ABSTRACT
Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model.Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes.Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups.Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.
Subject(s)
Cold Temperature/adverse effects , Hypothermia, Induced/adverse effects , Infarction, Middle Cerebral Artery/therapy , Ischemic Stroke/therapy , Angiography, Digital Subtraction/methods , Animals , Carotid Artery, Common/diagnostic imaging , Carotid Artery, Common/pathology , Carotid Artery, Common/surgery , Catheterization/methods , Disease Models, Animal , Endovascular Procedures/methods , Feasibility Studies , Hypothermia, Induced/instrumentation , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/pathology , Ischemic Stroke/veterinary , Neuroprotective Agents/pharmacology , Outcome Assessment, Health Care , Perfusion Imaging/methods , Safety , Sheep , Thrombectomy/methodsABSTRACT
An important factor for successful translational stroke research is study quality. Low-quality studies are at risk of biased results and effect overestimation, as has been intensely discussed for small animal stroke research. However, little is known about the methodological rigor and quality in large animal stroke models, which are becoming more frequently used in the field. Based on research in two databases, this systematic review surveys and analyses the methodological quality in large animal stroke research. Quality analysis was based on the Stroke Therapy Academic Industry Roundtable and the Animals in Research: Reporting In Vivo Experiments guidelines. Our analysis revealed that large animal models are utilized with similar shortcomings as small animal models. Moreover, translational benefits of large animal models may be limited due to lacking implementation of important quality criteria such as randomization, allocation concealment, and blinded assessment of outcome. On the other hand, an increase of study quality over time and a positive correlation between study quality and journal impact factor were identified. Based on the obtained findings, we derive recommendations for optimal study planning, conducting, and data analysis/reporting when using large animal stroke models to fully benefit from the translational advantages offered by these models.
Subject(s)
Disease Models, Animal , Stroke/etiology , Translational Research, Biomedical/methods , Translational Research, Biomedical/standards , Animal Experimentation/standards , Animal Experimentation/statistics & numerical data , Animals , Humans , Reproducibility of Results , Translational Research, Biomedical/statistics & numerical dataABSTRACT
Neuroendovascular procedures have led to breakthroughs in the treatment of ischemic stroke, intracranial aneurysms, and intracranial arteriovenous malformations. Due to these substantial successes, there is continuous development of novel and refined therapeutic approaches. Large animal models feature various conceptual advantages in translational research, which makes them appealing for the development of novel endovascular treatments. However, the availability and role of large animal models have not been systematically described so far. Based on comprehensive research in two databases, this systematic review describes current large animal models in neuroendovascular research including their primary use. It may therefore serve as a compact compendium for researchers entering the field or looking for opportunities to refine study concepts. It also describes particular applications for ischemic stroke and aneurysm therapy, as well as for the treatment of arteriovenous malformations. It focuses on most promising study designs and readout parameters, as well as on important pitfalls in endovascular translational research including ways to circumvent them.
