Henrik D. Pedersen

Allometric scaling of M-mode cardiac measurements in normal adult dogs

Indices for M-mode measurements in dogs usually have been based on the assumption that a linear relationship exists between these measurements and body weight (BW) or body surface area (BSA). The relationships between the geometry of 3-dimensional objects do not support this assumption. The purposes of this study were to retrospectively examine M-mode data from a large number of dogs of varying sizes and breeds that were examined by a large number of ultrasonographers, to use the allometric equation to determine the appropriate BW exponent required to predict these cardiac dimensions, and to determine normal mean values and prediction intervals for common M-mode variables. Linear regression analyses of data from 494 dogs (2.2-95 kg) revealed a good correlation between M-mode measurements and BW after logarithmic transformation of the data (r2 = .55-.88). Most variables were most closely related to an index of body length, BW(1/3), although the exponent that best predicted diastolic and systolic left ventricular wall thicknesses was closer to 0.25. No variable indexed well to BW or BSA. With these data, appropriate mean values and prediction intervals were calculated for normal dogs, allowing veterinarians to correctly and appropriately index M-mode values. The equations developed from this study appear to be applicable to adult dogs of most breeds.

Heart rate variability in young, clinically healthy Dachshunds: influence of sex, mitral valve prolapse status, sampling period and time of day.

OBJECTIVE This study investigatest the influence of sampling period duration, time of day, age, sex, body weight and degree of mitral valve prolapse (MVP) on various measures of heart rate variability (HRV) in the dog. The correlations between the HRV parameters were also investigated. BACKGROUND Holter recording is increasingly being used in dogs but method studies are sparse. Previous studies suggest that canine MVP is related to a high vagal tone. METHODS Twenty-four hour ambulatory electrocardiographic recording (Holter recording) was performed on 24 Dachshunds (11 males and 13 females). All dogs were between 2 and 6 years of age and without heart murmurs. RESULTS The majority of the HRV parameters depended on the duration of the sampling period and they generally exhibited circadian variation. Higher values in males than in females were found for several parameters, especially low frequency power (LF) during 24 hour recording (P = 0.0002). Although a number of HRV parameters correlated positively with MVP severity and negatively with age, the influence of these two factors was not clear and consistent in all sampling periods. The degree of MVP related to the number of episodes of supraventrucular tachycardia occuring during the day. Generally, a large inter-individual variation was found with regard to the HRV parameters and the correlations between the parameters were weaker than correlations reported in humans. Two manually measured ECG parameter related to vagal tone correlated strongly with 2 out of 3 vagal indexes derived from the HRV analysis. CONCLUSION HRV parameters are influenced especially by sex and sampling period duration, but also by age and MVP status in young, clinically healthy Dachshunds.

Mitral valve prolapse in the dog: a model of mitral valve prolapse in man

Time for primary review 31 days. Mitral valve prolapse (MVP), i.e. abnormal systolic protrusion of mitral valve leaflets into the left atrium, is a common cause of severe mitral regurgitation (MR) requiring operation in people living in industrialized nations [1,2]. MVP has been reported to have many causes but in the majority of cases it is a primary condition (called primary MVP in this paper) characterized by a progressive myxomatous degeneration of the mitral valve leaflets and chordae tendineae [1–3]. The disease typically emerges in adolescence but complications such as severe MR usually do not occur until middleage or senescence [1–3]. An animal model with a shorter course of disease could be useful in several ways, for instance, by making it feasible to evaluate the effects of different drugs on disease progression. Despite this, no animal model of primary MVP has been described so far. From pathological studies, it has long been known that most dogs develop myxomatous mitral valve disease with age and that this disease is very similar macroscopically as well as microscopically to primary MVP in humans [4,5]. Traditionally, however, the canine disease has been given names other than MVP, including endocardiosis and chronic valvular disease. Recently, a number of studies, including many based on well-defined echocardiographic criteria for the diagnosis of MVP, have increased our understanding of this disease in the dog. The purpose of this article is to compare the knowledge which has been accumulated about myxomatous mitral valve disease/MVP in the dog with knowledge of primary MVP in humans. Pathologically, primary MVP in humans is very similar to canine myxomatous mitral valve disease [4,5]. In both species, the principal macroscopic findings are enlarged, thickened leaflets, interchordal hooding and elongated chordae tendineae (Fig. 1A, B) [4–9]. In addition, affected … * Corresponding author. Tel.: +45-35-282-526; fax: +45-35-282-525 hdp{at}kvl.dk

Predictive value of natriuretic peptides in dogs with mitral valve disease

Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination and the status of the dogs 5 years after the initial examination was determined by telephone calls to the owner. All dogs were evaluated by clinical examination and echocardiography. CKCS with severe MR had higher NT-proANP and NT-proBNP compared to controls and CKCS with less severe MR. Dogs with clinical signs of HF had markedly elevated NT-proANP and NT-proBNP. Plasma concentrations of the natriuretic peptides measured at re-examination could predict progression in regurgitant jet size.

Increased endothelin-receptor density in myxomatous canine mitral valve leaflets.

In dogs and humans, myxomatous mitral valve disease results in mitral valve prolapse and mitral regurgitation. Diseased leaflets display endothelial damage, which in turn might lead to subendothelial growth through release of paracrine mediators such as endothelin-1. The aim of the study was to investigate the presence and distribution of endothelin receptors and relate these to the presence and severity of myxomatous valve disease in the dog. Valves with clear macroscopic signs of disease were taken at postmortem from five old dogs. Control valves without macroscopic signs of disease were taken from five young dogs. Endothelin receptors in the leaflets were examined by using radiolabeled endothelin-1 detected by autoradiography. The endothelin-receptor density was graded semiquantitatively. To determine disease severity, adjacent sections stained with periodic acid-Schiff (PAS)/Alcian blue were examined histologically. The leaflet thickness was measured, and the mucopolysaccharide deposition, collagen degeneration, and fibrosis were graded semiquantitatively. Diseased areas displayed high endothelin-receptor densities; normal-looking areas showed low densities. The endothelin-receptor density within as well as on the leaflets correlated positively with all four measures of disease severity in the distal most affected third of the cusps, suggesting that endothelin plays a pathogenetic role in canine myxomatous mitral valve disease.

Idiopathic Asymptomatic Thrombocytopenia in Cavalier King Charles Spaniels Is an Autosomal Recessive Trait

Cavalier King Charles Spaniels (CKCS) often have idiopathic asymptomatic thrombocytopenia. In affected dogs, the thrombocytes often are large, and it has been speculated that the condition could be an inherited macrothrombocytopenia. The aim of this study was to examine the inheritance of idiopathic, asymptomatic thrombocytopenia in CKCS. Sixteen families (both parents and > or = 3 offspring) of privately owned CKCS were included. There were 105 clinically healthy dogs (50 from Denmark and 55 from Sweden): 81 offspring and 26 parents (2 dogs had both roles). Because autoanalyzers have difficulty counting large platelets, the platelets were counted manually, with a counting chamber. Platelet counts were not influenced by age, gender, or heart murmur status. Thrombocytopenia (< or = 100,000 platelets/microL) was found in 46% of the parents. The pedigrees indicated that thrombocytopenia segregated as an autosomal recessive trait and that 100,000 platelets/microL was appropriate as a lower limit of normal. Affected offspring were found in all families, showing that all of the included parents were at least carriers. Therefore, the expected segregation ratios (which were in good accordance with the observed ones) were 1:0, 1:1, and 1:3 for the 3 crosses: affected x affected, normal x affected, and normal x normal. Within a given cross, the mean parental platelet count had no influence on the platelet counts of the offspring. We conclude that idiopathic, asymptomatic thrombocytopenia in CKCS is inherited in an autosomal recessive manner. The condition most likely constitutes an inherited macrothrombocytopenia in dogs.

Activation of the renin-angiotensin system in dogs with asymptomatic and symptomatic dilated cardiomyopathy

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were assessed in 23 dogs, nine of which had asymptomatic dilated cardiomyopathy (DCM) (New York Heart Association [NYHA] class I), eight had symptomatic DCM (NYHA class III) and six had severe congestive heart failure due to DCM (NYHA class IV). None of the dogs had received any drugs before the study. PRA was increased in dogs with DCM (NYHA classes III and IV) (median values 3.8 and 30.8 ng ml-1 hour-1) compared with normal dogs (median 0.89 ng ml-1 hour-1). However, PRA was only marginally increased in dogs with DCM NYHA class I (P = 0.06). The PAC was also increased in dogs with DCM (NYHA classes III and IV) (median values 123 and 600 pg ml-1) compared with normal dogs (median 61 pg ml-1). The PAC was not significantly increased in the early stage of DCM (NYHA class I). It was concluded that in dogs with DCM, the activity of the renin-angiotensin system (RAS) was increased in NYHA functional classes III and IV, and that the increase was correlated with the severity of the disease. The fact that the RAS tended to be activated in dogs with asymptomatic DCM supports the rationale of early therapeutic intervention with inhibitors of the angiotensin-converting enzyme (ACE) as first line therapy in congestive heart failure.

Dogs with heart diseases causing turbulent high-velocity blood flow have changes in platelet function and von Willebrand factor multimer distribution.

The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into 4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis (SAS). Clinical examinations and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma with 3 different agonists), and vWf multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS had longer closure times and a lower percentage of the largest vWf multimers than did controls. Maximal aggregation responses were unchanged in dogs with SAS but enhanced in Cavaliers with MVP (regardless of MR status) compared with control dogs. No significant difference in platelet activation markers was found among groups. The data suggest that a form of platelet dysfunction detected at high shear rates was present in dogs with MR and SAS, possibly associated with a qualitative vWf defect. Aggregation results suggest increased platelet reactivity in Cavaliers, but the platelets did not appear to circulate in a preactivated state in either disease.

Holter monitoring in clinically healthy Cavalier King Charles Spaniels, Wire-haired Dachshunds, and Cairn Terriers.

BACKGROUND Few reported studies describe normal values from 24-hour ECG (Holter) recordings of small breed dogs. OBJECTIVES To investigate influence of breed, age, sex, body weight, degree of recording artifact, and mitral valve prolapse (MVP) on Holter recordings of 3 breeds of small dogs that have differing predispositions for myxomatous mitral valve disease. The study also assessed if heart rate (HR) at clinical examination (HRex) was associated with HR during Holter monitoring and evaluated the reproducibility of Holter variables. ANIMALS Fifty clinically healthy, privately owned dogs of the breeds Cavalier King Charles Spaniel (CKCS), Wire-haired Dachshund (wD), or Cairn Terrier (CT). METHODS Prospective, longitudinal observational study. Dogs were recruited for clinical examination, echocardiography, and Holter monitoring. In 8 CKCS, Holter recordings were performed twice with a 7-day interval. Arrhythmia and heart rate variability (HRV) analysis (time and frequency domain analysis) were performed on Holter recordings. RESULTS Fifteen out of 27 Holter derived variables were significantly associated with breed (P < .03), but not with age (P > .7), sex (P > .2), body weight (P > .7), degree of recording artifact (P > .4), or MVP (P > .6). During Holter recording, minimum (P = .0001) and mean HR (P = .0001) were higher in CKCS compared with wD. CKCS had significantly lower values than wD, CT, or both in 10 out of 13 HRV variables (P < .03). Minimum and mean HR during Holter recording were correlated with HRex (r = 0.55, P = .0003). HR and time domain variables had a coefficient of variation <10%. CONCLUSIONS AND CLINICAL IMPORTANCE There is an influence of breed on Holter-derived variables in 3 breeds of small dogs. Arrhythmia and HRV analysis can be performed on 24-hour ambulatory ECG (Holter) recordings. Arrhythmia analysis includes HR measurements and identification of arrhythmias.

Circulating cytokine concentrations in dogs with different degrees of myxomatous mitral valve disease.

Cytokines have been associated with the progression of congestive heart failure (CHF) in humans and may be implicated in the pathophysiology of myxomatous mitral valve disease (MMVD) in dogs. The aim of this study was to determine the serum concentrations of cytokines in dogs with MMVD. The study included 16 Cairn terriers with no or minimal mitral regurgitation (MR), 41 Cavalier King Charles Spaniels (CKCS) with different degrees of MR and 11 dogs of different breeds with CHF due to MMVD. Granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, keratinocyte-derived chemokine, interferon-γ-induced protein and monocyte chemoattractant protein-1 (MCP-1) were measured using a canine-specific multiplex immunoassay. CHF dogs had significantly higher MCP-1 concentrations than dogs with no or minimal MR. Among the CKCS, IL-2 and IL-7 decreased with increasing left atrial size and IL-7 also decreased with increasing MR. IL-8 decreased with increasing left ventricular end-systolic internal dimensions. MCP-1 was increased in CHF dogs compared to healthy control dogs and IL-2, IL-7 and IL-8 decreased with increasing indices of disease severity. The results suggest a role for these cytokines in canine MMVD and CHF.