Laboratory Animals Flashcards
Three Regulatory Bodies Associated with Welfare of Lab Animals
- USDA Animal Welfare Act
- Office of Laboratory Animal Welfare
- Guide for Care and Use of Laboratory Animals
USDA Animal Welfare Act
o All warm-blooded species except laboratory bred mice, rats, birds
o Animal Welfare Regulations (AWRs) dictate housing requirements, care during transport, enrichment requirements
Office of Laboratory Animal Welfare
NIH funded research facilitates –> all animals involved in research, teaching
Guide for Care and Use of Labratory Animal
o Minimum welfare standard for laboratory animals for husbandry, housing, etc
o Reference document for all other regulations
Three Rs
o Reduction
o Replacement
o Refinement
Pathogens-Free Species
free of pathogens, environmental pathogens
o Biological safety cabinets, sterilized equipment
o GLOVES ALWAYS
Challenges Assoc with Small Patient Size
Difficult IV access: intraperitoneal (IP), IM, SC
IP: high failure rate – inadvertent drug delivery into fat, SQ, gut tissue
Need insulin/TB syringes, 25-30g
High metabolic rate – rapid drug metabolism
Prone to hypothermia
High surface area to body weight ratio –> increase heat loss
o Ventilation: need appropriately sized circuit, equipment
Rodents - General Features
Obligate nasal breathers
Nocturnally active – almost all feeding/drinking occurs during dark phase
Post sx pain, stress during light phase can suppress activity
Short fasting periods: hypoglycemia, dehydration
Rodents - central/head features
o Protruding eyeballs: lubricant (ointment less useful)
o Lack complete circle of Willis (anastomosis of arteries at base of brain): susceptible to cerebral ischemia upon ligation of common carotid
o Idiopathic epilepsy, hereditary diabetes reported
Rodents - Resp Changes
High chest wall compliance
Low residual capacity
Robust Bohr effect: small changes in pH have stronger effect on hemoglobin ‘s affinity for oxygen
Single left lobe, right separated into four or five lobes
Rats, hamster: cardiac striated muscle extends along pulmonary vessel walls, into lung tissue making them susceptible of spread of infection between agents
Blood Volume in Rodents
60-80mL/kg (6-8% BW)
Blood collection = 10% BW
Transfusion trigger: PCV <20%
Laboratory Mice
Large incisors with broad tongue difficult intubation
Fast, agile, do not acclimate well to handling – hand restraint requires knowledge, practice
Commercial restrainers, transfer boxes/containers
Laboratory Mice Drug Access
o IV access: lateral tail veins, submandibular venous plexus (blood draw only), orbital sinus
o SQ: flank, scruff
Rat Features
No gall bladder
Heart blood supply largely extra coronary from branches of mammary, subclavian arteries
Large incisors with broad tongue difficult intubation
Acclimate well to handling, intelligent
Hand restraint requires knowledge, practice
Commercial restrainers, transfer boxes/containers
“Tickling” acclimation
Rats IV Access
IV access: lateral tail veins, saphenous vein, jugular vein
Hamsters
o Cheek pouches with orifices near the angle of mouth: source of aspirated food material if not addressed prior to anesthesia
o Don’t usually vomit
o Hibernating: become mildly acidotic
o Anesthetic mortality = 3.7%
Drug Access Hamsters
o IV: jugular, cephalic, saphenous (medial or lateral)
o IO: tibial crest, intertrochanteric fossa of femur, ileal crest, proximal humerus
Induction in Rodents
Rapid induction, easy titration of ax
Can be challenge to maintain sterility, control ax if one person doing everything
Mask induction: technically easy to perform, not routinely intubated
Increased exposure to personnel
Decreases variations btw subjects –> minimize # of animals used in a study
o Rapid recovery vs injectables
Orden et al 2021 (VAA)
MACsevo in rats unchanged by CBD alone, MAC reduction by morph not enhanced by CBD (CBD + opioids = synergistic effect)
Propofol Use in Rodents
o Propofol if IV (rats)
IP admin: inconsistent depth, not recommended
Requires IVC Placement
Telazol in Rodents
High Mortality Rate
Tribomethanol (mice) (TBE)
Common in-vitro oocyte implantations
Peritonitis, high mortality of incorrectly stored or prepared
When successful, 15-20’ ax
Urethane
Ethyl carbamate, long-lasting, stable sx ax (6-10hr)
Few CV, resp AEs
Non-recovery procedures: CNS studies
* Depressed spinal reflexes, EEG comparable to sleep patterns, ANS reflexes preserved
Water soluble, metabolized by liver into ethanol+carbamic acid, renal excretion
Urethane MOA
- GABAA 23%
- a1 glycine R agonist 33%
- NMDA R antag 10%
- AMPA R antag 18%
- +/- AChR?
Adverse Effects of Urethane
IP: endocrine, metabolic effects = peritonitis, necrosis of abdo contents, massive leakage of plasma in pleural cavity
Carcinogen: PPE, proper disposal
alpha-chloralose
Numerous dose-dependent excitatory, inhibitory CNS effects
Long-lasting light ax with minimal CV effects
Prolonged induction, recovery – insufficient depth for sx
Analgesics in Rodents
Buprenorphine most commonly used: 35% of rodents that receive analgesia
Consider SR formulas – up to 72hr in mice, rats
* 40% rats skin irritation
Poor PO avail 5-10%, significant first pass hepatic metabolism –> PO DOA 1-2hr
SE: pica behavior
SE Opioids in Rodents
o Immunosuppression with very high doses of opioids for prolonged periods, potential effects on tumor growth
Ventilation in Rodents
rodents normally maintain themselves at 1:1IE
1:2, 1:3 to minimize effects of PPV (prolong expiratory time) on CV system
Depth in Rodents
o Depth: pedal withdrawal, auricular reflexes
o Minor changes in heart rate, respiratory rate equal indicators of changes in depth
CV Monitoring in Rodents
Pulse oximetry: pulsatile flow of RBCs past probe required
HR > 400bpm may cause difficulty in acquiring reading
ETCO2: requires intubation, limitations with both mainstream and side stream
BP:
Constraints with BP cuffs DT small patient size
High heart rate can decrease accuracy of oscillometric readings
Difficult to find artery for catheterization
Positioning of Rodents
little horses – weight of organs on diaphragm limits appropriate depth of breath
Ensure straight head slash neck for better air flow in non intubated patients
Pain Assessment in Rodents
Grimace scores validated for mice, rodents
Pain assessment: hunched posture, bruxism, grimace, tachycardia
Recovery of Rodents
–Ensure warming, avoid excessive fluid admin to minimize hypothermia = recover, eat quickly
–Home cage: no particulate bedding to avoid airway obstruction
–Often housed in corn cob bedding, replace with paper towel
–Keep separate from others while recovering: will attack, esp males
Clean off all detergents, chemicals from skin
–Grooming: may consume toxic small quantities from fur
Gel based hydration, electrolyte packs in cage
Common Peri-Anesthetic Complications with Rodents
o Hypothermia
o Insufficient depth of ax, movement – esp with mask maintenance if move nose from cone
o Excessive depth
o Labored respirations +/- resp arrest
o Inadvertent inj into spleen, GIT via IP
Delayed onset, slow recovery
o Difficulty monitoring: specialized equipment, patient visualization