humo/efectos adversos , Femenino , Ejercicio Físico/fisiología , Exposición a Riesgos Ambientales/efectos adversos , Microcirculación/fisiología , Microcirculación/efectos de los fármacos , Adulto Joven , Consumo de Oxígeno/fisiología , Rigidez Vascular , Espectroscopía Infrarroja Corta , Presión SanguíneaRESUMEN
Coronary microcirculation dysfunction (CMD) is one of the main causes of cardiovascular disease. Traditional treatment methods lack specificity, making it difficult to fully consider the differences in patient conditions and achieve effective treatment and intervention. The complexity and diversity of CMD require more standardized diagnosis and treatment plans to clarify the best treatment strategy and long-term outcomes. The existing treatment measures mainly focus on symptom management, including medication treatment, lifestyle intervention, and psychological therapy. However, the efficacy of these methods is not consistent for all patients, and the long-term efficacy is not yet clear. GSEA is a bioinformatics method used to interpret gene expression data, particularly for identifying the enrichment of predefined gene sets in gene expression data. In order to achieve personalized treatment and improve the quality and effectiveness of interventions, this article combined GSEA (Gene Set Enrichment Analysis) technology to conduct in-depth research on potential drug targets and their interaction networks in coronary microcirculation dysfunctions. This article first utilized the Coremine medical database, GeneCards, and DrugBank public databases to collect gene data. Then, filtering methods were used to preprocess the data, and GSEA was used to analyze the preprocessed gene expression data to identify and calculate pathways and enrichment scores related to CMD. Finally, protein sequence features were extracted through the calculation of autocorrelation features. To verify the effectiveness of GSEA, this article conducted experimental analysis from four aspects: precision, receiver operating characteristic (ROC) curve, correlation, and potential drug targets, and compared them with Gene Regulatory Networks (GRN) and Random Forest (RF) methods. The results showed that compared to the GRN and RF methods, the average precision of GSEA improved by 0.11. The conclusion indicated that GSEA helped identify and explore potential drug targets and their interaction networks, providing new ideas for personalized quality of CMD.
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Biología Computacional , Microcirculación , Humanos , Microcirculación/efectos de los fármacos , Biología Computacional/métodos , Redes Reguladoras de Genes , Perfilación de la Expresión GénicaAsunto(s)
Angiotensina II , Modelos Animales de Enfermedad , Hemodinámica , Riñón , Microcirculación , Sepsis , Animales , Microcirculación/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Riñón/irrigación sanguínea , Riñón/efectos de los fármacos , Riñón/fisiopatología , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Ratas , Masculino , Ratas Wistar , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patologíaRESUMEN
INTRODUCTION: Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock. METHODS AND ANALYSIS: In this single centre, mechanistically focussed, randomised controlled study, 45 patients with septic shock will be randomly allocated to either of the study vasopressors (vasopressin or angiotensin II) or standard therapy (norepinephrine). Infusions will be titrated to maintain a mean arterial pressure (MAP) target set by the attending clinician. Renal microcirculatory assessment will be performed for the cortex and medulla using contrast-enhanced ultrasound (CEUS) and urinary oxygen tension (pO2), respectively. Renal macrovascular flow will be assessed via renal artery ultrasound. Measurement of systemic macrovascular flow will be performed through transthoracic echocardiography (TTE) and microvascular flow via sublingual incident dark field (IDF) video microscopy. Measures will be taken at baseline, +1 and +24hrs following infusion of the study drug commencing. Blood and urine samples will also be collected at the measurement time points. Longitudinal data will be compared between groups and over time. DISCUSSION: Vasopressors are integral to the management of patients with septic shock. This study aims to further understanding of the relationship between this therapy, renal perfusion and the development of AKI. In addition, using CEUS and urinary pO2, we hope to build a more complete picture of renal perfusion in septic shock by interrogation of the constituent parts of the kidney. Results will be published in peer-reviewed journals and presented at academic meetings. TRIAL REGISTRATION: The REPERFUSE study was registered on Clinical Trials.gov (NCT06234592) on the 30th Jan 24.
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Lesión Renal Aguda , Microcirculación , Choque Séptico , Vasoconstrictores , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Angiotensina II/administración & dosificación , Riñón/efectos de los fármacos , Riñón/fisiopatología , Riñón/irrigación sanguínea , Microcirculación/efectos de los fármacos , Norepinefrina/administración & dosificación , Norepinefrina/uso terapéutico , Circulación Renal/efectos de los fármacos , Choque Séptico/tratamiento farmacológico , Choque Séptico/fisiopatología , Vasoconstrictores/uso terapéutico , Vasoconstrictores/administración & dosificación , Vasopresinas/administración & dosificación , Vasopresinas/uso terapéuticoRESUMEN
The transcriptional regulator nuclear factor-κB (NF-κB) is a mediator of endothelial dysfunction. Inhibiting NF-κB with salsalate is used to investigate inflammatory mechanisms contributing to accelerated cardiovascular disease risk. However, in the absence of disease, inhibition of NF-κB can impact redox mechanisms, resulting in paradoxically decreased endothelial function. This study aimed to measure microvascular endothelial function during inhibition of the transcriptional regulator NF-κB in reproductive-aged healthy women. In a randomized, single-blind, crossover, placebo-controlled design, nine healthy women were randomly assigned oral salsalate (1,500 mg, twice daily) or placebo treatments for 5 days. Subjects underwent graded perfusion with the endothelium-dependent agonist acetylcholine (ACh, 10-10 to 10-1 M, 33°C) alone and in combination with 15 mM NG-nitro-l-arginine methyl ester [l-NAME; nonselective nitric oxide (NO) synthase inhibitor] through intradermal microdialysis. Laser-Doppler flux was measured over each microdialysis site, and cutaneous vascular conductance (CVC) was calculated as flux divided by mean arterial pressure and normalized to site-specific maximum (CVC%max; 28 mM sodium nitroprusside + 43°C). The l-NAME sensitive component was calculated as the difference between the areas under the dose-response curves. During the placebo and salsalate treatments, the l-NAME sites were reduced compared with the control sites (both P < 0.0001). Across treatments, there was a significant difference between the control and l-NAME sites, where both sites shifted upward following salsalate treatment (both P < 0.0001), whereas the l-NAME-sensitive component was not different (P = 0.94). These data demonstrate that inhibition of the transcriptional regulator NF-κB improves cutaneous microvascular function in reproductive-aged healthy women through non-NO-dependent mechanisms.NEW & NOTEWORTHY The transcription factor nuclear factor-κB (NF-κB) regulates multiple aspects of innate and adaptive immunity by encoding for genes that participate in inflammation and impact endothelial function following NF-κB inhibition with salsalate treatment. Our results show that cutaneous microvascular function is increased through non-nitric oxide (NO)-dependent mechanisms following salsalate treatment in reproductive-aged healthy women.
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Estudios Cruzados , Microcirculación , FN-kappa B , Óxido Nítrico , Piel , Humanos , Femenino , Adulto , Piel/irrigación sanguínea , Piel/efectos de los fármacos , Piel/metabolismo , FN-kappa B/metabolismo , Método Simple Ciego , Microcirculación/efectos de los fármacos , Óxido Nítrico/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Vasodilatación/efectos de los fármacos , Adulto Joven , Acetilcolina/farmacología , Voluntarios Sanos , Vasodilatadores/farmacología , Inhibidores Enzimáticos/farmacología , Salicilatos/farmacología , Microvasos/efectos de los fármacos , Microvasos/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
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.
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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
OBJECTIVE: The clinical advantage of alprostadil [prostaglandin E1 (PGE1)] in the treatment of microcirculatory disturbances (defined as no-reflow or slow-flow) in acute percutaneous coronary intervention (PCI) is still disputed. The purpose of our study was to review the efficacy of PGE1 supplements in patients with acute myocardial infarction (AMI) who had urgent PCI. DESIGN: This study was a meta-analysis of randomized controlled trials. DATA SOURCES: PubMed, Embase, the Cochrane Library, Ovid, ProQuest, Scopus, the Chinese BioMedical Literature Database, China National Knowledge Internet, the China Science and Technology Journal Database, and the Wanfang Data Knowledge Service Platform were used as sources. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomized controlled trials including PGE1 for the treatment of intraoperative microcirculatory disorders and major cardiovascular adverse events in emergency PCI in people with AMI. Independent data extraction was conducted, and study quality was assessed. The meta-analysis was carried out by using random effects models to calculate the risk ratio (RR) of microcirculatory disorders between groups receiving PGE1 and those receiving placebo, nitroglycerin, or tirofiban. MAIN OUTCOME MEASURES: The primary endpoint of the study was the incidence of microcirculatory disturbances. Secondary outcomes included corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), the percentage of patients with TIMI myocardial perfusion grade 3 (TMPG3), and the percentage of patients with myocardial blush grade 3 (MBG3) as efficacy indicators. Additionally, major adverse cardiovascular events (MACE) at 30 days and 180 days were assessed as safety indicators. RESULTS: There were 18 trials involving a total of 1458 participants. PGE1 significantly reduced the occurrence of microcirculation disorders compared with conventional medications and placebo [risk ratio 0.48, 95% confidence interval (CI) 0.36-0.63, I2 = 46%; cTFC (RR -4.74, 95% -6.85 to -2.63, I2 93%); percentage of patients with TMPG3 (RR 1.34, 95% CI 1.07-1.68, I2 70%) or MBG3 (RR 1.33, 95% CI 1.19-1.49, I2 0%); major adverse cardiovascular events (MACEs) in 30 days (RR 0.48, 95% CI 0.27-0.86, I2 0%); and MACEs in 180 days (RR 0.41, 95% CI 0.28-0.60, I2 0%)]. CONCLUSIONS: We found that PGE1 decreased the occurrence of micro-circulation disturbance in AMI and enhanced the outcome of PCI. Additional studies should be conducted to confirm these findings.
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Alprostadil , Microcirculación , Infarto del Miocardio , Intervención Coronaria Percutánea , Ensayos Clínicos Controlados Aleatorios como Asunto , Alprostadil/uso terapéutico , Alprostadil/efectos adversos , Alprostadil/administración & dosificación , Humanos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Microcirculación/efectos de los fármacos , Vasodilatadores/uso terapéutico , Vasodilatadores/efectos adversosRESUMEN
Endothelial dysfunction (ED) is associated with progressive changes contributing to clinical complications related to macro- and microvascular diseases. Garlic (Allium sativum L.) and its organosulfur components have been related to beneficial cardiovascular effects and could improve endothelial function. The ENDOTALLIUM Study aimed to evaluate the effect of the regular consumption of encapsulated purple garlic oil on microvascular function, endothelial-related biomarkers, and the components of metabolic syndrome (MetS) in untreated subjects with cardiometabolic alterations. Fifty-two individuals with at least one MetS component were randomized (1:1) in a single-center, single-blind, placebo-controlled, parallel-group study. The participants received encapsulated purple garlic oil (n = 27) or placebo (n = 25) for five weeks. Skin microvascular peak flow during post-occlusive reactive hyperemia significantly increased in the purple garlic oil group compared to the placebo group (between-group difference [95%CI]: 15.4 [1.5 to 29.4] PU; p = 0.031). Likewise, hs-CRP levels decreased in the purple garlic group compared to the control group (-1.3 [-2.5 to -0.0] mg/L; p = 0.049). Furthermore, we observed a significant reduction in the mean number of MetS components in the purple garlic group after five weeks (1.7 ± 0.9 vs. 1.3 ± 1.1, p = 0.021). In summary, regular consumption of encapsulated purple garlic oil significantly improved microvascular function, subclinical inflammatory status, and the overall MetS profile in a population with cardiometabolic alterations.