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Cardiovascular Histopathological Changes Associated with Chronically-Implanted Blood Pressure Telemetry Devices in Mice
J. Comp. Path. 2017, Vol. 156, 54e141
ESVP and ECVP Proceedings 2016
CARDIOVASCULAR HISTOPATHOLOGICAL CHANGES ASSOCIATED WITH CHRONICALLY-IMPLANTED BLOOD PRESSURE TELEMETRY DEVICES IN MICE G. Pellegrini *, P. Seebeck y, A. Marowsky z, K. Mitchell x, C. Schwarzwald x,{ and A. Kipar* *Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, yZurich Integrative Rodent Physiology, University of Zurich, zInstitute of Pharmacology and Toxicology, University of Zurich, xClinic for Equine Internal Medicine, Equine Department, Vetsuisse Faculty, University of Zurich and {Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland Introduction: Radiotelemetry offers continuous long-term blood pressure measurement in conscious, freely moving animals and thus is the gold standard for blood pressure analysis in rodents. This work presents the histopathological changes that can be induced by blood pressure catheters. Materials and Methods: As part of the phenotypic assessment of the microsomal epoxide hydrolase (mEH) gene manipulation, twenty 3-month-old male C57BL/6 mice (wild type, knock-out and knock-in mice for mEH) were implanted with pressure sensing catheters into the left carotid artery and, 8 weeks post surgery, underwent ultrasonographical examination before being killed and subjected to a thorough post-mortem analysis with particular emphasis on the cardiovascular system. Results: Ultrasound examination demonstrated obvious turbulence within the blood flow of the aortic arch in all animals, regardless of the genotype. Indeed, the tip of the catheter occasionally struck the aortic wall as a result of pulsation during the cardiac cycle. In the majority of animals, the post-mortem examination revealed focal proliferative lesions (i.e. increased wall thickness, cartilage metaplasia and intimal proliferation) of variable severity in the aortic arch; this was associated with partial luminal occlusion and thrombosis. Conclusions: Our study provides strong evidence that implanted pressure sensing catheters frequently induce vascular changes. Without appropriate sham-operated controls and an alternative simultaneous way to measure blood pressure, it is impossible to assess the extent to which these lesions influence pressure measurements. However, our results suggest that telemetry blood pressure recordings in mice should be interpreted with caution and always in association with the results of the histological assessment.
85
AORTOCARDIAC FISTULA IN A WARMBLOOD STALLION V. Saey *, G. van Loon y, A. Dufourni y, R. Ducatelle * and K. Chiers* *Department of Pathology, Bacteriology and Avian Medicine, Merelbeke and y Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Introduction: A 19-year-old Grand Prix dressage horse was admitted to the hospital with a history of colic, tachycardia, jugular pulsation, sweating and peripheral oedema. A right-sided pansystolic and early mid-diastolic 3/6 murmur was noticed and electrocardiography revealed paroxysmal monomorphic ventricular tachycardia (140/min) and atrial fibrillation. After anti-arrhythmic treatment the general condition improved, but the horse suddenly died in the stable, 14 days after initial presentation. Materials and Methods: Full post-mortem examination and histology were performed. Results: Necropsy examination revealed cardiomegaly with multifocal subendocardial fibrosis in both the left and right sides of the heart. An aortocardiac fistula was present between the right aortic sinus of Valsalva and the right ventricle. The ruptured right sinus of Valsalva, but also the non-ruptured non-coronary sinus, showed an aneurysmal dilation. The aneurysmal sinus wall consisted of dense fibrous tissue with loss of smooth muscle cells and elastin fibres. Conclusions: In horses, but also in human patients, the right coronary sinus is the most common site to dilate or to tear with rupture into the right atrium or ventricle. These coronary sinus aneurysms are considered to be congenital in man with a predisposition for males. A congenital weakness in the wall of the sinus of Valsalva, as seen in man, seems unlikely in our horse as a lack of continuity between aortic media and aortic annulus was not noticed. Further research is needed to elucidate the pathogenesis of this rare, but often fatal disease in horses.
ESVP and ECVP Proceedings 2016
CARDIOVASCULAR HISTOPATHOLOGICAL CHANGES ASSOCIATED WITH CHRONICALLY-IMPLANTED BLOOD PRESSURE TELEMETRY DEVICES IN MICE G. Pellegrini *, P. Seebeck y, A. Marowsky z, K. Mitchell x, C. Schwarzwald x,{ and A. Kipar* *Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, yZurich Integrative Rodent Physiology, University of Zurich, zInstitute of Pharmacology and Toxicology, University of Zurich, xClinic for Equine Internal Medicine, Equine Department, Vetsuisse Faculty, University of Zurich and {Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland Introduction: Radiotelemetry offers continuous long-term blood pressure measurement in conscious, freely moving animals and thus is the gold standard for blood pressure analysis in rodents. This work presents the histopathological changes that can be induced by blood pressure catheters. Materials and Methods: As part of the phenotypic assessment of the microsomal epoxide hydrolase (mEH) gene manipulation, twenty 3-month-old male C57BL/6 mice (wild type, knock-out and knock-in mice for mEH) were implanted with pressure sensing catheters into the left carotid artery and, 8 weeks post surgery, underwent ultrasonographical examination before being killed and subjected to a thorough post-mortem analysis with particular emphasis on the cardiovascular system. Results: Ultrasound examination demonstrated obvious turbulence within the blood flow of the aortic arch in all animals, regardless of the genotype. Indeed, the tip of the catheter occasionally struck the aortic wall as a result of pulsation during the cardiac cycle. In the majority of animals, the post-mortem examination revealed focal proliferative lesions (i.e. increased wall thickness, cartilage metaplasia and intimal proliferation) of variable severity in the aortic arch; this was associated with partial luminal occlusion and thrombosis. Conclusions: Our study provides strong evidence that implanted pressure sensing catheters frequently induce vascular changes. Without appropriate sham-operated controls and an alternative simultaneous way to measure blood pressure, it is impossible to assess the extent to which these lesions influence pressure measurements. However, our results suggest that telemetry blood pressure recordings in mice should be interpreted with caution and always in association with the results of the histological assessment.
85
AORTOCARDIAC FISTULA IN A WARMBLOOD STALLION V. Saey *, G. van Loon y, A. Dufourni y, R. Ducatelle * and K. Chiers* *Department of Pathology, Bacteriology and Avian Medicine, Merelbeke and y Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium Introduction: A 19-year-old Grand Prix dressage horse was admitted to the hospital with a history of colic, tachycardia, jugular pulsation, sweating and peripheral oedema. A right-sided pansystolic and early mid-diastolic 3/6 murmur was noticed and electrocardiography revealed paroxysmal monomorphic ventricular tachycardia (140/min) and atrial fibrillation. After anti-arrhythmic treatment the general condition improved, but the horse suddenly died in the stable, 14 days after initial presentation. Materials and Methods: Full post-mortem examination and histology were performed. Results: Necropsy examination revealed cardiomegaly with multifocal subendocardial fibrosis in both the left and right sides of the heart. An aortocardiac fistula was present between the right aortic sinus of Valsalva and the right ventricle. The ruptured right sinus of Valsalva, but also the non-ruptured non-coronary sinus, showed an aneurysmal dilation. The aneurysmal sinus wall consisted of dense fibrous tissue with loss of smooth muscle cells and elastin fibres. Conclusions: In horses, but also in human patients, the right coronary sinus is the most common site to dilate or to tear with rupture into the right atrium or ventricle. These coronary sinus aneurysms are considered to be congenital in man with a predisposition for males. A congenital weakness in the wall of the sinus of Valsalva, as seen in man, seems unlikely in our horse as a lack of continuity between aortic media and aortic annulus was not noticed. Further research is needed to elucidate the pathogenesis of this rare, but often fatal disease in horses.