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Serotonin 2B Receptor Expression in Canine Cardiac Disease
150:1, 2014
ESVP/ECVP Proceedings 2013
89
Cardiovascular Disease SEROTONIN 2B RECEPTOR EXPRESSION IN CANINE CARDIAC DISEASE S. Fonfara y,*, U. Hetzel * and A. Kipar* *Veterinary Pathology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland and yCompanion Animal Studies, University of Bristol, UK Introduction: Serotonin (5-HT) signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). While contribution of serotonin to canine valvular disease is reported, the role of 5-HTR2B in other canine cardiac diseases is not yet known. Materials and Methods: Blood samples from nine healthy control dogs and nine dogs with congestive heart failure (CHF), and myocardial samples from eight healthy control dogs, nine dogs with cardiac disease and six dogs with systemic non-cardiac disease were investigated for 5-HTR2B transcription by quantitative PCR (qPCR). Myocardial results were correlated with the transcription of cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). To identify cells producing 5HTR2B, laser microdissection with subsequent qPCR and immunohistology were applied. Results: Control dogs exhibited constitutive 5-HTR2B transcription in blood and myocardium. Dogs with CHF showed significantly higher circulating 5-HTR2B levels than control dogs, while myocardial 5-HTR2B transcription was significantly highest in dogs with dilated cardiomyopathy (DCM) compared with all other groups, and a positive correlation of 5-HTR2B with several cytokines, MMPs and TIMPs was observed. Myocytes were identified as the source of 5-HTR2B mRNA and protein. Conclusions: Serotonin plays a role in normal cardiac structure and function and is involved in CHF and the pathogenesis of DCM. AORTIC MEDIA ULTRASTRUCTURE IN A HEALTHY FRIESIAN HORSE AND IN A FRIESIAN HORSE WITH AORTOPULMONARY FISTULA V. Saey *, K. D’Herde y, M. Ploeg z, K. Chiers *, one z, W. Back x,k, C.M. de Bruijn {, C.J.G. Delesalle x, A. Gr€ G. van Loon # and R. Ducatelle* *Department of Pathology, Bacteriology and Avian Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, yDepartment of Basic Medical Sciences, University Hospital, Ghent University, Ghent, Belgium, z Department of Pathobiology, xDepartment of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, k Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium, {Wolvega Equine Hospital, Oldeholtpade, The Netherlands and #Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Introduction: Thoracic aortic rupture is rare in any animal species and in man. Recently, a series of 24 cases was reported in Friesian horses (Ploeg et al., 2013). The rupture typically was a straight transverse tear near the scar of the ligamentum arteriosum and was in many cases associated with aortopulmonary fistulation. To improve our understanding of the presumably genetic pathway of this disease, an ultrastructural study of the aortic media distant to the lesion was performed. Materials and Methods: Samples from the middle thoracic aorta of a clinically healthy Friesian horse (FH) and a Friesian horse with aortopulmonary fistulation (FAP) were fixed in cacodylate buffered glutaraldehyde/paraformaldehyde solution and processed for transmission electron microscopy. Results: The FAP showed a significant increase in density and size of the smooth muscle cells. These cells had more pronounced organelles in the perinuclear cytoplasm (mitochondria, rough endoplasmic reticulum, Golgi) and subplasmalemmal vacuoles. Conclusions: Hypertrophy, hyperplasia and increased metabolic activity of vascular smooth muscle cells were found in the clinical fistula/rupture case and has also been reported in man and animal models of hypertension. It is likely that the compensatory changes of the smooth muscle cells are due to mechanical stresses.
ESTABLISHING A RAT MODEL FOR PROLONGED CARDIAC ARREST: INFLUENCE OF ARREST DURATION ON HIPPOCAMPAL LESIONS S. H€ ogler *, U. Teubenbacher *, A. Janata y, W. Weihs y, I.A.M. Magnet y, F. Ettl y, F. Sterz y and P. Schmidt* *University of Veterinary Medicine Vienna and yMedical University of Vienna, Austria Introduction: Cardiac arrest (CA) is a major health issue in modern society. Strategies to increase the survival rate and to reduce neurological sequelae are crucial. Materials and Methods: Male Sprague-Dawley rats underwent artificial CA for 6 or 8 min (n 5 10/group), followed by 2 min of cardiopulmonary resuscitation. After defibrillation and restoration of spontaneous circulation, the animals were killed at day 14. Sham animals (n 5 4) were subjected to the same procedure except for CA. Formalin-fixed and paraffin wax-embedded slides of the hippocampal CA1 region were stained with haematoxylin and eosin and lesions were assessed using a semiquantitative scoring system. Results: Seven animals of the 6 min group and six animals of the 8 min group gained restoration of spontaneous circulation and were included in histological analysis as well as all sham animals. All animals subjected to CA showed consistent lesions in the hippocampal CA1 region, while sham animals showed no damage. There were statistically significant differences between the sham group and both arrest groups. Furthermore, we found significantly more severe lesions in the 8 min group compared with the 6 min group. Conclusions: We were able to establish a rat model for CA causing consistent lesions in the hippocampal CA1 region. Eight min of CA will be used for further research regarding neuroprotective therapies.
ESVP/ECVP Proceedings 2013
89
Cardiovascular Disease SEROTONIN 2B RECEPTOR EXPRESSION IN CANINE CARDIAC DISEASE S. Fonfara y,*, U. Hetzel * and A. Kipar* *Veterinary Pathology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland and yCompanion Animal Studies, University of Bristol, UK Introduction: Serotonin (5-HT) signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). While contribution of serotonin to canine valvular disease is reported, the role of 5-HTR2B in other canine cardiac diseases is not yet known. Materials and Methods: Blood samples from nine healthy control dogs and nine dogs with congestive heart failure (CHF), and myocardial samples from eight healthy control dogs, nine dogs with cardiac disease and six dogs with systemic non-cardiac disease were investigated for 5-HTR2B transcription by quantitative PCR (qPCR). Myocardial results were correlated with the transcription of cytokines, matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). To identify cells producing 5HTR2B, laser microdissection with subsequent qPCR and immunohistology were applied. Results: Control dogs exhibited constitutive 5-HTR2B transcription in blood and myocardium. Dogs with CHF showed significantly higher circulating 5-HTR2B levels than control dogs, while myocardial 5-HTR2B transcription was significantly highest in dogs with dilated cardiomyopathy (DCM) compared with all other groups, and a positive correlation of 5-HTR2B with several cytokines, MMPs and TIMPs was observed. Myocytes were identified as the source of 5-HTR2B mRNA and protein. Conclusions: Serotonin plays a role in normal cardiac structure and function and is involved in CHF and the pathogenesis of DCM. AORTIC MEDIA ULTRASTRUCTURE IN A HEALTHY FRIESIAN HORSE AND IN A FRIESIAN HORSE WITH AORTOPULMONARY FISTULA V. Saey *, K. D’Herde y, M. Ploeg z, K. Chiers *, one z, W. Back x,k, C.M. de Bruijn {, C.J.G. Delesalle x, A. Gr€ G. van Loon # and R. Ducatelle* *Department of Pathology, Bacteriology and Avian Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, yDepartment of Basic Medical Sciences, University Hospital, Ghent University, Ghent, Belgium, z Department of Pathobiology, xDepartment of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands, k Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium, {Wolvega Equine Hospital, Oldeholtpade, The Netherlands and #Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Introduction: Thoracic aortic rupture is rare in any animal species and in man. Recently, a series of 24 cases was reported in Friesian horses (Ploeg et al., 2013). The rupture typically was a straight transverse tear near the scar of the ligamentum arteriosum and was in many cases associated with aortopulmonary fistulation. To improve our understanding of the presumably genetic pathway of this disease, an ultrastructural study of the aortic media distant to the lesion was performed. Materials and Methods: Samples from the middle thoracic aorta of a clinically healthy Friesian horse (FH) and a Friesian horse with aortopulmonary fistulation (FAP) were fixed in cacodylate buffered glutaraldehyde/paraformaldehyde solution and processed for transmission electron microscopy. Results: The FAP showed a significant increase in density and size of the smooth muscle cells. These cells had more pronounced organelles in the perinuclear cytoplasm (mitochondria, rough endoplasmic reticulum, Golgi) and subplasmalemmal vacuoles. Conclusions: Hypertrophy, hyperplasia and increased metabolic activity of vascular smooth muscle cells were found in the clinical fistula/rupture case and has also been reported in man and animal models of hypertension. It is likely that the compensatory changes of the smooth muscle cells are due to mechanical stresses.
ESTABLISHING A RAT MODEL FOR PROLONGED CARDIAC ARREST: INFLUENCE OF ARREST DURATION ON HIPPOCAMPAL LESIONS S. H€ ogler *, U. Teubenbacher *, A. Janata y, W. Weihs y, I.A.M. Magnet y, F. Ettl y, F. Sterz y and P. Schmidt* *University of Veterinary Medicine Vienna and yMedical University of Vienna, Austria Introduction: Cardiac arrest (CA) is a major health issue in modern society. Strategies to increase the survival rate and to reduce neurological sequelae are crucial. Materials and Methods: Male Sprague-Dawley rats underwent artificial CA for 6 or 8 min (n 5 10/group), followed by 2 min of cardiopulmonary resuscitation. After defibrillation and restoration of spontaneous circulation, the animals were killed at day 14. Sham animals (n 5 4) were subjected to the same procedure except for CA. Formalin-fixed and paraffin wax-embedded slides of the hippocampal CA1 region were stained with haematoxylin and eosin and lesions were assessed using a semiquantitative scoring system. Results: Seven animals of the 6 min group and six animals of the 8 min group gained restoration of spontaneous circulation and were included in histological analysis as well as all sham animals. All animals subjected to CA showed consistent lesions in the hippocampal CA1 region, while sham animals showed no damage. There were statistically significant differences between the sham group and both arrest groups. Furthermore, we found significantly more severe lesions in the 8 min group compared with the 6 min group. Conclusions: We were able to establish a rat model for CA causing consistent lesions in the hippocampal CA1 region. Eight min of CA will be used for further research regarding neuroprotective therapies.