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1.
ObjectivesTo evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease.AnimalsSeventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease.MethodsProspective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed.ResultsThe hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6–12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6–12.6 months), compared to 54 months (46 – infinity) for dogs with concentrations ≤1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥3/6).ConclusionsThe risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.  相似文献   

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ObjectivesCaudal vena cava (CVC) diameter and collapsibility index (CVCD and CVCCI) have been used to assess intravascular volume status (IVS). Maladaptations with progressive degenerative mitral valve disease (DMVD) lead to hypervolemia. We hypothesised that stages of DMVD will affect ultrasonographic CVC variables in dogs without clinically important right heart disease.Animals, materials and methodsThis retrospective study included 79 dogs with DMVD presented to the cardiology department between January 2017 and 2019. Subxiphoid views were used to obtain CVC cineloops. By visual inspection, CVC was subjectively scored as flat, normal or fat. Maximal and minimal CVCD were measured and indexed to aortic diameter (CVCD-max/Ao and CVCD-min/Ao); CVCCI was calculated as (CVCD-max-CVCD-min)/CVCD-max. Fisher's exact and Kruskal–Wallis tests were used to compare CVC variables.ResultsSubjective assessment was associated with American College of Veterinary Internal Medicine (ACVIM) stages (P < 0.001). The proportion of fat CVC was greater in stages C and D. In stage D, CVCD-max/Ao was larger compared with stages B1, B2 and C (P = 0.002, P = 0.002 and P = 0.035, respectively). In stages C and D, CVCD-min/Ao was larger compared with B1 (P = 0.016 and P = 0.001) and B2 (P = 0.002 and P < 0.001. In stages C and D, CVCCI was less than stage B1 (P = 0.016 and P = 0.044) and B2 (P = 0.001 and P = 0.010).ConclusionsIn dogs with DMVD without clinically important right heart disease, CVC variables differ across ACVIM stage. Subjective and objective CVC variables may be used to predict hypervolemia.  相似文献   

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Introduction/ObjectivesUrine chemistry has received growing attention to estimate the diuretic response in dogs with cardiac disease.The aim of the study was to evaluate the impact of time elapsed between the oral furosemide administration and sample collection on urine chemistry in dogs with myxomatous mitral valve disease (MMVD) receiving diuretic therapy in American College of Veterinary Internal Medicine (ACVIM) stage C.Materials and methodsSeventy-three dogs with MMVD ACVIM stage C and 106 healthy dogs were prospectively included. Dogs with MMVD were divided, based on the time of sampling, in morning group (MMVD-MG) of one to 6 h and an evening group (MMVD-EG) over 6 h from oral furosemide administration. Analogously, healthy dogs sampled between 9 a.m. and 1 p.m. and between 2 and 7 p.m. were divided in a morning group (H-MG) and an evening group (H-EG), respectively. Urine chemistry, including fractional excretion of electrolytes, was evaluated and compared among groups.ResultsHigher excretion of sodium and chloride and higher urine sodium to urine potassium ratio (uNa+:uK+) were detected in MMVD-MG than MMVD-EG (P = 0.021, P = 0.038, and P = 0.016, respectively). Natriuresis, chloriuresis, and uNa+:uK+ were higher in MMVD-MG than H-MG, while no differences were found in the comparison between H-MG and H-EG and between MMVD-EG and H-EG.ConclusionsUrinary electrolyte excretion is significantly increased within 6 h from furosemide administration in MMVD ACVIM stage C dogs. Time of sampling from furosemide administration significantly affects urine chemistry in MMVD dogs and should be considered in clinical practice and the research field.  相似文献   

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Introduction/objectivesIt has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility.Animals, materials and methodsForty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared.ResultsAt the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83–155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not.ConclusionsVLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.  相似文献   

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Objective

To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD).

Animals, materials and methods

Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery.

Results

Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09).

Conclusions

Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.  相似文献   

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ObjectivesSerotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD.Animals43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23).Methods5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA).ResultsMedian plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/109 platelets and 176.6 ng/109 platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration.ConclusionsCirculating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different.  相似文献   

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IntroductionFew studies have evaluated the utility of echocardiographic indices of right ventricular (RV) function in predicting prognosis in dogs with myxomatous mitral valve disease (MMVD).AnimalsSixty-seven client-owned dogs were diagnosed with MMVD.Materials and methodsclinical cohort study. Dogs diagnosed with American college of veterinary internal medicine (ACVIM) stage B2, C or D between April 2014 and March 2017 were enrolled. Long-term outcomes were assessed by telephone or from the medical record. The primary end-point was defined as cardiac-related death. Echocardiographic indices of RV function, including the RV Tei index, free wall and septal RV longitudinal strain, were obtained. Univariable and multivariable Cox proportional hazard analyses were used to identify variables predictive of cardiac-related death.ResultsTwenty-four dogs died during the follow-up period. The median follow-up time was 482 days, and the median survival time for dogs with cardiac-related death was 230 days. For cardiac-related death, peak early diastolic mitral inflow velocity, ACVIM stage C or D, tricuspid regurgitation velocity, RV Tei index and RV end-diastolic area were predictors in univariable Cox proportional hazard analysis. In multivariable Cox proportional analysis adjusted for the left atrial to aorta ratio, peak early diastolic mitral inflow velocity and ACVIM stage, an increase in the Tei index by 0.1 increased the hazard ratio of cardiac-related death by 33% (95% confidence interval, 16–70%; P = 0.002).ConclusionsIn dogs with MMVD, RV dysfunction assessed by the Tei index is an independent predictor of cardiac-related death.  相似文献   

9.
IntroductionTo determine whether dogs with atrial fibrillation (AF) are more likely to develop right-sided manifestations of congestive heart failure (R-CHF) than dogs without AF.AnimalsTwo hundred twenty dogs diagnosed with congestive heart failure (CHF) secondary to degenerative mitral valve disease (DMVD, n = 155) or dilated cardiomyopathy (DCM, n = 65) at a referral institution.MethodsMedical records were reviewed to extract relevant clinical and echocardiographic data.ResultsFifty dogs had AF at the time of CHF diagnosis, including 17/155 (11.0%) dogs with DMVD and 33/65 (50.8%) dogs with DCM. Sixty dogs had R-CHF evidenced by cavitary effusions. Among DMVD dogs, R-CHF occurred in 13/17 (76.5%) dogs with AF compared with 10/138 (7.2%) dogs without AF; among DCM dogs, R-CHF occurred in 24/33 (72.7%) dogs with AF compared with 13/32 (40.6%) dogs without AF. Dogs with AF were more likely to manifest R-CHF signs than dogs without AF (p < 0.0001 for DMVD; p = 0.0125 for DCM). The presence of AF, diagnosis of DCM, and moderate to severe tricuspid regurgitation were associated with R-CHF in multivariate analysis. AF was the strongest predictor of R-CHF (odds ratio, 14.44; 95% confidence interval, 5.75–36.26).ConclusionsDogs with AF are more likely to manifest R-CHF than dogs without AF. Cavitary effusions are an expected finding in approximately three-quarters of dogs with AF and CHF secondary to either DCM or DMVD.  相似文献   

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ObjectiveThe objective of this study was to clinically assess myocardial deformations in dogs with chronic mitral valve insufficiency (CMVI) using two-dimensional speckle-tracking echocardiography (2D-STE).Animals87 dogs with CMVI.MethodsDogs were placed into 1 of 3 classes, based on the International Small Animal Cardiac Health Council classification. In addition, 20 weight- and age-matched healthy dogs were enrolled as controls. The dogs were examined for myocardial deformations using 2D-STE, and strain and strain rate in the longitudinal, circumferential, and radial directions were evaluated.ResultsClass II and III dogs had higher circumferential strain than class I dogs (P = 0.002 and P = 0.001, respectively) and controls (P < 0.001 and P < 0.001, respectively). Class III dogs had higher radial strain than class I dogs (P = 0.001) and controls (P < 0.001). Class III dogs had higher radial strain rate than class I dogs (P = 0.006) and controls (P = 0.001). Other deformations, including longitudinal deformations, were not significantly different between classes of CMVI or between CMVI dogs and controls.ConclusionsIn the clinical progression of CMVI in dogs, myocardial deformations, as assessed by 2D-STE, differed according to myocardial contractile direction. Thus, assessments of multidirectional myocardial deformations may be important for better assessment of clinical cardiac function in dogs with CMVI.  相似文献   

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ObjectiveTo identify risk factors for first-onset congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD).AnimalsEighty-two dogs with and without CHF secondary to DMVD were retrospectively assigned to a derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a prospective validation cohort.MethodsVariables associated with risk of CHF in dogs were identified in a derivation cohort and used to construct a predictive model, which was then prospectively tested through longitudinal examination of a validation cohort.ResultsLogistic regression analysis of the derivation cohort yielded a predictive model that included the left atrial to aortic root dimension ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When this model was prospectively applied to the validation cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of the validation cohort revealed that plasma NT-proBNP concentration and indexed left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors for development of first-onset CHF in dogs with DMVD (NT-proBNP ≥1500 pmol/L, odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37–24.28, P = 0.017; LVIDd:Ao ≥3, OR, 6.11, 95% CI, 1.09–34.05, P = 0.039).ConclusionsMeasures of left heart size and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with DMVD. These parameters can contribute to the management of dogs with DMVD.  相似文献   

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In degenerative valve disease, the highly organized mitral valve leaflet matrix stratification is progressively destroyed and replaced with proteoglycan rich, mechanically inadequate tissue. This is driven by the actions of originally quiescent valve interstitial cells that become active contractile and migratory myofibroblasts. While treatment for myxomatous mitral valve disease in humans ranges from repair to total replacement, therapies in dogs focus on treating the consequences of the resulting mitral regurgitation. The fundamental gap in our understanding is how the resident valve cells respond to altered mechanical signals to drive tissue remodeling. Despite the pathological similarities and high clinical occurrence, surprisingly little mechanistic insight has been gleaned from the dog. This review presents what is known about mitral valve mechanobiology from clinical, in vivo, and in vitro data. There are a number of experimental strategies already available to pursue this significant opportunity, but success requires the collaboration between veterinary clinicians, scientists, and engineers.  相似文献   

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Mitral regurgitation (MR) due to myxomatous mitral valve disease (MMVD) is a frequent finding in Cavalier King Charles Spaniels (CKCSs). Sinus arrhythmia and atrial premature complexes leading to R-R interval variations occur in dogs. The aim of the study was to evaluate whether the duration of the R-R interval immediately influences the degree of MR assessed by echocardiography in dogs. Clinical examination including echocardiography was performed in 103 privately-owned dogs: 16 control Beagles, 70 CKCSs with different degree of MR and 17 dogs of different breeds with clinical signs of congestive heart failure due to MMVD. The severity of MR was evaluated in apical four-chamber view using colour Doppler flow mapping (maximum % of the left atrium area) and colour Doppler M-mode (duration in ms). The influence of the ratio between present and preceding R-R interval on MR severity was evaluated in 10 consecutive R-R intervals using a linear mixed model for repeated measurements.MR severity was increased when a short R-R interval was followed by a long R-R interval in CKCSs with different degrees of MR (P < 0.005 when adjusted for multiple testing). The relationship was not significant in control dogs with minimal MR and in dogs with severe MR and clinical signs of heart failure. In conclusion, MR severity increases in long R-R intervals when these follow a short R-R interval in CKCSs with different degrees of MR due to asymptomatic MMVD. Thus, R-R interval variations may affect the echocardiographic grading of MR in CKCSs.  相似文献   

15.
ObjectivesIn humans with congestive heart failure (CHF), better outcome is correlated with lower natriuretic peptide (NP) levels after starting treatment and greater percentage reduction of NP levels. Therefore, the aim of this study was to determine the relationship between absolute and relative changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and pro-atrial natriuretic peptide 31–67 (proANP 31–67) and overall cardiac survival in patients with symptomatic myxomatous mitral valve disease (MMVD). Furthermore, we sought to compare clinical and echocardiographic status of 12-month survivors and non-survivors.Animals, materials and methods26 dogs with CHF due to MMVD. Initial NP levels, as well as absolute and percentage changes of follow-up NP levels (between 7 and 30 days after treatment start) and heart failure (HF) class were tested as potential predictors of overall cardiac survivorship. Additionally, various echocardiographic parameters, creatinine concentrations and furosemide doses were compared between 12-month survivors and non-survivors.ResultsDogs with follow-up NT-proBNP level <965 pmol/l had a significantly longer overall cardiac survival than patients with NT-proBNP level >965 pmol/l (P = 0.03). Dogs in a higher HF class had a significantly (P = 0.03) higher probability of shorter survival independent of their NP levels. When dogs were grouped by 12-month survival, only follow-up NT-proBNP levels were significantly different between groups.ConclusionsHF class at presentation and NT-proBNP levels after initiating treatment are predictive of mortality in patients with symptomatic MMVD. ProANP 31–67 levels, percentage reduction in NPs levels, creatinine or urea concentration, echocardiographic parameters and furosemide dose did not predict outcome.  相似文献   

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Objective Describe the presence of arrhythmias in dogs with myxomatous mitral valve disease (MMVD) and the potential association with class of heart failure and left atrial enlargement. Compare the standard electrocardiogram (ECG) with Holter monitoring for assessing heart rate (HR). Experimental procedure The study group of 36 dogs weighing less than 20 kg was divided into MMVD and no clinical signs (preclinical) or MMVD and clinical signs (clinical). A standard echocardiogram, ECG and 24-h Holter recording were obtained in all dogs. Results Minimum and mean Holter HRs were higher in the clinical group than in the preclinical group. Clinical dogs had more ventricular arrhythmias than preclinical dogs. An enlarged left atrium was associated with the presence of more supraventricular arrhythmias. Conclusions Arrhythmias are a common finding in dogs with MMVD and Holter monitoring is a reliable tool for both HR monitoring and diagnosis.  相似文献   

17.
OBJECTIVE: To describe surgical techniques for and assess outcome of treatment of mitral regurgitation in dogs. DESIGN: Uncontrolled prospective study. ANIMALS: 18 dogs with naturally occurring mitral regurgitation. PROCEDURE: All dogs weighed > 5 kg (11 lb) and had severe mitral regurgitation, congestive heart failure (CHF), and no serious noncardiac disease. Left ventricular volume indices, left atrial size, and degree of mitral regurgitation were determined echocardiographically before and after surgery. Repair techniques included circumferential annuloplasty, placement of artificial chordae, chordal fenestration and papillary muscle splitting, and edge-to-edge repair. Factors predictive for surgery survival and resolution of CHF were determined. RESULTS: 12 dogs survived surgery. Factors predictive for surgery survival included weight > 10 kg (22 lb) and CHF of less than 6 months' duration. In 9 dogs, CHF resolved for a median period of 1 year (range, 4 months to 3 years) after surgery. One dog had stable CHF at 12 months. One dog died as a result of progressive CHF; another was euthanatized for a noncardiac reason. Left ventricular diastolic volume index was 226.9 +/- 117.7 cm3/m2 before surgery and 134.9 +/- 70.4 cm3/m2 at 6 months after surgery (n = 10). Factors predictive for resolution of CHF included left ventricular diastolic volume index < 250 cm3/m2 and systolic volume index < 70 cm3/m2. CONCLUSION AND CLINICAL RELEVANCE: Mitral valve repair may resolve CHF in dogs with severe mitral regurgitation, particularly in dogs that weigh > 10 kg and are treated within 6 months of the onset of CHF.  相似文献   

18.
Mitral valve repair is one of the treatment options for mitral regurgitation. Expanded polytetrafluoroethylene (ePTFE) is a polymer that has been widely used in cardiovascular surgery. In this case series, we report the autopsy and histological findings in 6 dogs that underwent cardiopulmonary bypass for mitral annuloplasty using ePTFE sheets and chordoplasty using ePTFE sutures.From May 2005 to October 2009, 3 female and 3 male dogs with severe mitral regurgitation underwent mitral valve repair. This case series included 3 Cavalier King Charles spaniels, 2 Maltese, and 1 Shih Tzu. The survival period after surgery was 19–72 (35 ± 19) months.In all the cases, autopsy revealed that the ePTFE sheets and sutures were not damaged and well integrated into the surrounding highly differentiated, connective tissues. Low-power microscopy revealed that in all cases, the tissues surrounding the ePTFE sheet in the mitral valve annulus had almost completely been covered by granulation tissue. No inflammatory infiltrate or thrombogenesis was observed around the ePTFE in any of the cases.There was no evidence of reactive changes in the region surrounding the ePTFE. These results suggest that ePTFE has excellent tissue compatibility and durability and can be effectively used for canine mitral valve repair.  相似文献   

19.
IntroductionDilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy.HypothesisPrior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF).Animals and methodsA retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan–Meier curves and the Cox proportional-hazards model.ResultsThe median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs.ConclusionsPrior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.  相似文献   

20.
This study aimed to characterize the composition and distribution of the extracellular matrix (ECM) components in normal canine mitral valves (MV) and in chronic heart valve disease (CVD).MV of 50 dogs (normal (n = 9), mild (n = 13), moderate (n = 17), severe (n = 11) CVD) were investigated macroscopically, histologically (H.-E., picrosirius red) and immunohistochemically (collagen I, III, IV, V, VI, elastin, laminin, fibronectin, heparan sulphate).In normal MV, ECM components were expressed in a typical layered pattern. In mild CVD, basement membrane components (laminin, collagen IV, fibronectin) were increased. Advanced CVD was characterized by myxomatous nodular lesions displaying a marginal and a central region comprised mainly of collagen I, VI and fibronectin in the former and collagen I and III in the latter. Collagen IV and laminin appeared multifocally in marked CVD.In conclusion, not only an accumulation of proteoglycans, but also a distinctly altered expression of basement membrane components, and collagens characterizes CVD.  相似文献   

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