Bevacizumab effect on viability of free groin flaps in rats / Efeito do bevacizumabe na viabilidade de retalho inguinal livre em ratos

Introduction: Bevacizumab is among the most frequently used drugs in cancer treatment. There is evidence that some anti-angiogenic drugs reduce flap survival, but it is unclear whether this applies to Bevacizumab. We investigated the effect of Bevacizumab on the viability of free flaps in rats. Methods: The animals were randomly assigned to one of three groups. The Graft group received intravascular saline and was submitted to a full-thickness skin graft. The Flap-Saline and the Flap- BVZ groups underwent a free groin flap after receiving, respectively, intravascular saline solution or intravascular administration of Bevacizumab. Results: The Graft group showed a lower percentage of the viable area (22.81%) relative to the Flap- Saline (83.98%; p<0.0001) and the Flap-BVZ groups (60.50%; p=0.0048). The lowest vascular pedicle patency was observed in the Flap-BVZ group, but the difference relative to the Flap-Saline was not significant (arteries, p=0.0867; veins, p=0.9999). A significant difference was observed in the occurrence of necrosis (p=0.0010), which was higher in the histological samples of the Graft (87.50%) and the Flap- BVZ (60.00%) relative to the Flap-Saline Group (0%). Inflammation occurred less frequently in the Flap-Saline (33.33%) compared to the Graft (87.5%) and Flap- BVZ group (70.00%), but the difference did not reach significance (p=0.0588). No significant differences emerged in the occurrence of hemorrhage or intraluminal thrombosis. Conclusion: The increase in inflammation, decrease in patency and reduction of viable area, though not significant, are in line with the histological analysis and call for further research on the potential adverse effects of the drug.

Introdução: Bevacizumabe é um dos fármacos mais utilizados no tratamento do câncer. Existem evidências de que drogas antiangiogênicas reduzem a taxa de sobrevivência dos retalhos, porém não está claro se isso se aplica ao bevacizumabe. Investigamos o efeito de bevacizumabe na viabilidade de retalhos livres em ratos. Método: Os animais foram randomizados em três grupos. O grupo Enxerto recebeu injeção intravenosa de soro fisiológico 0,9% (SF 0,9%) e foi submetido a uma enxertia de pele total. Os grupos Retalho-SF e Retalho-BVZ foram submetidos a retalhos inguinais livres e receberam injeções intravenosas, respectivamente, de SF 0,9% e Bevacizumabe. Resultados: O grupo Enxerto apresentou menor percentual de área de retalho viável (22,81%) em relação ao grupo Retalho-SF (83,98%; p<0,0001) e Retalho-BVZ (60,50%; p=0,0048). Os pedículos do grupo Retalho-BVZ apresentaram menor patência, mas a diferença em relação ao grupo Retalho-SF não foi significante (artérias, p=0,0867; veias, p=0,9999). A ocorrência de necrose foi significativamente maior nos grupos Enxerto (87,50%) e Retalho-BVZ (60,00%) em relação ao grupo Retalho-SF (0%) (p=0,0010). A ocorrência de inflamação foi menor no grupo Retalho-SF (33,33%) em relação aos grupos Enxerto (87,5%) e Retalho-BVZ (70,00%), porém essa análise não atingiu significância (p=0,0588). Não houve diferenças significantes na ocorrência de hemorragia ou trombose intraluminal entre os grupos. Conclusão: O aumento da inflamação, redução da patência e das áreas viáveis dos retalhos, apesar de não significantes, corroboram com efeitos deletérios do bevacizumabe evidenciados na análise histológica e demandam futuros estudos dos potenciais efeitos adversos da droga.

Assessment of myocardial viability in ischemic heart disease by integrated PET/MR / 中华核医学与分子影像杂志

Objective:To evaluate the value of integrated PET/MR in assessing myocardial viability in ischemic heart disease.Methods:A total of 39 patients (28 males, 11 females; age (60.1±12.0) years) diagnosed with ischemic heart disease in Xuanwu Hospital, Capital Medical University were retrospectively enrolled from September 2020 to December 2021. All patients underwent cardiac 13N-NH 3·H 2O and 18F-FDG PET/MR examinations. Late gadolinium enhancement (LGE) sequence was included in MRI scan. PET and MRI images were analyzed and myocardial viability of each myocardial segment was evaluated according to the American Heart Association (AHA) 17 segment method. The extent of left ventricular infarcted myocardium was measured based on PET and MRI images. Weighted Kappa test was used to evaluate the agreement of PET and MRI in assessing myocardial viability. The extent of infarcted myocardium measured by PET and MRI was compared by paired- t test, and Pearson correlation analysis was used to assess the correlation between them. Results:There was a moderate agreement between PET and MRI in assessing myocardial viability ( Kappa=0.532, P<0.001), with the agreement rate of 69.83%(463/663). There was no significant difference but strong correlation between the extents of infarcted myocardium measured by PET and MRI ((23.89±14.23)% vs (23.55±11.90)%; t=-0.24, P=0.809; r=0.79, P<0.001). In segments with normal perfusion and metabolism on PET, 22.52% (100/444) showed abnormal enhancement on MRI. On the other hand, 39.89% (73/183) of the segments classified as non-viable on MRI showed normal or viable on PET. Conclusion:Integrated PET/MR is able to take full advantage of the complementary nature of PET and MRI, achieving the comprehensive and accurate evaluation of myocardial viability.

Practical Implications of Myocardial Viability Studies / Implicações Práticas da Pesquisa de Viabilidade Miocárdica

Abstract Many non-invasive methods, such as imaging tests, have been developed aiming to add a contribution to existing studies in estimating patients' prognosis after myocardial injury. This prognosis is proportional to myocardial viability, which is evaluated in coronary artery disease and left ventricular dysfunction patients only. While myocardial viability represents the likelihood of a dysfunctional muscle (resulting from decreased oxygen supply for coronary artery obstruction), hibernation represents post-interventional functional recovery itself. This article proposes a review of pathophysiological basis of viability, diagnostic methods, prognosis and future perspectives of myocardial viability. An electronic bibliographic search for articles was performed in PubMed, Lilacs, Cochrane and Scielo databases, according to pre-established criteria. The studies showed the ability of many imaging techniques in detecting viable tissues in dysfunctional areas of left ventricle resulting from coronary artery injuries. These techniques can identify patients who may benefit from myocardial revascularization and indicate the most appropriate treatment.

Resumo Diversos métodos não invasivos, como novos exames de imagem, vem sendo aprimorados, a fim de somar esforços com os atuais em estimar o prognóstico de pacientes pós-injúria miocárdica. Este prognóstico é proporcional à viabilidade miocárdica, a qual tem sua avaliação reservada para pacientes portadores de doença arterial coronariana e insuficiência ventricular esquerda. Enquanto a viabilidade miocárdica se mostra como a capacidade de recuperação funcional do músculo com disfunção por redução de oxigênio fornecido por artérias coronárias obstruídas, a hibernação consiste na própria recuperação funcional após intervenções. Este artigo propõe uma revisão sobre as bases fisiopatológicas do processo de viabilidade, métodos diagnósticos disponíveis, prognóstico e perspectivas para o futuro acerca dessa condição. Realizou-se pesquisa de busca bibliográfica informatizada em bases eletrônicas de dados, como PubMed, Lilacs, Cochrane e Scielo, onde foram selecionados os estudos de acordo com critérios pré-determinados. Os estudos demonstram a capacidade de várias técnicas de imagem de identificar tecido viável em regiões disfuncionais do ventrículo esquerdo em decorrência de lesões em artérias coronárias. Estas técnicas podem identificar pacientes com potencial benefício da revascularização miocárdica e orientar o tratamento mais adequado.

Myocardial Viability on Cardiac Magnetic Resonance / Viabilidade Miocárdica pela Ressonância Magnética Cardíaca

Abstract The study of myocardial viability is of great importance in the orientation and management of patients requiring myocardial revascularization or angioplasty. The technique of delayed enhancement (DE) is accurate and has transformed the study of viability into an easy test, not only for the detection of fibrosis but also as a binary test detecting what is viable or not. On DE, fibrosis equal to or greater than 50% of the segmental area is considered as non-viable, whereas that below 50% is considered viable. During the same evaluation, cardiac magnetic resonance (CMR) may also use other techniques for functional and perfusion studies to obtain a global evaluation of ischemic heart disease. This study aims to highlight the current concepts and broadly emphasize the use of CMR as a method that over the last 20 years has become a reference in the detection of infarction and assessment of myocardial viability.

Resumo O estudo de viabilidade miocárdica é de grande importância para a orientação e manejo de pacientes que necessitam de cirurgia de revascularização miocárdica ou angioplastia. A técnica de realce tardio (RT) é precisa e transformou o estudo de viabilidade em um teste fácil, não só para a detecção de fibrose, mas também como um modelo binário para a detecção do que é ou não é viável. Uma fibrose identificada pelo RT é considerada como não viável quando igual ou maior do que 50% da área segmentar e como viável quando menor que 50%. A ressonância magnética cardíaca (RMC) também pode lançar mão de outras técnicas para estudo funcional e de perfusão para uma avaliação global da doença isquêmica do coração no mesmo exame. Este estudo tem como objetivo destacar os conceitos atuais e enfatizar amplamente o uso da RMC como um método que nos últimos 20 anos se tornou referência na detecção de infarto e avaliação de viabilidade miocárdica.

Usefulness of Skin Explants for Histologic Analysis after Fractional Photothermolysis

BACKGROUND: Fractional laser resurfacing treatment has been extensively investigated and is widely used. However, the mechanism underlying its effects is poorly understood because of the ethical and cosmetic problems of obtaining skin biopsies required to study the changes after laser treatment. OBJECTIVE: To evaluate the usefulness of human skin explants for the investigation of fractional photothermolysis. METHODS: Full-thickness discarded skin was treated in 4 ways: no treatment (control), fractional carbon dioxide laser, fractional Er:YAG laser, and fractional 1,550-nm erbium-doped fiber laser. Both treated and non-treated skin samples were cultured ex vivo at the air-medium interface for 7 days. Frozen tissue was sectioned and stained with hematoxylin & eosin for histologic examination and nitro blue tetrazolium chloride for viability testing. RESULTS: Skin explants cultured for up to 3 days exhibited histologic changes similar to those observed in in vivo studies, including microscopic treatment zones surrounded by a thermal coagulation zone, re-epithelialization, and formation of microscopic epidermal necrotic debris. However, the explant structure lost its original form within 7 days of culture. The viability of skin explants was maintained for 3 days of culture but was also lost within 7 days. CONCLUSION: The skin explant model may be a useful tool for investigating the immediate or early changes following fractional photothermolysis, but further improvements are required to evaluate the long-term and dermal changes.

A Simple Strategy in Avulsion Flap Injury: Prediction of Flap Viability Using Wood's Lamp Illumination and Resurfacing with a Full-thickness Skin Graft

BACKGROUND: Extensive degloving injuries of the extremities usually result in necrosis of the flap, necessitating comprehensive skin grafting. Provided there is a sufficient tool to evaluate flap viability, full-thickness skin can be used from a nonviable avulsed flap. We used a Wood's lamp to determine the viability of avulsed flaps in the operation field after intravenous injection of fluorescein dye. METHODS: We experienced 13 cases during 16 months. Fifteen minutes after the intravenous injection of fluorescein dye, the avulsed skin flaps were examined and non-fluorescent areas were marked under Wood's lamp illumination. The marked area was defatted for full-thickness skin grafting. The fluorescent areas were sutured directly without tension. The non-fluorescent areas were covered by defatted skin. Several days later, there was soft tissue necrosis within the flap area. We measured necrotic area and revised the flap. RESULTS: Among all the cases, necrotic area was 21.3% of the total avulsed area. However, if we exclude three cases, one of a carelessly managed patient and two cases of the flaps were inappropriately applied, good results were obtained, with a necrotic area of only 8.4%. Eight patients needed split-thickness skin grafts, and heel pad reconstruction was performed with free flap. CONCLUSIONS: A full-thickness skin graft from an avulsed flap is a good method for addressing aesthetic concerns without producing donor site morbidity. Fluorescein dye is a useful, simple, and cost-effective tool for evaluating flap viability. Avulsed flap injuries can be managed well with Wood's lamp illumination and a full-thickness skin graft.

Infrared imaging contribution for intestinal ischemia detection in wound healing / Contribuição da imagem infravermelha para detecção da isquemia intestinal na cicatrização das feridas

PURPOSE: To study thermal variations obtained through infrared image in rats, and to evaluate the relationship between intestinal ischemic time and histopathological findings. METHODS: Thirty Wistar rats were operated after distribution in 5 groups with different times of ischemia. Thermograms were obtained by using a infrared camera. The surgical technique has been standardized for all groups: abdominal cavity opening by a 5cm length incision in the midline, abdominal wall plans section and cavity exposure, and exteriorization of the intestine. In group I (control), it was proceeded only laparotomy without superior mesenteric artery ligature. After first thermogram done, incision was closed with continuing suture. In each rat in groups II, III, IV and V, the superior mesenteric artery was located at its origin on abdominal aorta, dissected and occluded with a vascular microclamp, subjecting the intestine to ischemia in variable times. RESULTS: Rats submitted to a 30 minutes ischemia presented reactive hyperemia, thermal differential of 1.8°C and normal pathological examination. The 1 hour ischemia produced reactive hyperemia with ischemic areas, thermal differential of 1.0°C and injuries at villosities' tips. However, the 90 minutes ischemia had not shown reactive hyperemia with large ischemic areas, thermal differential of -1.0°C and injury in the upper third of the villosities. The 2 hours ischemia demonstrated a severe ischemia, thermal differential of -2.0°C and injury throughout the all villosities' extension. CONCLUSION: It has been possible studying thermal variations through infrared image in rats, showing correlation between thermal response in thermograms, ischemic time and histopathological findings.

OBJETIVO: Estudar as variações térmicas obtidas por meio da imagem infravermelha em ratos, e avaliar sua correlação com o tempo de isquemia intestinal e os achados histopatológicos. MÉTODOS: Trinta ratos Wistar foram operados após distribuição em cinco grupos com diferentes tempos de isquemia. Os termogramas foram obtidos utilizando-se uma câmera infravermelha. A técnica operatória foi padronizada para todos os grupos, abertura da cavidade abdominal por uma incisão na linha média de 5 cm de comprimento com secção de todos os planos da parede abdominal e exposição da cavidade e as alças intestinais exteriorizadas. No grupo I (controle) foi feito apenas laparotomia sem ligadura da artéria mesentérica superior. Após realizado o primeiro termograma, foi fechada a incisão com sutura contínua. Em cada rato dos grupos II, III, IV e V a artéria mesentérica superior foi localizada em sua origem na aorta abdominal, dissecada com e ocluída por um microclampe vascular submetendo o intestino à isquemia em tempos variáveis. RESULTADOS: Os ratos submetidos à isquemia de 30 minutos apresentaram hiperemia reativa, diferencial térmico de 1,8°C e exame anatomopatológico normal. A isquemia de 1 hora produziu hiperemia reativa com áreas de isquemia, diferencial térmico de 1,0°C e lesões na ponta das vilosidades. Já a de 90 minutos não demonstrou hiperemia reativa com grandes áreas de isquemia, diferencial térmico de -1,0°C e lesão no terço superior das vilosidades. A isquemia de 2 horas mostrou isquemia grave, diferencial térmico de -2,0°C e lesão em toda a extensão das vilosidades. CONCLUSÃO: Foi possível estudar as variações térmicas por meio da imagem infravermelha em ratos, que mostrou haver correlação entre a resposta térmica dos termogramas, o tempo de isquemia e achados histopatológicos.

Effects of venous supercharging in deep inferior epigastric artery perforator flap

PURPOSE: To evaluate the effects of venous supercharging in deep inferior epigastric artery perforator flap in rats. METHODS: 20 Wistar rats were randomized in 2 groups: control group (C), all had flaps raised based on the deep inferior epigastric perforator vessels (DIEP), and experimental group (E), which was identical to group C, except that the contralateral superficial inferior epigastric vein was also kept with the flap. Flow studies using laser Doppler flowmetry where performed daily in the four zones of the flap. On the 7th postoperative day rats were killed and flap survival was determined using digital planimetry. RESULTS: Flow values were presented as a percentage of the baseline flow after incision of the flap edges. The surviving flap area was demonstrated as a percentage of the total flap area. Evaluation by digital planimetry showed that flap survival in group E was higher than in group C (97,38 percent±1,32 percentvs.44,13 percent±4,83 percent, p=0,0006). CONCLUSION: This study shows that venous supercharging of the rat DIEP flap results in greater flap survival.

OBJETIVO: Avaliar o efeito da vascularização venosa ampliada na viabilidade do retalho perfurante da artéria epigástrica profunda em ratos. MÉTODOS: Vinte ratos foram divididos em 2 grupos: controle(C), no qual se realizou o retalho perfurante da artéria epigástrica profunda e experimento(E), no qual se realizou o mesmo retalho e se manteve a veia epigástrica superficial inferior contralateral ao pedículo. Foi realizada determinação diária do fluxo sanguíneo por fluxometria por laser-doppler em quatro quadrantes do retalho previamente estabelecidos e a viabilidade foi determinada, no 7º pós-operatório, através de planimetria. RESULTADOS: A análise do fluxo sangüíneo demonstrou não haver diferença entre o grupo C e E nas médias de fluxo entre as zonas do retalho (Zona I:103,44±8,09vs.84,70±7,98, p=0,114)(Zona II: 109,18±6,99 vs. 113,67±26,89, p=0,401)(Zona III: 89,15±11,11 vs. 106,79±15,93, p=0,599)(Zona IV: 104,43±11,50 vs. 124,90±23,17, p=1,00). A viabilidade do grupo E foi superior do que no grupo C quando determinada por planimetria digital (97,38 por cento±1,32 por cento vs. 44,13 por cento±4,83 por cento, p=0,0006). CONCLUSÃO: Há aumento da viabilidade do retalho DIEP submetidos à supercharging.

Experimental model of cranially pedicled TRAM flap in rats

In a simple, reproducible, and non-expensive experimental model the transverse rectus abdominis muscle (TRAM) flap has been described in male, adult Wistar rats (Rattus norvegicus albinus, Rodentia, Mammalia), weighing approximately 300g, at the central biotery of the Federal University at São Paulo, Paulista Medical School (UNIFESP - EPM). This article describes the use of a cranially based pedicled rectus abdominis muscle flap sling, unilaterally to the right, with the purpose to better understand the pathophysiology of and the research on new treatments to prevent partial or total flap necrosis. This experimental model sponsors quite a number of studies to be conducted to assess the effects of different drugs of physical methods on the feasibility of standard, cranial monopedicled TRAM.As a standard model, it also harbors the comparison among results from different studies.

Em um modelo experimental simples, reprodutível e não oneroso, descrevemos o Retalho Músculo-cutâneo Transverso de Músculo Reto do Abdome (TRAM flap), em rato Wistar (Rattus norvegicus albinus, Rodentia, Mammalia), macho, adulto com peso aproximado de 300 g, procedente do biotério central da UNIFESP - EPM. O presente artigo descreve o retalho de base cranial com o pedículo no músculo reto do abdome, unilateral à direita, com objetivo de proporcionar um melhor entendimento da fisiopatologia e pesquisa de novos tratamentos que previnam a necrose parcial ou total do retalho. Este modelo experimental permite realizar inúmeros estudos, avaliando o efeito de diferentes drogas ou métodos físicos sobre a viabilidade do retalho TRAM monopediculado de pedículo cranial padrão. Sendo um modelo padronizado admite, ainda, a comparação entre resultados de diferentes estudos.