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1.
Zhonghua Xue Ye Xue Za Zhi ; 41(4): 302-307, 2020 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-32447934

RESUMO

Objective: To investigate the clinical and coagulation characteristics in patients with critical Coronavirus disease 2019 (COVID-19) and acro-ischemia. Methods: The retrospective study included 7 critical COVID-19 patients with acro-ischemia in an intensive care unit (ICU) in Wuhan, from Feb 4 to Feb 15, 2020. The clinical and laboratory data before and during the ICU stay were analyzed. Results: The median age of 7 patients was 59 years and 4 of them were men. Three patients were associated with underlying comorbidities. Fever, cough, dyspnea and diarrhea were common clinical symptoms. All patients had acro-ischemia presentations including finger/toe cyanosis, skin bulla and dry gangrene. D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients. Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation. Four patients were diagnosed with disseminated intravascular coagulation (DIC) . Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms. Five patients died finally and the median time from acro-ischemia to death was 12 days. Conclusions: Coagulation parameters should be monitored closely in critical COVID-2019 patients. The timing and protocol of anticoagulation therapy are still under investigation based on more clinical data.


Assuntos
Anticoagulantes/uso terapêutico , Infecções por Coronavirus/complicações , Heparina de Baixo Peso Molecular/uso terapêutico , Isquemia/tratamento farmacológico , Pneumonia Viral/complicações , Betacoronavirus , China , Infecções por Coronavirus/tratamento farmacológico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Isquemia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Estudos Retrospectivos
2.
Angiology ; 71(3): 226-234, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31769315

RESUMO

For many years, the only pharmacological option for patients with critical limb ischemia (CLI) unsuitable for revascularization has been prostanoids; however, some recent guidelines have become very restrictive regarding their use. We review the available evidence on the use of prostanoids and analyze the guideline positions as well as the possible reasons for changes over time. In most placebo-controlled trials and meta-analyses, prostanoids showed a significant effect in improving rest pain, promoting ulcer healing and reducing major amputations. Results for iloprost were especially consistent. Different prostanoid drugs have different evidence of efficacy, thus using a generic term "prostanoids" is misleading. Unfortunately, the available evidence is often of low quality and probably not sufficient to support an extensive use of prostanoids in all patients, and further high-quality randomized trials are needed. Consequently, some recent guidelines do not recommend treatment with prostanoids in this setting. However, in our opinion, pending definitive evidence, patients with CLI who have a viable limb in whom revascularization is unfeasible or has a poor chance of success, without alternative to amputation, may benefit from treatment with iloprost, balancing harms and benefits in each case.


Assuntos
Iloprosta/farmacologia , Isquemia/tratamento farmacológico , Dor/tratamento farmacológico , Prostaglandinas/farmacologia , Alprostadil/uso terapêutico , Amputação/métodos , Humanos , Resultado do Tratamento , Vasodilatadores/uso terapêutico
3.
Plast Reconstr Surg ; 145(1): 161-164, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881617

RESUMO

Posttraumatic hand injuries from crush injury, infusion, or iatrogenic vascular cannulation can cause ischemic finger damage that can progress to necrosis and digital amputation. Botulinum toxin type A (Botox) improves blood flow in chronic vasospastic disorders of the hand. Botox's efficacy in salvaging ischemic loss in digits in acute traumatic and iatrogenic injury has not been previously reported. From February of 2015 to December of 2016, 11 patients at a Level I trauma center (West Virginia University) presented to the hand surgery service with early ischemic injury and vascular compromise to hand and fingers as a result of crush, direct drug injection, or proximal arterial injury from drug injection or catheterization. Before 2015, all patients with vascular compromise were treated with standard protocol. After January of 2016, patients were treated with additional injection of 80 to 100 U of Botox into the palm and wrist. Before administration of Botox, six patients with vascular compromise of one or more fingers were treated with a conservative protocol and 83 percent had amputation of necrotic digits. After January of 2016, five patients with ischemia were treated with Botox into the palm and proximal arteries. All Botox-treated digits were preserved (100 percent salvage). Pain scores were lower in Botox-treated fingers. We conclude that (1) in the acute traumatic vascular hand injury, early Botox injection markedly increases digital salvage; (2) direct nerve effects after Botox injections improve postinjury pain scores; and (3) early use of Botox in finger injuries is our standard approach to impending ischemia in the hand.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Traumatismos dos Dedos , Dedos/irrigação sanguínea , Isquemia/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Doenças Vasculares Periféricas/tratamento farmacológico , Terapia de Salvação/métodos , Adulto , Idoso , Traumatismos dos Dedos/complicações , Traumatismos dos Dedos/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/etiologia
4.
Biomed Res Int ; 2019: 8080564, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886253

RESUMO

Purpose: To determine the effects of selenium, melatonin, and selenium + melatonin administered for one month on anterior chamber (AC) malondialdehyde (MDA) and AC glutathione (GSH) levels in patients with ocular ischemic syndrome. Materials and Methods: Thirty-five patients were included in the study. Study groups were formed as follows: (1) control group, (2) ischemia group, (3) selenium + ischemia group, (4) melatonin + ischemia group, and (5) selenium + melatonin + ischemia group. AC samples were obtained. MDA and GSH levels in AC samples were evaluated. Results: MDA levels were significantly increased in ischemia groups. Selenium and melatonin supplementation resulted in reduction of MDA levels and significant increase in GSH values. Discussion: Increased lipid peroxidation associated with ischemia of the anterior segment has been prevented by selenium and melatonin supplementation. This trial is registered with ClinicalTrials.gov NCT04005222.


Assuntos
Olho/irrigação sanguínea , Isquemia/tratamento farmacológico , Melatonina/uso terapêutico , Selênio/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Olho/patologia , Feminino , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído , Melatonina/farmacologia , Pessoa de Meia-Idade , Selênio/farmacologia , Síndrome
5.
J Cardiovasc Surg (Torino) ; 60(6): 642-651, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31603294

RESUMO

INTRODUCTION: The aim of this article is to systematically review the literature on medical adjunctive therapy for patients with chronic limb-threatening ischemia (CLTI). EVIDENCE ACQUISITION: MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched for studies published between January 1st, 2009, and June 1st, 2019. Articles that studied medical treatment of CLTI patients and reported clinical outcomes were eligible. Main exclusion criteria were case reports <20 patients, incorrect publication type, and CLTI caused by Buerger disease. The primary end point was major amputation (above the ankle) in studies with a follow-up of ≥6 months. Secondary end points were other clinical end points such as death and wound healing. Study quality was assessed according to the Downs and Black checklist. EVIDENCE SYNTHESIS: Included were 42 articles: four focused on antiplatelet therapy, five on antihypertensive medication, 6 on lipid-lowering therapy, 16 on stem cell therapy, three on growth factors, five on prostanoids, and one study each on cilostazol, glucose-lowering therapy, spinal cord stimulation, sulodexide, and hemodilution. Calcium channel blockers, iloprost, cilostazol, and hemodilution showed significant improvement of limb salvage, but data are limited. Stem cell therapy showed no significant improvement of limb salvage but could potentially improve wound healing. Antiplatelets, antihypertensives, and statins showed significantly lower cardiovascular events rates but not evident lower major amputation rates. The quality of the studies was fair to good. CONCLUSIONS: Certain medical therapies serve to improve limb salvage next to revascularization in CLTI patients, whereas others are important in secondary prevention. Because high quality evidence is limited, further research is needed.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Isquemia/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Amputação , Fármacos Cardiovasculares/efeitos adversos , Estado Terminal , Humanos , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Isquemia/fisiopatologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Fatores de Risco , Resultado do Tratamento
6.
Arq Bras Cir Dig ; 32(3): e1451, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31644671

RESUMO

BACKGROUND: Hypovolemic shock is a common disease in polytrauma patients and may develop ischemia in various organs, increasing morbidity and mortality. The bowel is usually most affected by this condition. AIM: To evaluate the effects of copaiba oil on the intestinal mucosa's injury of rats submitted to hypovolemic shock. METHOD: Fifteen rats were divided into three groups: sham - simulated surgery; ischemia - animals submitted to hypovolemic shock; and copaiba - animals submitted to hypovolemic shock previously treated with copaiba oil. Mean blood pressure, arterial blood gas after shock induction, degree of intestinal lesion and villus length were evaluated. RESULTS: The sham presented the lowest values of lactate and PaCO2 and the highest values of mean arterial pressure, pH and bicarbonate in relation to the other groups. The degree of mesenteric lesion was zero in the sham group; 3.00±1.00 in the ischemia group; and 3.00±0.71 in the copaiba group. The villus length was 173.60±8.42 in the sham, 142.77±8.33 in the ischemia and 143.01±9.57 in the copaiba group. There was a significant difference between the sham and the other groups (p<0.05); however, there not significant difference between groups Ischemia and copaiba. CONCLUSION: Administration of copaiba oil did not reduce the intestinal mucosa lesion of rats after hypovolemic shock.


Assuntos
Anti-Inflamatórios/farmacologia , Fabaceae/química , Mucosa Intestinal/efeitos dos fármacos , Óleos Vegetais/farmacologia , Choque , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Íleo/patologia , Mucosa Intestinal/patologia , Isquemia/tratamento farmacológico , Masculino , Óleos Vegetais/química , Óleos Vegetais/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Choque/tratamento farmacológico
7.
Zhonghua Yi Xue Za Zhi ; 99(35): 2785-2788, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550804

RESUMO

Objective: To explore the risk factors and treatment of acute lower limb ischemia with catheter-directed thrombolysis combined with endovascular interventions. Methods: Totally 191 patients (191 lower limbs) with acute lower limb ischemia in department of vascular surgery of the First Affiliated Hospital of Chongqing Medical University from June 2012 to June 2017 who underwent catheter-directed thrombolysis combined with endovascular interventions were collected. According to imaging findings and clinical characteristics, the patients were divided into acute arterial embolism group (n=36) and acute arterial thrombosis group (n=155). The treatment effect, long-term follow-up and the risk factors closely related to primary patency were analyzed. Results: Among the 191 patients, the immediate success rate of surgery was 100%, the amputation rate within 30 days was 8.4% (16/191), and the mortality rate within 30 days was 2.6% (5/191). The mean follow-up was 31.0 (1.0-60.0) months. The 1-year overall survival rate was 92.1% and the 5-year was 79.5%. The primary patency rate was 74.3% within 1 year and 61.5% within 5 years. Primary vascular patency rate within 1 year and 5 years was mainly affected by occlusion segment (OR=3.5, 2.9, P<0.05), outflow tract (OR=3.2, 2.8, P<0.05) and ischemia degree (OR=3.4, 3.6, P<0.05). Conclusion: Catheter-directed thrombolysis combined with endovascular interventions for acute lower limb ischemia is a safe and effective method. Risk factors for primary patency at 1 and 5 years are occlusion segment, outflow tract and ischemia degree.


Assuntos
Isquemia/tratamento farmacológico , Terapia Trombolítica , Seguimentos , Humanos , Extremidade Inferior , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Grau de Desobstrução Vascular
8.
Angiol Sosud Khir ; 25(3): 29-37, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31503245

RESUMO

AIM: The study was aimed at assessing efficacy and safety of treatment with Aducil® (cilostazol) compared with Trental® 400 in patients with moderate-to-severe intermittent claudication due to peripheral atherosclerosis. PATIENTS AND METHODS: The study included a total of one hundred and forty-five 36-to-75-year-old patients. The participants were distributed into 2 groups according to the inclusion/exclusion criteria in a 2 to 1 proportion: patients in group 1 received Aducil® 100 mg BID, in group 2 - Trental® 400 TID for 12 weeks. 142 subjects completed the protocol. RESULTS: Analysis of the effectiveness of treatment according to the primary criterion showed a better effectiveness of Aducil® as compared with Trental® 400. Subjects who received Aducil® had a higher increase in the absolute maximum walking distance after 12 weeks of treatment as compared with those taking Trental® 400: 126±110 m versus 45±39 m, respectively (р<0.001). Subjects who received Aducil® had a statistically significant improvement in quality of life parameters such as physical and mental health components according to the SF-36 questionnaire after 12 weeks of treatment (р≤0.01). Subjects in Aducil® group had better quality of life with an increase from 34 to 40 points according to the physical component score, while patients in Trental® 400 group demonstrated minor positive changes (from 35 to 37 points); mean mental component score increased from 45 to 48 points in Aducil® group as compared with an increase from 45 to 47 points in Trental® 400 group. While self-reported physical health status was similar between the groups at baseline, subjects in Aducil® group reported better physical functioning after treatment (р=0.016). Two adverse events were registered in two subjects in Aducil® group. CONCLUSION: Analysis of the study endpoints demonstrated that Aducil® had better treatment effectiveness in patients with chronic lower limb ischemia stage IIB according to the classification of A.V. Pokrovsky-Fontaine as compared with Trental® 400, while the safety profile and drug tolerance were similar between the two.


Assuntos
Cilostazol , Claudicação Intermitente , Isquemia , Inibidores da Agregação de Plaquetas , Cilostazol/uso terapêutico , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Extremidade Inferior , Inibidores da Agregação de Plaquetas/uso terapêutico , Qualidade de Vida , Caminhada
11.
A A Pract ; 13(8): 306-309, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31313663

RESUMO

We report the clinical case of a septic patient with antiphospholipid syndrome who developed ischemia in all 4 limbs, despite a normal systemic blood pressure. Prolonged coagulation times suggested a hemorrhagic diathesis, requiring transfusion of fresh-frozen plasma and discontinuation of heparin infusion. In contrast, the study of the viscoelastic properties of the clot by thromboelastography suggested an uncontrolled activation of the coagulation cascade. This observation led to the reintroduction of heparin with improvement in the patient's laboratory findings. Anesthesiologists should consider thromboelastography to correct coagulopathies in patients with septic shock in the presence of antiphospholipid antibodies.


Assuntos
Síndrome Antifosfolipídica , Transtornos da Coagulação Sanguínea/diagnóstico , Choque Séptico , Tromboelastografia , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Celulite (Flegmão)/tratamento farmacológico , Extremidades/irrigação sanguínea , Evolução Fatal , Feminino , Heparina/uso terapêutico , Humanos , Isquemia/tratamento farmacológico , Pessoa de Meia-Idade , Choque Séptico/tratamento farmacológico
12.
J Zhejiang Univ Sci B ; 20(8): 687-692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273966

RESUMO

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.


Assuntos
Claudicação Intermitente/sangue , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Metaloproteinase 9 da Matriz/sangue , Neovascularização Patológica , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Idoso , Inibidores da Angiogênese/farmacologia , Feminino , Regulação da Expressão Gênica , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue
13.
Oxid Med Cell Longev ; 2019: 1302985, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354899

RESUMO

The therapeutic effects of telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, have been demonstrated in several disorders. It has antioxidant and immune response modulator properties and has shown promising results in the treatment of an ischemia/reperfusion (I/R) lesion. In this study, a skeletal muscle (right gastrocnemius muscle) I/R lesion was induced in rats and different reperfusion times (1 h, 24 h, 72 h, 7-day, and 14-day subgroups) were assessed. Furthermore, levels of oxidative markers such as enzymatic scavengers (catalase (CAT) and superoxide dismutase (SOD)) and metabolites (nitrates and 8-oxo-deoxyguanosine) were determined. The degree of tissue injury (total lesioned fibers and inflammatory cell count) was also evaluated. We observed an increase in CAT and SOD expression levels under telmisartan treatment, with a decrease in injury and oxidative biomarker levels in the 72 h, 7-day, and 14-day subgroups. Telmisartan reduced oxidative stress and decreased the damage of the I/R lesion.


Assuntos
Anti-Hipertensivos/uso terapêutico , Isquemia/tratamento farmacológico , Telmisartan/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Humanos , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Traumatismo por Reperfusão , Telmisartan/farmacologia
14.
Vasc Med ; 24(5): 422-430, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31339474

RESUMO

In patients with symptomatic peripheral artery disease (PAD), the impact of chronic kidney disease (CKD) on major adverse cardiovascular events has not been fully evaluated. The Examining Use of Ticagrelor In PAD (EUCLID) trial randomized 13,885 patients with PAD to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. This post hoc analysis compared the incidence of the primary composite endpoint (cardiovascular death, myocardial infarction (MI), or ischemic stroke) in patients with CKD (eGFR < 60 mL/min/1.73 m2) with those without CKD (eGFR ⩾ 60 mL/min/1.73 m2). The primary safety endpoint was thrombolysis in MI (TIMI) major bleeding. A total of 13,483 patients were included; 3332 (25%) had CKD, of whom 237 had stage 4/5 disease. Median follow-up was approximately 30 months. After statistical adjustment, patients with CKD had a higher rate of the primary endpoint compared with those without CKD (6.75 vs 3.72 events/100 patient-years; adjusted hazard ratio (HR) 1.45, 95% CI 1.30-1.63). CKD was not associated with increased risk of hospitalization for acute limb ischemia (ALI) (adjusted HR 0.96, 95% CI 0.69-1.34) or major amputation (adjusted HR 0.92, 95% CI 0.66-1.28). CKD was not associated with a significantly increased risk of major bleeding (adjusted HR 1.21, 95% CI 0.89-1.64), but minor bleeding was significantly increased (adjusted HR 1.51, 95% CI 1.07-2.15). In conclusion, patients with PAD and CKD had higher rates of cardiovascular death, MI, and ischemic stroke, but similar rates of ALI, major amputation, and TIMI major bleeding when compared with patients without CKD. ClinicalTrials.gov Identifier: NCT01732822.


Assuntos
Clopidogrel/administração & dosagem , Taxa de Filtração Glomerular , Isquemia/tratamento farmacológico , Rim/fisiopatologia , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Insuficiência Renal Crônica/fisiopatologia , Ticagrelor/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Amputação , Isquemia Encefálica/mortalidade , Isquemia Encefálica/prevenção & controle , Clopidogrel/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/mortalidade , Humanos , Incidência , Isquemia/diagnóstico , Isquemia/mortalidade , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
Oxid Med Cell Longev ; 2019: 7857082, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191804

RESUMO

Intestinal ischemia/reperfusion (I/R), which is associated with high morbidity and mortality, is also accompanied with abnormal energy metabolism and liver injury. Irisin, a novel exercise-induced hormone, can regulate adipose browning and thermogenesis. The following study investigated the potential role of dexmedetomidine in liver injury during intestinal I/R in rats. Adult male Sprague-Dawley rats underwent occlusion of the superior mesenteric artery for 90 min followed by 2 h of reperfusion. Dexmedetomidine or irisin-neutralizing antibody was intravenously administered for 1 h before surgery. The results demonstrated that severe intestine and liver injuries occurred during intestinal I/R as evidenced by pathological scores and an apparent increase in serum diamine oxidase (DAO), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels. In addition, the hepatic irisin, cleaved caspase-3, Bax, and NLRP3 inflammasome components (including NLRP3, ASC, and caspase-1), protein expressions, apoptotic index, reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- (TNF-) α, and interleukin- (IL-) 6 levels increased; however, the serum irisin level and hepatic Bcl-2 protein expression and superoxide dismutase (SOD) activity decreased after intestinal I/R. Interestingly, dexmedetomidine could reduce the above listed changes and increase the irisin levels in plasma and the liver in I/R rats. Dexmedetomidine-mediated protective effects on liver injury and NLRP3 inflammasome activation during intestinal I/R were partially abrogated via irisin-neutralizing antibody treatment. The results suggest that irisin might contribute to the hepatoprotection of dexmedetomidine during intestinal ischemia/reperfusion.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Dexmedetomidina/uso terapêutico , Fibronectinas/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Isquemia/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Fibronectinas/antagonistas & inibidores , Fibronectinas/sangue , Isquemia/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Fator de Necrose Tumoral alfa/metabolismo
17.
Clin Sci (Lond) ; 133(9)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988131

RESUMO

Renal vasoconstriction, an early manifestation of ischemic acute kidney injury (AKI), results in renal hypoperfusion and a rapid decline in kidney function. The pathophysiological mechanisms that underlie ischemia-reperfusion (IR)-induced renal insufficiency are poorly understood, but possibilities include alterations in ion channel-dependent renal vasoregulation. In the present study, we show that pharmacological activation of TRPV4 channels constricted preglomerular microvessels and elicited renal hypoperfusion in neonatal pigs. Bilateral renal ischemia followed by short-term reperfusion increased TRPV4 protein expression in resistance size renal vessels and TRPV4-dependent cation currents in renal vascular smooth muscle cells (SMCs). Selective TRPV4 channel blockers attenuated IR-induced reduction in total renal blood flow (RBF), cortical perfusion, and glomerular filtration rate (GFR). TRPV4 inhibition also diminished renal IR-induced increase in AKI biomarkers. Furthermore, the level of angiotensin II (Ang II) was higher in the urine of IR- compared with sham-operated neonatal pigs. IR did not alter renal vascular expression of Ang II type 1 (AT1) receptors. However, losartan, a selective AT1 receptor antagonist, ameliorated IR-induced renal insufficiency in the pigs. Blockade of TRPV4 channels attenuated Ang II-evoked receptor-operated Ca2+ entry and constriction in preglomerular microvessels. TRPV4 inhibition also blunted Ang II-induced increase in renal vascular resistance (RVR) and hypoperfusion in the pigs. Together, our data suggest that SMC TRPV4-mediated renal vasoconstriction and the ensuing increase in RVR contribute to early hypoperfusion and renal insufficiency elicited by renal IR in neonatal pigs. We propose that multimodal signaling by renal vascular SMC TRPV4 channels controls neonatal renal microcirculation in health and disease.


Assuntos
Losartan/farmacologia , Circulação Renal/efeitos dos fármacos , Insuficiência Renal/tratamento farmacológico , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Animais Recém-Nascidos , Pressão Sanguínea/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Isquemia/tratamento farmacológico , Isquemia/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Substâncias Protetoras/farmacologia , Receptores de Angiotensina/efeitos dos fármacos , Receptores de Angiotensina/metabolismo , Insuficiência Renal/metabolismo , Suínos , Canais de Cátion TRPV/metabolismo , Vasoconstrição/efeitos dos fármacos
18.
Vasa ; 48(4): 321-329, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30958111

RESUMO

Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.


Assuntos
Isquemia , Inibidores da Agregação de Plaquetas/uso terapêutico , Anticoagulantes , Quimioterapia Combinada , Seguimentos , Humanos , Isquemia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento
19.
Phytomedicine ; 55: 320-329, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940361

RESUMO

BACKGROUND: It has been reported that n-butanol extract of Potentilla anserina L (NP) had protective effect against acute myocardial ischemia/reperfusion (I/R) injury in mice. Because of limited phytochemical study on NP, its bioactive compounds and underlying protective mechanisms are largely unclear. PURPOSE: The purpose of this study was to investigate the major bioactive compounds and possible mechanism for the cardioprotective effect of NP on rat with I/R injury. METHODS: We analyzed the phytochemical isolation of NP and identified the structure of compounds, which was elucidated by a combination of spectroscopic analyses. An I/R model was established by I-30 min/R-2 h in Sprage-Dawley rats. The rats were given intragastric administration of NP (49.3, 98.6, and 197.2 mg•kg-1) continuously for 10 days before I/R operation. The morphological changes and apoptosis of cardiomyocytes were observed by H&E staining, Transmission electron microscope and TUNEL staining respectively. The activities or contents of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in plasma were detected. Apoptosis related factors were also measured by RT-PCR and western blot. In order to discover the underlying mechanism of NP on I/R, we performed proteomic analysis using two-dimensional gel electrophoresis (2D-DIGE) and matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/MS) to describe differential proteins expression. Potential target protein resulted from 2D-DIGE coupled to MALDI-TOF/MS analysis were further confirmed by immunohistochemical staining, RT-PCR, and western blot. RESULTS: We isolated and identified 14 compounds, of which 7 compounds belong to triterpenes. Rats pretreated with NP showed a significant increase on the activities of GSH, SOD and CAT, and remarkable decrease on the content of MDA. NP significantly inhibited the apoptosis of cardiomyocyte and decreased the expression of Cyt C and cleaved-caspase-3. Proteomic analysis revealed that alpha B-crystallin (CryAB) might participate in the NP protective effect against I/R. NP enhanced the level of pCryAB Ser59, whereas the expression of CryAB was decreased. CONCLUSION: NP was showed to alleviate I/R injury and inhibit myocardial apoptosis, which might be associated with reduction on oxidative stress and apoptosis. CryAB as a possible target involved in the NP protective effect. This study supplied valuable information to develop novel cardioprotective agents from NP extract.


Assuntos
Cardiotônicos/farmacologia , Isquemia/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Extratos Vegetais/farmacologia , Potentilla/química , Cadeia B de alfa-Cristalina/uso terapêutico , Animais , Cardiotônicos/uso terapêutico , Masculino , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley
20.
Contrast Media Mol Imaging ; 2019: 2538909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863219

RESUMO

Purpose: Peripheral artery disease (PAD) causes narrowing of arteries in the limbs, leading to tissue ischemia, gangrene, and eventually limb amputation. The presence of diabetes greatly exacerbates the course of PAD, accounting for the majority of lower limb amputations. Therapeutic strategies focussing on macrovascular repair are less effective in diabetic patients where smaller vessels are affected, and proangiogenic therapies offer a viable adjunct to improve vascularisation in these at risk individuals. The purpose of the current study was to assess the proangiogenic effects of drugs routinely used to treat cardiovascular disease in a diabetic murine model of hind limb ischemia longitudinally using multimodal imaging. Procedures: Diabetic mice underwent surgical intervention to induce hind limb ischemia and were treated with simvastatin, metformin, or a combination orally for 28 days and compared to diabetic and nondiabetic mice. Neovascularisation was assessed using [18F]FtRGD PET imaging, and macrovascular volume was assessed by quantitative time of flight MRI. At each imaging time point, VEGF expression and capillary vessel density were quantified using immunohistochemical analysis, and functional recovery and disease progression were assessed. Results: Combined use of simvastatin and metformin significantly increased neovascularisation above levels measured with either treatment alone. Early angiogenic events were accurately assessed using PET [18F]FtRGD, showing maximal retention in the ischemic hind limb by day 8, which translated to a sustained increase in vascular volume at later time points. Immunohistochemical analysis shows that combined therapy significantly increased VEGF expression and capillary density (CD31+) in a similar time course and also slowed disease progression while simultaneously improving functional foot use. Conclusions: Combined treatment with simvastatin and metformin led to a significant improvement in limb angiogenesis, vascular volume, and sustained functional recovery in a diabetic murine model of HLI. PET imaging with [18F]FtRGD provides a robust method for early detection of these proangiogenic effects preclinically and may be useful for the assessment of proangiogenic therapies used clinically to treat diabetic PAD patients.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Membro Posterior/diagnóstico por imagem , Isquemia/diagnóstico por imagem , Isquemia/tratamento farmacológico , Animais , Membro Posterior/efeitos dos fármacos , Membro Posterior/patologia , Imuno-Histoquímica , Imagem por Ressonância Magnética/métodos , Masculino , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos dos fármacos , Oligopeptídeos/química , Sinvastatina/uso terapêutico
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