ABSTRACT
Coronary heart disease and ischaemic stroke caused by atherosclerosis are leading causes of illness and death worldwide. Small animal models have provided insight into the fundamental mechanisms driving early atherosclerosis, but it is increasingly clear that new strategies and research tools are needed to translate these discoveries into improved prevention and treatment of symptomatic atherosclerosis in humans. Key challenges include better understanding of processes in late atherosclerosis, factors affecting atherosclerosis in the coronary bed, and the development of reliable imaging biomarker tools for risk stratification and monitoring of drug effects in humans. Efficient large animal models of atherosclerosis may help tackle these problems. Recent years have seen tremendous advances in gene-editing tools for large animals. This has made it possible to create gene-modified minipigs that develop atherosclerosis with many similarities to humans in terms of predilection for lesion sites and histopathology. Together with existing porcine models of atherosclerosis that are based on spontaneous mutations or severe diabetes, such models open new avenues for translational research in atherosclerosis. In this review, we discuss the merits of different animal models of atherosclerosis and give examples of important research problems where porcine models could prove pivotal for progress.
Subject(s)
Atherosclerosis/etiology , Disease Models, Animal , Animals , Animals, Genetically Modified , Atherosclerosis/drug therapy , Cardiovascular Agents/pharmacology , Diagnostic Imaging , Drug Discovery , Drug Evaluation, Preclinical , Forecasting , Genetic Engineering/methods , Humans , Mice , Rabbits , Swine , Swine, MiniatureABSTRACT
Forty surf lifeguards attempted to ventilate a manikin through one out of three supraglottic airways inserted in random order: the Portex® Soft Seal®; the Intersurgical® i-gel™; and the Ambu® AuraOnce™. We recorded the time to ventilate and the proportion of inflations that were successful, without and then with concurrent chest compressions. The mean (SD) time to ventilate with the Soft Seal, i-gel and AuraOnce was 35.2 (7.2)s, 15.6 (3.3)s and 35.1 (8.5) s, respectively, p < 0.0001. Concurrent chest compression prolonged the time to ventilate by 5.0 (1.3-8.1)%, p = 0.0072. The rate of successful ventilations through the Soft Seal (100%) was more than through the AuraOnce (92%), p < 0.0001, neither of which was different from the i-gel (97%). The mean (SD) tidal volumes through the Soft Seal, i-gel and AuraOnce were 0.65 (0.14) l, 0.50 (0.16) l and 0.39 (0.19) l, respectively. Most lifeguards (85%) preferred the i-gel. Ventilation through supraglottic airway devices may be considered for resuscitation by surf lifeguards.
