Effects of Endotracheal Epinephrine on Pharmacokinetics and Survival in a Swine Pediatric Cardiac Arrest Model.

OBJECTIVES: The aim of this study was to compare the endotracheal tube (ET) and intravenous (IV) administration of epinephrine relative to concentration maximum, time to maximum concentration, mean concentration over time (MC), area under the curve, odds, and time to return of spontaneous circulation (ROSC) in a normovolemic pediatric cardiac arrest model. METHODS: Male swine weighing 24-37 kg were assigned to 4 groups: ET (n = 8), IV (n = 7), cardiopulmonary resuscitation (CPR) + defibrillation (CPR + Defib) (n = 5), and CPR only (n = 3). Swine were placed arrest for 2 minutes, and then CPR was initiated for 2 minutes. Epinephrine (0.1 mg/kg) for the ET group or 0.01 mg/kg for the IV was administered every 4 minutes or until ROSC. Defibrillation started at 3 minutes and continued every 2 minutes for 30 minutes or until ROSC for all groups except the CPR-only group. Blood samples were collected over a period of 5 minutes. RESULTS: The MC of plasma epinephrine for the IV group was significantly higher at the 30- and 60-second time points (P = 0.001). The ET group had a significantly higher MC of epinephrine at the 180- and 240-second time points (P < 0.05). The concentration maximum of plasma epinephrine was significantly lower for the ET group (195 ± 32 ng/mL) than for the IV group (428 ± 38 ng/mL) (P = 0.01). The time to maximum concentration was significantly longer for the ET group (145 ± 26 seconds) than for the IV group (42 ± 16 seconds) (P = 0.01). No significant difference existed in area under the curve between the 2 groups (P = 0.62). The odds of ROSC were 7.7 times greater for the ET versus IV group. Time to ROSC was not significantly different among the IV, ET, and CPR + Defib groups (P = 0.31). CONCLUSIONS: Based on the results of this study, the ET route of administration should be considered a first-line intervention.

Cardiac biomarkers associated with epilepsy in a captive baboon pedigree.

The epileptic baboon provides a natural model of idiopathic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). This retrospective, case-controlled study aims to evaluate cardiac biomarkers of epilepsy, specifically QT-interval prolongation and heart rate variability (HRV), in pedigreed, captive baboons undergoing scalp electroencephalography (EEG). We retrospectively identified 21 epileptic (nine females, mean age = 11.4 ± 5.4 years) and 19 asymptomatic control (12 females, mean age = 10.5 ± 6.3 years) baboons, who had undergone scalp EEG studies with an artifact-free, 10-beat electrocardiogram sample. All baboons were sedated with subanesthetic doses of ketamine prior to electrode placement. PR, QT, and RR intervals were measured, and Fridericia-corrected QT duration (QTcF) and root mean square of successive differences between RR intervals (RMSSD; representative of HRV) values were compared between the groups. The epilepsy group had significantly prolonged QT and QTcF intervals (P = .005) compared to controls. RMSSD values were nonsignificantly decreased in epileptic baboons compared to the control group. This study demonstrates cardiac repolarization anomalies and reduction of HRV in epileptic baboons, providing new cardiac biomarkers in pedigreed baboons and potential risk factors for SUDEP.

Perspectives on SARS-CoV-2 Cases in Zoological Institutions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in a zoological institution were initially reported in March 2020. Since then, at least 94 peer-reviewed cases have been reported in zoos worldwide. Among the affected animals, nonhuman primates, carnivores, and artiodactyls appear to be most susceptible to infection, with the Felidae family accounting for the largest number of reported cases. Clinical symptoms tend to be mild across taxa; although, certain species exhibit increased susceptibility to disease. A variety of diagnostic tools are available, allowing for initial diagnostics and for the monitoring of infectious risk. Whilst supportive therapy proves sufficient in most cases, monoclonal antibody therapy has emerged as a promising additional treatment option. Effective transmission of SARS-CoV-2 in some species raises concerns over potential spillover and the formation of reservoirs. The occurrence of SARS-CoV-2 in a variety of animal species may contribute to the emergence of variants of concern due to altered viral evolutionary constraints. Consequently, this review emphasizes the need for effective biosecurity measures and surveillance strategies to prevent and control SARS-CoV-2 infections in zoological institutions.

Naturally Occurring Endocrine Disorders in Non-Human Primates: A Comprehensive Review.

Literature concerning veterinary medicine of non-human primates is continuously updated, yet endocrine disorders remain underreported. While case or survey reports of individual endocrinopathies are available, a comprehensive review is not. An exhaustive literature search on this subject via widely used academic search systems, (e.g., Google Scholar, PubMed, BioOne complete and Web of Science), and peer-reviewed publications, proceedings, and newsletters was performed. Selected major endocrine entities will be described with emphasis on clinical signs, morphologic appearances, concomitant diseases, as well as available treatment options. Mostly, no clinical signs were noted and on gross pathology, the endocrine organs were unremarkable. An endocrine-related diagnosis was frequently made as an incidental finding after standard histopathological examination. During the review, the pancreas represented the most affected endocrine organ and diabetes mellitus represented the most clinically significant disorder. Currently, no standard procedure for diagnosing, monitoring, or treating endocrine disorders in non-human primates exists.

Inguinal Hernia in Nonhuman Primates: From Asymptomatic to Life-Threatening Events.

In this study, a review of available data and literature on the epidemiology and anamnesis of inguinal hernias in nonhuman primates, as well as on their clinical evaluation and surgical management, was conducted. Inguinal hernias are assumed to be relatively common in male nonhuman primates. Clinical signs are usually limited to a visible or palpable mass in the groin region without pain or systemic illness. Most hernias contain omentum. Careful monitoring is an acceptable treatment option for those animals. Size, the danger of incarceration, and the presence of strangulation are important factors when considering surgical repair. A strangulated inguinal hernia is an emergency, requiring prompt surgery to avoid tissue necrosis and death. Imaging techniques, as well as computed tomography (CT), ultrasonography, and magnetic resonance imaging (MRI), provide information about the anatomical characteristics of the suspected region, allowing for a diagnosis and treatment. An inguinal hernia repair can be performed with either open surgery or laparoscopic surgery. The hernia repair can be achieved by mesh or suture. Decisions regarding which repair technique to use depend on the surgeon's skill level and preference. Complication and recurrence rates are generally low. The most common postsurgical complication is a recurrence of the hernia. Contraceptive measures are not indicated in breeders, as there is no known hereditary component, and the presence of hernia does not appear to affect fertility, nor does it predispose to occurrence, recurrence, or incarceration.

Cardiac changes in epileptic baboons with high-frequency microburst VNS therapy: A pilot study.

The epileptic baboon provides a natural model of idiopathic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). We sought to evaluate autonomic differences, including heart rate (HR), heart rate variability (HRV) and corrected QT-duration (QTc) between two epileptic (EB1, EB2) and one control (CB) baboon, and the autonomic effects of high-frequency (HF) microburst Vagal Nerve Stimulation (VNS) Therapy in the epileptic baboons. At baseline, EB2's HR was increased over both EB1 and CB, and EB1's HRV was decreased compared to the others. QTc-intervals were significantly prolonged in both epileptic baboons. EB1 became free of generalized tonic-clonic seizures (GTCS) with VNS therapy, whereas EB2's GTCS were reduced by a third. HR decreased in both epileptic baboons, but while HRV improved in EB1, it decreased in EB2. EB2 succumbed to SUDEP after 9 months. This pilot study demonstrates abnormalities in HR, HRV and QTc-intervals in epileptic baboons. HF VNS Therapy demonstrated different effects on HRV in the two epileptic baboons, which, in addition to persistent GTCS and elevated HR, may have contributed to SUDEP risk in EB2. Future studies are needed to establish normative values for HRV and determine variability of HR, HRV and QTc-intervals in epileptic baboons.

A Non-Human Primate Model of Severe Pneumococcal Pneumonia.

RATIONALE: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. OBJECTIVE: To develop a non-human primate model of pneumococcal pneumonia. METHODS: Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. RESULTS: Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. CONCLUSIONS: We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes.

Establishment of a neonatal rhesus macaque model to study Mycobacterium tuberculosis infection.

Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4-6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS.

Morphometric variables related to metabolic profile in captive chimpanzees (Pan troglodytes).

Obesity is a risk factor for several diseases including type 2 diabetes and cardiovascular disease. The aim of this study was to compare the relationships of waist circumference and body weight with circulating markers of metabolic, cardiovascular, and hepatic function in chimpanzees (Pan troglodytes). After a 12-h fast, blood was collected from 39 adult captive chimpanzees for measurement of serum glucose, BUN, creatinine, albumin, cholesterol, ALT, AST, ALP, total and direct bilirubin, triglyceride, and insulin, and waist circumference and body weight were measured. Waist circumference was positively correlated with systolic and diastolic blood pressure, glucose, insulin resistance as estimated by the homeostatic model assessment method, and albumin in female chimpanzees and with triglyceride in female and male chimpanzees. Body weight was correlated significantly with systolic and diastolic blood pressure in female chimpanzees and triglyceride in male chimpanzees. Male chimpanzees were heavier and had lower diastolic blood pressure, greater creatinine, albumin, AST, ALP, total bilirubin, and direct bilirubin values than did female chimpanzees. The relationships between waist circumference and blood pressure and triglyceride are consistent with those reported in humans and other primate species. In conclusion, our study is the first work to demonstrate a relationship between waist circumference and metabolic risk factors in chimpanzees. Results demonstrated that waist circumference was associated with more metabolic risk factors than was body weight, particularly in female chimpanzees.