Pathophysiologie des Herzens

Cardiac Pathophysiology

The Veterinary Cardiac Pathophysiology Consortium (VCPC) is an interdisciplinary group of veterinarians at the Universities of Zurich (Switzerland), Guelph (Canada), Helsinki (Finland) and Perugia (Italy). The group consists of clinical cardiologists and pathologists that combine their complementary expertise to gain further insight into the pathophysiology of cardiac diseases in animals.

Current research projects focus on acquired cardiac diseases in dogs and cats and the influence of systemic diseases on the heart. We also have an interest in the effect of gender and age on the constitutive examination of inflammatory and remodelling mediators as a basis for the reactive status of the myocardium and its resultant response to systemic influences.  

Common acquired cardiac diseases in dogs are degenerative valvular disease and dilated cardiomyopathy (DCM), cats frequently present with hypertrophic cardiomyopathy (HCM). All these diseases are of adult onset, a genetic aetiology with incomplete penetrance is suspected, and mutations have been identified for some dog and cat breeds. Similar to human medicine, these mutations affect sarcomere function and energy metabolism. However, the pathogenesis of the diseases is not yet completely understood. The association between mutation, the observed functional defects and the development of microscopic changes characteristic for the diseases and the factors involved in disease development, presentation and progression is so far unknown.

Furthermore, the role of gender, and the influence of systemic diseases, such as kidney diseases, diabetes mellitus, systemic hypertension, and obesity, known comorbidities in human cardiology, and common in the aging pet population, on cardiac function and disease has not been studied in the veterinary patient population.

Combining clinical and pathological aspects of cardiac and systemic diseases allows a diversified approach to investigate the relevance of clinical findings for the progression of cardiac diseases and the influence of systemic diseases on cardiac structure and function.

Current research projects include:

  • Studies on the pathogenesis of canine DCM and feline HCM,
  • Cardiac inflammation and extracellular matrix remodelling in dogs and cats with cardiac and systemic diseases,
  • The role of adhesion molecules in canine cardiac diseases,
  • The relevance of heart fatty acid binding protein (HFABP) as potential marker for canine DCM and degenerative valvular disease,
  • Age- and gender-related structural and functional myocardial variations in cats,
  • Functional changes in the myocardium in feline infectious peritonitis,
  • The role of adipokines (i.e. leptin) in canine and feline cardiac disease;
  • The expression of miRNA in feline HCM and canine DVD.

Sonja Fonfara, Dr med vet, PhD, PGCertHE, FHEA, MRCVS, CertVC, DECVIM-CA (Cardiology), is a cardiologist with strong interest in age and disease associated myocardial changes and how these translate into clinical practice. SF works as Associate Professor at the University of Guelph; she is member of the Centre for Cardiovascular Investigations (CCVI, http://www.uoguelph.ca/CardiovascularResearch/) at the University of Guelph, where she collaborates with other members of the CCVI (Drs. Tami Martino, Glen Pyle, Lynne O’Sullivan).

The team in Zurich currently focusses on the pathomorphological aspects of companion animal cardiac diseases. Anja Kipar, Prof. Dr. med. vet., DiplECVP, FRCPath, FVH & FTA (Pathologie), is a veterinary pathologist with a strong interest in the immunopathological effect of infectious and non-infectious diseases on the myocardium, while Udo Hetzel, Dr.med.vet. Dr.rer.nat., FTA (Pathologie), is an expert ultrastructural pathologist with a strong interest also in the embryology and congenital alterations of the heart.

In Helsinki, Docent Maria Wiberg, PhD, a specialist in small animal cardiology and internal medicine, works on the development of clinical markers for DCM of Doberman Pinschers and Salukis and investigates the pathophysiological mechanisms of the disease in these breeds. She further studies breed variations of stress and neuroendocrine factors and their potential involvement in cardiac disease development and progression. 

The group from Perugia is represented by Elvio Lepri, PhD, DiplECVP, a veterinary pathologist interested in cardiac pathology of companion animals and horses, and Dr. Gabriella Guelfi, with expertise in molecular biotechnology predominantly on the manipulation of DNA, mRNA and non-coding RNA. Their more recent studies are on miRNA expression in feline HCM and canine DVD.

The group is complemented by five postgraduate students. Stefania Gasparini, Sarah Kitz and Josep Monné Rodríguez are based in Zurich and undertake research projects on the pathomorphological changes in canine DCM and feline HCM, and Michelle Colpitts and Christopher Lam are based in Guelph and are involved in the research into feline HCM and canine cardiac biomarkers. In Zurich and Guelph, the VCPC also offers Master projects for veterinary under- and postgraduate students with an interest in pathology.

Its clinical members (http://www.kltmed.uzh.ch/de/fachgebiete/kardiologie.html), and in particular Prof. Tony Glaus, work closely in the case based approach to pathophysiological questions.

Our research is currently supported by the Natural Sciences and Engineering Council of Canada (NSERC) and the Center for Applied Biotechnology and Molecular Medicine (CABMM) at the University of Zurich.

 

Relevant recent publications

Fonfara S, Kitz S, Hetzel U, Kipar A, 2017. Myocardial leptin transcription in feline hypertrophic cardiomyopathy. Res Vet Sci. 2017 Jun;112:105-108. doi: 10.1016/j.rvsc.2017.02.006.

Fonfara, S., Hetzel, U, Hahn, S., Kipar A, 2015. Age- and gender-dependent myocardial transcription patterns of cytokines and extracellular matrix remodelling enzymes in cats with non-cardiac diseases. Exp Gerontol 72, 117-123.

Fonfara, S., Hetzel, U, Oyama, MA., Kipar A, 2014. The potential role of myocardial 2B receptor expression in canine dilated cardiomyopathy. Vet J 199, 406-412.

Linney CJ, Dukes-McEwan J, Stephenson HM, López-Alvarez J, Fonfara S, 2014. Left atrial size, atrial function and left ventricular diastolic function in cats with hypertrophic cardiomyopathy. J Sm Anim Pract 55(4), 198-206.

Casamian-Sorrosal D, Chong SK, Fonfara S, Helps C, 2014. Prevalence and demographics of the MYBPC3 mutations in Ragdoll and Maine Coons in the British Isles. J Sm Anim Pract 55(5), 269-273.

Fonfara S, Hetzel U, Tew S, Cripps P, Dukes-McEwan J, Clegg P, 2013. Expression of matrix metalloproteinases, their inhibitors, and lysyl axidase in myocardial samples from dogs with end-stage systemic and cardiac diseases. Am J Vet Res 74(2), 216-223.

Fonfara S, Hetzel U, Tew S, Cripps P, Dukes-McEwan J, Clegg P, 2013. Myocardial cytokine expression in dogs with end-stage systemic and naturally occurring cardiac diseases. Am J Vet Res 74(3), 408-416.

Stephenson H, Fonfara S, Lopez-Alvarez J, Cripps P, Dukes-McEwan J, 2012. Screening for dilated cardiomyopathy in Great Danes in the United Kingdom. J Vet Int Med 26(5), 1140-1147.

Fonfara S, Hetzel U, Tew SR, Cripps P, Dukes-McEwan J, Clegg P, 2011. Leptin expression in dogs with cardiac disease and congestive heart failure. J Vet Int Med 25, 1017-1024.

Fonfara S, Loureiro J, Swift S, James R, Cripps P, Dukes-McEwan J, 2010. Cardiac troponin I as marker for severity and prognosis of cardiac disease in dogs. Vet J 184, 334-339.