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Sheep Model (sheep + model)
Selected AbstractsA Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRIEPILEPSIA, Issue 8 2002Helen I. Opdam Summary: ,Purpose: We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI). Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000,10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level,dependent (BOLD) weighted signal intensity at different times during the evolution of seizures. Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala. Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico,subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain. [source] Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep ModelPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2001RIK WILLEMS WILLEMS, R. et al.: Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep Model. In different animal models rapid atrial stimulation led to a shortening and maladaptation to rate of the atrial effective refractory period (AERP). This atrial electrical remodeling resulted in an increased vulnerability to atrial fibrillation (AF). These experimental findings formed the rationale for a stringent pursuit of sinus rhythm in patients with AF, since this would prevent or reverse atrial remodeling. This study tested the hypothesis that a reduction of arrhythmia burden would lead to a decreased vulnerability for AF. Different rapid atrial pacing protocols in a sheep model were used. During 15 weeks, 13 animals were continuously rapid paced and 7 animals were intermittently burst-paced, resulting in rapid atrial activation during 100% versus 33 ± 4% of the time, respectively. In the continuously paced group, 77% of the animals developed sustained AF (i.e., >1 hour) versus only 29% in the burst-paced group (P < 0.05). However, there was no difference in mean AERP shortening over time, nor maximal AERP shortening per animal, between both protocols. Minimal AERP was 103 ± 5 ms in the continuously paced group and 107 ± 5 in the burst-paced group (P = NS). Significant changes could be identified in effect on P wave duration, AVN function, and atrial dilation. Conduction slowing was more pronounced in the continuously paced group with a maximal P wave duration of 136 ± 4 ms in this group versus 116 ± 5 in the burst-paced group (P < 0.05). In the continuously paced group, the right atrial area significantly increased from 2.5 ± 0.1 cm2 at baseline to 4.2 ± 0.2 cm2. In the burst-paced group there was no significant atrial dilatation (from 2.6 ± 0.1 to 2.8 ± 0.1 cm2). In conclusion, limiting atrial arrhythmia burden slowed the development of sustained AF in this sheep model. This was not mediated by a decreased influence on atrial refractoriness but seemed to be dependent on smaller changes in atrial conduction and dimensions. [source] A Sheep Model for the Study of Focal Epilepsy with Concurrent Intracranial EEG and Functional MRIEPILEPSIA, Issue 8 2002Helen I. Opdam Summary: ,Purpose: We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI). Methods: Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000,10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level,dependent (BOLD) weighted signal intensity at different times during the evolution of seizures. Results: Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 ± 11.2 s and 17.3 ± 12.1 min after penicillin administration, respectively. An average of 13 ± 4.8 seizures were seen per animal, each lasting 27.3 ± 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala. Conclusions: We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico,subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain. [source] Reduction in Atrial Defibrillation Threshold by a Single Linear Ablation LesionJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2001JAMES B. WHITE Ph.D. Single Lesion Lowers ADFT.Introduction: This study investigated a hybrid approach to reduce the atrial defibrillation threshold (ADFT) by determining the effect of a single linear radiofrequency ablation (RFA) lesion on both the ADFT and activation patterns during atrial fibrillation (AF). Methods and Results: In 18 open chest sheep (45 to 57 kg), coil defibrillation electrodes were placed in a superior vena cava/right ventricular configuration. AF was induced by burst pacing and maintained with acetyl ,-methylcholine (2 to 42 ,L/min). ADFTs were obtained before and after a linear RFA lesion was created in the left atrium (LAL; n = 6), right atrium (RAL; n = 6), or neither atrium as a control (n = 6). In animals receiving an LAL, a 504-unipolar-electrode plaque was sutured to the LA. For animals receiving an RAL, two 504-electrode plaques were placed, one each on the LA and RA. From each plaque, activations were recorded before and after ADFT shocks, and organizational characteristics of activations were analyzed using algorithms that track individual wavefronts. In sham-treated controls, the ADFT did not change. In contrast, LAL reduced ADFT energy 29%, from 4.5 ± 2.3 J to 3.2 ± 2.0 J (P < 0.05). RAL reduced ADFT energy 25%, from 2.0 ± 0.9 J to 1.5 ± 0.7 J (P < 0.05). AF activation was substantially more organized after RFA than before RFA for both the RAL- and LAL-treated animals. Conclusion: A single RFA lesion in either the RA or LA reduces the ADFT in this sheep model. This decrease is associated with an increase in fibrillatory organization. [source] Percutaneous Treatment for Mitral Regurgitation: The QuantumCor SystemJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2008RICHARD R. HEUSER M.D. Aims:Percutaneous edge-to-edge techniques and annuloplasty have been used to treat mitral regurgitation (MR). However, neither intervention can be performed reliably a second time and, with annuloplasty, a foreign body is left behind. The mitral and tricuspid annuli are areas of dense collagen (Fig. 1); treatment with radiofrequency (RF) energy in sheep reduces their size, and can be repeated without affecting the coronary sinus. RF energy may also be used in leaflet procedures. Our aim was to improve mitral valve competence using techniques that can be incorporated into a minimally invasive approach. Figure 1. This trichrome stain slide shows the amount of collagen present in the mitral annulus (in green). Methods:In open-heart procedures in 16 healthy sheep (6 with naturally occurring MR), we used a malleable probe (QuantumCor, Inc., Lake Forest, CA) that conforms to the annular shape to deliver RF energy via a standard generator to replicate a surgical mitral annular ring. Four segments of the posterior mitral valve annulus were treated while on cardiopulmonary support via a left thoracotomy with access via the atrial appendage. Seven sheep were followed chronically. Results:All sheep underwent intracardiac echocardiography (ICE) or direct circumferential measurement of the mitral annulus before and after RF therapy. RF therapy was administered in less than 4 minutes in each case, and the mean anteroposterior (AP) annular distance was reduced by a mean of 5.75 ± 0.86 mm (23.8% reduction, P< 0.001). In the 6 sheep with nonischemic MR, regurgitation was eliminated. Acute histopathology (HP) demonstrated no damage to the leaflets, coronary sinuses, or coronary arteries. At 30 days, the AP distance continued to be reduced in the 7 surviving sheep (mean 5.0 ± .6 mm, 21.4% reduction, P< 0.001). Conclusions:In a sheep model, RF energy applied for less than 4 minutes per case at subablative temperatures in four quadrants of the posterior mitral valve annulus reduced the AP and circumferential annular distances significantly, and eliminated nonischemic MR. Results will need to be confirmed in follow-up studies to determine safety and efficacy. RF energy administered as a novel, percutaneous method of mitral valve annuloplasty may have the potential to reduce morbidity and mortality associated with current surgical techniques. [source] Evidence That Gonadotropin-Releasing Hormone II Is Not a Physiological Regulator of Gonadotropin Secretion in MammalsJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2003P. M. Gault Abstract Gonadotropin-releasing hormone (GnRH)-II stimulates luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion when administered at high doses in mammals, and this effect has been assumed to be mediated through the GnRH-II receptor expressed on gonadotropes. This study used two selective GnRH-I receptor antagonists to test the alternative hypothesis that GnRH-II acts through the GnRH-I receptor to elicit gonadotropin secretion. The antagonist, antide, was used to characterize the receptor-relay because it was a pure antagonist in vitro based on inositol phosphate responses in COS-7 cells transfected with either mammalian GnRH-I and GnRH-II receptors and, in vivo, potently antagonized the gonadotropin-releasing effect of a single injection of 250 ng GnRH-I in our sexually inactive sheep model. In a series of studies in sheep, antide (i) blocked the acute LH response to a single injection of GnRH-II (20 µg antide: 10 µg GnRH-II); (ii) blocked both the acute, pulsatile LH response and the FSH priming response to 2-hourly injections of GnRH-II over 36 h (100 µg antide/8 h: 4 µg GnRH-II/2 h); and (iii) chronically blocked both the pulsatile LH response and the marked FSH priming response to 4-hourly injections of GnRH-II over 10 days (75 µg antide/8 h: 4 µg GnRH-II/4 h). In two final experiments, the GnRH-I antagonist 135-18, shown previously to agonize the mammalian GnRH-II receptor, blocked the gonadotropin-releasing effects of GnRH-I (250 ng) but failed to elicit an LH response when given alone, and simultaneous administration of GnRH-II (250 ng) failed to alter the LH-releasing effect of GnRH-I (50,500 ng). These data thus support our hypothesis. Based on additional literature, it is unlikely that the GnRH-II decapeptide is a native regulator of the gonadotrope in mammals. [source] Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008C. 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] A pathomechanical concept explains muscle loss and fatty muscular changes following surgical tendon releaseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Dominik C. Meyer Abstract Following tendon tear, the musculo-tendinous unit retracts permanently, looses muscle fibre volume and is infiltrated with fat. This is currently considered to be an unexplained degenerative process. In a sheep model of chronic tendon tear with delayed tendon repair (35 weeks after tendon release), we studied the nature of these muscle changes in eight experimental animals. At sacrifice (75 weeks after tendon release) the muscle had retracted by 1.7±0.5 cm (9% of entire length, P < 0.0001), the pennation angle had increased from 22±2.5° to 50±11° (P < 0.0001) and the mean muscle fibre length had shortened from 32±3 to 16±5 mm (50%, P < 0.0001). In electron and light microscopy, we found essentially normal muscle fibres with an unaltered fibre diameter and myofibrillar structure, while interstitial fat and fibrous tissue had increased from 3.9% to 45.9% (P < 0.0001) of the muscle volume. Geometric modelling showed that the increase of the pennation angle separates the muscle fibre bundles mechanically like limbs of a parallelogram. Infiltrating fat cells fill the created space between the reoriented muscle fibres which may be quantitatively calculated without affecting the structural properties of the muscle cells. Fatty infiltration is therefore not seen as a degenerative process but a necessary rearrangement of the tissue after macroarchitectural changes caused by musculo-tendinous retraction. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] The use of OP-1 in femoral impaction grafting in a sheep modelJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Margaret A. McGee Abstract The aim of this pilot study was to examine bone graft incorporation in femurs impacted with allograft bone alone (control group) or with allograft containing the bone morphogenetic protein OP-1 (BMP-7) (OP-1 group) in a sheep model of cemented hemiar-throplasty. Two sheep in each group were sacrificed at 6, 18 and 26 weeks. Successful bone graft incorporation was evident in both groups by six weeks but in the OP-1 group, there had been more extensive resorption of the graft. There was one case of excessive stem subsidence in the OP-1 group at six weeks. By 18 weeks, there was remodelling and trabeculation of the new bone in the OP-1 group, but this appeared less advanced in the control group. By 26 weeks, there was remodelling of bone in the graft bed. The results of this small study suggest that OP-1 promotes initial graft resorption, thus hastening bone graft incorporation and remodelling in femoral impaction grafting. The one case of stem subsidence may be associated with the early resorption seen in the OP-1 group and reinforces the need for further studies, examining dose response and using precise measures of stem movement, before this BMP is used in femoral impaction grafting at revision hip arthroplasty. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Biomechanical evaluation of healing in a non-critical defect in a large animal model of osteoporosisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2003C. A. Lill Abstract Current methods for fracture treatment in osteoporosis are not always sufficient. To develop new fixation strategies (both mechanical and biological) requires pre-clinical testing utilizing appropriate models. The aim of this study was to apply a recently developed sheep model of osteoporosis to the study of healing in a non-critical long bone defect. A standardized transverse mid-shaft tibial osteotomy (with a fracture gap of 3 mm) was performed in seven osteoporotic and seven normal sheep and stabilized with a special external fixator for 8 weeks. The fixator was used for weekly in vivo bending stiffness measurements. Ex vivo bending stiffness and torsional stiffness of the callus zone were also determined. Callus area, callus density, and osteoporosis status were determined at 0, 4, and 8 weeks using peripheral quantitative computed tomography. The increase of in vivo bending stiffness of the callus was delayed approximately 2 weeks in osteoporotic animals. A significant difference (33%) in torsional stiffness was found between the osteotomized and contralateral intact tibia in osteoporotic animals, but no significant difference occurred in normal sheep (2%). In osteoporotic animals, ex vivo bending stiffness was reduced 21% (p = 0.05). Bending stiffness was correlated with callus density (r = 0.76, r = 0.53); torsional stiffness was correlated with callus area (r = 0.60) and to a lesser extent with callus density (r = 0.53). This study demonstrated a delay of fracture healing in osteoporotic sheep tibiae with respect to callus formation, mineralization, and mechanical properties. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Effect of chitosan on the intranasal absorption of salmon calcitonin in sheepJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2005Michael Hinchcliffe The effects of a chitosan-based delivery system on the pharmacokinetics of intranasally administered salmon calcitonin (sCT) were investigated in a sheep model. In particular, the feasibility of producing a formulation with a comparable or improved bioavailability and/or less variability than the currently marketed nasal product (Miacalcin nasal spray, Novartis Pharmaceuticals) was assessed. A comparator (control) formulation comprising sCT solution was also tested. Sheep (n = 6) were dosed intranasally according to a randomized crossover design. The intranasal sCT dose was 1100 IU (equivalent to approximately 17 IU kg,1). After completion of the nasal dosing legs, five of the sheep received 300 IU sCT (equivalent to approximately 5 IU kg,1) by subcutaneous injection to estimate relative bioavailability. After intranasal or subcutaneous dosing, serial blood samples were taken and plasma separated by centrifugation before measuring sCT concentrations by ELISA. Pharmacokinetic (non-compartmental) and statistical (analysis of variance or non-parametric alternative) analyses were performed. No systemic or local adverse effects were observed following intranasal or subcutaneous administration of sCT. The mean relative bioavailability of sCT from the chitosan solution was improved twofold compared with Miacalcin nasal spray and threefold compared with sCT control solution. Inter-animal variability in sCT absorption appeared to be lower with use of the chitosan-based solution compared with the control solution or commercial product. Based on the reported sheep data, a chitosan delivery system could offer the potential to significantly improve the intranasal absorption of sCT and reduce the variability in absorption. In the clinical setting, this may allow relatively lower doses of the drug to be given intranasally and/or lead to improvements in the efficacy or quality of intranasal therapy. [source] Variant Creutzfeldt,Jakob disease and its transmission by bloodJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2003J. W. Ironside Summary., Variant Creutzfeldt,Jakob disease (vCJD) is a novel acquired human prion disease resulting from human exposure to the agent causing bovine spongiform encephalopathy (BSE). vCJD differs from all other human prion diseases in that the disease-associated form of the prion protein and infectivity are present in lymphoid tissues throughout the body. Lymphoid tissues and lymphocytes are implicated in the peripheral pathogenesis of prion diseases (where infectivity may be detected during the preclinical phase of the illness), giving rise to concerns that blood and blood products may also contain infectivity, thus representing a possible source of iatrogenic spread of vCJD. These concerns have been reinforced by the recent transmission of BSE in an experimental sheep model by blood transfusion from an infected animal in the preclinical phase of the illness. Studies in other animal models suggest that most infectivity in blood may be cell-associated, with lower levels in the plasma, and there is evidence to indicate that any infectivity present may be reduced during the process of plasma fractionation. At present, the attempts to detect disease-associated prion protein and infectivity in buffy coat from vCJD patients have been negative, but these studies have been limited in size and in the sensitivity of the detection systems employed. Further studies are required to develop more sensitive means of detection of disease-associated prion protein in blood; such techniques could also be employed for screening purposes, both individually and to help ascertain more precisely the likely numbers of future cases of vCJD. [source] Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ1H-MRS of the brainNMR IN BIOMEDICINE, Issue 3 2005Eva Scheurer Abstract Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915,920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250,h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs. Copyright © 2004 John Wiley & Sons, Ltd. [source] Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep ModelPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2001RIK WILLEMS WILLEMS, R. et al.: Effect of Different Pacing Protocols on the Induction of Atrial Fibrillation in a Transvenously Paced Sheep Model. In different animal models rapid atrial stimulation led to a shortening and maladaptation to rate of the atrial effective refractory period (AERP). This atrial electrical remodeling resulted in an increased vulnerability to atrial fibrillation (AF). These experimental findings formed the rationale for a stringent pursuit of sinus rhythm in patients with AF, since this would prevent or reverse atrial remodeling. This study tested the hypothesis that a reduction of arrhythmia burden would lead to a decreased vulnerability for AF. Different rapid atrial pacing protocols in a sheep model were used. During 15 weeks, 13 animals were continuously rapid paced and 7 animals were intermittently burst-paced, resulting in rapid atrial activation during 100% versus 33 ± 4% of the time, respectively. In the continuously paced group, 77% of the animals developed sustained AF (i.e., >1 hour) versus only 29% in the burst-paced group (P < 0.05). However, there was no difference in mean AERP shortening over time, nor maximal AERP shortening per animal, between both protocols. Minimal AERP was 103 ± 5 ms in the continuously paced group and 107 ± 5 in the burst-paced group (P = NS). Significant changes could be identified in effect on P wave duration, AVN function, and atrial dilation. Conduction slowing was more pronounced in the continuously paced group with a maximal P wave duration of 136 ± 4 ms in this group versus 116 ± 5 in the burst-paced group (P < 0.05). In the continuously paced group, the right atrial area significantly increased from 2.5 ± 0.1 cm2 at baseline to 4.2 ± 0.2 cm2. In the burst-paced group there was no significant atrial dilatation (from 2.6 ± 0.1 to 2.8 ± 0.1 cm2). In conclusion, limiting atrial arrhythmia burden slowed the development of sustained AF in this sheep model. This was not mediated by a decreased influence on atrial refractoriness but seemed to be dependent on smaller changes in atrial conduction and dimensions. [source] Computer-assisted navigation applied to fetal cardiac interventionTHE INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY, Issue 3 2007Stephen P. Emery Abstract Background Prenatal cardiac interventions (PCI) for human fetal aortic valve (AoV) stenosis can reduce left ventricular hypoplasia and restore ventricular growth and function. However, ,freehand' needle delivery from the maternal skin through the uterine wall, fetal chest and ventricular apex to cross the fetal AoV remains technically challenging and time intensive, and is the rate-limiting step in the procedure. Methods We developed a computer-assisted navigation (CANav) system that tracks the position and orientation of a two-dimensional (2D) ultrasound image relative to the trajectory of an electromagnetic (EM) embedded needle and stylet. We tested the CANav system in vitro using a water bath phantom, then in vivo using adult rats and pregnant (fetal) sheep. Results The CANav system accurately tracked the delivered needle position in both in vitro phantom and adult rat model experiments. We performed 22 PCI attempts with or without CANav in a fetal sheep model. Maternal laparotomy was required to adjust the fetal position in 50% of the procedures. The time required to deliver the needle from the skin into the left ventricle (LV) using CANav was 2.9 ± 1.7 (range 2,7) min (n = 14) vs. 5.5 ± 4.3 (range 1,12) min (n = 8) without CANav (p < 0.05). The time needed to cross the aortic valve once the needle was within the LV was similar with and without CANav (p = 0.19). Conclusions CANav reduces the PCI time required to accurately deliver a needle to the fetal heart. Adaptations of this technical approach may be relevant to other congenital cardiac conditions and ultrasound-guided medical procedures. Copyright © 2007 John Wiley & Sons, Ltd. [source] AMP-activated protein kinase signalling pathways are down regulated and skeletal muscle development impaired in fetuses of obese, over-nourished sheepTHE JOURNAL OF PHYSIOLOGY, Issue 10 2008Mei J. Zhu Maternal obesity and over-nutrition give rise to both obstetric problems and neonatal morbidity. The objective of this study was to evaluate effects of maternal obesity and over-nutrition on signalling of the AMP-activated protein kinase (AMPK) pathway in fetal skeletal muscle in an obese pregnant sheep model. Non-pregnant ewes were assigned to a control group (Con, fed 100% of NRC nutrient recommendations, n= 7) or obesogenic group (OB, fed 150% of National Research Council (NRC) recommendations, n= 7) diet from 60 days before to 75 days after conception (term 150 days) when fetal semitendinosus skeletal muscle (St) was sampled. OB mothers developed severe obesity accompanied by higher maternal and fetal plasma glucose and insulin levels. In fetal St, activity of phosphoinositide-3 kinase (PI3K) associated with insulin receptor substrate-1 (IRS-1) was attenuated (P < 0.05), in agreement with the increased phophorylation of IRS-1 at serine 1011. Phosphorylation of AMP-activated protein kinase (AMPK) at Thr 172, acetyl-CoA carboxylase at Ser 79, tuberous sclerosis 2 at Thr 1462 and eukaryotic translation initiation factor 4E-binding protein 1 at Thr 37/46 were reduced in OB compared to Con fetal St. No difference in energy status (AMP/ATP ratio) was observed. The expression of protein phosphatase 2C was increased in OB compared to Con fetal St. Plasma tumour necrosis factor , (TNF,) was increased in OB fetuses indicating an increased inflammatory state. Expression of peroxisome proliferator-activated receptor , (PPAR,) was higher in OB St, indicating enhanced adipogenesis. The glutathione: glutathione disulphide ratio was also lower, showing increased oxidative stress in OB fetal St. In summary, we have demonstrated decreased signalling of the AMPK system in skeletal muscle of fetuses of OB mothers, which may play a role in altered muscle development and development of insulin resistance in the offspring. [source] Percutaneous implantation of an aortic valve prosthesisCATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 2 2005J.C. Laborde MD Abstract Recently, percutaneous aortic valve implantation has become an alternative technique to surgical valve replacement in patient at high risk for surgery. Our animal experimentation evaluated the technical feasibility of aortic valve replacement using a bovine pericardium valve sutured on a self-expandable stent in a sheep model. Precise implantation with satisfactory attachment on the adjacent tissues and absence of migration was obtain in 8 out of 14 animals. This study confirmed the feasibility of the endovascular implantation of a pericardium valve sutured on a self-expandable stent in a sheep model. © 2005 Wiley-Liss, Inc. [source] Is Prenatal Glucocorticoid Administration Another Origin Of Adult Disease?CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001John P Newnham SUMMARY 1. The intra-uterine environment is now believed to play a major role in the origin of many adult diseases. Illnesses in which there is significant ,programming' before the time of birth include hypertension, diabetes, coronary heart disease and stroke. Acting on a genetic predisposition, intra-uterine triggers appear to programme the individual's metabolism and endocrine milieu and, after birth, these risk factors are then either amplified or minimized by environmental influences. The triggers operative during fetal life that have been studied most extensively are undernutrition and glucocorticoid exposure. 2. Over the past decade, a series of studies in sheep have focused on the perinatal and life-long consequences of glucocorticoid exposure in mid- to late-pregnancy. These studies in the sheep model have shown that maternal injections with glucocorticoids, in a manner similar to clinical treatment for women at risk of preterm birth, enhance fetal lung maturation, but were also associated with developmental and other functional alterations that are of concern. With weekly doses to the mother, there is restricted fetal growth, delayed myelination of the central nervous system, altered blood pressure soon after birth and increased insulin response to glucose challenge in early adulthood. If the glucocorticoids are given to the fetus by ultrasound-guided intramuscular injection, rather than to the mother, the effects on lung maturation are similar, but growth is spared and blood pressure after birth is unaltered. Increased insulin response to glucose challenge occurs in early adulthood with glucocorticoid by either route and is independent of growth restriction. 3. The findings in experimental animals are supported by studies of children in the Western Australian Preterm Infant Follow-up Study. Multivariate analyses have shown that increasing the number of glucocorticoid exposures, for the purpose of enhancing lung maturation prior to preterm birth, is associated with reduced birthweight and behavioural disorders at 3 years of age. 4. The results of these animal and clinical studies provide further support for a role of prenatal glucocorticoid exposure in triggering predisposition to adult disease. Further exploration of these models is expected to uncover the mechanisms and lead to effective strategies that may underpin clinical interventions. [source] Biodegradable polylactide membranes for bone defect coverage: biocompatibility testing, radiological and histological evaluation in a sheep modelCLINICAL ORAL IMPLANTS RESEARCH, Issue 4 2006Gerhard Schmidmaier Abstract: Large bony defects often show a delayed healing and have an increasing risk of infection. Several materials are used for the coverage of large defects. These materials must be biocompatible, easy to use, and must have an appropriate stability to present a mechanical hindrance. Aim of this study was to investigate two different biodegradable membranes for defect coverage in a sheep model. Round cranial defects (1.5 cm diameter) were created in sheep. Six different treatments were investigated: defects without membrane, defects covered with a poly(d,l -lactide) or with a 70/30 poly(l/d,l -lactide) membrane and all defects with or without spongiosa filling. The sheep were sacrificed 12 or 24 weeks postoperatively. Bone formation in the defects was quantified by computer-assisted measurements of the area of the residual defect on CT radiographs. Histomorphometry and host-tissue response were evaluated by light microscopy. The biocompatibility was investigated by analyzing the amount of osteoclasts and foreign body cells. Both membranes served as a mechanical hindrance to prevent the prolapse of soft tissue into the defect. The biocompatibility test revealed no differences in the amount and distribution of osteoclasts at the two investigated time points and between the investigated groups. No negative effect on the tissue regeneration was detectable between the investigated groups related to the type of membrane, but a foreign body reaction around the two membrane types was observed. In the membrane-covered defects, the spongiosa showed a progressing remodeling to the native bony structure of the cranium. The groups without spongiosa partly revealed new bone formation, without complete bridging in any group or at any time point. Comparing the 12 and 24 weeks groups, an increased bone formation was detectable at the later time point. In conclusion, the results of the present in vivo study reveal a good biocompatibility and prevention of soft tissue prolapse of the two used membranes without differences between the membranes. An enhanced remodeling of the spongiosa into native bony structures under the membranes was detectable, but no osteopromoting effect was observed due to the membranes. [source] The effect of three different calcium phosphate implant coatings on bone deposition and coating resorption: a long-term histological study in sheepCLINICAL ORAL IMPLANTS RESEARCH, Issue 3 2005Christian Schopper Abstract: The present study investigated the hypothesis that hydroxyapatite (HA), tricalcium phosphate (TCP), and a HA-gel coated on endosseous titanium (Ti) implants by spark discharging (SD) and dip coating would achieve predictable osseointegration without evident bioresorption of the coatings on the long term. A costal sheep model was used for the implantation of the HA/SD, HA/TCP/SD, and HA-gel/SD specimens, which were retrieved 6 and 12 months following implantation. HA and Ti coatings on implants obtained by conventional plasma spraying (HA/PS, Ti/PS) were used as controls. Microscopy showed that osseointegration was achieved from all types of implants. No evidence for bioresorption of the HA/SD, HA/TCP/SD, and HA-gel/SD coatings was present but cohesive failure with disruption of the coating/implant interface was seen. A statistical analysis of the histomorphometrical data showed no time-dependent effect, however. HA/PS coatings achieved significantly higher bone,implant contact (BIC) percentages of the total implant surface (toBIC) than the other types of coatings (P=0.01). If the BIC percentages were traced separately for implant portions placed into cortical and cancellous bone (coBIC and caBIC, respectively), detailed analysis showed that the caBIC values of HA-gel/SD and HA/PS coatings were significantly higher than that of the other types of coatings (P=0.01). CaBIC values were highly correlated with toBIC values (P<0.001). The present study showed that the preparation techniques used produced thin, dense, and unresorbable coatings that achieved osseointegration. Compared with the control coatings, however, only HA-gel/SD coating can be recommended from the investigated preparation techniques for a future clinical use if a better coating cohesion is achieved. Résumé L'étude présente a étudié l'hypothèse que le recouvrement par de l'hydroxyapatite, du phosphate tricalcique et un gel d'hydroxyapatite sur les implants en titane par décharges spark et recouvrement par trempage pourrait apporter une ostéïntégration prévisible sans biorésorption importante des recouvrements à long terme. Un modèle de mouton a été utilisé pour l'implantation de spécimens HA/SD, HA/TCP/SD et gel-HA/SD qui ont été enlevés six et douze mois après leur insertion. Les implants recouverts d'hydroxyapatite et de titane obtenus par plasma-spray conventionnel (HA/PS et Ti/PS) ont été utilisés comme contrôles. La microscopie a montré que l'ostéoïntégration a été réalisée pour tous les types d'implants. Aucune évidence pour la biorésorption de HA/SD, HATCP/SD, et gel-HA/SD n'était présente mais un échec de cohésion avec destruction de l'interface implant/recouvrement a été mis en évidence. Une analyse statistique des données histomorphométriques ne montrait cependant aucun effet dépendant du temps. Les recouvrements HA/PS montraient des pourcentages de contact os/implant significativement plus importants de la surface implantaire totale (BIC) que les autres types de recouvrement (p=0,01). Lorsque les pourcentages de contact os-implant étaient lus séparément pour les portions implantaires placées dans l'os cortical ou l'os spongieux (respectivement coBIC et caBIC), l'analyse détaillée montrait que les valeurs caBIC du gel- HA/SD et des recouvrements HA/PS étaient significativement plus importants que dans les autres types de recouvrement (p<0,01). Les valeurs CaBIC étaient en relation étroite avec les valeurs toBIC (p<0,001). L'étude présente a montré que les techniques de préparation utilisées produisaient des recouvrements non-résorbables denses et fins qui permettaient l'ostéoïntégration. Cependant, comparé aux recouvrements contrôles, seul le recouvrement gel-HA/SD pouvait être recommandé avec les techniques de préparation étudiées pour une utilisation clinique future si une cohésion de recouvrement meilleure est assurée. Zusammenfassung Die vorliegende Studie untersuchte die Hypothese, dass Hydroxyapatit, Trikalziumphoshat und ein Hydroxyapatit-Gel als Beschichtung auf enossalen Ti-Implantaten zur voraussagbaren Osseointegration über einen langen Zeitraum ohne Bioresorption der Beschichtung führen. Die Beschichtungen wurden durch Funkenentladung und Tauchbeschichtung aufgetragen. Für die Implantation der HA/SD, HA/TCP/SD und HA-Gel/SD wurde ein Schafmodell verwendet. Die Proben wurden 6 und 12 Monate nach Implantation entnommen. Als Kontrolle dienten Hydroxyapatit- und Titanbeschichtungen (HA/PS und Ti/PS), welche mittels Plasmaspray aufgetragen worden waren. Die mikroskopische Untersuchung zeigte, das bei allen Implantattypen eine Osseointegration erreicht wurde. Bei den HA/SD, HA/TCP und HA-Gel/SD Beschichtungen waren keine Anzeichen von Bioresorption vorhanden, aber es konnten kohäsive Misserfolge mit Abrissen im Bereich der Implantat/Beschichtung-Berührungsfläche gesehen werden. Eine statistische Analyse der histomorphometrischen Daten zeigte jedoch keinen zeitabhängigen Effekt. Die HA/PS Beschichtungen erreichten signifikant höhere Knochen-Implantat-Kontakt Prozentwerte der gesamten Implantatoberfläche (toBIC) als die anderen Beschichtungen (P=0.01). Wenn die Knochen-Implantat-Kontakt Prozentwerte für Implantatbereiche, welche im kortikalen und spongiösen Knochen (coBIC und caBIC) lagen, separat ausgemessen wurden, so zeigte die detaillierte Analyse, dass die caBIC Werte von HA-Gel/SD und HA/PS Beschichtungen signifikant höher waren als bei allen anderen Typen von Beschichtungen (P=0.01). Die caBIC Werte zeigten eine starke Korrelation mit den toBIC Werten (P<0.001). Die Studie zeigte, dass das verwendete Herstellungsverfahren dünne, dichte und nicht resorbierbare Beschichtungen ergab, welche eine Osseointegration erreichten. Im Vergleich mit den Kontrollbeschichtungen können jedoch nur die HA-Gel/SD Beschichtungen der untersuchten Herstellungsverfahren für den weiteren klinischen Gebrauch empfohlen werden, falls eine bessere Kohäsion der Beschichtung erreicht werden kann. Resumen El presente estudio investigó la hipótesis de que la hidroxiapatita, el fosfato tricálcico y un gel de hidroxiapatita cubriendo implantes endoóseos de Ti por medio de chisporroteo e inmersión pueden lograr una osteointegración predecible sin una biorreabsorción evidente de las cubiertas a largo plazo. Se usó un modelo costal de oveja para la implantación de especímenes HA/SD, HA/TCP/SD, y gel-HA/SD que se retiraron a los 6 y a los 12 meses de la implantación. Como control se usaron cubiertas de hidroxiapatita y titanio en implantes obtenidos por medio de pulverización de plasma convencional (HA/SD, Ti/PS). La microscopía demostró que la osteointegración se logró en todos los tipos de implantes. No existió evidencia de biorreabsorción de las cubiertas HA/SD, HA/TCP/SD, y gel-HA/SD pero se observó fallos en la cohesión con disrupción de la interfase cubierta/implante. Un análisis estadístico de los datos histomorfométricos no mostró, sin embargo efectos dependientes del tiempo. Las cubiertas HA/PS lograron unos porcentajes de contacto hueso-implante significativamente mayores del total de la superficie del implante (toBIC) que los otros tipos de cubiertas (P=0.01). Si se ubicaran los porcentajes de contacto hueso-implante separadamente para porciones situadas dentro de hueso cortical o esponjoso (coBIC y caBIC respectivamente), un análisis detallado mostró que los valores caBIC de las cubiertas de HA-gel/SD y HA/PS fueron significativamente mayores que aquellos de los otros tipos de cubiertas (P<0.001). El presente estudio mostró que las técnicas de preparación usadas produjeron cubiertas finas, densas y no reabsorbibles que alcanzaron la osteointegración. De todos modos, comparadas con las cubiertas de control, solo la cubierta HA-gel/SD pude ser recomendada desde las técnicas de preparación investigadas para un futuro uso clínico si se lograse una mejor cohesión de cubierta. [source] | |||||||||||||