Intradermal methylene blue administration on the progression of burn injuries.

OBJECTIVE: A burn injury has two defined areas: central necrosis and an adjacent area of ischaemia, which may or may not progress to necrosis. The concentration of nitric oxide (NO) increases after burn injury and may originate from potent oxidising agents. Methylene blue (MB) may act as an antioxidant and is supposed to reduce burn progression. This investigation was carried out to evaluate the effects of intradermal MB on necrosis progression in burns. METHODS: Full-thickness burn injuries were performed by applying a heated metal comb on the shaved back of male Wistar rats. The animals were divided into three groups: Control (C, n=7); MB (2mg/kg) one hour after burn injury (MB1h, n=11); and MB (2mg/kg) six hours after burn injury (MB6h, n=8). After seven days the lesions were photographed for visual assessment of burn necrosis; full-thickness cuts of lesions were dyed with Masson and Giemsa for microscopic histopathology; and tissue fragments of unburned interspaces were processed for chemiluminescence with nitrite/nitrate (NOX) and malondialdehyde (MDA) as oxidative stress markers. RESULTS: No statistically significant differences between groups were observed during visual analysis and NOX dosage. However, in microscopic analysis, the MB1h and MB6h groups showed smaller areas of necrosis, less inflammatory infiltration, and a more significant extension of interspaces. Furthermore, the dosage of MDA revealed that the MB1h group showed lower values when compared with the control group (p=0.001). CONCLUSIONS: The study provided good evidence that MB intradermal injection can reduce necrosis progression in ischaemic perilesional areas and suggests an alternative to treating burns.

Characterization of the kallikrein-kinin system, metalloproteinases, and their tissue inhibitors in the in-stent restenosis after peripheral percutaneous angioplasty.

BACKGROUND: The kallikrein-kinin system (KKS) has several direct and indirect effects on cells and cellular mediators involved in the inflammatory process. Studies about inflammation on percutaneous transluminal angioplasty with stent (PTA/stent) to treat peripheral arterial disease (PAD) in humans are scarce. The matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases expressed in various cells and tissues such as fibroblasts, inflammatory cells, and, smooth muscle cells. Changes in the extracellular matrix (ECM) take place in the pathogenesis of many cardiovascular pathologies. MMPs and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are crucial in ECM remodeling in both physiologic and pathologic conditions. The aim of this study was to evaluate the role of the KKS and the MMP metabolism, which are important mediators that may contribute to tissue repair, in the process of arterial restenosis due to intimal hyperplasia in the femoropopliteal segment with the aim of developing new interventions. METHODS: Thirty-nine consecutive patients were selected (regardless of ethnic group, age, or sex) for revascularization, who underwent PTA/stent of the femoropopliteal segment. Twenty-five patients with the same clinical characteristics who were scheduled for diagnostic angiography but not subjected to PTA/nitinol stent were also selected. The concentrations in blood of total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein was evaluated by the colorimetric method. Tissue kallikrein was evaluated by the spectrophotometric method. The activity of kininase II was measured by fluorometric analysis. Quantification of MMPs was performed by zymography, which is an electrophoresis technique, and TIMPs were measured by enzyme-linked immunosorbent assay. RESULTS: Among the 31 patients who completed the survey, there were 10 cases of angiographically defined restenosis of >50%, and 21 cases without restenosis. There was an increase in the concentrations of the substrates (high-molecular-weight kininogens and lower molecular weight kininogens) and enzymes (plasma and tissue kallikrein) in patients with restenosis, indicating activation of this inflammatory pathway in these patients. The activity of kininase II was not significantly different between the groups of patients studied. There were no statistical differences between restenosis and no restenosis patients for both MMPs and TIMPs dosage, but there is an upward trend of MMPs in time 6 months in patients with restenosis. CONCLUSIONS: With the aim of identifying factors contributing to restenosis after endovascular intervention, this study showed evidence of high activation of the KKS in the pathologic inflammatory process of PTA/stent restenosis. In the other hand, it could not show participation of metalloproteinase metabolism in PTA/stent restenosis.

Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia.

Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Infective Endocarditis Surgery. Insights from 328 Patients Operated in a University Tertiary Hospital. / Cirurgia de Endocardite Infecciosa. Análise de 328 Pacientes Operados em um Hospital Universitário Terciário.

BACKGROUND: Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves. OBJECTIVE: This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil. METHOD: Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020. RESULTS: The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis. CONCLUSION: For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

FUNDAMENTO: A endocardite infecciosa (EI) refere-se à infecção da superfície endocárdica do coração e geralmente ocorre em valvas nativas ou protéticas. OBJETIVO: Este estudo teve como objetivo levantar dados de EI refletindo a terapêutica cirúrgica, em um Hospital Universitário do interior do estado de São Paulo ­ Brasil. MÉTODO: Abordagem retrospectiva e observacional de 328 pacientes com EI operados entre 1982 e 2020. RESULTADOS: Os principais dados (n=121/37%), insuficiência cardíaca congestiva (n=114/35%), valvopatia (n=92/28%), diabetes mellitus (n=85/26%), doença renal crônica (n=59/18%) e febre reumática (49/15%). A insuficiência renal é um dos principais e mais relevantes fatores de risco pré-cirúrgicos para um mau prognóstico. CONCLUSÃO: Para um melhor resultado clínico e cirúrgico é necessário o diagnóstico sindrômico e etiológico precoce da EI, principalmente em pacientes com múltiplas comorbidades.

Guanylate cyclase inhibition by methylene blue as an option in the treatment of vasoplegia after a severe burn. A medical hypothesis.

Today it is known that severe burns can be accompanied by the phenomenon of vasoplegic syndrome (VS), which is manifested by persistent and diffuse vasodilation, hypotension and low vascular resistance, resulting in circulatory and respiratory failure. The decrease in systemic vascular resistance observed in VS is associated with excessive production of nitric oxide (NO). In the last 2 decades, studies have reported promising results from the administration of an NO competitor, methylene blue (MB), which is an inhibitor of the soluble guanylate cyclase (sGC), in the treatment of refractory cases of vasoplegia. This medical hypothesis rationale is focused on the tripod of burns/vasoplegia catecholamine resistant/methylene blue. This article has 3 main objectives: 1) to study the guanylate cyclase inhibition by MB in burns; 2) to suggest MB as a viable, safe and useful co-adjuvant therapeutic tool of fluid resuscitation, and; 3) to suggest MB as burns hypotensive vasoplegia amine-resistant treatment.

Indigo Carmine Hemodynamic Studies to Treat Vasoplegia Induced by Compound 48/80 in a Swine Model of Anaphylaxis.

INTRODUCTION: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale. METHODS: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output. RESULTS: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites). CONCLUSION: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.

After Thirty Years, We Still Cannot Understand Why Methylene Blue is not a Reference to Treat Vasoplegic Syndrome in Cardiac Surgery.

Vasoplegic syndrome (VS) comprises a constellation of concurrent signs and symptoms: hypotension, high cardiac index, low systemic vascular resistance, low filling pressures, the tendency to occur diffuse bleeding, and sustained hypotension. All of these parameters may persist even despite the use of high doses of vasoconstrictor amines. VS arises from vasoplegic endothelial dysfunction with excessive release of nitric oxide by polymorphonuclear leukocytes mediated by the nitric oxide synthase's inducible form and is associated with systemic inflammatory reaction and high morbimortality. The achievements regarding the treatment of VS with methylene blue (MB) are a valuable Brazilian contribution to cardiac surgery. The present text review was designed to deliver the accumulated knowledge in the past ten years of employing MB to treat VS after cardiac surgery. Considering that we have already published two papers describing acquired experiences and concepts after 15 and 20 years, now, as we achieve the 30-year mark, we compose a trilogy.

Post-Traumatic Giant Left Ventricular Pseudoaneurysm: a Multimedia Presentation.

Traumatic left ventricular pseudoaneurysms are rare and surgical correction is the treatment of choice. In this article, it is reported a case of a myocardial stab injury with primary suture and development of a giant pseudoaneurysm, five years later, that underwent surgical repair.

Intravital Microscopy Evidence That Methylene Blue Should Be a Vasopressor-Sparing Agent in Sepsis Vasoplegia

ABSTRACT Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Report of a lung carcinoma extended to the left atrium through pulmonary vein.

Lung cancers may extend along or grow through the pulmonary veins to invade or lie within the left atrium (LA). A 62-year-old man, previously healthy, presented with 1-month ventilatory-independent right hemithorax back pain, dry cough and large effort dyspnea. He also referred weight loss of 12 kg in 10 months and denied hemoptysis. As antecedents, he smoked for 40 years and moderate daily alcoholism. On physical examination, the patient was in good general condition, hydrated and regular respiration at rest [blood pressure (BP) =120/80 mmHg; heart rate (HR) =90 bpm; respiratory rate (RR) =16 rpm]. Cardiac auscultation revealed two standard rhythmic sounds without murmurs. Pulmonary auscultation revealed a slightly diminished vesicular murmur in the lower 1/3 of the right hemithorax without adventitious noises. Chest radiography showed a mass over the right lower lung. A CT scan confirmed the radiography image with the mass extending along the right inferior pulmonary vein and a tumor in the LA. Transthoracic and transesophageal echocardiography revealed large mass within the LA (occupying almost the entire cavity), measuring about 10 cm × 3 cm at its largest diameter, prolapsing into the left ventricle. Bronchoscopy, head CT scan, and whole-body bone scintigraphy investigation did not show any distant metastasis. The patient was successfully operated removing the intracardiac and inferior pulmonary vein tumor with the aid of cardiopulmonary bypass, followed by a right inferior lobectomy carried out after 25 days. After 30 days from surgery presented seizures associated a brain metastasis evidenced by CT when adjuvant radio and chemotherapy was started. During the next 90 days, the clinical conditions worsened, and the patient died 4 months after the surgical treatment. The case report has two primary justifications, even considering the poor outcome: (I) rarity and (II) the possibility of the surgical treatment.

Cirurgia de Endocardite Infecciosa. Análise de 328 Pacientes Operados em um Hospital Universitário Terciário / Infective Endocarditis Surgery. Insights from 328 Patients Operated in a University Tertiary Hospital

Resumo Fundamento A endocardite infecciosa (EI) refere-se à infecção da superfície endocárdica do coração e geralmente ocorre em valvas nativas ou protéticas. Objetivo Este estudo teve como objetivo levantar dados de EI refletindo a terapêutica cirúrgica, em um Hospital Universitário do interior do estado de São Paulo - Brasil. Método Abordagem retrospectiva e observacional de 328 pacientes com EI operados entre 1982 e 2020 Resultados Os principais dados (n=121/37%), insuficiência cardíaca congestiva (n=114/35%), valvopatia (n=92/28%), diabetes mellitus (n=85/26%), doença renal crônica (n=59/18%) e febre reumática (49/15%). A insuficiência renal é um dos principais e mais relevantes fatores de risco pré-cirúrgicos para um mau prognóstico. Conclusão Para um melhor resultado clínico e cirúrgico é necessário o diagnóstico sindrômico e etiológico precoce da EI, principalmente em pacientes com múltiplas comorbidades.

Abstract Background Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves. Objective This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil. Method Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020 Results The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis. Conclusion For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

Left Internal Thoracic Artery Graft to Left Anterior Descending Coronary Artery after Blunt-Chest-Trauma Myocardial Infarction: 14-Year Outcome.

In 2005, we reported an acute myocardial infarction secondary to a left anterior descending coronary artery injury sustained in a motorcycle accident. The treatment was late myocardial revascularization with in situ left internal thoracic artery-to-left anterior descending coronary artery anastomosis. There is little information available about the natural history of acute myocardial infarction after blunt chest trauma, especially when treated in this manner. This present communication reports the 14-year outcome in our patient.