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Feline autosomal dominant polycystic kidney disease (PKD) is common in Persian and Persian-cross cats. This study aims to investigate proteins that can be potential biomarkers for early disease diagnosis in cats with PKD1 heterozygous gene mutations and compare them with chronic kidney disease cats and normal wild-type cats. Thirty-three client-owned cats of variable breeds (ten PKD1 gene mutation cats, twelve wild-type cats with normal blood profiles, and eleven wild-type cats with chronic renal disease) were enrolled in this study. This study used serum-based proteomic profiling analysis in cats. Abdominal ultrasounds were examined in all cats. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). One hundred and fifty-nine proteins were significantly differentially expressed between each group. The proteins identified in this study are known to regulate the apoptosis pathway. The apoptosis regulator Bcl-2 (BCL2) was overexpressed in the chronic kidney disease (CKD) group, while apoptotic peptidase activating factor 1 (APAF1) and BCL2-associated X apoptosis regulator (BAX) were only expressed in the PKD group. Ingenuity pathway analysis revealed that proteins uniquely expressed in the PKD group were linked to the Wnt signaling pathway and MAPK pathway. Asparagine synthetase domain-containing and secreted frizzled-related proteins were interesting proteins that should be studied further for the possibility of a candidate protein for disease detection. The proteomic profiles identified in this study could be used as potential novel biomarkers for the early detection of PKD in cats.
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BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM. RESULTS: Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway. CONCLUSIONS: Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.
Subject(s)
Cardiomyopathy, Hypertrophic , Cat Diseases , Fibrin Fibrinogen Degradation Products , Proteomics , Animals , Cats , Cat Diseases/blood , Cardiomyopathy, Hypertrophic/veterinary , Cardiomyopathy, Hypertrophic/blood , Male , Female , Fibrin Fibrinogen Degradation Products/metabolism , Fibrin Fibrinogen Degradation Products/analysis , Blood Coagulation/physiology , Prothrombin Time/veterinary , Biomarkers/blood , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinary , Tandem Mass Spectrometry/veterinaryABSTRACT
Background and Aim: Cardiogenic embolism (CE) is a common complication of feline hypertrophic cardiomyopathy (HCM), leading to severe clinical symptoms. This study compared the effects of rivaroxaban and enoxaparin combined with clopidogrel on cats. Materials and Methods: This was a single-center, prospective, randomized controlled trial. In this study, rivaroxaban or enoxaparin plus clopidogrel was prescribed to 23 cats for at least one of the following events: Abnormal movement of the anterior mitral leaflet during systole, enlargement of the left atrium, spontaneous echocardiographic contrast, or presence of arterial thromboembolism. Oral rivaroxaban (2.5 mg, q24 h) was prescribed to six cats. Subcutaneous injections of enoxaparin (1 mg/kg, q24 h) plus oral clopidogrel (3 mg/kg, PO q24 h) for 60 days were administered to 17 cats. Renal insufficiency and bleeding complications were observed. Plasma concentrations of D-dimer, prothrombin time (PT), partial thromboplastin time, and international normalized ratio (INR) were evaluated. We analyzed the relationship between echocardiography parameters and the effects of coagulation. Blood samples were collected from all cats at baseline and at 1 and 2 months post-treatment. Results: Rivaroxaban alone and in combination with enoxaparin and clopidogrel significantly affected PT and INR. In cats treated with 2.5 mg/kg rivaroxaban for 60 days, no bleeding or recurrence of thrombus formation was observed. These data support the use of rivaroxaban for the treatment of HCM-associated thromboembolism in cats. Conclusion: Treatment of HCM-associated thromboembolism with rivaroxaban alone demonstrated clinical effectiveness with no clinical complications in cats.
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Heart rate variability (HRV) is one of the assessments of cardiovascular risk during general anesthesia. This study aimed to assess the effects of an anesthetic drug on HRV in cats and to provide information for clinical applications. Twenty-four healthy client-owned cats of various breeds, 12 females and 12 males scheduled for elective surgery, were enrolled in this study. The cats were premedicated and induced with 4 protocols: protocol 1, diazepam (0.3 mg/kg) and propofol (2-4 mg/kg) IV; protocol 2, diazepam (0.3 mg/kg) and alfaxalone (1-3 mg/kg) IV; protocol 3, diazepam (0.3 mg/kg) and ketamine (3-5 mg/kg) IV; and protocol 4, xylazine (1 mg/kg) and tiletamine/zolazepam (Zoletil) (5 mg/kg) IM. The heart rate and HRV of the 24 cats were collected before and at least 1 h after administering the anesthetic drugs. Echocardiography was performed to evaluate heart function. Oscillometric blood pressure monitoring was used to obtain the mean blood pressure. After anesthetic drug administration, higher heart rates were found in cats premedicated and induced with alfaxalone (p = 0.045) than in the other protocols. The lowest heart rate (HR) values were found in cats in protocol 4 using xylazine and Zoletil. The HRV low frequency (LF) and high frequency (HF) power ratios increased in all protocols except for cats premedicated and intubated with propofol. The standard deviation of the regular sinus beats (SDNN) was higher in cats premedicated and induced with ketamine than in other anesthetic protocols (p = 0.015). An increase in sympathetic activity and reduced HRV is associated with high blood pressure and left atrial dimension. The percentage of fractional shortening (FS) decreased in cats premedicated with ketamine. The results showed that the anesthesia method using diazepam and propofol caused the least disturbance of HRV compared with other anesthesia methods that were used in this study.
Subject(s)
Anesthetics , Ketamine , Propofol , Humans , Male , Female , Animals , Cats , Ketamine/pharmacology , Heart Rate , Propofol/pharmacology , Xylazine/pharmacology , Anesthetics/pharmacology , Diazepam/pharmacology , Anesthesia, General/adverse effects , EchocardiographyABSTRACT
Background: Polycystic kidney disease (PKD) has a complex phenotype partly explained by genetic variants related to this disease. Ultrasonography is a promising approach for defining clinical signs. This study aimed to assess kidney characteristics in cats with Polycystin-1 (PKD1) gene mutations and wild-type cats. Kidney characteristics were identified by ultrasonography. Methods: A total of 108 cats of variable breeds aged an average of 37.01±3.50 months were included. Blood examination and biochemical tests were evaluated. For cystic formation, renal ultrasound was performed. The PKD1 gene mutation was identified via polymerase chain reaction (PCR) and DNA sequencing. Matrix correlation and effectiveness of ultrasound for PKD1 mutation detection were determined. Results: The results showed that 19.44% of cats had PKD1 mutations, a high prevalence in Persian and Persian-related breed cats. Our results demonstrated the characteristics of kidneys in wild-type cats and cats with gene mutations. Based on ultrasonography results, there was an association between cats with gene mutations and cyst formation. The findings indicated that ultrasound did not detect cysts in cats aged 4-36 months, supporting the evidence that PKD1 gene mutations may not be present. This study found high sensitivity and renal specificity ultrasound for PKD1 heterozygous mutation. Moreover, cystic formation via renal ultrasound showed an increased risk for PKD1 mutation 2,623 times compared to normal kidneys. Conclusions: Ultrasonographic examination, coupled with genetic investigations, may help to clarify the phenotypic variability of PKD1. The phenotypic profile of PKD1 will guide therapeutic outcomes and reduce the prevalence of PKD morbidity and mortality in cats.
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This study aimed to identify the potential peptide candidates and expected proteins associated with MYBPC3-A74T gene mutations in Bengal cats and determine if peptidome profiles differ between healthy controls and cats with MYBPC3-A74T gene mutations. All animals were evaluated using echocardiography. DNA was isolated and followed by the screening test of MYBPC3 gene mutation. The MALDI-TOF mass spectrometry was conducted for analyzing the targeted peptide and protein patterns. The expected protein candidates were searched for within the NCBI database. Our results demonstrated that the MYBPC3-A74T gene mutation was dominant in Bengal cats but not in domestic shorthair cats. Correlations between baseline characteristics and echocardiographic parameters were discovered in Bengal cats. Mass spectrometry profiles of the candidate proteins were suspected to accompany the cat with the MYBPC3-A74T gene mutation, involving integral protein-membrane, organization of nucleus, DNA replication, and ATP-binding protein. Therefore, MYBPC3-A74T gene mutations occur frequently in Bengal cat populations. The high incidence of homozygotes for the mutation supports the causal nature of the MYBPC3-A74T mutation. In addition, peptidomics analysis was established for the first time under this condition to promise a complementary technique for the future clinical diagnosis of the MYBPC3-A74T mutation associated with physiological variables and cardiac morphology in cats.
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Background and Aim: Hypertrophic cardiomyopathy (HCM) is a common heart problem that affects many cats. Although cats with HCM are symptomatic, some die suddenly or develop congestive heart failure. Therefore, this study aimed to estimate the prevalence of myosin-binding protein C3 (MYBPC3), A31P, and A74T polymorphisms in Maine Coon cats to assess risk factors for diagnosing HCM in cats. Materials and Methods: Forty-nine Maine Coon cats of at least 10 months of age were enrolled in this study. First, clinical parameters, such as heart rate, systolic blood pressure, and echocardiography, were evaluated. Then, polymerase chain reaction, followed by DNA sequencing, was conducted using specific primers for amino acid substitutions caused by genetic variants of MYBPC3-A31P and -A74T polymorphisms. Results: Investigations showed that the prevalence of MYBPC3-A31P and -A74T mutations in this study was 16.33% and 24.45%, respectively. Moreover, HCM in cats with MYBPC3-A31P and A74T mutations increased with age, body weight, high heart rate, and prolonged isovolumic relaxation time. Conclusion: Therefore, we propose that Maine Coon cats develop HCM due to multiple genetic factors and underlying clinical characteristics in individual cats. Furthermore, relaxation time assessments can be a sensitive technique for HCM screening during its preclinical phase and can help identify the risk of developing HCM. However, further studies are warranted to evaluate the effect of MYBPC3 mutations on the phenotypic expression of HCM.
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Background: Myosin-binding protein C3 A31P (MYBPC3-A31P) missense mutation is a genetic deviation associated with the development of hypertrophic cardiomyopathy (HCM) in Maine Coon cats. The standard detection of the MYBPC3-A31P mutation is complicated, time-consuming, and expensive. Currently, there has been a focus on the speed and reliability of diagnostic tools. Therefore, this study aimed to develop a loop-mediated isothermal amplification assay (LAMP) coupled with a lateral flow dipstick (LFD) test to detect MYBPC3-A31P mutations in Maine Coon cats. Materials and Methods: Fifty-five Maine Coon cats were enrolled in this study, and blood samples were collected. MYBPC3-A31P was genotyped by DNA sequencing. Primers for LAMP with a LFD test were designed. The optimal conditions were determined, including temperature and time to completion for the reaction. The sensitivity of A31P-LAMP detection was compared between agarose gel electrophoresis (the standard method) and the LFD test. The A31P-LAMP-LFD test was randomly performed on seven cats (four with the A31P mutation and three wild-type cats). Results: The A31P-LAMP procedure was able to distinguish between cats with MYBPC3-A31P wild-type cats and MYBPC3-A31P mutant cats. The LAMP reactions were able to be completed in 60 min at a single temperature of 64â¦C. Moreover, this study demonstrated that A31P-LAMP coupled with the LFD test allowed for A31P genotype detection at a lower DNA concentration than agarose gel electrophoresis. Discussions: This new A31P-LAMP with a LFD test is a successful and reliable assay with a rapid method, cost-effectiveness, and low requirements for sophisticated equipment for the detection of MYBPC3-A31P mutations. Thus, this assay has excellent potential and can be recognized as a novel screening test for hypertrophic cardiomyopathy associated with MYBPC3-A31P mutations in felines.
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Background: Hypertrophic cardiomyopathy (HCM) has a complex phenotype that is partly explained by genetic variants related to this disease. The serum peptidome profile is a promising approach to define clinically relevant biomarkers. This study aimed to classify peptide patterns in serum samples between cats with sarcomeric gene mutations and normal cats. Materials and Methods: In the total serum samples from 31 cats, several essential proteins were identified by peptidomics analysis. The 5,946 peptides were differentially expressed in cats with sarcomeric gene mutations compared with cats without mutations. Results: Our results demonstrated characteristic protein expression in control cats, Maine Coon cats, and Maine Coon cats with gene mutations. In cats with gene mutations, peptide expression profiling showed an association with three peptides, Cytochrome 3a132 (CYP3A132), forkhead box O1 (FOXO1), and ArfGAP, with GTPase domains, ankyrin repeats, and PH domain 2 (AGAP2). Discussion: The serum peptidome of cats with mutations might provide supporting evidence for the dysregulation of metabolic and structural proteins. Genetic and peptidomics investigations may help elucidate the phenotypic variability of HCM and treatment targets to reduce morbidity and mortality of HCM in cats.
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PURPOSE: The potential cardio-protective property of germinated brown rice (GBR) has been revealed by ameliorating risk factors related to cardiovascular diseases. This study hypothesized that the combination of GBR and cardioplegic solution could protect the cardiomyocytes exposed to simulated ischemic reperfusion injury in vitro study and preserve cardiac function during cardiopulmonary bypass surgery in animal models. METHODS: Primary porcine cardiomyocytes were isolated and experimented cell viability against simulated ischemic reperfusion injury. In a cardiac surgical animal model, six pigs were randomly assigned to receive the two types of cardioplegic solution: i) St. Thomas cardioplegic solution (20 cc/kg); and ii) St. Thomas cardioplegic solution plus GBR (1 mg/kg). During open-heart surgery, the aorta was cross-clamped for 20 minutes, followed by reperfusion for 1 hour. Cardiopulmonary bypass parameters were recorded until the end of the procedure. Furthermore, hemodynamic parameters and arterial blood gas characteristics of animals among groups were monitored at different time points, including baseline before cardiopulmonary bypass (T1), during cardiopulmonary bypass (T2), during aortic clamp on (T3), and aortic clamp off (T4). RESULTS: Primarily, GBR cotreatment with cardioplegic solution essentially resulted in the improvement of cell viability in primary porcine cardiomyocytes against simulated ischemic reperfusion induction. The findings from cardiac surgery demonstrated that mean arterial pressure and heart rate are constantly stable in cardioplegic solution combined with the GBR group, while the trend of potassium and lactase concentration was decreased in the animals receiving GBR group. Consistently, all parameters from arterial blood gas showed better outcomes in animals receiving GBR; however, there were no statistically significant differences between groups, except hepatic enzymes. CONCLUSION: Therefore, GBR might exert cardio-protective effects against ischemic reperfusion injury in the porcine cardiac surgery model due to anti-inflammatory response. These protective actions of GBR may explain the benefits gained from applying GBR products as a possible therapeutic supplement on cardiac diseases.
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PURPOSE: Ischemic/reperfusion (I/R) injury is the principal mechanism during Ischemic Heart Disease (IHD). The key modulator of I/R injury is dysregulation of mitochondria function. Germinated Brown Rice (GBR) has been recommended as a bio-functional food and has clarified the potential properties in several effects. However, the effect of GBR mediated cardioprotective properties, focusing on mitochondrial function's role, remains unexplored. Thus, this study aims to investigate the cardioprotective effects of GBR pretreatment against simulated I/R injury. METHODS: H9c2 cardiomyocytes were incubated with GBR at a five Æg/mL concentration for 24 hours and simulated I/R (sI/R) for 40 minutes. Cell viability and cell apoptosis were assessed by 7-AAD staining and Annexin V/PI staining, respectively. The mitochondrial membrane potential was determined by JC-1 staining and mitochondrial respiration represented by oxygen consumption rate (OCR) using Seahorse Flux analyzer. RESULTS: The results revealed that the administration of GBR before sI/R significantly decreased the percentage of cell death and total cell apoptosis in H9c2 during stimulation of ischemic/reperfusion. Besides, pretreatment of cardiomyocytes with GBR remarkably stabilized mitochondrial membrane potential and improved impaired mitochondrial respiration in simulated-H9c2 injury. CONCLUSION: The present research is the first study to report the effective cardioprotection of GBR. Pretreatment of GBR potentially protects H9c2 cardiomyocytes against sI/R injury through mitochondrial function. The underlying therapeutic activities are possibly associated with its bio-functional compounds. However, the underlying mechanism on the cardioprotective effects of GBR needs further studies.
Subject(s)
Cardiotonic Agents/pharmacology , Mitochondria/drug effects , Myocardial Reperfusion Injury/drug therapy , Myocytes, Cardiac/drug effects , Oryza/chemistry , Animals , Apoptosis/drug effects , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/chemistry , Cells, Cultured , Dose-Response Relationship, Drug , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Molecular Structure , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Rats , Structure-Activity RelationshipABSTRACT
BACKGROUND: Degenerative mitral valve disease is a common heart problem in dogs. The aims are to evaluate the relationships between right and left ventricular function, and blood lactate concentrations, assess prognostic contribution, and investigate whether serum peptidomics profile could reveal markers or determine the stage in dogs with valve degeneration. MATERIALS AND METHODS: Ninety-three dogs were evaluated in this study. Thirty-nine dogs' serum was collected and analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The Kaplan-Meier curve was used to predict the outcomes of mitral valve disease. Follow-up was obtained by a questionnaire or telephone to determine a survival time. RESULTS: The BUN/creatinine ratio, vertebral heart score, and left atrium/aorta ratio were the independent predictors of cardiac mortality. Right ventricular systolic dysfunction was found in 50% of dogs with mitral valve disease. Dogs with right ventricular dysfunction had a significantly higher incidence of lower fractional shortening and larger right ventricular dimensions. The occurrence of right-sided dysfunction is proportionate to age and the degree of left ventricular dysfunction. High blood lactate concentrations were investigated in dogs with mitral valve disease stage C compared with stage B. The peptides such as mitogen-activated protein kinase, kallikrein, and tenascin-C appeared in the heart disease progression group. CONCLUSION: Right-hearted function assessment, blood lactate levels, and peptidomics analysis may help early detection and prognosis of this disease in dogs. Peptidomics profiles from this study demonstrate the possibility for prognosis indicators of heart valve degeneration.
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BACKGROUND AND AIM: The medical treatment of horses with nephrosplenic entrapment (NSE) of the large colon through administrating phenylephrine and rolling during general anesthesia was effective and less expensive than surgical treatment. However, the selection of drugs for non-surgical treatment of NSE is not a usual method for clinical practice. This study aimed to identify the effects of combined drugs on the cardiac and splenic response in horses and provide information on the NSE of the large colon for clinical application. MATERIALS AND METHODS: Six healthy Thai native crossbred horses were enrolled in this study. Horses received two protocols with a withdrawal period of 14 days: Group 1 received xylazine (0.5 mg/kg IV) and adrenaline (1 mcg/kg IV), and Group 2 received xylazine (0.5 mg/kg IV) and adrenaline (3 mcg/kg IV). Heart rate (HR), HR variability (HRV), heart dimensions, and the splenic response of six horses were measured before the sedation, 30 and 60 min later, and 65, 70, 75, 80, 90, and 100 min after adrenaline administration. Doppler was used to obtain systolic blood pressure. RESULTS: The HRV low-frequency and high-frequency power ratios decreased after using xylazine. Hypertension was observed after adrenaline administration. In this study, there were only minimal differences in the HR and respiratory rate between groups. However, overall cardiac and splenic parameters were statistically higher in Group 2. CONCLUSION: This study suggested that xylazine and three micrograms of adrenaline preserved the cardiac autonomic activity balance and were safe to use non-surgical applicability in horses.
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AIM: The objective of this study was to assess a new lead system method to improve electrocardiographic measurement in horses. MATERIALS AND METHODS: Twenty-two horses with an average age of 8.8±0.8 years were enrolled in this study. Horses were divided into two groups, consisting of a control group (n=11) and athlete group (n=11). Electrocardiography (ECG) and echocardiography were performed to provide information on the structure and function of the heart. Two lead systems, base apex and modified precordial leads, were used for the electrocardiogram to assess the cardiac electrophysiological functions. RESULTS: PR interval, QT interval, and QRS-T angle presented significant differences between the control and athlete groups when the modified precordial lead system was used. However, significant variations in the mean electrical axis were found when the base apex lead system was used. The modified precordial lead system resulted in more significant differences in cardiac electrophysiological parameters than the base apex lead system. In the athlete group, echocardiography showed cardiac adaptations such as increases in the left atrial and left ventricular dimensions and stroke volume and a decrease in heart rate in response to exercise and training. The observed differences in cardiac morphology and function between groups suggested differences in health performance in the athlete group. CONCLUSION: These data provided the first evidence that the modified precordial lead system improved statistical variation in ECG recording and provided the most reliable method for health screening in horses.
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A 17-year-old mixed breed pony was presented with intermittent neck stiffness during regular training rides in the six months preceding its admission. All parameters were within the normal range, except for an increase in heart rate (48 bpm) during the examination. Concave areas were observed at the level between the atlas and axis vertebrae (C1-C2) on both the left and right sides of the neck. Radiographs were taken of the laterolateral, left ventrodorsal oblique, and right ventrodorsal oblique projections in the cranial cervical region. The images revealed severe structural disorders, including trauma with luxation of the atlantoaxial joint, a fusion of the atlas and axis vertebrae, and evidence of a false joint in the axis bone. Subsequent ultrasonography showed hyperechoic areas in the rectus capitis caudalis and obliquus capitis caudalis muscles. Neck mobility was improved after two weeks of stall rest, administration of oral phenylbutazone (4.4 mg/kg), and topical cold gel treatment. The overstretching of surrounding soft tissues accompanying chronic injury of cranial cervical area may result in neck stiffness in the aging pony. Radiographic and ultrasonographic findings were consistent with the presence of cranial cervical trauma leading to neck stiffness. These findings emphasized the essential role of imaging diagnostics in treating a pony with intermittent neck stiffness.
Subject(s)
Atlanto-Axial Joint , Horse Diseases , Joint Dislocations , Animals , Atlanto-Axial Joint/diagnostic imaging , Horses , Joint Dislocations/diagnostic imaging , Joint Dislocations/veterinary , RadiographyABSTRACT
Ischemic heart disease is a leading cause of mortality in the world. This study aimed to investigate the cardioprotective effects of germinated brown rice (GBR) on a rabbit model of chronic myocardial infarction. Eighteen New Zealand white rabbits were randomly divided into three groups receiving: 1) regular rabbit food; 2) regular rabbit food plus vehicle; and 3) regular rabbit food plus GBR for 120 d. The left circumflex coronary artery was ligated to induce myocardial ischemia 60 d after starting the experiment (baseline). Heart functions were monitored by electrocardiography and echocardiography at 0, 30, and 60 d after coronary artery ligation. The incidences of heart rate (HR) and ventricular arrhythmias have been compared between groups. GBR showed the effects to prevent life-threatening ventricular tachycardia and electrocardiographic signs of myocardial ischemia in a model of arrhythmias. GBR consumption group exhibited significantly improved cardiac function and reduced the HR, along with reduced mean arterial pressure and plasma glucose level. The results demonstrated that GBR exerts cardioprotective effects against chronic myocardial injury in rabbits. These biological actions of GBR may explain the benefits gained from the use of GBR products as a possible prophylactic lifestyle intervention.
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INTRODUCTION: Ischemic heart disease is closely associated with many risk factors. Germinated brown rice extract (GBR) has potent antioxidant activities for alleviating the factors for developing heart failure such as hypertension and diabetes mellitus. AIM: The objective of the present study was to determine the cardio-protective effects of GBR and to elucidate the mechanisms underlying these effects in a model of simulated myocardial ischemic/ reperfusion injury (sI/R). METHODS: An in vitro study was performed on cultured rat cardiomyoblasts (H9c2) exposed to sI/R. The expression of apoptosis and signaling proteins was assessed using Western blot analyses. Eighteen New Zealand White rabbits were divided into 3 groups and the left circumflex coronary artery was ligated to induce myocardial ischemia. Heart functions were monitored by electrocardiography and echocardiography 0, 30, and 60 days after coronary artery ligation. RESULTS: GBR consumption group showed significantly improved cardiac function and reduced the heart rate, along with reduced mean arterial pressure and plasma glucose level. Also, GBR showed good scavenging activity, pretreatment with GBR inhibited I/R induced apoptosis by suppressing the production of caspase 3 and p38 MAPK. CONCLUSIONS: These results suggest that intake of germinated brown rice may effectively to protect cell proliferation and apoptosis and may provide important nutrients to prevent heart failure due to myocardial ischemia.
Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Cell Proliferation/drug effects , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/prevention & control , Myocytes, Cardiac/drug effects , Oryza/microbiology , Plant Extracts/pharmacology , Animals , Antioxidants/isolation & purification , Caspase 3/metabolism , Cell Line , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/metabolism , Fermentation , Hemodynamics/drug effects , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , Rabbits , Rats , Reactive Oxygen Species/metabolism , Signal Transduction , Ventricular Function, Left/drug effects , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Diabetic cardiomyopathy, especially myocardial ischemia reperfusion (I/R) injury, is a major cause of morbidity and mortality in type 2 diabetic patients. The increasing of basal p38 MAP Kinase (p38 MAPK) activation is a major factor that aggravates cardiac death on diabetic cardiomyopathy. In addition, metformin also shows cardio-protective effects on myocardial ischemia/reperfusion injury. In this study, we investigated the effect of the combination between metformin and p38 MAPK inhibitor (SB203580) in diabetic rats subjected to I/R injury. H9c2 cells were induced into a hyperglycemic condition and treated with metformin, SB203580 or the combination of metformin and SB203580. In addition, cells in both the presence and absence of drug treatment were subjected to simulated ischemia/reperfusion injury. Cell viability and cellular reactive oxygen species (ROS) were determined. Moreover, the Goto-Kakizaki (GK) rats were treated with metformin, SB203580, and the combination of metformin and SB203580 for 4 weeks. Diabetic parameters and cardiac functions were assessed. Finally, rat hearts were induced ischemia/reperfusion injury for the purpose of infarct size analysis and determination of signal transduction. A high-glucose condition did not reduce cell viability but significantly increased ROS production and significantly decreased cell viability after induced sI/R. Treatment using drugs was shown to reduce ROS generation and cardiac cell death. The GK rats displayed diabetic phenotype by increasing diabetic parameters and these parameters were significantly decreased when treated with drugs. Treatment with metformin or SB203580 could significantly reduce the infarct size. Interestingly, the combination of metformin and SB203580 could enhance cardio-protective ability. Myocardial I/R injury significantly increased p38 MAPK phosphorylation, Bax/Bcl-2 ratio and caspase-3 level. Treatment with drugs significantly decreased the p38 MAPK phosphorylation, Bax/Bcl-2 ratio, caspase-3 level and increased Akt phosphorylation. In conclusion, using the combination of metformin and SB203580 shows positive cardio-protective effects on diabetic ischemic cardiomyopathy.
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OBJECTIVE: The objective of this study was to assess the effects of anesthetic drugs on heart rate (HR) and heart rate variability (HRV) in dogs. MATERIALS AND METHODS: Twelve healthy client-owned dogs of various breeds, including five females and seven males were used for elective surgery in this study. The dogs were pre-medicated with four protocols; (1) alfaxalone [at 3 mg/kg body weight (bwt)], (2) zolazepam + tiletamine (Zoletil) (at 5 mg/kg bwt), (3) diazepam (at 0.3 mg/kg bwt) + ketamine (at 5 mg/kg bwt), and (4) diazepam (at 0.3 mg/kg bwt) + propofol (at 5 mg/kg bwt). The HR and HRV of 12 dogs were recorded 20 min before and after the administration of the anesthetic drugs. Doppler was used to obtain systolic, diastolic, and mean blood pressures. RESULTS: After anesthetic drug administration, the dogs pre-medicated and inducted with alfaxalone had the lowest HR values as compared with those of other protocols. The HRV low frequency and high frequency power ratio decreased in the dogs pre-medicated and intubated with alfaxalone. CONCLUSION: This study demonstrates that alfaxalone preserves the cardiovascular function; and hence, is considered as safe to use for the surgical applicability in dogs.
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AIM: The objective of this study is to investigate the improvement of heart function in dogs with chronic valvular heart disease after puppy deciduous teeth stem cells (pDSCs) administration. MATERIALS AND METHODS: 20 client-owned dogs with degenerative valvular heart disease underwent multiple intravenous injections of allogeneic pDSCs. Dogs were randomly assigned to two groups: (i) Control group (n=10) with standard treatment for heart failure and (ii) group with standard treatment and multiple administrations of pDSCs (n=10). Electrocardiography, complete transthoracic echocardiography, thoracic radiography, and blood pressure were recorded before and after pDSCs injections for 15, 30 and 60 days. RESULTS: Post pDSCs injection showed measurable improvement in left ventricular ejection fraction, American College of Veterinary Internal Medicine (ACVIM) functional class significantly improved and improved quality of life scores were observed. In the control group, there were no significant enhancements in heart function or ACVIM class. CONCLUSIONS: This finding suggests that pDSCs could be a supplement for valvular heart disease treatment.