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ABSTRACT: The objective of the present study was to evaluate clinical, cardiorespiratory, and Doppler echocardiographic changes in rabbits sedated with midazolam and morphine combined with or without dexmedetomidine. This study was a blinded, randomized, controlled experiment that included 16 adult male New Zealand rabbits weighing 3.1 ± 0.3 kg. The animals were sedated using one of the following protocols: 1 mg/kg midazolam and 2 mg/kg morphine (MIDA, n = 8), or 25 mg/kg dexmedetomidine, 2 mg/kg morphine and 1 mg/kg midazolam (DEX, n = 8). Sedation latency, duration of the sedation and recovery period, sedation scores, heart rate (HR), respiratory rate (f), peripheral oxygen saturation (SpO2), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), and recta temperature were recorded, and Doppler echocardiography was performed. Latency periods were 7.3±1.6 min in the DEX group and 10.9 ± 5.0 min in the MIDA group (P = 0.112). Sedation duration was 122.4±14 min in the DEX group and 71.2 ± 32 min in the MIDA group (P = 0.005), whereas recovery time was 35.7±17.7 min in the DEX group and 32.5 ± 25.3 min in the MIDA group (P = 0.743). The sedation scores for the DEX group were significantly higher than those for the MIDA group throughout the monitoring period. Reductions in HR, SAP, MAP, and DAP values were observed in both groups relative to baseline values, and were significantly lower in the DEX group compared to the MIDA group. Minimal Doppler echocardiographic changes were observed. Dexmedetomidine used in combination with midazolam and morphine incremented the quality and duration of sedation in rabbits. Both protocols elicited cardiorespiratory changes that were well-tolerated, with minimal changes in myocardial function.

RESUMO: O objetivo do presente estudo foi avaliar alterações clínicas, cardiorrespiratórias e ecodopplercardiográficas, bem como o nível de sedação em coelhos sedados com midazolam e morfina combinadas, ou não, com dexmedetomidina. O design do estudo foi experimental controlado randomizado cego, com 16 coelhos adultos machos Nova Zelândia, pesando 3,1 ± 0,3 Kg. Os animais foram sedados aleatoriamente com um dos seguintes tratamentos: MIDA (n = 8): 1 mg/kg de midazolam e 2 mg/kg de morfina; DEX (n = 8) 25 mcg/kg de dexmedetomidina, 2 mg/kg de morfina e 1 mg/kg de midazolam; Latência, sedação e períodos de recuperação, escores de sedação, FC, f, SpO2, PAS, PAM, PAD, ToC, foram mensurados e ecoDopplercardiografia foi realizada. Os períodos de latência foram 7.3 ± 1.6 minutos no grupo DEX e 10.9 ± 5.0 minutos no grupo MIDA (P = 0,112). A duração da sedação foi de 122.4 ± 14 minutos no grupo DEX e 71.2 ± 32 minutos no grupo MIDA (P = 0,005). Os tempos totais de recuperação foram de 35.7 ± 17.7 minutos no grupo DEX e 32.5 ± 25.3 minutos no MIDA (P = 0,743). Os escores de sedação obtidos do grupo DEX foram estatisticamente superiores aos do grupo MIDA durante todas as observações (de 5 a 40 minutos). A redução dos valores de FC, PAS, PAM e PAD foi observada em ambos os grupos, em relação ao momento baseline, e foram significativamente menores no grupo DEX quando comparado ao MIDA. Alterações ecodopplercardiográficas mínimas foram observadas ambos os grupos. A adição de dexmedetomidina à associação midazolam/morfina aumentou o nível, a qualidade e a duração do protocolo sedativo. Ambos os protocolos causaram alterações cardiorrespiratórias bem toleradas em animais normais e com mínimas alterações na função miocárdica.

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Abstract Doxorubicin (Dox) is a medication used in the treatment of cancerous tumors and hematologic malignancies with potentially serious side effects, including the risk of cardiotoxicity. Flavonoids are plant metabolites with antioxidant properties and can be extracted from Camellia sinensis (CS). The aim of this study is to evaluate the possible cardioprotective effect of CS against injuries induced by Dox in rats. A total of 32 animals were distributed into four groups: (1) control - intraperitoneal injection (I.P.) of 0.5 mL saline weekly and 1.0 mL water by gavage daily; (2) CS - 0.5 mL saline I.P. weekly and 200 mg/kg CS by gavage daily; (3) Dox - 5.0 mg/kg Dox I.P. weekly and 1.0 mL water by gavage daily; and (4) Dox+CS -5.0 mg/kg Dox I.P. weekly and 200 mg/kg CS by gavage daily. Clinical examinations, blood profiles, electrocardiograms, echocardiograms, and histological analyses of hearts were performed over 25 days. The animals in the Dox group showed changes in body weight and in erythrogram, leukogram, electrocardiography, and echocardiography readings. However, animals from the dox+CS group had significantly less change in body weight, improved cardiac function, and showed more preserved cardiac tissue. This study demonstrated that CS prevents dox-induced cardiotoxicity, despite enhancing the cytotoxic effect on blood cells

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This study aimed to evaluate the efficacy of mesenchymal stem cells (MSC), alone or associated with dapsone (DAP), in treating dermonecrotic wounds caused by Loxosceles laeta venom. Twenty-five male rabbits were distributed into five groups. Negative control received ultrapure water (C-), whilst all other groups were injected with 20 μg of L. laeta venom. After 4 hours, each group received one of the following treatments: PBS (C+), DAP, MSC, and DAP+MSC. Animals were evaluated daily and photographic records made for analysis of wound area. Twelve days after, animals were euthanized and skin samples removed for histological analysis. We observed that DAP showed the best percentage of wound contraction at day 3. In the treatments using MSCs, a negative value of wound contraction was observed for the isolated MSCs, as well as a lower contraction value for the association of the MSC + DAP when compared to PBS, probably, by the increase in initial infammation after the application of stem cells, due to the fact that MSCs secrete a broad spectrum of bioactive molecules such as cytokines and growth factors that favor regeneration. Histologically, it was observed that animals of C+ showed extensive areas of necrosis, ulcers, neutrophilic infiltrate, and mineralization. Collagen deposition showed increase in MSC+DAP treatment, however vascularization remained unchanged. This is the first report using MSC and MSC+DAP as a treatment for cutaneous loxoscelism and more studies are needed to determine its use as an alternative therapy for dermonecrotic lesions caused by Loxosceles spider.

Este estudo teve como objetivo avaliar a eficácia das células-tronco mesenquimais (CTMs), isoladas ou associadas à dapsona (DAP), no tratamento de feridas dermonecróticas causadas pelo veneno de Loxosceles laeta. Vinte e cinco coelhos machos foram distribuídos em cinco grupos. O controle negativo recebeu água ultrapura (C-), enquanto todos os outros grupos foram injetados com 20 μg de veneno de L. laeta. Após 4 horas, cada grupo recebeu um dos seguintes tratamentos: PBS (C+), DAP, CTMs e DAP + CTMs. Os animais foram avaliados diariamente durante 12 dias, e feitos registros fotográficos para análise da ferida e no 12º dia, foram eutanasiados e, retiradas amostras de pele para análise histológica. Observou-se que a DAP apresentou o melhor percentual de contração da ferida no terceiro dia. Nos tratamentos com CTMs, observou-se uma contração negativa da ferida tanto para as CTMs isoladas, bem como a associação CTMs + DAP em relação ao PBS, possivelmente, pelo aumento da infamação inicial após a aplicação de células-tronco. Isso é devido ao fato de que as CTMs secretam um amplo espectro de moléculas bioativas como citocinas e fatores de crescimento que favorecem a regeneração. Histologicamente, observou-se que os animais de C+ apresentaram extensas áreas de necrose, úlceras, infiltrado neutrofílico, além de mineralização. Houve aumento de deposição de colágeno no tratamento CTMs + DAP, no entanto, a vascularização permaneceu inalterada. Este é o primeiro relato usando CTMs e CTMs + DAP como tratamento para loxoscelismo cutâneo e mais estudos são necessários para determinar seu uso como terapia alternativa para lesões demonecróticas causadas pela aranha Loxosceles.

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Micrurus surinamensis is a coral snake from the Elapidae family of wide distribution in Amazonia Forest. Its venom contains neurotoxins that induce muscular and respiratory paralysis; however, its cardiovascular action is not yet characterized. The aim of this study was to investigate the cardiotoxic effects caused by M. surinamensis poisoning in rodents. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6) named as control and envenomed. The control group received 0.2 ml of PBS/BSA via intramuscular injection (IM), while envenomed animals received 0.75 µg of venom per g of body weight, also via IM. Electrocardiographic examination (ECG) and biochemical serum tests were conducted before and 2 h after inoculation. ECG of the envenomed animals revealed severe progressive arrhythmias including atrioventricular block, supraventricular, and ventricular extrasystoles. Serum biochemistry showed significant increase in CK, CK-MB, and LDH enzymes corroborating the skeletal and cardiac muscle damage. Myonecrosis and degeneration were observed in both skeletal and heart muscle; nevertheless, transmission electron microscopy revealed cardiac muscle fibers fragmentation. In conclusion, M. surinamensis venom has a potent cardiotoxic activity eliciting arrhythmogenic effects and heart damage after only 2 h of envenomation.

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