Protective effect of Guanxin Danshen formula on myocardial ischemiareperfusion injury in rats

Purpose: Myocardial ischemia/reperfusion injury (MIRI) leads to myocardial tissue necrosis, which will increase the size of myocardial infarction. The study examined the protective effect and mechanism of the Guanxin Danshen formula (GXDSF) on MIRI in rats. Methods: MIRI model was performed in rats; rat H9C2 cardiomyocytes were hypoxia-reoxygenated to establish a cell injury model. Results: The GXDSF significantly reduced myocardial ischemia area, reduced myocardial structural injury, decreased the levels of interleukin (IL-1ß, IL-6) in serum, decreased the activity of myocardial enzymes, increased the activity of superoxide dismutase (SOD), and reduced glutathione in rats with MIRI. The GXDSF can reduce the expression of nucleotide- binding oligomerization domain, leucine-rich repeat and pyrin domain containing nod-like receptor family protein 3 (NLRP3), IL-1ß, caspase-1, and gasdermin D (GSDMD) in myocardial tissue cells. Salvianolic acid B and notoginsenoside R1 protected H9C2 cardiomyocytes from hypoxia and reoxygenation injury and reduced the levels of tumor necrosis factor α (TNF-α) and IL-6 in the cell supernatant, decreasing the NLRP3, IL-18, IL-1ß, caspase-1, and GSDMD expression in H9C2 cardiomyocytes. GXDSF can reduce the myocardial infarction area and alleviate the damage to myocardial structure in rats with MIRI, which may be related to the regulation of the NLRP3. Conclusion: GXDSF reduces MIRI in rat myocardial infarction injury, improves structural damage in myocardial ischemia injury, and reduces myocardial tissue inflammation and oxidative stress by lowering inflammatory factors and controlling focal cell death signaling pathways.

Remote ischemic preconditioning-induced late cardioprotection: possible role of melatonin-mitoKATP-H2S signaling pathway

Purpose: Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2 S, TNF-α and mitoKATP in melatoninmediated effects in RIPC. Methods: Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. Results: RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2 S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). Conclusion: RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2 S levels.

Sarcocystis spp. detection in cattle using different diagnostic methods / Detecção de Sarcocystis spp. em bovinos usando diferentes métodos de diagnóstico

Cattle are considered intermediate hosts of Sarcocystis, which can cause clinical signs and lower performance in the acute phase of infection. Sarcocystis spp. are usually not visible to the naked eye during the post mortem inspection. Moreover, fresh microscopic examination and transmission electron microscopy techniques are difficult to apply to large samples. Therefore, extensive studies on Sarcocystis infection in cattle using molecular and serological methods are required. Here, we investigated Sarcocystis spp. infection in cattle using fresh microscopic examination and polymerase chain reaction of myocardium samples and compared the results with the presence of antibodies against Sarcocystis spp. in corresponding serum samples detected using indirect fluorescent antibody test. Microscopic Sarcocystis were observed in 100% of the myocardial samples, and Sarcocystis DNA was present in 86% (43/50) of these samples. Antibodies against Sarcocystis spp. were detected in 96% (48/50) and 80% (40/50) of the serum samples at 1:25 and 1:200 dilutions, respectively. The three associated methods (fresh microscopic examination, PCR and serology) showed good sensitivity and detection for Sarcocystis spp. compared with fresh microscopic examination (only), and they may facilitate diagnosis in live animals on a large scale as well as monitoring of the herd status.

Os bovinos são considerados hospedeiros intermediários de Sarcocystis, podendo causar sinais clínicos e menor desempenho na fase aguda da infecção. Sarcocystis spp. geralmente não são visíveis a olho nu durante a inspeção post mortem. Além disso, o exame microscópico a fresco e as técnicas de microscopia eletrônica de transmissão são difíceis de aplicar a uma amostras de grande tamanho. Portanto, são necessários extensos estudos sobre a infecção por Sarcocystis em bovinos usando métodos moleculares e sorológicos. Aqui, investigamos a infecção de Sarcocystis spp. em bovinos por meio de exame microscópico a fresco e reação em cadeia da polimerase de amostras de miocárdio e comparado os resultados com a presença de anticorpos contra Sarcocystis spp. em amostras de soro correspondentes detectadas usando o teste de anticorpos fluorescentes indiretos. Sarcocistos microscópicos foram observados em 100% das amostras de miocárdio, e o DNA de Sarcocystis estava presente em 86% (43/50) dessas amostras. Anticorpos contra Sarcocystis spp. foram detectados em 96% (48/50) e 80% (40/50) das amostras de soro nas diluições 1:25 e 1:200, respectivamente. Os três métodos associados (exame microscópico a fresco, PCR e sorologia) mostraram boa sensibilidade e detecção para Sarcocystis spp. em comparação com o exame microscópico fresco (apenas) e podem facilitar o diagnóstico em animais vivos em larga escala, bem como o monitoramento do status do rebanho.

Felinos portadores de cardiomiopatia fenótipo hipertrófica - eixo elétrico da onda P / Cats with hypertrophic phenotype cardiomyopathy - P-wave electrical axis

Background: Hypertrophic phenotype cardiomyopathy is the most common heart disease in cats. Although the echocardiogram is the gold standard test for diagnosing fHCM, patients with the disease may have electrocardiographic changes. Despite being reported in most 12-lead electrocardiograms, the P wave axis generally receives little attention when compared to other wave parameters. We performed a Doppler echocardiographic and electrocardiographic study in cats, in order to verify the presence of correlation between the electrical axis average P wave and the presence of fCMH, aiming to investigate the possibility of its aid in the early diagnosis of cardiac disorders. Materials, Methods & Results: One hundred cats of different breeds, ages, males and females were evaluated. Those animals with a history of previous disease other than hypertrophic cardiomyopathy were excluded from the study. The groups were formed after obtaining the results of the echocardiographic examination. Eight of the 100 cats did not allow echocardiographic evaluation, and the remaining 92 were divided into 2 groups (control group, n = 64 and heart disease group, n = 28) after the examination. Of these 92 animals, 28 cats had the hypertrophic cardiomyopathy phenotype. The electrocardiographic examination was performed after the allocation of animals into groups lasting 5 min with the recording of tracings for later interpretation. To calculate the axis of the P wave, leads D1 and D3 were used, measuring the amplitude of the P wave in these leads and calculating the resulting amplitude. All cats studied had mean electrical axis of the P wave within the normal range for the species (0º to 90º). Based on mean electrical axis P wave values, there was no significant difference between groups. The control group had a median of 63.7° with a maximum value of 80°, a minimum value of 60° and a mean of 65.1°. The fCMH group had a median of 68.7° with a maximum value of 85.3°, a minimum value of 56.3° and a mean of 68.8°. Of the fCMH group, 3 cats had increased P wave duration (50.33 ± 5.77 ms), suggesting left atrial overload, and 13 cats had increased QRS complex duration (66.30 ± 11.23 ms). Also, 18 cats (Control group: 11; fCMH group: 7) showed T wave amplitude greater than 25% of R, suggesting the presence of myocardial hypoxia and/or electrolyte disturbance. One cat had a prolonged PR interval (from the fCMH group). As for the QT interval, 6 cats had an interval < 120 (2 from the control group and 4 from the affected group) and 3 had an interval > 180 (1 from the control group and 2 from the affected group). The ST segment remained isoelectric in all segments. As for the mean electrical axis of the QRS complex, 5 cats (10.42%) had axis deviation to the right (control: 1; fCMH: 4) suggesting right ventricular overload; 7 cats (14.58%) had left axis deviation (control: 5; fCMH: 2), suggestive of left ventricular overload; and 36 cats (75%) had a normal mean electrical axis. Discussion: Based on the results obtained in the present study, it can be concluded that screening studies in asymptomatic felines should be increasingly implemented in the veterinary clinical routine, since the frequency found was high (30.44%) and that patients may remain asymptomatic for years until the development of signs. It should be concluded that there was no correlation between the mean electric axis of P-wave and the presence of subclinical phenotype hypertrophic cardiomyopathy. Therefore, more studies are needed, with felines at different stages of the disease, to evaluate whether this electrocardiographic measurement allows us to assist in its diagnosis, since it is a feasible measure in cats. Furthermore, it is concluded that the electrocardiogram should be used as an aid method in the diagnosis of the disease and not as a screening test.

Kukoamine A activates Akt/GSK-3ß signaling pathway to inhibit oxidative stress and relieve myocardial ischemia-reperfusion injury

Purpose: Myocardial ischemia/reperfusion (MI/R) injury refers to a pathological condition of treatment of myocardial infarction. Oxidative stress and inflammation are believed to be important mechanisms mediating MI/R injury. Kukoamine A (KuA), a sperm, is the main bioactive component extracted from the bark of goji berries. In this study, we wanted to investigate the possible effects of KuA on MI/R injury. Methods: In this experiment, all rats were divided into sham operation group, MI/R group, KuA 10 mg + MI/R group, KuA 20 mg + MI/R group. After 120 min of ischemia/reperfusion treatment, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rates of rising and fall of left ventricular pressure (±dp/dtmax), and ischemic area were detected. Serum samples of rats in each group were collected. The enzyme activities of catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), levels of malondialdehyde (MDA), CK muscle/brain (CK-MB), tumor necrosis factor (TNF), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardium in each group was detected according to the instructions of the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of mammalian target of glycogen synthase kinase-3ß (GSH-3ß) and protein kinase B (Akt) mRNA level in myocardial tissues were detected via reverse transcription-polymerase chain reaction (RT-PCR). Results: MI/R rats showed a significant increase in oxidative stress and inflammation. In addition, we showed that KuA significantly improved the myocardial function such as LVSP, left ventricular ejection fraction, +dp/dt, and -dp/dt. Here, it attenuated dose-dependent histological damage in ischemia-reperfused myocardium, which is associated with the enzyme activities of SOD, GSH-PX, and levels of MDA, IL-6, TNF-α, L-1ß. Conclusions: KuA inhibited gene expression of Akt/GSK-3ß, inflammation, oxidative stress and improved MR/I injury. Taken together, our results allowed us to better understand the pharmacological activity of KuA against MR/I injury.

Tanshinone IIA ameliorates myocardial ischemia/reperfusion injury in rats by regulation of NLRP3 inflammasome activation and Th17 cells differentiation

Purpose: Tanshinone IIA is a well-known lipophilic active constituent refined from traditional Chinese medicines, danshen. It has been previously demonstrated to possess various biological properties, including anti-inflammatory, antioxidant, promoting angiogenesis effect and so on. However, the mechanism of tanshinone IIA on myocardial ischemia-reperfusion injury (MI/RI) remains unclear. In this study, we investigated the effect of tanshinone IIA on MI/RI. Methods: MI/RI rat models were set up. Echocardiographic evaluation and hematoxylin and eosin staining were performed to analyze the cardiac function and morphology of MI/RI. Western blot was conducted for the detection of protein expression of pyrin domain containing 3 (NLRP3) and caspase-1 in heart tissues. Flow cytometry and real-time polymerase chain reaction were used for the detection of proinflammatory cytokines and Th17 cells differentiation. Results: We found that tanshinone IIA alleviated the myocardial damage of MI/RI, ameliorated the overall and local inflammatory reaction, and produced a cardioprotective effect by inhibiting of NLRP3 inflammasome activation and Th17/Treg cells differentiation. Conclusions: Our results highlighted the cardio-protective effect of tanshinone IIA on MI/RI and uncovered its underlying mechanism related to the NLRP3 inflammasome inhibition and the modulation of Th17/Treg cells differentiation.

Ionóforos e intoxicação em equinos / Ionophores and poisoning in horses

Ionóforos são substâncias que foram inicialmente utilizadas como coccidiostáticos na produção de frangos de corte e, posteriormente, passaram a ser adicionados como aditivos na dieta de ruminantes. A intoxicação por ionóforos pode ocorrer em diversas espécies animais, no entanto, a espécie equina é especialmente sensível. O quadro clínico e anatomopatológico relacionado à intoxicação em equinos é caracterizado por sinais clínicos decorrentes de cardiomiopatia e miopatia da musculatura esquelética devido a necrose causada nestes tecidos. Não existe tratamento específico para os quadros de intoxicação por ionóforos, sendo assim, a prevenção deve ser preconizada de modo a evitar exposição dos equinos a alimentos que contenham ionóforos, especialmente nas criações em que bovinos e equinos compartilham do mesmo ambiente de criação. O objetivo deste artigo é abordar os principais aspectos relacionados aos ionóforos, bem como a intoxicação por estas substâncias em equinos.(AU)

Ionophores are substances that were initially used as coccidiostats in the production of broilers and later were added as additives in the diet of ruminants. Ionophores poisoning can occur in several animal species, however, horses are especially sensitive. The clinical and anatomopathological features related to poisoning in horses are characterized by clinical signs resulting from cardiomyopathy and myopathy of the skeletal musculature due to necrosis caused in these tissues. There is no specific treatment for ionophores poisoning conditions, therefore, prevention must be advocated in order to avoid exposure of horses to feed containing ionophores, especially in breeding where cattle and horses share the same rearing environment. The aim of this article is to address the main aspects related to ionophores, as well as poisoning by these substances in horses.(AU)

Naringin attenuates acute myocardial ischemia-reperfusion injury via miR126/GSK-3ß/ß-catenin signaling pathway

Introduction: Myocardial ischemia-reperfusion (I/R) injury is one of the mechanisms contributing to the high mortality rate of acute myocardial infarction. Purpose: This study intended to study the role of naringin in cardiac I/R injury. Methods: AC16 cells (human cardiomyocyte cell line) were subjected to oxygen-glucose deprivation/recovery (OGD/R) treatment and/or naringin pretreatment. Then, the apoptosis was examined by flow cytometry and Western blotting. The concentration of IL-6, IL-8 and TNF-α was measured by enzyme-linked immunosorbent assay (ELISA) kits. How naringin influenced microRNA expression was examined by microarrays and quantitative real-time polymerase chain reaction (qRT-PCR). Dual luciferase reporter assay was employed to evaluate the interaction between miR-126 and GSK-3ß. The GSK-3ß/ß-catenin signaling pathway was examined by Western blotting. Finally, rat myocardial I/R model was created to examine the effects of naringin in vivo. Results: Naringin pretreatment significantly decreased the cytokine release and apoptosis of cardiomyocytes exposed to OGD/R. Bioinformatical analysis revealed that naringin upregulated miR-126 expression considerably. Also, it was found that miR-126 can bind GSK-3ß and downregulate its expression, suggesting that naringin could decrease GSK-3ß activity. Next, we discovered that naringin increased ß-catenin activity in cardiomyocytes treated with OGD/R by inhibiting GSK-3ß expression. Our animal experiments showed that naringin pre-treatment or miR-126 agomir alleviated myocardial I/R. Conclusions: Naringin preconditioning can reduce myocardial I/R injury via regulating miR-126/GSK-3ß/ß-catenin signaling pathway, and this chemical can be used to treat acute myocardial infarction.

Cardioprotective action of aprepitant in a rat model of ischemia-reperfusioninduced myocardial injury: role of PI3K-AkT-GSK-3ß-HIF-1α signaling pathway

Purpose: The present study explored the role and mechanism involved in aprepitant-induced cardioprotective effects in rat model of ischemia-reperfusion injury. Methods: The isolated hearts of Wistar male albino rats were subjected to ischemia-reperfusion injury on Langendorff apparatus. The extent of myocardial injury was assessed by measuring lactate dehydrogenase 1 and CK-MB release in the coronary effluent. The rats were treated with aprepitant (5, 10 and 20 mg/kg) before isolating hearts. After injury, the levels of HIF-1α, p-AkT, p-GSK-3ß/GSK-3ß were measured in heart homogenates. LY294002 was employed as PI3K inhibitor. Results: Ischemia-reperfusion led to significant myocardial injury and decreased the levels of HIF-1α, p-AkT and ratio of p-GSK-3ß/GSK-3ß. Aprepitant attenuated myocardial injury and restored the biochemical changes in a dose-dependent manner. Pre-treatment with LY294002 (10 and 20 mg/kg) abolished aprepitant-mediated cardioprotective effects and restored the biochemical parameters in the heart homogenate. Conclusions: Aprepitant may be effective in preventing ischemia-reperfusion-induced myocardial injury, which may be due to activation of PI3K-AkT-GSK-3ß and HIF-1α signaling pathway.

Jatrorrhizine reduces myocardial infarction-induced apoptosis and fibrosis through inhibiting p53 and TGF-ß1/Smad2/3 pathways in mice

Purpose: To explore the mechanism of jatrorrhizine on apoptosis and fibrosis induced by myocardial infarction (MI) in an animal model. Methods: The left anterior descending branch of coronary artery was surgically ligated to duplicate the mouse model of MI. The sham and infarcted mice were treated with normal saline once a day, while mice in experimental groups received low-dose (LD) and high-dose (HD) jatrorrhizine once a day respectively. Two weeks later, cardiac function was detected by echocardiography, and histopathological examination was performed using hematoxylin and eosin (H&E) and Masson staining. The expressions of p53, TGF-ß1, Smad/2/3, Bax, Bcl-2, collagen I and collagen III were quantified using qRT-PCR and western blot assays. Results: Jatrorrhizine significantly improved left ventricular ejection fraction (LVEF) and left ventricle end-systolic (LVES) in mice. Histopathological, administration of jatrorrhizine weakened infiltration of inflammatory cells and cardiac fibrosis in myocardium of mice caused by MI. Additionally, jatrorrhizine suppressed cardiomyocyte apoptosis exhibited as its capability to reverse changes of Bax and Bcl-2 levels in myocardium caused by MI. Jatrorrhizine statistically significantly downregulated expression of collagen I and collagen III, as well as TGF-ß1, Smad2/3 and p53. Conclusions: Jatrorrhizine reduce cardiomyocyte apoptosis and fibrosis through inhibiting p53/Bax/Bcl-2 and TGF-ß1/Smad2/3 signaling pathways.

Feline aortic thromboembolism diagnosed by thermography

Background: In cats, arterial thromboembolism is one of the most devastating diseases, with an acute presentation, andis often caused by undiagnosed cardiomyopathy. Defined as the obstruction of one or more arterial lumens by emboli,the arterial thromboembolism is responsible for hypoperfusion signs. As the temperature of the skin surface is directlyrelated to tissue perfusion, thermography can be promising for the early diagnosis of thromboembolism. Therefore, thisstudy reports the importance of thermography as a complementary examination for the diagnosis of thromboembolism inthe abdominal aorta of a domestic cat.Case: A 4-year-old mixed-breed cat weighing 2.95 kg was presented with a history of sudden onset paraplegia, apathy,and pain when handled, with greater intensity in the sacro-coccidian region. During physical exam, it was noted that thefemoral artery pulse was undetectable bilaterally during manual pulse measurement. Superficial and deep sensitivity inthe pelvic limbs and proprioception were also absent and the plantar cushions and nail beds of the posterior limbs werepale to cyanotic. Thermographic images revealed that the temperature of both hind limbs was lower than that of forelimbs,with difference of 3.2ºC and 2.9ºC between the left and right limbs, respectively. Doppler ultrasonography revealed theabsence of pulse and flow in the femoral arteries bilaterally. Electrocardiography revealed sinus tachycardia, with a heartrate of 250 bpm. Echocardiography revealed dilation of the left atrium and concentric cardiac hypertrophy. After 24 h, dueto the worsening of the clinical condition and unfavorable prognosis, the animal was euthanized and sent for necropsy.Necropsy revealed that the arterial lumen of the caudal abdominal aorta and bifurcation of the iliac arteries were obliterated...

Feline aortic thromboembolism diagnosed by thermography

Background: In cats, arterial thromboembolism is one of the most devastating diseases, with an acute presentation, andis often caused by undiagnosed cardiomyopathy. Defined as the obstruction of one or more arterial lumens by emboli,the arterial thromboembolism is responsible for hypoperfusion signs. As the temperature of the skin surface is directlyrelated to tissue perfusion, thermography can be promising for the early diagnosis of thromboembolism. Therefore, thisstudy reports the importance of thermography as a complementary examination for the diagnosis of thromboembolism inthe abdominal aorta of a domestic cat.Case: A 4-year-old mixed-breed cat weighing 2.95 kg was presented with a history of sudden onset paraplegia, apathy,and pain when handled, with greater intensity in the sacro-coccidian region. During physical exam, it was noted that thefemoral artery pulse was undetectable bilaterally during manual pulse measurement. Superficial and deep sensitivity inthe pelvic limbs and proprioception were also absent and the plantar cushions and nail beds of the posterior limbs werepale to cyanotic. Thermographic images revealed that the temperature of both hind limbs was lower than that of forelimbs,with difference of 3.2ºC and 2.9ºC between the left and right limbs, respectively. Doppler ultrasonography revealed theabsence of pulse and flow in the femoral arteries bilaterally. Electrocardiography revealed sinus tachycardia, with a heartrate of 250 bpm. Echocardiography revealed dilation of the left atrium and concentric cardiac hypertrophy. After 24 h, dueto the worsening of the clinical condition and unfavorable prognosis, the animal was euthanized and sent for necropsy.Necropsy revealed that the arterial lumen of the caudal abdominal aorta and bifurcation of the iliac arteries were obliterated...(AU)

Study on the mechanisms of Suaeda rigida polysaccharides on the heart inhibition and skeletal muscle promotion in the frog / [Estudo sobre os mecanismos dos polissacarídeos de Suaeda rigida na inibição do coração e promoção da musculatura esquelética no sapo]

The objectives of this study were to investigate the effects of different concentrations of Suaeda rigida polysaccharides (SRPs) on the physiological characteristics of the frog heart and gastrocnemius muscle, compare their similarities and differences, and analyze the mechanisms. CaCl2 and acetylcholine (Ach) were selected respectively to be co-incubated with the high concentration SRPs to observe the effects on the heart contraction of frog. The effects of different concentrations of the SRPs on the activities of acetylcholinesterase (A-CHE), Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the isolated frog heart were detected by UV-Vis spectrophotometry. The gastrocnemius muscle was immersed in the high concentration of SRPs for 10 min, and the systolic indexes were recorded. The effects of SRPs on the Ach content and A-CHE activity at the sciatic nerve-gastrocnemius junction were determined by UV-Vis spectrophotometry and enzyme-linked immunosorbent assay (ELISA). The results showed that the SRPs had significant inhibitory effects on the contractile amplitude of isolated heart and the contractile amplitude induced by CaCl2 and Ach, respectively (P<0.01). The activity of Ca2+-Mg2+-ATPase was significantly promoted, and the activity of A-CHE was significantly inhibited (P<0.01). The contraction amplitude, contraction rate, relaxation rate of gastrocnemius muscle and the Ach content at the junction of sciatic nerve-gastrocnemius muscle were significantly increased (P<0.01), and the activity of A-CHE at the junction was significantly inhibited (P<0.01) by the SRPs. All the results suggested that the SRPs could inhibit the contraction of heart and promote the contraction and relaxation of skeletal muscle. The mechanism was related to blocking the fast INa channel, inhibiting the ICa-L and activating the M receptors of myocardial membrane and then inhibiting external Ca2+ influx, increasing Ca2+-Mg2+-ATPase activity, decreasing a-che activity.

Os objetivos deste estudo foram investigar os efeitos de diferentes concentrações de Suaeda rigida polissacarídeos (SRPs) sobre as características fisiológicas do coração de rã e do músculo gastrocnêmio, comparar suas semelhanças e diferenças, e analisar os mecanismos. CaCl2 e acetilcolina (Ach) foram selecionados respectivamente para serem co-incubados com os SRPs de alta concentração para observar os efeitos sobre a contração do coração de rã. Os efeitos das diferentes concentrações dos SRPs sobre as atividades da acetilcolinesterase (A-CHE), Na+-K+-ATPase e Ca2+-Mg2+-ATPase no coração isolado de rã foram detectados pela espectrofotometria UV-Vis. O músculo gastrocnêmio foi imerso na alta concentração de SRP por 10 min, e os índices sistólicos foram registrados. Os efeitos das SRPs no conteúdo de Ach e na atividade de A-CHE na junção nervo-gastrocnêmio ciático foram determinados pela espectrofotometria UV-Vis e pelo ensaio de imunoabsorção enzimática (ELISA). Os resultados mostraram que os SRPs tiveram efeitos inibidores significativos sobre a amplitude contrátil do coração isolado e a amplitude contrátil induzida por CaCl2 e Ach, respectivamente (P<0,01). A atividade do Ca2+-Mg2+-ATPase foi significativamente promovida e a atividade do A-CHE foi significativamente inibida (P<0,01). A amplitude de contração, a taxa de contração, a taxa de relaxamento do músculo gastrocnêmio e o conteúdo de Ach na junção do músculo nervo ciático-gastrocnêmio foram significativamente aumentados (P<0,01), e a atividade do A-CHE na junção foi significativamente inibida (P<0,01) pelas SRPs. Todos os resultados sugeriram que os SRPs poderiam inibir a contração do coração e promover a contração e o relaxamento do músculo esquelético. O mecanismo estava relacionado ao bloqueio do canal INa rápido, inibindo a ICa-L e ativando os receptores M da membrana miocárdica e depois inibindo o influxo externo de Ca2+, aumentando a atividade de Ca2+-Mg2+-ATPase, diminuindo a atividade a-che.

Main risk factors of dogs with congestive heart failure diagnosed by doppler echocardiographic parameters / Principais fatores de risco em cães com insuficiência cardíaca congestiva diagnosticada por parâmetros ecocardiográficos

Nowadays, congestive heart failure is one of the major complications of heart disease in small animals, which is characterized by a clinical condition in which the heart is unable to eject the blood efficiently. At long term, some compensatory mechanisms it will eventually become detrimental and, mainly, due to the congestion caused by it. In dogs, the main cause of CHF is chronic mitral valve degeneration, it is responsible for the degeneration of collagen present in the mitral valve structure that will have detrimental consequences on the entire circulatory system. The aim of the present study was to perform a retrospective study of 498 echocardiographic reports collected at a veterinary cardiology service of the Bauru region, from January 2017 to June 2019. Two groups were formed according to the Doppler echocardiographic alterations found, one that included animals with characteristics of congestive heart failure (CHF), and the other formed by non-CHF patients. Of the total number of animals evaluated, 61 were classified as affected by congestive heart failure and after classification, it was considered the main epidemiological factors (race, sex and age) of animals belonging to this group. Small breed animals were overrepresented and also elderly animals, with no apparent sexual predisposition. In addition, animals with CHF presented higher values when compared to animals without CHF of LA/Ao ratio (2.31 ± 0.30 vs. 1.46 ± 0.35), E/IRTV ratio (2.96 ± 0.39 vs. 1.16 ± 0.43) and E-wave velocity (1.45 m/s ± 0.18 vs. 0.75 m/s ± 0.22) on echocardiographic examination.(AU)

A insuficiência cardíaca congestiva (ICC) é uma das principais complicações das cardiopatias em pequenos ani-mais atualmente, sendo que é caracterizada por uma condição clínica em que o coração não é capaz de bombear a quantidade necessária de sangue para todo o corpo. A longo prazo, alguns mecanismos compensatórios acabam se tornando prejudiciais ao mesmo principalmente por decorrência do quadro de congestão que ela ocasiona. Em cães, a principal causa de ICC é a degeneração valvar crônica mitral, a qual é responsável pela degeneração do colágeno presente na estrutura da valva mitral que trará consequências prejudiciais a todo o sistema circulatório. O presente trabalho teve por objetivo a realização de um estudo retrospectivo de 498 laudos ecodopplercardiográficos provenientes de serviço de cardiologia veterinária da região de Bauru, no período de janeiro de 2017 a junho de 2019. Foi realizada a classificação em dois grupos, de acordo com as alterações ecodop-plercardiográficas encontradas, sendo os grupos formados por animais portadores de insuficiência cardíaca congestiva e animais não portadores. Do número total de animais, 61 foram classificados como acometidos por insuficiência cardíaca congestiva e, após a classificação, foram avaliados os principais fatores epidemiológicos (raça, sexo e idade) dos animais pertencentes a esse grupo. As raças de pequeno porte foram as mais representadas, sendo os animais idosos mais acometidos, sem predisposição sexual aparente. Além disso, animais com ICC apresentaram valores maiores quando comparados aos animais sem ICC of LA/Ao razão (2.31 ± 0.30 vs. 1.46 ± 0.35), E/IRTV razão (2.96 ± 0.39 vs. 1.16 ± 0.43) e velocidade E-wave (1.45 m/s ± 0.18 vs. 0.75 m/s ± 0.22) no exame ecocardiográfico.(AU)

Digoxin for atrial fibrillation: good, but not too good: a case report / Digoxina para fibrilação atrial: boa, mas não muito: relato de caso

Digoxin is a cardiotonic glycoside that is traditionally used for the treatment of heart failure and atrial fibrillation in humans and animals. However, the use of digoxin is still a challenge in clinical practice due to its narrow therapeutic range and its potential interaction with several drugs, which could facilitate the development of toxicity. A 12-year-old Labrador retriever was referred with a clinical diagnosis of heart failure and atrial fibrillation, anorexia, vomiting, and diarrhea. He had been medicated with digoxin, furosemide, lisinopril, and amiodarone. The patient also showed clinical signs of hip osteoarthritis and received firocoxib for four days. He additionally received drugs for gastrointeritis. The electrocardiogram demonstrated atrial fibrillation and signs of digitalis toxicity. Laboratory examination showed a high concentration of plasma digoxin, and 5 days after withdrawal of the drugs, the symptoms disappeared, as did the digitalis effects seen in the previous electrocardiogram.(AU)

A digoxina é um glicosídeo cardiotônico tradicionalmente utilizado no tratamento de insuficiência cardíaca e fibri-lação atrial em humanos e animais. Porém, o uso da digoxina continua sendo um desafio na prática clínica devido a sua estreita faixa terapêutica, bem como a sua potencial interação com diversos fármacos, facilitando o desenvolvimento de toxicidade. Um Labrador Retriever de 12 anos de idade foi encaminhado com diagnóstico clinico de insuficiência cardíaca, apresentando fibrilação atrial, anorexia, vômitos e diarreia. Ele vinha sendo medicado com digoxina, furosemida, lisinopril e amiodarona. Ele havia sido concomitantemente medicado com firocoxibe por quatro dias para tratamento de osteoartrite coxo-femoral, além de medicamentos para gastroenterite. O eletrocardiograma demonstrou fibrilação atrial e sinais de toxicidade digitalica. O exame laboratorial revelou alta concentração de digoxina plasmática sendo que, cinco dias após a suspensão dos medica-mentos, o paciente já apresentava melhora clinica acentuada, enquanto os efeitos digitálicos observados no eletrocardiograma anterior desapareceram.(AU)

Polymyositis associated with brainstem signs in a dog

Background: Polymyositis is a generalized inflammatory myopathy which can lead to rhabdomyolysis. This affection may have several origins, including degenerative, metabolic, autoimmune, infectious, inflammatory, ischemic, traumatic, by drug use, induced by toxins and also of idiopathic origin. Diagnosis is made with seric dosage, electrodiagnostic tests and muscle biopsy. Lesions in the rostral oblong medulla may affect the central vestibular system, and there may be signs such as opisthotonos, nystagmus, and strabismus. The aim of this report is to describe a case of a mixed breed dog with manifestation of polymyositis associated with brainstem signs of probable idiopathic origin. Case: A 5-year-old mixed breed male dog was attended with opisthotonos episodes for 2 days, and pelvic limbs extension and thoracic limbs flexion that lasted 10 to 20 min at intervals of approximately 1 h. The animal was anorexic and had also presented one episode of emesis. Upon neurological examination, ventromedial strabismus and Horner's syndrome was observed on the right side, besides vertical nystagmus, flaccid tetraparesis and absence of proprioception in the four limbs. Biochemical analyses revealed creatine kinase (CK) increased (2,433.9 UI/L - reference: 1.5-28.4 UI/L), and urinalysis showed dark color and presence of occult blood without, however, erythrocyturia. Electrocardiogram (ECG) showed QS wave and deviation of the electrical axis. Treatment with prednisolone (1 mg/kg, BID), phenobarbital (2 mg/kg, BID), maropitant citrate (1 mg/kg in 2 doses), and crystalloid fluid therapy (50 mL/kg/day) were prescribed. On the 4th day, the dog was more active and feeding without a tube, so it recommended keep the treatment at home. On the 10th day, the animal had proprioception present on the 4 limbs and normorexia. Biochemical analyses and urinalysis showed no alterations, but normochromic normochromic anemia with thrombocytopenia and leukocytosis by neutrophilia showed in blood count exam. PCR to Ehrlichia canis, Hepatozoon sp., and Babesia canis resulted negative. On the 15th day, blood count, biochemical analyses and urinalysis showed no alterations. Neurological examination revealed only positional vertical nystagmus. which remained as a sequel. Discussion: Polymyositis may be accompanied by rhabdomyolysis, characterized by acute muscle necrosis, increased CK and myoglobinuria. The animal had polymyositis of acute onset, with myoglobinuria and elevated CK values, whose presentation included myalgia and muscle weakness. In humans, polymyositis is accompanied by changes in electrocardiographic tracing without clinical alterations. In dogs, the first report that showed cardiac involvement was compatible with myocarditis. The changes in ECG in the present case was attributed to failure in myocardial electrical conduction. The patient also showed signs of brainstem and central vestibular system injuries. Stress myopathy, intoxication, snakebite, infectious, and metabolic diseases were discarded leading to a clinical suspicion as idiopathic origin. Similar to a published case, the patient of this report received symptomatic and supportive treatment, being discharged from the hospital 20 days after the onset of clinical signs. Thus, polymyositis may be accompanied by signs indicative of brainstem injury. Patients with rhabdomyolysis require intense monitoring due to the high risk of developing acute renal failure. Since no causative agent was identified, symptomatic treatment combined with the prevention of possible complications were fundamental for the maintenance of the animal's life.

Risk of arrhythmias in dogs with structural heart disease / Potencial arrítmico de cardiopatias em cães

Presently, pet life expectancy is becoming longer and several diseases inherent to age have been diagnosed, with heart disease being a frequent finding. Although various heart diseases have different pathophysiologies, many morphological and hemodynamic changes can predispose patients to arrhythmias. The presence of arrhythmias can worsen the underlying heart disease and predispose patients to develop new alterations, making arrhythmia detection important for establishing adequate therapeutic protocols and a better prognosis. The present study aimed to determine the arrhythmias most frequently found in dogs treated at the Cardiology and Respiratory Diseases Service (SCDR) of the Small Animals Sector of the Veterinary Hospital of the Federal Rural University of Rio de Janeiro (UFRRJ), during the period from January to 2014 to December 2017, relating them to sex, age group, size, and the presence or absence of heart disease. A total of 586 medical records of dogs treated with SCDR-UFRRJ were retrospectively evaluated. Of these, 15.4% had arrhythmias, 95.6% had diagnoses of heart disease, 61.1% (55/90) were diagnosed with mitral valve disease, and 27.8% (25/90) had dilated cardiomyopathies. The most frequent rhythm disturbances were premature ventricular complexes associated with chronic degenerative mitral valve disease or dilated cardiomyopathy. Statistical analysis confirmed the risk of a cardiac patient developing rhythm or conduction alterations (OR, 4.46; p = 0.0003). In conclusion, the pathophysiology of heart failure can lead to the development of rhythm and conduction disorders.

Com a maior expectativa de vida dos animais de estimação, diversas enfermidades inerentes a idade têm sido diagnosticadas, sendo as cardiopatias um achado frequente. Apesar das diferentes cardiopatias terem fisiopatologias distintas, diversas alterações morfológicas e hemodinâmicas podem ocorrer predispondo ao aparecimento de arritmias. A presença de arritmias pode agravar a doença cardíaca de base e predispor ao desenvolvimento de novas alterações, tornando-se importante a sua detecção para instituição de protocolos terapêuticos adequados e melhor prognóstico da doença. O presente estudo teve como objetivo determinar as arritmias mais frequentemente encontradas em cães atendidos no Serviço de Cardiologia e Doenças Respiratórias (SCDR) do Setor de Pequenos Animais do Hospital Veterinário da Universidade Federal Rural do Rio de Janeiro (UFRRJ), no período de janeiro de 2014 a dezembro de 2017, relacionando-as com sexo, faixa etária, porte e presença ou não de cardiopatias. De maneira retrospectiva, foram avaliados 586 prontuários de cães atendidos no SCDR-UFRRJ. Destes, 15.4% apresentavam alguma arritmia e 95,6% apresentavam diagnostico de alguma cardiopatia, sendo 61.1% (55/90) diagnosticados com endocardiose de mitral e 27.8% (25/90) com cardiomiopatia dilatada. O distúrbio de ritmo mais frequente foram os complexos ventriculares prematuros associados a doença valvar degenerativa crônica de mitral ou a cardiomiopatia dilatada. Na análise estatística, o risco de um paciente cardiopata desenvolver alterações de ritmo ou de condução foi confirmado (OR: 4,46; p=0,0003). Conclui-se que a fisiopatologia da insuficiência cardíaca pode levar ao desenvolvimento de distúrbios de ritmo e também distúrbios de condução.

Bilateral auricular aneurysm with intact pericardial sac in a dog

A nine-year-old, male, Pekingese dog was presented with a history of dyspnea, lethargy, syncope, polyuria, polydipsia, and selective appetite over two years. When the clinical signs first began, a radiographic exam revealed a radiopaque mass in the cranial mediastinum. An adequate treatment was not performed and the dog was presented to the hospital with severe tachycardia, dyspnea, and tachypnea, and died during physical examination. On necropsy, the heart presented bilateral auricular aneurysms. The pericardial sac was intact, and no other defects were found within the heart. Microscopically, the cardiomyocytes were marked degenerated and proliferation of connective tissue. This is the first case report of a bilateral auricular aneurysm with intact pericardial sac in a dog.~ien

Bilateral auricular aneurysm with intact pericardial sac in a dog

A nine-year-old, male, Pekingese dog was presented with a history of dyspnea, lethargy, syncope, polyuria, polydipsia, and selective appetite over two years. When the clinical signs first began, a radiographic exam revealed a radiopaque mass in the cranial mediastinum. An adequate treatment was not performed and the dog was presented to the hospital with severe tachycardia, dyspnea, and tachypnea, and died during physical examination. On necropsy, the heart presented bilateral auricular aneurysms. The pericardial sac was intact, and no other defects were found within the heart. Microscopically, the cardiomyocytes were marked degenerated and proliferation of connective tissue. This is the first case report of a bilateral auricular aneurysm with intact pericardial sac in a dog.(AU)~ien

Pimobendan em gatos / Pimobendan in cats

As miocardiopatias são as cardiopatias mais comumente diagnosticadas em felinos domésticos. A cardiomiopatia hipertrófica (CMH) soma a maioria dos casos de cardiomiopatias em pacientes atendidos na rotina da medicina interna de felinos. Gatos com doenças cardíacas podem não apresentar manifestações clínicas evidentes podendo apresentar sinais sutis de insuficiência cardíaca (IC) ao longo do tempo de modo que em um dado momento descompensam e evidenciam sinais clínicos. O pimobendan é um fármaco denominado inodilatador devido a sua capacidade de promover inotropismo positivo e vasodilatação. Apesar de escassos, os estudos existentes com a utilização de pimobendan demonstram boa tolerância em gatos saudáveis e com cardiopatias diversas. Atualmente, o uso do pimobendan em gatos é extra bula e a dose baseia-se em estudos realizados com cães. No entanto, sabe-se que as concentrações plasmáticas diferem entre as espécies o que pode requerer possíveis ajustes. A terapia da IC em gatos é bastante discutida e evidências recentes demonstram que o pimobendan pode ser um aliado no tratamento de diversas doenças cardíacas que levem à disfunção sistólica sendo capaz de prover melhora dos sinais clínicos e até aumento da expectativa de vida desses pacientes. Contudo, pesquisas são necessárias para melhor entendimento dos efeitos hemodinâmicos do medicamento em gatos com disfunção diastólica.

Myocardiopathies are the most diagnosed heart disease in domestic cats. Hypertrophic cardiomyopathy (HCM) adds up to most cases of cardiomyopathies in patients seen in the routine of feline internal medicine. Cats with heart disease may not have evident clinical manifestations and may show subtle signs of heart failure (HF) over time so that at a given moment they decompensate and show clinical symptoms. Pimobendan is an inodilator drug due to its ability to promote positive inotropism and vasodilation. Although scarce, the existing studies with the use of pimobendan demonstrate good tolerance in healthy cats with various heart diseases. Currently, the use of pimobendan in cats is off-label and the dose is based on studies conducted in dogs. However, it is known that plasma concentrations differ between species, which may require possible adjustments. The therapy of HF in cats is widely discussed and recent evidence shows that pimobendan can be an ally in the treatment of various heart diseases that lead to systolic dysfunction, being able to provide improvement in clinical signs and even increase the life expectancy of these patients. However, research is necessary to better understand the hemodynamic effects of the drug in cats with diastolic dysfunction.