Genetic welfare problems of companion animals

 

Dilated Cardiomyopathy

 

Breed: Dogue de Bordeaux (ddB)

 

Condition:  Dilated Cardiomyopathy

Related terms: systolic heart failure, Primary Idiopathic Myocardial Failure (PIMF), Dilative cardiomyopathy, Primary idiopathic myocardial failure, DCM

Outline: Dilated cardiomyopathy (DCM) is disease of the heart muscle in which the heart becomes thin walled and dilated. Dogs with this heart disease – which causes progressive loss of heart function and abnormalities of heart beat rhythm – often show no obvious signs for several years and then may die suddenly or after several weeks or months due to progressive heart failure. Inadequate blood circulation results in fluid build up in the lungs or other parts of the body and can cause chronic malaise whose nature depends upon which parts of the body are affected. There is no genetic test but the disease can be detected in the early stages using ultrasound or 24 hour electrocardiographic monitoring. Breeding from affected dogs will perpetuate the problem.

 


 

Summary of Information

(for more information click on the links below)

 

 

1.           Brief description

Dilated cardiomyopathy (DCM) is a disease of the heart muscle in which the heart becomes thin walled and dilated. There are two common, important consequences of this for the affected dog: firstly, it will experience congestive heart failure which leads to a build up of fluid in the body, especially the lungs, and, secondly, it will show dysrhythmia (abnormal heart beat) which may result in its sudden death due to inadequate blood circulation (Martin et al 2010).

Dogues de Bordeaux with heart disease, but without heart failure, are likely to appear normal to their owners and will not have any welfare problems at that time. Heart disease can be detected through electrocardiography (ECG) which records the electrical activity of the heart as it beats.

The reason why some Dogues de Bordeaux (ddB) develop DCM is unknown. Genetic factors are certainly very important but the mechanism is unclear. Heart muscle cells have a reduced capacity to contract adequately but whether this is due to a defect in the cell structure, the proteins that make up the contractile apparatus, or in the cellular components that provide energy for contraction is unclear (O’Brien et al 1992, O’Brien 1997, Meurs et al 2001, Spier et al 2001).

 

 

2.           Intensity of welfare impact             

Dogues de Bordeaux with DCM generally have a long period of subclinical disease during which there are no (or only slight) welfare problems. If examined with ultrasound or by electrocardiogram (ECG) testing during this period the changes in heart structure and function associated with DCM can be detected but there are no other clinical signs at this time.

Subsequently, they typically then go on to experience dysrhythmia (abnormalities of the heart beat) or congestive (backwards) heart failure.

Some dogs die in hours to days from congestive heart failure that does not respond to treatment and survival for more than a few months is unusual. Heart failure also causes coughing. As this fluid accumulates, breathing becomes an increasing struggle and the dog effectively dies from drowning in its own body fluids. This is a severe welfare problem although the affected dog is often euthanased at an earlier stage in this process to avoid this suffering.

Dysrhythmias may cause or contribute to congestive heart failure occurring and the welfare implication described above. They also directly cause welfare problems by making the dog feel ill, faint or collapse and lead to its sudden death.

 

3.           Duration of welfare impact

 

Dilated cardiomyopathy reduces life-span in the ddB. The duration of suffering may be very short in cases in which apparently healthy animals affected by the disease die suddenly due to dysrhythmia. It can be much longer – weeks or months – in cases in which there is progressive congestive heart failure. A study has shown that the mean survival time after presentation of dogs of all breeds with DCM at a cardiorespiratory referral centre was 19 weeks (Martin et al 2009).

 

4.           Number of animals affected

 

The ddB is one of the breeds of dog most commonly affected by DCM (Borgarelli et al 2006, Koch et al 1996, Martin et al 2009, O’Grady & O’Sullivan 2004). The disease is the second commonest cause of death in this breed (http://www.ddbs.org/Health/Cause%20of%20Death/CauseofdeathResults.htm).

 

5.           Diagnosis

DCM is usually diagnosed by ultrasound examination but the diagnosis may be supported by findings from other cardiological examinations – physical examination, radiography of the chest and ECG (Dukes-McEwan et al 2003).

Occult disease (the hidden form in which there are heart abnormalities but before any clinical signs become apparent) can also be detected using ECG examination or 24-hour Holter ECG monitoring.

Currently there are no genetic tests available.

 

6.           Genetics

 

There is a breed predisposition for DCM in ddBs. In other giant breeds DCM has often been found to have an autosomal dominant pattern of inheritance (Meurs et al 2007) but this has not yet been shown in the ddB. Autosomal dominant conditions affect both sexes equally and all individuals with the mutant gene are at risk of developing the condition. Whether or not they do so may depend, however, on the actions of other genes and environmental factors. Individuals with the mutant gene will pass it on to 50% of their offspring.

 

7.           How do you know if an animal is a carrier or likely to become affected?

There are currently no genetic tests for DCM as the gene or genes involved have not been identified. The only way to determine if an apparently normal dog is likely to develop clinical DCM, is by detection of heart abnormalities. The most sensitive methods for this are ultrasound examination, ECG and 24-hour Holter ECG monitoring, which are only available from specialist veterinary cardiologists.

 

8.          Methods and prospects for elimination of the problem

 

As far as we are aware, there are currently no formal breeding schemes in operation to reduce or eliminate this common condition from the Dogue de Bordeaux breed.

In the absence of a genetic test, any scheme to reduce the prevalence of this disease would have to be based on detection of affected animals by veterinary cardiologists.

Animals that have clinical DCM are not suitable for breeding. Animals with occult DCM (the early stage of the disease before it causes clinical signs) may be capable of breeding but should not be used as this would perpetuate the problem. Since the disease is so common in ddB, there is concern that excluding all affected individuals from the breeding pool might limit the size of the breeding population to the extent that the risk of other genetic defects (of which several are known) might be significantly increased. Such problems could be avoided by out-breeding with dogs of other breeds unaffected by DCM.

 

 


 

For further details about this condition, please click on the following:

 

 

 

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1.           Clinical and pathological effects

 

Dilated cardiomyopathy (DCM) is disease of the heart muscle in which the heart becomes thin walled and dilated. There are two common, important consequences of this for the affected dog: firstly, it will experience congestive heart failure which leads to a build up of fluid in the body, especially the lungs, and secondly, it will show dysrhythmia (abnormal heart beat) which may result in its sudden death due to inadequate blood circulation (Martin et al 2010).

The heart is a four-chambered pump which is divided into left and right sides. Each side has two chambers. Blood enters into the thin-walled upper chambers (atria) and then flows into the larger, lower chambers (ventricles). The ventricles have thick muscular walls. Between the atria and the ventricles are valves that prevent back flow of blood. On contraction, blood is pumped from the ventricles into the major blood vessels. There are also valves at the junction of the ventricles and these blood vessels that prevent back flow.

Figure 1. The four chambers of the heart and direction of blood flow. Note the four valves, which in a normal healthy heart prevent the backflow of blood. (Image property of The Cardiomyopathy Association to whom we are grateful for permission for its reproduction here).

Figure 1. The four chambers of the heart and direction of blood flow. Note the four valves, which in a normal healthy heart prevent the backflow of blood. (Image property of The Cardiomyopathy Association to whom we are grateful for permission for its reproduction here).

 

The right side of the heart receives blood from the whole of the body other than the lungs, via the venae cavae. It accumulates in the right atrium and during a heart beat it flows through the tricuspid valve into the right ventricle and then, as the right ventricle contracts (squeezes) its muscular wall, the blood is pushed through the pulmonary valves into the pulmonary arteries and on to the lungs (to take up oxygen).

The left side of the heart receives this oxygenated blood from the lungs, via the pulmonary veins. The blood accumulates in the left atrium and during a heart beat it flows past the mitral valve into the left ventricle. Then, as the left ventricle contracts, the blood is pushed through the aortic valves into the aorta and on to the other major arteries which carry it around the body to deliver oxygen and nutrients and to transport heat and metabolic products throughout the body.

The part of the heart’s relaxation and contraction cycle (that together make up the ‘heart beat’) when contraction (squeezing of blood) is occurring is referred to as systole and the relaxation phase is called diastole.

To co-ordinate the contractions of the different parts of the heart there is a pathway for conduction of nerve impulses. Conduction of impulses can be disrupted by damage to the heart muscle.

So, the left hand side of the heart has to pump blood around the major organs of the body, whilst the right hand side only has to push blood through the adjacent lungs. This difference does not affect the structure and function of the atria very much but requires that the muscles of the left ventricle have to be much stronger than the right. As strength is largely a function of muscle size the muscle wall of the left ventricle is thicker than the right.


Figure 2. In a normal healthy heart, nerve signals travel through the heart muscle to stimulate coordinated contractions. However if the muscle tissue becomes thinner, as occurs in dilated cardiomyopathy, the nerve signals are disrupted leading to a variety of detrimental effects (see below). (Image property of The Cardiomyopathy Association to whom we are grateful for permission for its reproduction here).

 

The heart changes shape in animals with dilated cardiomyopathy. It becomes generally larger, the chambers have a greater volume and the muscle walls are thinned. These changes lead to various ‘knock on’ problems which, at some stage, prevent the heart from functioning normally. Exactly what happens in an individual depends on which parts dilate, how rapidly and to what degree, whether or not the valves are affected, and the degree to which conduction of heart beat signals are interfered with. The consequences of various manifestations of the disease are outlined below.

  • The thin heart wall contracts poorly so the heart may fail to empty. This causes a backflow problem so that blood cannot enter the heart normally. This is backward or congestive heart failure. When the left side of the heart is affected, the result is fluid build up in the lungs (pulmonary oedema). When the right side is affected, the fluid builds up in the body and usually shows as fluid accumulating in the chest cavity (pleural fluid), the abdomen (ascities) or in the body tissues generally (oedema).
  • As the heart shape changes as a result of DCM, the valves can become distorted and leak. When the tricuspid and mitral valves, between the ventricles and atria are affected, they may allow back flow into the atria during contractions which causes further backwards  heart failure and the problems, outlined above, that are associated with this.
  • In DCM, the abnormal muscle often contains scar tissue or fatty infiltrates which interfere with the conduction of nerve signals through the heart resulting in uncoordinated contractions (dysrhythmia or arrhythmia). Irregular heart beats can contribute to both forward and backward heart failure (Calvert et al 1997). Forwards heart failure occurs when the left ventricle provides inadequate blood flow to the body and this can lead to weakness, collapse, fainting and sudden death. In DCM the weakness of the heart muscle also contributes to forward heart failure.


Figure 3. In cases of dilated cardiomyopathy, the ventricles dilate and become larger, and the cardiac muscle surrounding them becomes thinner causing the heart to change shape. This in turn impedes the muscle contraction and effectiveness of the valves, which can lead to irregular heartbeats and the backflow of blood (labelled mitral regurgitation in Figure 3), leading to further complications such as a build up of fluid in the lungs or the rest of the body. (Image property of The Cardiomyopathy Association to whom we are grateful for permission for its reproduction here).

 

The body is able to compensate, to some extent, for impending heart failure through various mechanisms. However, some of these can, themselves, lead to further problems.

When there is inadequate blood flow from the heart, heart rate is increased so that blood supply to the organs is maintained. However, this raised heart rate may further restrict the ability of the ventricles to relax and fill as there is less time between each contraction; time in which the ventricles can relax and fill. Increasing heart rate can cause backward heart failure to worsen such that eventually the volume of blood that the heart can push forwards around the body also decreases. A further problem is that during relaxation the heart muscle itself receives blood via its coronary arteries and when it has to beat abnormally rapidly, its own oxygen supply may can decrease leading to death of heart muscle.

Inadequate blood flow from the heart can also cause the body to react as though there has been a loss of circulating blood volume. Hormones are released in response causing fluid to be retained even though there has been no loss of blood. The amount of fluid in the body thus increases and this is one of the reasons that fluid accumulates in the lungs (pulmonary oedema) or elsewhere in the body (pleural fluid or oedema).

Dogs with heart disease, but without heart failure, are likely to appear normal to their owners and will not have any welfare problems at that time. An owner might be able to detect a fast and abnormally strong heart beat if feeling their dog’s chest and an elevated heart rate may be apparent on veterinary examination. The heart rate is measured by feeling the heart beat, or, more usually, by listening to the heart using a stethoscope. The pulse rate is measured by feeling the pulsing of blood flowing through a major artery - in dogs, usually the femoral artery in the upper inside leg. Normally heart and pulse rates are the same, but this is not always the case in heart failure – sometimes an ineffectual heart beat occurs that does not generate a pulse that can be detected. This is called a pulse deficit.

Examination with a stethoscope may reveal a heart murmur. This is often the way in which the disease is first detected. Murmurs are caused by abnormally turbulent blood flow. They usually indicate the presence of a structural abnormality of the heart, for example, in DCM they may be caused by an abnormal valve allowing backflow of blood.

On detection of a murmur, further investigations should be carried out to determine the cause. Another change that may be detected is a 'gallop' rhythm. Normally a heart beat has two sounds, “lub – dub”. A gallop rhythm has three sounds and this is a reliable indication that heart disease is present.

Other signs of heart disease (before it becomes apparent due to heart failure) can only be detected using more sophisticated equipment. Radiographs (x-rays) of the chest may show evidence of heart enlargement but this is a relatively crude method. (Chest radiographs are very useful for detecting common signs of heart failure – see below). A disadvantage of chest radiographs is the need for heavy sedation or a general anaesthetic.

Electrocardiographic (ECG) recording of the electrical activity of the heart is carried out in dogs without sedation or anaesthesia. Some individuals may have irregular heart beats on occasions whilst being normal most of the time. These dogs may have fainting episodes during the periods of irregularity but on later veterinary examination may appear completely normal. Normal ECGs record the electrical activity for a few minutes only and fail to detect problems that occur infrequently (Wess et al 2010a). It is better therefore to use a Holter monitor that records ECG over an extended period.

The most powerful tool for examining the heart is ultrasonography. This enables measurement of the thickness of the heart muscle; the size of each chamber, and the position and movement of each valve. With colour-flow ultrasonography it is also possible to measure the speed and direction of blood flow in the heart and the great vessels.

The reason why some Dogues de Bordeaux develop this disease is not known. Genetic factors are certainly important but the mechanism is unclear. In the disease, heart muscle cells have a reduced capacity to contract adequately but whether this is due to a defect in the cell structure, the proteins that make up the contractile apparatus, or in the cellular components that provide energy for cellular contraction is unclear (O’Brien et al 1992, O’Brien 1997, Meurs et al 2001, Spier et al 2001).

Dogs can also be affected for other reasons including: nutritional deficiencies, drug side effects, viral infection and possibly hormonal imbalance, and autoimmune disease (Calvert & Meurs 2000, Rishniw 2004, Buse et al 2008).

When heart tissue affected by DCM is examined post-mortem under the microscope two distinctive forms can be distinguished: (i) a fatty infiltration-degenerative type and (ii) an attenuated wavy fibre type – in which heart muscle cells are deformed. The second form is most common in giant-breed dogs but it is not possible to determine which type of disease is present in an individual dog prior to death (Tidholm et al 2001).

 

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2.               Intensity of welfare impact

Dogue de Bordeaux with DCM generally have a period of subclinical disease during which there are little or no welfare problems. If examined with ultrasonography or ECG during this period the changes in heart structure and function associated with DCM can be detected but there are no other clinical signs.  However, affected dogs typically go on to develop dysrythmia or (backwards) heart failure

Some dogs die in hours to days from congestive heart failure that does not respond to treatment and survival for more than a few months is unusual. Left-sided congestive heart failure leads to fluid build up in the lungs which makes breathing difficult and also causes coughing. As this fluid accumulates, breathing becomes an increasing struggle and the dog may die from what is, in effect, drowning in its own body fluids. This is a severe welfare problem although the affected dog is often euthanased for welfare reasons at an earlier stage in this process o avoid further suffering.

Disturbances to heart rhythm (dysrhythmias) may contribute to congestive heart failure and may also have direct welfare effects when they cause acute cardiac insufficiency making the dog feel ill or faint and perhaps causing collapse or sudden death.

Investigations into and treatments of heart failure may also have adverse welfare effects related to travel to and from veterinary practices, hospitalisations and medications – for example, medications may cause gastrointestinal disease.

 

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3.           Duration of welfare impact

 

DCM causes a reduction in life-span for Dogue de Bordeaux. The mean survival time of dogs of all breeds with DCM from their first presentation at a cardiorespiratory referral centre was found to be 19 weeks in one study (Martin et al 2009),

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4.           Number of animals affected

 

The ddB is one of the breeds most commonly affected by DCM Borgarelli et al 2006, Koch et al 1996, Martin et al 2009, O’Grady & O’Sullivan 2004), and it is the second most frequent cause of death in this breed (http://www.ddbs.org/Health/Cause%20of%20Death/CauseofdeathResults.htm). However, we are not aware of data on the proportion of ddBs that is affected by DCM.

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5.           Diagnosis

 

DCM is usually diagnosed by ultrasound examination although this may be supported by findings from other cardiological examinations – physical examination, radiography of the chest and ECG (Dukes-McEwan et al 2003, Locatelli et al 2011).

ECG can be used to detect occult disease (eg heart rhythm abnormalities at a stage before the animal shows any clinical signs) but short-term recordings are less sensitive than 24-hour Holter monitoring (Wess et al 2010a). The stage of disease can be estimated from the results of 24-hour Holter monitoring, physical examination and chest radiographs. There has been some interest in using a blood test to detect evidence of heart muscle damage but this has not yet become well established (Wess et al 2010b)

Currently there are no genetic tests available for detection of affected animals.

 

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6.           Genetics

There is a breed predisposition for DCM in ddBs. In other giant breeds DCM has often been found to have an autosomal dominant pattern of inheritance (Meurs et al 2007) but this has not yet been shown in the ddB. Autosomal dominant conditions affect both sexes equally and all individuals with the mutant gene are at risk of developing the condition. Whether or not they do so may depend, however, on the actions of other genes and environmental factors. Individuals with the mutant gene will pass it on to 50% of their offspring.

 

Return to top

 

7.           How do you know if an animal is a carrier or likely to become affected?

There are currently no genetic tests for DCM as the gene or genes involved have not been identified. The only way to determine if an apparently normal dog is likely to develop clinical DCM, is by detection of heart abnormalities. The most sensitive methods for this are ultrasound examination, ECG and 24-hour Holter ECG monitoring, which are only available from specialist veterinary cardiologists.

Return to top

 

 

8.          Methods and prospects for elimination of the problem

As far as we are aware, there are currently no formal breeding schemes in operation to reduce or eliminate this common condition from the Dogue de Bordeaux breed.

In the absence of a genetic test, any scheme to reduce the prevalence of the disease would have to be based on detection of affected animals by veterinary cardiologists.

Animals that have clinical DCM are not suitable for breeding. Animals with occult DCM (the disease in its early stages before it causes clinical signs) may be capable of breeding but should not be used as this would perpetuate the problem. Animals that have clinical DCM are not suitable for breeding. Animals with occult DCM (the early stage of the disease before it causes clinical signs) may be capable of breeding but should not be used as this would perpetuate the problem. Since the disease is so common in ddB, there is concern that excluding all affected individuals from the breeding pool might limit the size of the breeding population to the extent that the risk of other genetic defects (of which several are known) might be significantly increased. Such problems could be avoided by out-breeding with dogs of other breeds unaffected by DCM.

 
 

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9.          Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section and to Stephanie Kaufman for assistance in illustrating it.

 

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10.          References

Borgarelli M, Santilli RA, Chiavegato D, D’Agnolo G, Zanatta R, Mannelli A and Tarducci A (2006) Prognostic Indicators for Dogs with Dilated Cardiomyopathy. Journal of Veterinary Internal Medicine 20: 104–110

Buse C, Altmann F, Amann B, Hauck SM, Poulsen Nautrup C, Ueffing M, Stangassinger M and Deeg CA (2008) Discovering novel targets for autoantibodies in dilated cardiomyopathy. Electrophoresis 29: 1325–1332

Calvert CA and Meurs KM (2000) CVT update: Doberman pinscher occult cardiomyopathy. In: Kirk’s Current Veterinary Therapy XIII editor JD Bonagura, WB Saunders, Philadelphia. pp 756

Calvert CA, Hall G, Jacobs G and Pickus C (1997) Clinical and pathologic findings in Doberman pinschers with occult cardiomyopathy that died suddenly or developed congestive heart failure: 54 cases (1984-1991). Journal of the American Veterinary Medical Association 210: 505-11

Calvert CA, Jacobs GJ and Pickus CW (2004) Unfavorable influence of anesthesia and surgery on Doberman pinschers with occult cardiomyopathy. Journal of the American Animal Hospital Association 32: 57-62

Dukes-McEwan J, Borgarelli M, Tidholm A, Vollmar AC, Häggström J and The ESVC Taskforce for Canine Dilated Cardiomyopathy (2003) Proposed Guidelines for the Diagnosis of Canine Idiopathic Dilated Cardiomyopathy. Journal of Veterinary Cardiology 5: 7-19

Koch J, Pedersen HD, Jensen AL and Flagstad A (1996) M-mode echocardiographic diagnosis of dilated cardiomyopathy in giant breed dogs. Journal of the American Veterinary Medical Association 43: 297-303

Locatelli C, Santini A, Bonometti GA, Palermo V, Scarpa P, Sala E and Brambilla PG (2011) Echocardiographic values in clinically healthy adult dogue de Bordeaux dogs. Journal of Small Animal Practice 52: 246–253

Martin MWS, Stafford Johnson MJ and Celona B (2009) Canine dilated cardiomyopathy: a retrospective study of signalment, presentation and clinical findings in 369 cases. Journal of Small Animal Practice 50: 23–29

Martin MWS, Stafford Johnson MJ, Strehlau G and King JN (2010) Canine dilated cardiomyopathy: a retrospective study of prognostic findings in 367 clinical cases. Journal of Small Animal Practice 51: 428–436

Meurs KM, Magnon AL, Spier AW, Miller MW, Lehmkuhl LB and Towbin JA (2001) Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy. American Journal of Veterinary Research 62: 33-36

Meurs KM, Fox PR, Norgard M, Spier AW, Lamb A, Koplitz SL and Baumwart RD (2007) A Prospective Genetic Evaluation of Familial Dilated Cardiomyopathy in the Doberman Pinscher. Journal of Veterinary Internal Medicine 21: 1016–1020

O'Brien PJ (1997) Deficiencies of myocardial troponin-T and creatine kinase MB isoenzyme in dogs with idiopathic dilated cardiomyopathy. American Journal of Veterinary Research 58: 11-16

O'Brien PJ, O'Grady M, McCutcheon LJ, Shen H, Nowack L, Horne RD et al (1992) Myocardial myoglobin deficiency in various animal models of congestive heart failure. Journal of Molecular and Cell Cardiology 24: 721-730

O’Grady MR and O’Sullivan ML (2004) Dilated cardiomyopathy: an update. Veterinary Clinics North America: Small Animal Practice 34: 1187-1207

Rishniw (2004) Systolic myocardial failure. VIN Associate accessed 3.11.2010

Spier AW, Meurs KM, Coovert DD, Lehmkuhl LB, O'Grady MR, Freeman LM, Burghes AH and Towbin JA (2001) Use of Western immunoblot for evaluation of myocardial dystrophin, alpha-sarcoglycan, and beta-dystroglycan in dogs with idiopathic dilated cardiomyopathy. American Journal of Veterinary Research 62: 67-71

Tidholm A, Haggstrom J, Borgarelli M and Tarducci A (2001) Canine idiopathic dilated cardiomyopathy. Part I: Aetiology, clinical characteristics, epidemiology and pathology. Veterinary Journal 162: 92-107

Wess G, Schulze A, Geraghty N and Hartmann K (2010a) Ability of a 5-Minute Electrocardiography (ECG) for Predicting Arrhythmias in Doberman Pinschers with Cardiomyopathy in Comparison with a 24-Hour Ambulatory ECG. Journal of Veterinary Internal Medicine 24: 367–371

Wess G, Simak J, Mahling M and Hartmann K (2010b) Cardiac Troponin I in Doberman Pinschers with Cardiomyopathy. Journal of Veterinary Internal Medicine 24: 843–849

http://www.ddbs.org/Health/Cause%20of%20Death/CauseofdeathResults.htm accessed 6.7.2011

 

 

 

 

© UFAW 2011

 

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