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.

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.

Liraglutide restores late cardioprotective effects of remote preconditioning in diabetic rats via activation of hydrogen sulfide and nuclear factor erythroid 2-related factor 2 signaling pathway

Purpose The present study explored the influence of liraglutide on remote preconditioning-mediated cardioprotection in diabetes mellitus along with the role of nuclear factor erythroid 2-related factor 2 (Nrf2), hypoxia inducible factor (HIF-1) and hydrogen sulfide (H2S). Methods Streptozotocin was given to rats to induce diabetes mellitus and rats were kept for eight weeks. Four cycles of ischemia and reperfusion were given to hind limb to induce remote preconditioning. After 24 h, hearts were isolated and subjected to 30 min of ischemia and 120 min of reperfusion on Langendorff system. Liraglutide was administered along with remote preconditioning. Cardiac injury was assessed by measuring the release of creatine kinase (CK-MB), cardiac troponin (cTnT) and development of left ventricular developed pressure. After ischemia-reperfusion, hearts were homogenized to measure the nuclear cytoplasmic ratio of Nrf2, H2S and HIF-1 levels. Results In diabetic rats, there was more pronounced injury and the cardioprotective effects of remote preconditioning were not observed. Administration of liraglutide restored the cardioprotective effects of remote preconditioning in a dose-dependent manner. Moreover, liraglutide increased the Nrf2, H2S and HIF-1 levels in remote preconditioning-subjected diabetic rats. Conclusions Liraglutide restores the lost cardioprotective effects of remote preconditioning in diabetes by increasing the expression of Nrf2, H2S and HIF-1.(AU)

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.

Cardioprotection stimulated by resveratrol and grape products prevents lethal cardiac arrhythmias in an animal model of ischemia and reperfusion

Purpose: To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion. Methods: Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion. Results: It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%). Conclusion: These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.(AU)

Involvement of HSP90 in ischemic postconditioning-induced cardioprotection by inhibition of the complement system, JNK and inflammation

Purpose To investigate whether heat shock protein 90 (HSP90) is involved in complement regulation in ischemic postconditioning (IPC). Methods The left coronary artery of rats underwent 30 min of occlusion, followed by 120 min of reperfusion and treatment with IPC via 3 cycles of 30s reperfusion and 30s occlusion. The rats were injected intraperitoneally with 1 mg/kg HSP90 inhibitor geldanamycin (GA) after anesthesia. Eighty rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R), IPC and IPC + GA. Myocardial infarct size, apoptosis index and the expression of HSP90, C3, C5a, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β and c-Jun N-terminal kinase (JNK) were assessed. Results Compared with the I/R injury, the IPC treatment significantly reduced infarct size, release of troponin T, creatine kinase-MB, and lactate dehydrogenase, and cardiomyocyte apoptosis. These beneficial effects were accompanied by a decrease in TNF-α, IL-1β, C3, C5a and JNK expression levels. However, all these effects were abrogated by administration of the HSP90 inhibitor GA. Conclusion HSP90 exerts a profound effect on IPC cardioprotection, and may be linked to the inhibition of the complement system and JNK, ultimately attenuating I/R-induced myocardial injury and apoptosis.(AU)

Cardioprotective effects of pharmacological blockade of the mitochondrial calcium uniporter on myocardial ischemia-reperfusion injury

Purpose To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR). Methods CIR was induced in adult male Wistar rats (300-350 g) by occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion. Results In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively. Conclusion The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.(AU)

A Cardioprotective role of Nerium oleander with the Expression of hypoxia inducible factor 2A mRNA by increasing antioxidant enzymes in rat heart tissue

Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes.Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene.[...]

A Cardioprotective role of Nerium oleander with the Expression of hypoxia inducible factor 2A mRNA by increasing antioxidant enzymes in rat heart tissue

Background: Nerium oleander (NO) distillate is used to either protect heart cells against oxidative stress or reduce the risk of cardiovascular disease by regulating the production of reactive oxygen species. Hypoxia-inducible factors (HIFs) regulate cellular antioxidant defense mechanisms under hypoxic conditions in which heart cells survive; however, the key responsible mechanism of NO distillate for cardioprotection remains elusive. The objective of this study was to evaluate the effects on heart tissue at different time intervals after administering NO distillate intraperitoneally (IP) while considering the transcriptional regulation of HIFs and representative antioxidant enzymes.Materials, Methods & Results: The NO plant was chopped, and distillated water was added. The mixture was distilled, and the distillate separated and collected into tubes, after which it was lyophilized to obtain dry material. Twenty male Wistar albino rats (2-3 month-old, 250-300 g each) were used in the study. The rats were randomly divided into four groups. The control group (n = 5) received IP injections of saline; the remaining 15 rats received IP injections of a single dose of 7.5 mL NO distillate. The NO distillate injected rats were divided into three groups according to the time from injection to harvest the heart tissue samples. The tissues were collected at 0 h (control; n = 5), 2 h (group 2; n = 5), 4 h (group 3; n = 5), and 8 h (group 4; n = 5) after injection and under general anesthesia (60 mg/kg ketamine, IP + 10 mg/kg xylazine, IP). Quantitative polymerase chain reaction (qPCR) was used to assess the expression profiles of the genes of interest in the heart tissues. Hypoxanthine phosphoribosyltransferase was used as the reference gene.[...](AU)

Cardioprotective effect of preconditioning is more efficient than postconditioning in rats submitted to cardiac ischemia and reperfusion

Purpose: To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. Methods: Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. Results: After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. Conclusion: The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.(AU)

Hypotension aggravated by dopamine in a dog under isoflurane anesthesia

Background: Hypotension (MAP < 60 mmHg) is the most common complication in anesthetic practice and has been identified in 38% of canine patients undergoing general anesthesia for variety of procedures. Normalization of arterial pressure can usually be achieved by decreases in inhalant anesthetic concentrations, fluid administration, and use of inotropes/ vasopressors in healthy animals (ASA I) or animals with mild systemic disease (ASA anesthetic risk II). The present report shows an ASA II dog with severe hypotensive crisis [mean arterial pressure (MAP) < 50 mmHg] during general anesthesia, in which the procedure was aborted because hypotension was aggravated by dopamine.Case: A 7-year-old male Bull Terrier was anesthetized for magnetic resonance imaging (MRI) of a tumor in the face. After intramuscular acepromazine (0.01 mg/kg) and meperidine (3 mg/kg), anesthesia was induced with intravenous (IV) ketamine (1 mg/kg) and propofol (2.3 mg/kg) and maintained with isoflurane in oxygen. Ten min after induction of anesthesia MAP was 45 mmHg, while end-tidal isoflurane (ETISO) concentration was 0.5%. End-tidal isoflurane was decreased to 0.3% and an IV bolus of Lactated Ringer’s was initiated (15 mL/kg over 10 min), followed by two ephedrine boluses (0.1 mg/kg, IV) administered 5 min apart. MAP remained low (< 50 mmHg) and dopamine constant rate infusion (CRI) was initiated (7.5 μg/kg/min). Ten minutes after dopamine CRI was commenced, MAP was further decreased to 25-22 mmHg. Dopamine CRI was increased to 10 μg/kg/min, but MAP remained < 25 mmHg. Infusion drugs and isoflurane anesthesia were stopped. After the animal was extubated MAP returned 60-70 mmHg.Discussion: Among the drugs used, isoflurane is known for decreasing blood pressure in a dose-related manner because of its vasodilating properties.[...]

Hypotension aggravated by dopamine in a dog under isoflurane anesthesia

Background: Hypotension (MAP < 60 mmHg) is the most common complication in anesthetic practice and has been identified in 38% of canine patients undergoing general anesthesia for variety of procedures. Normalization of arterial pressure can usually be achieved by decreases in inhalant anesthetic concentrations, fluid administration, and use of inotropes/ vasopressors in healthy animals (ASA I) or animals with mild systemic disease (ASA anesthetic risk II). The present report shows an ASA II dog with severe hypotensive crisis [mean arterial pressure (MAP) < 50 mmHg] during general anesthesia, in which the procedure was aborted because hypotension was aggravated by dopamine.Case: A 7-year-old male Bull Terrier was anesthetized for magnetic resonance imaging (MRI) of a tumor in the face. After intramuscular acepromazine (0.01 mg/kg) and meperidine (3 mg/kg), anesthesia was induced with intravenous (IV) ketamine (1 mg/kg) and propofol (2.3 mg/kg) and maintained with isoflurane in oxygen. Ten min after induction of anesthesia MAP was 45 mmHg, while end-tidal isoflurane (ETISO) concentration was 0.5%. End-tidal isoflurane was decreased to 0.3% and an IV bolus of Lactated Ringers was initiated (15 mL/kg over 10 min), followed by two ephedrine boluses (0.1 mg/kg, IV) administered 5 min apart. MAP remained low (< 50 mmHg) and dopamine constant rate infusion (CRI) was initiated (7.5 μg/kg/min). Ten minutes after dopamine CRI was commenced, MAP was further decreased to 25-22 mmHg. Dopamine CRI was increased to 10 μg/kg/min, but MAP remained < 25 mmHg. Infusion drugs and isoflurane anesthesia were stopped. After the animal was extubated MAP returned 60-70 mmHg.Discussion: Among the drugs used, isoflurane is known for decreasing blood pressure in a dose-related manner because of its vasodilating properties.[...](AU)

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion

Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.(AU)

Avaliação sensorial do pescado pelo método do índice de qualidade

O pescado tem um alto valor nutritivo e é caracterizado como um alimento saudável. Tem uma elevada digestibilidade sendo uma das principais fontes de proteína na alimentação humana, além de um elevado teor de ácidos graxos poli-insaturados. O alto teor de nutrientes, o pH próximo da neutralidade e a elevada atividade de água nos tecidos, facilitam o desenvolvimento de micro-organismos e a rápida ação destrutiva das enzimas presentes nos tecidos e nas vísceras do peixe. O intervalo de tempo em que o produto alimentício pode ser conservado depende de determinadas condições de temperatura, luminosidade, umidade relativa, oxigênio etc., de forma a garantir seus atributos sensoriais e nutricionais. Entre os métodos essenciais de avaliação do frescor, ressaltam-se os sensoriais, os físico-químicos e os microbiológicos. O Método de Índice de Qualidade é um método sensorial de pontuação para determinar o frescor e a qualidade do pescado, capaz de fornecer resultados confiáveis e rápidos, apresentando uma relação linear entre pontuação e frescor, e entre pontuação e tempo de armazenamento em gelo. (AU)

Avaliação sensorial do pescado pelo método do índice de qualidade

O pescado tem um alto valor nutritivo e é caracterizado como um alimento saudável. Tem uma elevada digestibilidade sendo uma das principais fontes de proteína na alimentação humana, além de um elevado teor de ácidos graxos poli-insaturados. O alto teor de nutrientes, o pH próximo da neutralidade e a elevada atividade de água nos tecidos, facilitam o desenvolvimento de micro-organismos e a rápida ação destrutiva das enzimas presentes nos tecidos e nas vísceras do peixe. O intervalo de tempo em que o produto alimentício pode ser conservado depende de determinadas condições de temperatura, luminosidade, umidade relativa, oxigênio etc., de forma a garantir seus atributos sensoriais e nutricionais. Entre os métodos essenciais de avaliação do frescor, ressaltam-se os sensoriais, os físico-químicos e os microbiológicos. O Método de Índice de Qualidade é um método sensorial de pontuação para determinar o frescor e a qualidade do pescado, capaz de fornecer resultados confiáveis e rápidos, apresentando uma relação linear entre pontuação e frescor, e entre pontuação e tempo de armazenamento em gelo.

Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts beneficial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril).Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fibrillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to...(AU)

Pimobendan improves clinical signs in short term compared to digoxin or placebo in dogs with heart failure due to chronic degenerative mitral valve disease

Background: Chronic degenerative mitral valve disease (CDMVD) continues to be the most common cause of heart failure (HF) in small breed dogs. Pimobendan (PIMO) is a mixed action drug with inotropic and vasodilator properties and is widely used to treat heart disease in dogs. Therefore, PIMO increases cardiac output, reduces both preload and afterload and increases myocardial contractility without increasing energy consumption and myocardial oxygen. Digoxin (DIG) is a cardiac glycoside acting through inhibition of the sarcolemmal Na+/K+ ATPase pump, hence increasing intracellular calcium. It exerts beneficial effects on left ventricular function, symptoms and exercise tolerance. The purpose of this prospective, randomized, double blind clinical trial was to evaluate the clinical response and QoLQ in heart failure (HF) dogs treated with digoxin or pimobendan in addition to conventional therapy (furosemide and benazepril).Materials, Methods & Results: Inclusion criteria: dogs in class III or stabilized class IV (NYHA). Exclusion criteria: use of positive inotrope and antiarrhythmic, presence of atrial fibrillation, renal or hepatic disease or neoplasia. Thirty three dogs were included and randomly assigned to DIG (n = 11), PIMO (n = 14) and placebo (PL) (n = 8) and followed up weekly. Data was evaluated for days zero, 7, 14 and 28. Increasing score was assigned to...

ÁCIDOS GRAXOS ÔMEGA 3 NA DIETA DE CÃES COM DOENÇA VALVAR MITRAL

A doença valvar mitral (DVM) é caracterizada pelo espessamento nos folhetos valvares e pode levar ao desenvolvimento de insuficiência cardíaca. O tratamento farmacológico da doença com vasodilatadores, inotrópicos positivos e diuréticos é utilizado em conjunto com o manejo dietético. A suplementação com ômega 3 (-3) tem sido associada à modulação da pressão arterial (PA) e da frequência cardíaca, melhora de índices ecodopplercardiográficos, efeitos antiarrítmico, antinflamatório e antidislipidêmico. Diante da ausência de estudos clínicos prospectivos, o objetivo foi avaliar a influência da suplementação com -3 em cães portadores de DVM. Para tanto, 41 cães foram acompanhados trimestralmente durante 12 meses por meio de avaliação clínica, mensuração de PA, eletrocardiografia, ecodopplercardiografia, radiografia torácica, exames laboratoriais, dosagens de mediadores inflamatórios e de biomarcador cardíaco. Os cães foram classificados nos estágios B1, B2 e C, segundo o consenso do ACVIM. De maneira aleatória os cães foram dividis no grupo -3, que recebeu alimento para cães cardiopatas com suplementação com -3 e grupo controle (mesmo alimento sem a suplementação). No estágio B1 foram avaliados apenas os cães do grupo -3. Ao final de 12 meses, não foram observadas alterações nos parâmetros avaliados. Nos cães estágio B2 e C ocorreu aumento nos níveis séricos de mediadores inflamatórios, em maior amplitude no grupo controle. O -3 preservou o ECC, ECM e reduziu em 2,96 vezes a chance de desenvolvimento de arritmias. As medidas DIVEdN e VHS foram superiores no grupo controle e se correlacionaram às concentrações do biomarcador cardíaco NT-proBNP. Conclui-se que a suplementação com -3 em pacientes nas classes B2 e C, atua mantendo a condição corporal, auxilia na redução da sobrecarga volumétrica, apresenta efeito antiarrítmico e mantem os cães portadores de DVM em estágios mais brandos da doença.

Mitral valve disease (MVD) is characterized by thickening in the valvular leaflets and may lead to heart failure. Pharmacological treatment of the disease with vasodilators, positive inotropes and diuretics is used in conjunction with dietary management. Omega 3 (-3) supplementation has been associated with modulation of blood pressure (BP) and heart rate, improvement of Doppler echocardiography, antiarrhythmic, anti-inflammatory and antidysiphyde effects. In the absence of prospective clinical studies, the objective was to evaluate the influence of -3 supplementation in dogs with MVD. For this purpose, 41 dogs were followed up every three months for 12 months by means of clinical evaluation, BP measurement, electrocardiography, Doppler echocardiography, chest radiography, laboratory tests, dosages of inflammatory mediators and cardiac biomarker. The dogs were classified in stages B1, B2 and C, according to the ACVIM consensus. Dogs were randomly divided into the -3 group, which received food for dogs with heart diseases supplemented with -3 and control group (even food without supplementation). In stage B1 only dogs from the -3 group were evaluated. At the end of 12 months, no changes were observed in the parameters evaluated. In dogs stage B2 and C, there was an increase in the serum levels of inflammatory mediators, in a larger amplitude in the control group. The -3 preserved body condition score, muscle condition score and reduced by 2.96 times the chance of developing arrhythmias. The DIVEdN and VHS measurements were higher in the control group and correlated with NTproBNP cardiac biomarker concentrations. It is concluded that the supplementation with -3 in patients in classes B2 and C, maintains the body condition, helps reduce volume overload, has an antiarrhythmic effect and keeps dogs with MVD in the firsts stages of the disease.

Participação de um agente adrenérgico não peptídico na ação inotrópica positiva da fração polar da Bryopsis pennata / Participation of a non-peptide adrenergic agent on positive inotropic effect of the polar fraction of Bryopsis pennata

As algas marinhas representam uma rica fonte de compostos bioativos, algumas delas precursoras de ferramentas farmacológicas e de substâncias potencialmente úteis para o desenvolvimento de novos fármacos. A macroalga Bryopsis pennata, Cloroficea pertencente à ordem Caulerpales, sin. Bryopsidales é uma espécie tropical encontrada em diversos costões rochosos. Essa espécie produz uma defesa química tóxica para organismos herbívoros e potencial de se tornar invasiva e dominante em condições ambientais favoráveis. Este trabalho é uma investigação do efeito cardiotônico da fração polar da B. pennata .O cultivo, em ambiente controlado destituído de contaminantes, foi realizado no intuito de comparar seus efeitos com os efeitos da alga coletada. O efeito cardiotônico cronotrópico positivo em tiras ventriculares de anuros ficou fortemente evidenciado nos testes com frações polares de algas coletadas e cultivadas, não apresentando diferenças significativas entre as frações. O propranolol antagonizou o efeito cardiotônico e enzimas endopeptidases não reagiram com a fração polar da B. pennata. Testes bioquímicos demonstraram que a fração com efeito cardiotônico é de caráter ácido e apresenta peso molecular menor que 10.000 daltons.(AU)

Marine algae are a rich source of bioactive compounds and some of them have shown to be useful for the development of new pharmacological tools and medicines. Bryopsis pennata, (Clorofícea, Caulerpales, sin. Bryopsidales) is a marine algae that can be found in the Southeastern Brazilian coast and elsewhere. The species produces a toxic chemical defense to the herbivorous organisms and possesses a potential to become invasive and dominant in favorable environmental conditions.The present study is about the investigation of the cardiotonic effect of the polar extract of B. pennata. The cultive in laboratory without any contaminants was made to compare studies performed with the collected algae extracts and the ones cultivated effect. The cardiotonic effect in the anurous ventricular strips was strongly unequivocal when it was tested with the polar extracts from the collected and cultivated algae. The propranolol antagonized polar effects of these algae and the endopeptidase enzyme did not change the effects of polar extracts of Bryopsis pennata. Biochemical tests showed that the polar fraction presenting the inotropic cardiac activity weighs less than 10.000 Daltons and has an acid character.(AU)

Uso do diurético torsemida no tratamento de cães com insuficiência cardíaca congestiva – relatos de três casos / Use of the diuretic torsemide in the treatment of dogs with congestive heart failure – a three-case report / Uso del diurético torsemida en perros con insuficiencia cardiaca congestiva – relato de tres casos

A insuficiência cardíaca congestiva é uma complicação comum, devido à progressão da insuficiência valvular atrioventricular crônica. O tratamento visa amenizar os sinais clínicos, melhorar a qualidade de vida e prolongar o tempo de sobrevida, e inclui, além dos diuréticos inibidores da enzima conversora de angiotensina, vasodilatadores e inotrópicos positivos. Os diuréticos têm sido considerados a pedra angular no tratamento dos quadros congestivos. A furosemida é o diurético de alça mais comumente prescrito. Seu uso crônico, errático ou em altas doses pode levar a perda da função diurética, conhecida como resistência a diuréticos. A torsemida é um diurético de alça que tem mostrado resultados satisfatórios e superioridade com relação à furosemida. Este artigo relata três casos de cães diagnosticados com insuficiência cardíaca congestiva refratária em que a furosemida foi substituída pela torsemida.

Congestive heart failure is a common complication due to the progression of chronic atrioventricular valve disease. The treatment aims to ameliorate the clinical signs, improve quality of life and lifespan, and includes inhibitors of the angiotensin converter enzyme, vasodilators and positive inotropes, in addition to diuretics. The latter have been considered the cornerstone in the treatment of congestive signs. Furosemide is the most frequently prescribed loop diuretic. Chronic incorrect usage or high doses of the drug may promote the loss of diuretic function, known as diuretic resistance. Torsemide is a loop diuretic that has shown satisfactory results and superiority in comparison to furosemide. This paper reports three cases of dogs diagnosed with refractory congestive heart failure, in which furosemide was replaced by torsemide.

La insuficiencia cardíaca congestiva es una complicación frecuente de los cuadros progresivos de insuficiencia crónica de válvula atrioventricular. El tratamiento tiene como objetivo amenizar los signos clínicos, mejorar la calidad de vida y prolongar el tiempo de supervivência, y dentro de las alternativas terapéuticas, se incluyen los diuréticos inhibidores de la enzima convertidora de la angiotensina, vasodilatadores e inotrópicos positivos. Los diuréticos han sido considerados el eje central en el tratamiento de los cuadros congestivos. La furosemida es el diurético de asa más indicado en estos casos. Su utilización crónica, errática o en altas dósis puede llevar a la pérdida de la función diurética conocida como resistencia a los diuréticos. La torsemida es un diurético de asa que ha mostrado resultados satisfactorios, e inclusive superiores en relación a la furosemida. Este trabajo describe tres casos de perros con insuficiencia cardíaca congestiva refractaria donde la furosemida fue reemplazada por la torsemida.