The Laboratory Woodchuck (Marmota monax)

Bellezza, Christine A.; Sexton, Sandra; Curtin, Leslie; Concannon, Patrick W.; Baldwin, Betty H.; Graham, Lou Ann; Hornbuckle, William E.; Roth, Lois; Tennant, Bud C.

doi:10.1016/b978-0-12-409527-4.00008-0

Cited by 3 publications

(5 citation statements)

References 179 publications

(170 reference statements)

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“…9,20 Despite the difference between the two protocols, all blood glucose levels were within 2.5 mmol/L (45 mg/dl) to reference values in woodchucks and Vancouver Island marmots. 4,14 A possible limitation in this study is the accuracy of the i-STAT chemical analyzer as this equipment has not been validated for use in woodchucks. In laboratory mice, the i-STAT analyzer is reliable for electrolytes, but showed poor agreement with benchtop analyzers for glucose.…”

Section: Discussionmentioning

confidence: 99%

“…They are considered plentiful in the wild and are frequently used in a research setting. 4 Safe handling of marmots often requires general anesthesia, and this is commonly achieved using only volatile inhalation agents such as isoflurane and sevoflurane. Sevoflurane is generally favored due to a less pungent odor, and faster induction and recovery times.…”

Section: Introductionmentioning

confidence: 99%

“…8,12,15 Laboratory animal and other veterinary referenc- es suggest the use of combinations that include ketamine, midazolam, and butorphanol for sedation and induction of anesthesia in marmots. 4,7,10,14,16 Ketamine is a dissociative anesthetic and a N -methyl-D-aspartate-methyl-D-aspartate receptor antagonist that has been used alone or in combination with xylazine for short-term anesthesia in marmots. 3,4,10,15,16 Midazolam is a benzodiazepine and a γ-aminobutyric acid A receptor agonist that provides good sedation with minimal cardiopulmonary depression; sedative effects may be reversed with flumazenil.…”

Section: Introductionmentioning

confidence: 99%

“…4,7,10,14,16 Ketamine is a dissociative anesthetic and a N -methyl-D-aspartate-methyl-D-aspartate receptor antagonist that has been used alone or in combination with xylazine for short-term anesthesia in marmots. 3,4,10,15,16 Midazolam is a benzodiazepine and a γ-aminobutyric acid A receptor agonist that provides good sedation with minimal cardiopulmonary depression; sedative effects may be reversed with flumazenil. 12,16 Butorphanol is an opioid that exhibits agonist activity on κ-opioid receptors and weak antagonist activity on µopioid receptors, providing dose-dependent analgesia.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of Ketamine–midazolam and Ketamine–midazolam–butorphanol Premedication Prior to Sevoflurane Anesthesia in Woodchucks (Marmota Monax)

Freedman¹,

Aymen²,

Beaufrère³

et al. 2023

Journal of Zoo and Wildlife Medicine

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Cardiovascular disease is a frequent cause of death in the critically endangered Vancouver Island marmots (Marmota vancouverensis). This warrants the use of anesthetic protocols with minimal cardiovascular adverse effects. In this study, 12 adult male woodchucks (Marmota monax) were used as models for Vancouver Island marmots. The objective was to compare the physiological effects of two premedication protocols during induction and maintenance of anesthesia with sevoflurane. The two premedications were ketamine 10 mg/kg and midazolam 0.5 mg/kg (KM) or ketamine 10 mg/kg, midazolam 0.5 mg/kg, and butorphanol 1.0 mg/kg (KMB), administered intramuscularly prior to mask induction. Each marmot underwent three anesthetic events and protocols were assigned using a blinded randomized crossover design. Heart rate, respiratory rate, oxygen saturation, and body temperature were recorded throughout, and blood gases were assessed following induction. Resistance to induction was scored and time to induction was recorded. Although mask induction with sevoflurane was successful in all events (mean induction time of 2.1 min), KMB premedication resulted in a faster induction (mean induction time reduced by 1.2 ± 0.3 min) and lower resistance scores. Both protocols resulted in significant cardiovascular and respiratory depression; however, animals that received KMB were more hypercapnic than KM by 8.8 ± 2.8 mm Hg (P = 0.03) (mean venous partial pressure of carbon dioxide [PvCO2] for all: 79.9 mm Hg). In conclusion, if shorter induction times are desired, KMB premedication is preferred. However, cardiorespiratory variables including blood pressure should be monitored, and endotracheal intubation is recommended to allow for ETCO2 monitoring and provision of intermittent positive pressure ventilation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparison of Ketamine–midazolam and Ketamine–midazolam–butorphanol Premedication Prior to Sevoflurane Anesthesia in Woodchucks (Marmota Monax)

Freedman¹,

Aymen²,

Beaufrère³

et al. 2023

Journal of Zoo and Wildlife Medicine

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“…Woodchuck hepatitis virus (WHV) infects naturally the Eastern woodchuck ( Marmota monax ) that habitats large areas within North America, including most eastern and midwestern states in the United States, southeastern Alaska, and southern Canada[ 22 ]. WHV was initially discovered in 1977 at the Philadelphia Zoo in a colony of woodchucks where several animals died due to chronic hepatitis B and HCC[ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

Suresh¹,

Menne²

2021

WJGO

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This review describes woodchucks chronically infected with the woodchuck hepatitis virus (WHV) as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma (HCC) induced by the hepatitis B virus (HBV). Since laboratory animal models susceptible to HBV infection are limited, woodchucks experimentally infected with WHV, a hepatitis virus closely related to HBV, are increasingly used to enhance our understanding of virus-host interactions, immune response, and liver disease progression. A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established, which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans. HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size, morphology, and molecular gene signature to those of HBV-infected patients. Accordingly, woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC. In addition, drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs, alone or in combination with other compounds, minimizes the risk of liver disease progression to HCC. More recently, woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute, self-limited and chronic infections. Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae, including the onset of HCC. Therefore, woodchucks with chronic WHV infection constitute a well-characterized, fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities, which are based on chemo, gene, and immune therapy, for the prevention and treatment of HCC in patients for which current treatment options are dismal.

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Recent Drug Development in the Woodchuck Model of Chronic Hepatitis B

Suresh

Menne²

2022

Viruses

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Infection with hepatitis B virus (HBV) is responsible for the increasing global hepatitis burden, with an estimated 296 million people being carriers and living with the risk of developing chronic liver disease and cancer. While the current treatment options for chronic hepatitis B (CHB), including oral nucleos(t)ide analogs and systemic interferon-alpha, are deemed suboptimal, the path to finding an ultimate cure for this viral disease is rather challenging. The lack of suitable laboratory animal models that support HBV infection and associated liver disease progression is one of the major hurdles in antiviral drug development. For more than four decades, experimental infection of the Eastern woodchuck with woodchuck hepatitis virus has been applied for studying the immunopathogenesis of HBV and developing new antiviral therapeutics against CHB. There are several advantages to this animal model that are beneficial for performing both basic and translational HBV research. Previous review articles have focused on the value of this animal model in regard to HBV replication, pathogenesis, and immune response. In this article, we review studies of drug development and preclinical evaluation of direct-acting antivirals, immunomodulators, therapeutic vaccines, and inhibitors of viral entry, gene expression, and antigen release in the woodchuck model of CHB since 2014 until today and discuss their significance for clinical trials in patients.

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The Laboratory Woodchuck (Marmota monax)

Cited by 3 publications

References 179 publications

Comparison of Ketamine–midazolam and Ketamine–midazolam–butorphanol Premedication Prior to Sevoflurane Anesthesia in Woodchucks (Marmota Monax)

Comparison of Ketamine–midazolam and Ketamine–midazolam–butorphanol Premedication Prior to Sevoflurane Anesthesia in Woodchucks (Marmota Monax)

Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer

Recent Drug Development in the Woodchuck Model of Chronic Hepatitis B

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