a-porcine-heterotopic-heart-transplantation-protocol-for-delivery

A Porcine Heterotopic Heart Transplantation Protocol for Delivery of Therapeutics to a Cardiac Allograft

Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts ...

North Carolina State University

Although tricaine methanesulfonate (MS-222) immersion has historically been standard of care for fish and anuran euthanasia, recent research has proven it insufficient for euthanasia of goldfish. To assess appropriateness for humane euthanasia of anurans, this study evaluated the efficacy of MS-222 in Smokey Jungle Frogs (). Eighteen frogs (21-33 g) were exposed to one of three MS-222 concentrations via partial immersion: 2.5 g/L for 90 min (M2.5/90), 5 g/L for 60 min (M5/60), or 10 g/L for 60 min (M10/60). Physiologic parameters and times to loss of spontaneous movement, righting reflex, and noxious stimulus response were recorded. Following exposure, frogs were rinsed with dechlorinated water, and time to cessation of heart beat was recorded. Survival in M2.5/90, M5/60, and M10/60 was one of six, zero of six, and zero of six, respectively. In M2.5/90, three of six frogs had continued purposeful, spontaneous movement throughout exposure. In M5/60 and M10/60, median (range) time to initial loss of movement was 14.3 (5.5-30.0) and 7.6 (4.8-19.7) min, respectively. Twelve of 18 frogs among all groups demonstrated a median (range) of two (one to six) episodes of regained consciousness with purposeful, spontaneous movement following loss of noxious stimulus response. Median (range) time to heart beat cessation in M2.5/90, M5/60, and M10/60 was 150 (135-210), 157.5 (60-225), and 90 (75-210) min, respectively. Although death was achieved in 17 of 18 frogs, given the repeated events of regained consciousness, MS-222 immersion when used at concentrations ≤10 g/L did not result in rapid and distress-free death and is not sufficient for humane euthanasia in this species.

IMMERSION IN TRICAINE METHANESULFONATE (MS-222) IS NOT SUFFICIENT FOR EUTHANASIA OF SMOKEY JUNGLE FROGS ().

To determine the effect of storage temperature on cadaveric small intestinal leakage pressures after enterotomy.

Ex vivo comparison of the effect of storage temperature on canine intestinal leakage pressures.

Transdermal administration is an important method of pharmacologic drug therapy in amphibians, made possible by their unique skin physiology and permeability. Despite this, there are relatively few studies that investigate transdermal pharmacokinetics in amphibians. The objective of this study was to investigate the pharmacokinetics of transdermal flunixin meglumine applied topically to marine toads (). Twenty-one adult marine toads were administered flunixin meglumine (3.3 mg/kg) topically on their dorsum and randomized ( = 7/group) to blood collection at two timepoints from the following: 1, 2, 4, 8, 12, and 24 hours (h), using a sparse sampling protocol. Plasma was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Samples were analyzed individually and reported as a mean of the samples at each timepoint. The mean peak plasma concentration was 6.31 g/ml, area under the curve was 29.37 g-h/mL, and elimination half-life was 2.79 h. No adverse effects were noted in any animals. A subset of 12 animals were euthanized at serial timepoints and necropsied. Histopathology of skin and major organs revealed one minimal superficial lesion in a single toad potentially attributable to flunixin meglumine administration; otherwise, no other treatment-related lesions were observed in 11 of 12 toads. A single topical dose of transdermal flunixin meglumine was rapidly absorbed in marine toads in the current study, and peak plasma concentrations exceeded therapeutic ranges established in cattle with no significant pathologic findings.

Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads ().

Immersion in tricaine methanesulfonate (MS-222) is insufficient for euthanasia in at least one species of fish. The current study investigated the effectiveness of potassium chloride (KCl) to euthanize anesthetized koi (). Twenty-eight healthy koi were anesthetized via immersion in 500 mg/L of buffered MS-222 for 10-12 min, manually removed to room air, and randomly administered 10 mEq/kg KCl (333 mg/ml) via one of three routes-intracardiac injection (IC) ( = 7), intracoelomic injection (ICe) ( = 7), or topical instillment over the gill filaments bilaterally (T) ( = 7)-or received no treatment (control, C) ( = 7). A Doppler ultrasonic flow detector was placed over the heart, and sounds were assessed continuously from immediately prior to treatment until 5 min posttreatment and every 5 min thereafter until Doppler sound cessation, resumption of operculation, or 30 min. Time to Doppler sound cessation or resumption of operculation was recorded. Doppler sound cessation occurred in 7/7 fish in IC (median 0.08, range 0-2.75 min) and 1/7 fish in T (10 min). In T, ICe, and C, 6/7, 7/7, and 7/7 fish, respectively, maintained Doppler sounds to 30 min. All fish in ICe (7/7) and C (7/7) resumed operculation with median (range) times of 22 (7-30) min and 16 (9-29) min from treatment, respectively. Intracardiac KCl at 10 mEq/kg rapidly ceases Doppler sounds and is a successful technique for euthanasia of anesthetized koi. Intracoelomic and topical KCl at 10 mEq/kg were not effective for euthanasia of koi.

EVALUATION OF POTASSIUM CHLORIDE ADMINISTERED VIA THREE ROUTES FOR EUTHANASIA OF ANESTHETIZED KOI ( ).

Veterinary care of ferrets often requires chemical restraint. This study hypothesized that IM alfaxalone and butorphanol would result in clinically useful sedation without clinically relevant cardiorespiratory effects. Twelve healthy 15-mo-old ferrets of equal sexes weighing 0.75 to 1.66 kg were enrolled. Using a prospective, blinded design, ferrets randomly received either IM alfaxalone 2.5 mg/kg and butorphanol 0.2 mg/kg (low dose [LD]) or IM alfaxalone 5 mg/kg and butorphanol 0.2 mg/kg (high dose [HD]) ( = 6/group). Sedation times and induction and recovery scores were recorded by a blinded observer. Anesthetic monitor placement was attempted in all recumbent ferrets, and physiologic parameters and reflexes were recorded every 5 min until return of spontaneous movement. Data were assessed for normality using a Shapiro-Wilk normality test and analyzed by two-sample  test or Mann-Whitney  test; one ferret in HD was excluded. Ferrets in LD and HD exhibited moderate and marked sedation, with one of six and four of five ferrets tolerating monitor placement, respectively. Mean ± SD time to first effects, recumbency, and recovery in LD and HD was 2.30 ± 1.13 and 2.054 ± 1.12 ( = 0.7240), 2.87 ± 1.25 and 2.72 ± 1.41 ( = 0.8529), and 65.43 ± 32.43 and 52.30 ± 13.19 ( = 0.4212), respectively. Median (range) duration of recumbency in LD and HD was 31.12 (25.58-115.72) and 35.47 (28.27-44.42) min ( = 0.3290), respectively. Among monitored ferrets, transient mild hypotension and hypoxemia were observed. Intramuscular alfaxalone 5 mg/kg with butorphanol 0.2 mg/kg provided clinically useful sedation in ferrets with mild transient cardiorespiratory derangements.

SEDATIVE AND CARDIORESPIRATORY EFFECTS OF INTRAMUSCULAR ALFAXALONE AND BUTORPHANOL AT TWO DOSAGES IN FERRETS ().

Butorphanol-azaperone-medetomidine (BAM™) has not been evaluated in horses.

Retrospective and prospective assessment of butorphanol, azaperone and medetomidine (BAM™) for immobilisation of feral horses (Equus ferus caballus).

Amphibians commonly are managed under human care for research, education, conservation, and companionship and frequently are in need of sedation, anesthesia, or end-of-life care involving euthanasia. Objective investigation of sedative and anesthetic protocols in these taxa still is in its infancy, but knowledge of current best practices is paramount to appropriate care. Tricaine methanesulfonate delivered via immersion (bath) is the most common anesthetic agent in amphibians, but several other effective techniques have been identified. This summary provides a comprehensive review of the current evidence-based literature regarding amphibian sedative, anesthetic, and euthanasia techniques.

Article	Year
IMMERSION IN TRICAINE METHANESULFONATE (MS-222) IS NOT SUFFICIENT FOR EUTHANASIA OF SMOKEY JUNGLE FROGS (). Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians\| PubMed ID: 31120666	2019
Ex vivo comparison of the effect of storage temperature on canine intestinal leakage pressures. Veterinary surgery : VS\| PubMed ID: 31721267	2020
Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (). Veterinary medicine international\| PubMed ID: 32908665	2020
EVALUATION OF POTASSIUM CHLORIDE ADMINISTERED VIA THREE ROUTES FOR EUTHANASIA OF ANESTHETIZED KOI ( ). Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians\| PubMed ID: 33480523	2020
SEDATIVE AND CARDIORESPIRATORY EFFECTS OF INTRAMUSCULAR ALFAXALONE AND BUTORPHANOL AT TWO DOSAGES IN FERRETS (). Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians\| PubMed ID: 33480564	2021
Retrospective and prospective assessment of butorphanol, azaperone and medetomidine (BAM™) for immobilisation of feral horses (Equus ferus caballus). Equine veterinary journal\| PubMed ID: 34145913	2021
Sedation and Anesthesia of Amphibians. The veterinary clinics of North America. Exotic animal practice\| PubMed ID: 34823696	2022

Julie A. Balko

Biography

JoVE Journal Publications

Other Publications