Spinal cord injury (SCI) researchers have predominately utilized rodents and mice for in vivo SCI modeling and experimentation. From these small animal models have come many insights into the biology of SCI, and a growing number of novel treatments that promote behavioral recovery. It has, however, been difficult to demonstrate the efficacy of such treatments in human clinical trials. A large animal SCI model that is an intermediary between rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies, prior to embarking upon lengthy and expensive clinical trials. Here, we describe the development of such a large animal model. A thoracic spinal cord injury at T10/11 was induced in Yucatan miniature pigs (20-25 kg) using a weight drop device. Varying degrees of injury severity were induced by altering the height of the weight drop (5, 10, 20, 30, 40, and 50 cm). Behavioral recovery over 12 weeks was measured using a newly developed Porcine Thoracic Injury Behavior Scale (PTIBS). This scale distinguished locomotor recovery among animals of different injury severities, with strong intra-observer and inter-observer reliability. Histological analysis of the spinal cords 12 weeks post-injury revealed that animals with the more biomechanically severe injuries had less spared white matter and gray matter and less neurofilament immunoreactivity. Additionally, the PTIBS scores correlated strongly with the extent of tissue sparing through the epicenter of injury. This large animal model of SCI may represent a useful intermediary in the testing of novel pharmacological treatments and cell transplantation strategies.
The bar-headed goose is famed for migratory flight at extreme altitude. To better understand the physiology underlying this remarkable behavior, we imprinted and trained geese, collecting the first cardiorespiratory measurements of bar-headed geese flying at simulated altitude in a wind tunnel. Metabolic rate during flight increased 16-fold from rest, supported by an increase in the estimated amount of O2 transported per heartbeat and a modest increase in heart rate. The geese appear to have ample cardiac reserves, as heart rate during hypoxic flights was not higher than in normoxic flights. We conclude that flight in hypoxia is largely achieved via the reduction in metabolic rate compared to normoxia. Arterial Po2 was maintained throughout flights. Mixed venous PO2 decreased during the initial portion of flights in hypoxia, indicative of increased tissue O2 extraction. We also discovered that mixed venous temperature decreased during flight, which may significantly increase oxygen loading to hemoglobin.
Previous work in this lab found that while both low and high‐altitude adapted species increase ventilation in response to hypoxia, high‐altitude species primarily increase tidal volume whereas low‐altitude species increase breathing frequency. Thus, we hypothesized that high‐altitude species should have higher respiratory compliance when compared to low‐altitude species to reduce the cost of breathing deeper. We measured dynamic and static compliance of the total system in five Andean species of ducks resident at Lake Titicaca, Peru and compared them to the low‐altitude migratory barnacle goose (n蠅6 for all groups). Static compliance was significantly higher in the high‐altitude ducks than the barnacle geese (1.8 ± 0.18 compared to 1.3 ± 0.06). Among the high‐altitude ducks the compliance was highest in the species that has spent the most evolutionary time at high‐altitude (2.98 ± 0.36), while the lowest compliance was found in the one species of diving duck studied (1.63 ± 0.23). The high‐altitude species also had a higher inspiratory capacity (215 ± 17 mL/kg) than the low‐altitude geese (154 ± 21 mL/kg). Thus high‐altitude species breathe with a more effective breathing pattern, reducing pulmonary dead space, without incurring an increased cost of overcoming elastic recoil forces, by increasing compliance of their respiratory system.
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