Prothrombin Time, Activated Partial Thromboplastin Time, and Fibrinogen Reference Intervals for Inbred Strain 13/N Guinea Pigs (Cavia porcellus) and Validation of Low Volume Sample Analysis

Inbred strain 13/N guinea pigs are used as small animal models for the study of hemorrhagic fever viruses. Coagulation abnormalities, including prolonged clotting times and bleeding, are characteristic of hemorrhagic fever in humans; patients often meet criteria for disseminated intravascular coagulation (DIC). Comprehensively evaluating coagulation function is critical in model development and studies of viral pathogenesis and therapeutic efficacy. Here, using the VetScan VSpro veterinary point-of-care platform, we developed reference intervals in both juvenile and adult strain 13/N guinea pigs for three coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen. In addition, for situations or species with limited availability of blood for clinical analysis, we investigated the validity of a modified collection approach for low-volume (0.1 mL) blood sample analysis of PT and aPTT

Neurons in the dorsomedial medulla contribute to swallow pattern generation: Evidence of inspiratory activity during swallow.

Active contraction of the diaphragm and other inspiratory pump muscles during swallow create a negative thoracic pressure to improve the movement of the bolus (food/liquid) into the esophagus. We tested the hypothesis that dorsomedial medullary inspiratory neurons, including the nucleus tractus solitarius (NTS, pre-motor to the phrenic) would be active during swallow induced by oral water infusion. We recorded neurons in the NTS and medial reticular formation in anesthetized spontaneously breathing cats, and induced swallow by injection of water into the oropharynx. Our results indicate that: 1) a majority of inspiratory cells in the dorsomedial medulla are active during swallow, 2) expiratory neurons are present in the medial reticular formation (deeper to the NTS) in unparalyzed cats and a majority of these cells decreased firing frequency during swallow. Our findings suggest that the dorsomedial medulla is a source of inspiratory motor drive during swallow and that a novel population of breathing-modulated neurons that also are modulated during swallowing exist in the medial reticular formation in unparalyzed animals

Correction: Suppression of Abdominal Motor Activity during Swallowing in Cats and Humans.

[This corrects the article DOI: 10.1371/journal.pone.0128245.]

Suppression of Abdominal Motor Activity during Swallowing in Cats and Humans.

Diseases affecting pulmonary mechanics often result in changes to the coordination of swallow and breathing. We hypothesize that during times of increased intrathoracic pressure, swallow suppresses ongoing expiratory drive to ensure bolus transport through the esophagus. To this end, we sought to determine the effects of swallow on abdominal electromyographic (EMG) activity during expiratory threshold loading in anesthetized cats and in awake-healthy adult humans. Expiratory threshold loads were applied to recruit abdominal motor activity during breathing, and swallow was triggered by infusion of water into the mouth. In both anesthetized cats and humans, expiratory cycles which contained swallows had a significant reduction in abdominal EMG activity, and a greater percentage of swallows were produced during inspiration and/or respiratory phase transitions. These results suggest that: a) spinal expiratory motor pathways play an important role in the execution of swallow, and b) a more complex mechanical relationship exists between breathing and swallow than has previously been envisioned

Volume-Associated Clinical and Histopathological Effects of Intranasal Instillation in Syrian Hamsters: Considerations for Infection and Therapeutic Studies

Syrian hamsters are a key animal model of SARS-CoV-2 and other respiratory viruses and are useful for the evaluation of associated medical countermeasures. Delivery of an infectious agent or intervention to the respiratory tract mirrors natural routes of exposure and allows for the evaluation of clinically relevant therapeutic administration. The data to support instillation or inoculation volumes are important both for optimal experimental design and to minimize or avoid effects of diluent alone, which may compromise both data interpretation and animal welfare. Here we investigate four intranasal (IN) instillation volumes in hamsters (50, 100, 200, or 400 µL). The animals were monitored daily, and a subset were serially euthanized at one of four pre-determined time-points (1, 3, 7, and 14 days post-instillation). Weight, temperature, oxygen saturation, CBC, radiographs, and respiratory tissue histopathology were assessed to determine changes associated with instillation volume alone. With all the delivery volumes, we found no notable differences between instilled and non-instilled controls in all of the parameters assessed, except for histopathology. In the animals instilled with 200 or 400 µL, inflammation associated with foreign material was detected in the lower respiratory tract indicating that higher volumes may result in aspiration of nasal and/or oropharyngeal material in a subset of animals, resulting in IN instillation-associated histopathology

Example of two <i>NTS</i> Inspiratory neurons during breathing and swallow.

<p>Unsorted and sorted spike trains, and instantaneous firing frequency (FF) (Hz) are displayed; demonstrating an increase in FF during swallow. The swallow is outlined in the gray box. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199903#pone.0199903.t002" target="_blank">Table 2</a> for anatomical location and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199903#pone.0199903.t001" target="_blank">Table 1</a> for neuron discharge pattern definitions. Recordings of EMG moving averages from the mylohyoid, thyrohyoid, parasternal, diaphragm and esophageal pressure are also shown.</p

Suppression of Abdominal Motor Activity during Swallowing in Cats and Humans - Table 1

<p><b>A</b>. Changes to inspiratory and expiratory EMG amplitude and duration comparing cycles with expiratory loading and expiratory loading with swallow. <b>B</b>. Changes to laryngeal, pharyngeal, and schluckatmung EMG amplitude during control swallows (rest breathing) and swallows during expiratory threshold loading.</p><p>Suppression of Abdominal Motor Activity during Swallowing in Cats and Humans - Table 1 </p

Neurons in the dorsomedial medulla contribute to swallow pattern generation: Evidence of inspiratory activity during swallow

<div><p>Active contraction of the diaphragm and other inspiratory pump muscles during swallow create a negative thoracic pressure to improve the movement of the bolus (food/liquid) into the esophagus. We tested the hypothesis that dorsomedial medullary inspiratory neurons, including the nucleus tractus solitarius (NTS, pre-motor to the phrenic) would be active during swallow induced by oral water infusion. We recorded neurons in the NTS and medial reticular formation in anesthetized spontaneously breathing cats, and induced swallow by injection of water into the oropharynx. Our results indicate that: <i>1)</i> a majority of inspiratory cells in the dorsomedial medulla are active during swallow, 2) expiratory neurons are present in the medial reticular formation (deeper to the NTS) in unparalyzed cats and a majority of these cells decreased firing frequency during swallow. Our findings suggest that the dorsomedial medulla is a source of inspiratory motor drive during swallow and that a novel population of breathing-modulated neurons that also are modulated during swallowing exist in the medial reticular formation in unparalyzed animals.</p></div