scholarly journals Quantitative Perfusion Measurements in a Novel Large Animal Stroke Model

2021 ◽  
Author(s):  
◽  
Alexandra King
Keyword(s):  
Animal Model ◽  
Cause Of Death ◽  
Vasogenic Edema ◽  
Measurement Techniques ◽  
Future Research ◽  
Large Animal ◽  
Dce Mri ◽  
Post Stroke ◽  
Perfusion Measurement ◽  
Parameter Values

<p><b>Stroke is a leading cause of death worldwide [1], and is the third leading cause of death and the leading cause of serious adult disability in New Zealand[2]. The aim of this project was to quantify perfusion changes in the brains of 20 sheep that underwent a novel surgical model of transient ischemic stroke. The sheep, with its large, gyrencephalic brain, presents a promising, potential animal model for stroke that could help to bridge the historical gap in translational research in stroke therapies [3]. However, we require that an animal model can replicate human patterns of disease in order for it to be a meaningful model for research into potential stroke therapies for humans. It was this replication of human patterns of disease, in terms of perfusion, thatwas under investigation in this project. Dynamic Contrast Enhanced (DCE) MRI images were obtained from each animal before stroke, and at 24 hours, 3 days, 6 days, and 28 days post-stroke. It was found that perfusion from the DCE-MRI series was quantifiable using the extended Tofts model in the form of the parameters Ktrans, ve and vp. The parameter values calculated from this project replicate known human patternsof disease in terms of global Ktrans changes in the affected hemisphere [4], which were found to increase by more than 60% in the stroke hemisphere,replicating the increased permeability following blood brain barrier breakdown.</b></p> <p>In manually selected regions of cytotoxic and vasogenic edema, it was found that the estimated parameters in these regions replicated known perfusionchanges in these types of edema in humans [5]. Finally, the peak post-stroke permeability time point, as determined by Ktrans, was found to align exactlywith when we would expect vasogenic edema, a type of cerebral swelling that causes increased barrier permeability, to dominate in humans [5].</p> <p>This thesis is the first time these DCE-MRI datasets have been analysed, and there remains a wealth of physiological and MRI data available forthis animal cohort. Avenues for future research include investigation into perfusion-diffusion mismatch in this animal model, further consideration ofindividual animal characteristics in analysis, and use of these results as a point of comparison for future research into pharmaceutical agents for treatment ofstroke, and in new non-contrast perfusion measurement techniques.</p>

scholarly journals Quantitative Perfusion Measurements in a Novel Large Animal Stroke Model

2021 ◽  
Author(s):  
◽  
Alexandra King
Keyword(s):  
Animal Model ◽  
Cause Of Death ◽  
Vasogenic Edema ◽  
Measurement Techniques ◽  
Future Research ◽  
Large Animal ◽  
Dce Mri ◽  
Post Stroke ◽  
Perfusion Measurement ◽  
Parameter Values

<p><b>Stroke is a leading cause of death worldwide [1], and is the third leading cause of death and the leading cause of serious adult disability in New Zealand[2]. The aim of this project was to quantify perfusion changes in the brains of 20 sheep that underwent a novel surgical model of transient ischemic stroke. The sheep, with its large, gyrencephalic brain, presents a promising, potential animal model for stroke that could help to bridge the historical gap in translational research in stroke therapies [3]. However, we require that an animal model can replicate human patterns of disease in order for it to be a meaningful model for research into potential stroke therapies for humans. It was this replication of human patterns of disease, in terms of perfusion, thatwas under investigation in this project. Dynamic Contrast Enhanced (DCE) MRI images were obtained from each animal before stroke, and at 24 hours, 3 days, 6 days, and 28 days post-stroke. It was found that perfusion from the DCE-MRI series was quantifiable using the extended Tofts model in the form of the parameters Ktrans, ve and vp. The parameter values calculated from this project replicate known human patternsof disease in terms of global Ktrans changes in the affected hemisphere [4], which were found to increase by more than 60% in the stroke hemisphere,replicating the increased permeability following blood brain barrier breakdown.</b></p> <p>In manually selected regions of cytotoxic and vasogenic edema, it was found that the estimated parameters in these regions replicated known perfusionchanges in these types of edema in humans [5]. Finally, the peak post-stroke permeability time point, as determined by Ktrans, was found to align exactlywith when we would expect vasogenic edema, a type of cerebral swelling that causes increased barrier permeability, to dominate in humans [5].</p> <p>This thesis is the first time these DCE-MRI datasets have been analysed, and there remains a wealth of physiological and MRI data available forthis animal cohort. Avenues for future research include investigation into perfusion-diffusion mismatch in this animal model, further consideration ofindividual animal characteristics in analysis, and use of these results as a point of comparison for future research into pharmaceutical agents for treatment ofstroke, and in new non-contrast perfusion measurement techniques.</p>

scholarly journals Quantitation of Gait and Stance Alterations Due to Monosodium Iodoacetate–induced Knee Osteoarthritis in Yucatan Swine

2020 ◽  
Vol 70 (3) ◽  
pp. 248-257
Author(s):  
Katherine T LaVallee ◽  
Timothy P Maus ◽  
Joseph D Stock ◽  
Kenneth J Stalder ◽  
Locke A Karriker ◽  
...  
Keyword(s):  
Animal Model ◽  
Knee Osteoarthritis ◽  
Gait Analysis ◽  
Weight Bearing ◽  
Measurement Techniques ◽  
Large Animal Model ◽  
Large Animal ◽  
Human Knee ◽  
Common Causes ◽  
Monosodium Iodoacetate

Knee osteoarthritis is one of the most common causes of chronic pain worldwide, and several animal models have been developed to investigate disease mechanisms and treatments to combat associated morbidities. Here we describe a novel method for assessment of locomotor pain behavior in Yucatan swine. We used monosodium iodoacetate (MIA) to induce osteoarthritis in the hindlimb knee, and then conducted live observation, quantitative gait analysis, and quantitative weight-bearing stance analysis. We used these methods to test the hypothesis that locomotor pain behaviors after osteoarthritis induction would be detected by multiparameter quantitation for at least 12 wk in a novel large animal model of osteoarthritis. MIA-induced knee osteoarthritis produced lameness quantifiable by all measurement techniques, with onset at 2 to 4 wk and persistence until the conclusion of the study at 12 wk. Both live observation and gait analysis of kinetic parameters identified mild and moderate osteoarthritis phenotypes corresponding to a binary dose relationship. Quantitative stance analysis demonstrated the greatest sensitivity, discriminating between mild osteoarthritis states induced by 1.2 and 4.0 mg MIA, with stability of expression for as long as 12 wk. The multiparameter quantitation used in our study allowed rejection of the null hypothesis. This large animal model of quantitative locomotor pain resulting from MIA-induced osteoarthritis may support the assessment of new analgesic strategies for human knee osteoarthritis.

Abstract TP107: Midline Shift Predicts Functional Outcomes in Porcine Ischemic Stroke Model

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Samantha Spellicy ◽  
Erin Kaiser ◽  
Michael Bowler ◽  
Brian Jurgielewicz ◽  
Robin Webb ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Functional Outcomes ◽  
Randomized Study ◽  
Large Animal Model ◽  
Control Group ◽  
Large Animal ◽  
Midline Shift ◽  
Post Stroke ◽  
Significant Difference

In this study, we sought to identify acute MRI parameters which are predictive of long-term functional outcomes as well as assess the effects of a neural stem cell extracellular vesicle (NSC EV) therapeutic in a large animal model of ischemic stroke. In this randomized study, stroke was induced through a permanent right-sided middle cerebral artery occlusion (MCAO) on 16 male landrace pigs, which were divided into either treatment or control group. NSC EVs or PBS was administered at 2, 14, and 24 hours, and MRI was conducted at day 1 and 84 post-stroke. Data on 65 gait and 25 behavior parameters were collected pre-stroke and at multiple timepoints over 84 days following MCAO. Of all 15 measured MRI parameters, axial and coronal midline shift (MLS), at day 1 post stroke, had the highest total number of significant correlations (52 parameters at p<0.05) to acute and chronic functional measurements in control animals such as step time in the left front limb (p=0.0322) and cycle time in the right hind limb (p=0.0011) respectively. This suggests MLS is the best overall predictor of specific functional deficits at both acute and chronic timepoints, which to our knowledge has never been shown in an animal model. Additionally, the parameters found to be correlated to MLS in control animals were not correlated in NSC EV-treated animals, suggesting NSC EV treatment disrupts this natural correlation between degree of MLS and functional outcomes. NSC EVs and control pigs were binned into either high or low MLS groups and their survival and recovery was assessed by the modified Rankin Scale (mRS). While there was a significant difference in mRS scores of control animals with high and low MLS at day 6 post-MCAO (p=0.0008), there was not in NSC EV-treated animals (p=0.6754). Further, there was a significant difference in survival of control animals with high and low axial MLS (p=0.0401), but not in the NSC EV group (p=0.4142). Additionally, mRNA expression of GFAP was significantly correlated with increasing MLS in non-treated but not NSC EV-treated animals. These findings show although NSC EV treatment does not significantly alter the degree of MLS 1-day post-MCAO, it does alter gene expression, increase survival, and improve functional recovery following large MLS alterations.

DEVELOPMENT OF A LARGE ANIMAL MODEL OF OPIATE ADDICTION TO EVALUATE CARDIOVASCULAR FUNCTION.

Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 598-602 ◽  
Author(s):  
L.D. Napier ◽  
Z. Mateo ◽  
D.A. Yoshishige ◽  
B.A. Barron ◽  
J.L. Caffrey
Keyword(s):  
Animal Model ◽  
Cardiovascular Function ◽  
Large Animal Model ◽  
Opiate Addiction ◽  
Large Animal

scholarly journals A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Premila D. Leiphrakpam ◽  
Hannah R. Weber ◽  
Andrea McCain ◽  
Roser Romaguera Matas ◽  
Ernesto Martinez Duarte ◽  
...  
Keyword(s):  
Animal Model ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Large Animal Model ◽  
Large Animal ◽  
X Ray ◽  
Chest X Ray

Abstract Background Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS. Methods Animals (n = 21) were exposed to smoke under general anesthesia for 1 to 2 h (median smoke exposure = 0.5 to 1 L of oak wood smoke) after the ultrasound-guided placement of carotid, pulmonary, and femoral artery catheters. Peripheral oxygen saturation (SpO2), vital signs, and ventilator parameters were monitored throughout the procedure. Chest x-ray, carotid, femoral and pulmonary artery blood samples were collected before, during, and after smoke exposure. Animals were euthanized and lung tissue collected for analysis 48 h after smoke inhalation. Results Animals developed ARDS 48 h after smoke inhalation as reflected by a decrease in SpO2 by approximately 31%, PaO2/FiO2 ratio by approximately 208 (50%), and development of bilateral, diffuse infiltrates on chest x-ray. Study animals also demonstrated a significant increase in IL-6 level, lung tissue injury score and wet/dry ratio, as well as changes in other arterial blood gas (ABG) parameters. Conclusions This study reports, for the first time, a novel large animal model of isolated smoke inhalation-induced ARDS without confounding variables such as cutaneous burn injury. Use of this unique model may be of benefit in studying the pathophysiology of inhalation injury or for development of novel therapeutics.

scholarly journals Impella RP versus pharmacologic vasoactive treatment in profound cardiogenic shock due to right ventricular failure: Unloading and end-organ perfusion in a large animal model

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
J Josiassen ◽  
OKL Helgestad ◽  
NLJ Udesen ◽  
A Banke ◽  
PH Frederiksen ◽  
...  
Keyword(s):  
Animal Model ◽  
Cardiogenic Shock ◽  
Oxygen Saturation ◽  
Treatment Strategies ◽  
Large Animal Model ◽  
Similar Degree ◽  
Large Animal ◽  
Organ Perfusion ◽  
Venous Oxygen Saturation ◽  
Cerebral Venous Oxygen Saturation

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation Unrestricted research grant from Abiomed Background No strong evidence exists regarding the treatment of cardiogenic shock (CS) caused by acute right ventricular (RV) failure which has mainly consisted of vasoactive drugs. There is expert agreement that treatment with the recently developed Impella RP is feasible, but no previous studies have compared vasoactive treatment strategies with the Impella RP in terms of cardiac unloading and end-organ perfusion. Hypothesis Treatment with the Impella RP device will be associated with lower RV myocardial workload (pressure-volume area) compared to vasoactive treatment strategies and can furthermore be achieved without compromising organ perfusion. Methods CS was induced by a stepwise injection of polyvinyl alcohol microspheres into the right coronary artery in twenty adult female Danish landrace pigs weighing 75-80 kg. After induction of CS, the pigs were allocated to one of the two interventions for 180 minutes: 1) vasoactive therapy comprised a continuous infusion of norepinephrine (0.1 µg/kg/min) for the first 30 minutes, supplemented by an infusion of milrinone (0.4 µg/kg/min) for the remaining 150 minutes or 2) immediate insertion of and treatment with the Impella RP.  The results are presented as median [Q1;Q3]. Results Treatment with the Impella RP was associated with a lower RV workload compared to the vasoactive group, while no difference was observed with regards to left ventricular workload among intervention groups, Figure 1. Renal venous oxygen saturation increased to a similar degree following both interventions compared to the state of CS. A trend towards a higher cerebral venous oxygen saturation was observed with norepinephrine compared to Impella RP (Impella RP 51 [47;61] % vs Norepinephrine 62 [57;71] % ; p = 0.07), which became significantly higher with the addition of milrinone (Impella RP 45 [32;63] % vs Norepinephrine +Milrinone 73 [66;81] %; p = 0.002). Conclusion In this large animal model of profound CS caused by predominantly RV failure the Impella RP unloaded the failing RV. The vasoactive treatment, however, caused a higher cerebral venous oxygen saturation, while both interventions increased renal venous oxygen saturation to a similar degree. Abstract Figure 1

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