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Ovine Model (ovine + model)

Distribution by Scientific Domains
Medical Sciences90%

Selected Abstracts

An Ovine Model of Chronic Heart Failure: Echocardiographic and Tissue Doppler Imaging Characterization

JOURNAL OF CARDIAC SURGERY, Issue 1 2006
M.Sc., Nicolas Borenstein D.V.M.
In order to validate novel surgical or pharmacological treatments, reproducible animal models of left ventricular dysfunction are necessary. In the current study, we report our data and experience with a model of toxin-induced heart failure in the sheep. Methods: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until standard echocardiographic and tissue Doppler imaging detection of myocardial systolic dysfunction. The animals were assessed 1 month later and harvested. Indices of cardiac function from baseline to last day of protocol were recorded and their differences were evaluated by a Wilcoxon rank test for paired data. Results: Ten sheep received 2.5 ± 0.7 intracoronary injections of a cumulative dose of 88.8 ± 25 mg/m2 doxorubicin. All available parameters demonstrated signs of severe cardiac dysfunction with statistical significance. All hearts demonstrated severe histological lesions, some of which were consistent with doxorubicin-induced toxicity. Conclusions: The present study shows that this ovine model is reproducible and stable. It can therefore be relevant to the study of chronic heart failure. It will be incorporated in our future studies concerning novel treatments (such as cell therapy) of nonischemic dilated cardiomyopathy. [source]

Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine Model

ALCOHOLISM, Issue 10 2007
Jayanth Ramadoss
Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. Methods: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. Results: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. Conclusions: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure. [source]

Implantation of One Piece Biventricular Assist Device by Left Thoracotomy in an Ovine Model

ARTIFICIAL ORGANS, Issue 9 2000
Won Gon Kim
Abstract: In this report, we describe an operative procedure for our implantable 1 piece biventricular assist device (BiVAD) based on a moving actuator mechanism, using an ovine model. Our implantable BiVAD is a volumetric coupled 1 piece unit including right and left blood sacs and an actuator assembly based on the moving actuator mechanism. The BiVAD was controlled by fixed rate control with 75 bpm for the most part. Both the left and the right full ejection modes with the maximum stroke angle were selected to minimize blood stasis in the blood sacs because of low assist flow condition. Three Corriedale sheep were used for the device implantation by a left thoracotomy incision. Cannulation was successfully performed in all cases. Although exposability of the right atrial appendage varied from animal to animal, the insertion of the cannula was easily performed. The cannulas were connected to the pump-actuator assembly in the preperitoneal pocket. All 3 animals survived the experimental procedure. During implantation of the device, in the 1 month survival animal, pump flow was maintained between 2.0 L/min and 2.5 L/min, mean aortic pressure was 90,110 mm Hg, and mean pulmonary artery pressure was 20,30 mm Hg. The left and right atrial pressure were maintained between 0 and 5 mm Hg. In conclusion, this ovine model for implantation of the 1 piece BiVAD can be an effective alternative for testing in vivo biocompatibility of the device although it needs more consideration for anatomical fittability for future human application. [source]

An Ovine Model of Chronic Heart Failure: Echocardiographic and Tissue Doppler Imaging Characterization

JOURNAL OF CARDIAC SURGERY, Issue 1 2006
M.Sc., Nicolas Borenstein D.V.M.
In order to validate novel surgical or pharmacological treatments, reproducible animal models of left ventricular dysfunction are necessary. In the current study, we report our data and experience with a model of toxin-induced heart failure in the sheep. Methods: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until standard echocardiographic and tissue Doppler imaging detection of myocardial systolic dysfunction. The animals were assessed 1 month later and harvested. Indices of cardiac function from baseline to last day of protocol were recorded and their differences were evaluated by a Wilcoxon rank test for paired data. Results: Ten sheep received 2.5 ± 0.7 intracoronary injections of a cumulative dose of 88.8 ± 25 mg/m2 doxorubicin. All available parameters demonstrated signs of severe cardiac dysfunction with statistical significance. All hearts demonstrated severe histological lesions, some of which were consistent with doxorubicin-induced toxicity. Conclusions: The present study shows that this ovine model is reproducible and stable. It can therefore be relevant to the study of chronic heart failure. It will be incorporated in our future studies concerning novel treatments (such as cell therapy) of nonischemic dilated cardiomyopathy. [source]

Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopy

JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008
C. W. Jones
Abstract The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig,<,0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:292,303, 2008 [source]

Temporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine Model

ALCOHOLISM, Issue 10 2007
Jayanth Ramadoss
Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. Methods: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. Results: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. Conclusions: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure. [source]

Implantation of One Piece Biventricular Assist Device by Left Thoracotomy in an Ovine Model

ARTIFICIAL ORGANS, Issue 9 2000
Won Gon Kim
Abstract: In this report, we describe an operative procedure for our implantable 1 piece biventricular assist device (BiVAD) based on a moving actuator mechanism, using an ovine model. Our implantable BiVAD is a volumetric coupled 1 piece unit including right and left blood sacs and an actuator assembly based on the moving actuator mechanism. The BiVAD was controlled by fixed rate control with 75 bpm for the most part. Both the left and the right full ejection modes with the maximum stroke angle were selected to minimize blood stasis in the blood sacs because of low assist flow condition. Three Corriedale sheep were used for the device implantation by a left thoracotomy incision. Cannulation was successfully performed in all cases. Although exposability of the right atrial appendage varied from animal to animal, the insertion of the cannula was easily performed. The cannulas were connected to the pump-actuator assembly in the preperitoneal pocket. All 3 animals survived the experimental procedure. During implantation of the device, in the 1 month survival animal, pump flow was maintained between 2.0 L/min and 2.5 L/min, mean aortic pressure was 90,110 mm Hg, and mean pulmonary artery pressure was 20,30 mm Hg. The left and right atrial pressure were maintained between 0 and 5 mm Hg. In conclusion, this ovine model for implantation of the 1 piece BiVAD can be an effective alternative for testing in vivo biocompatibility of the device although it needs more consideration for anatomical fittability for future human application. [source]

Use of biodegradable urethane-based adhesives to appose meniscal defect edges in an ovine model: a preliminary study

AUSTRALIAN VETERINARY JOURNAL, Issue 6 2008
JR FIELD
Objective To evaluate the biological response to two urethane-based adhesives used to repair full thickness meniscal wounds created in the partially vascularised (red-white) zone. Design An ovine bilateral meniscal defect model was used to evaluate the initial biological response of the meniscal cartilage and synovium over a 1-month period. A 10-mm full-thickness defect was created in the medial meniscus of each femorotibial joint. The defects were either left untreated or repaired using the urethane-based adhesives. Synovial fluid, synovial membrane and the meniscal cartilages were retrieved at necropsy for cytological and histological assessment. Results The ovine model proved to be a suitable system for examining meniscal repair. Untreated defects showed no tissue apposition or cellular healing response, whereas all eight defects repaired with the two urethane-based adhesive formulations showed signs of repair and tissue regeneration with indications of cell infiltration and new collagen deposition in and around the polymer. No adverse cellular response to the adhesives was observed in the meniscal defect or in the synovial membrane and fluid. Conclusion Trauma to the knee commonly results in tears to the meniscal cartilage, with the majority of these occurring in the partially vascularised (red-white) or non-vascularised (white) zones of the meniscus. Repair, and subsequent healing, of these tears is poor because of the reduced vascularity and limited surgical access. The present data indicate that an ovine model is a suitable system for examining meniscal repair, and that development of urethane-based adhesives offers a strategy that may be clinically effective for the treatment of these injuries. [source]

A possible pharmacological explanation for quinacrine failure to treat prion diseases: pharmacokinetic investigations in a ovine model of scrapie

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2005
Véronique Gayrard
1Quinacrine was reported to have a marked in vitro antiprion action in mouse neuroblastoma cells. On compassionate grounds, quinacrine was administered to Creutzfeldt,Jakob disease patients, despite the absence of preclinical in vivo studies to evaluate efficacy. Quinacrine failed to provide therapeutic benefit. The aim of the study was to investigate possible pharmacokinetic and/or pharmacodynamic explanations for the discrepancy between the proven action of quinacrine in vitro and its lack of clinical efficacy. 2We conducted in vitro experiments reproducing the culture conditions in which antiprion effects had been previously observed and recalculated the EC50 by determining the actual extracellular (120 nM) and intracellular (6713 nM) quinacrine neuroblastoma concentrations with the reported quinacrine EC50 (300 nM). 3A randomized clinical trial in scrapie-affected ewes confirmed the absence of therapeutic benefit of quinacrine. The in vivo quinacrine exposure was evaluated in a pharmacokinetic investigation in healthy ewes. Cerebrospinal fluid concentrations (<10.6 and 55 nM after administration of therapeutic and toxic quinacrine doses, respectively) were much lower than the quinacrine extracellular neuroblastoma concentrations corresponding to the reported EC50. The total brain tissue concentrations (3556 nM) obtained after a repeated therapeutic dosage regimen were within the range of the intracellular neuroblastoma quinacrine concentrations. 4In conclusion, in order to avoid in vivo trials for which failure can be predicted, the measurement in vitro of the antiprion EC50 in both intra- and extracellular biophases should be determined. It can then be established if these in vitro antiprion concentrations are achievable in vivo. British Journal of Pharmacology (2005) 144, 386,393. doi:10.1038/sj.bjp.0706072 [source]