Regenerative Peripheral Nerve Interfaces (RPNIs) in Animal Models and Their Applications: A Systematic Review.

Regenerative Peripheral Nerve Interfaces (RPNIs) encompass neurotized muscle grafts employed for the purpose of amplifying peripheral nerve electrical signaling. The aim of this investigation was to undertake an analysis of the extant literature concerning animal models utilized in the context of RPNIs. A systematic review of the literature of RPNI techniques in animal models was performed in line with the PRISMA statement using the MEDLINE/PubMed and Embase databases from January 1970 to September 2023. Within the compilation of one hundred and four articles employing the RPNI technique, a subset of thirty-five were conducted using animal models across six distinct institutions. The majority (91%) of these studies were performed on murine models, while the remaining (9%) were conducted employing macaque models. The most frequently employed anatomical components in the construction of the RPNIs were the common peroneal nerve and the extensor digitorum longus (EDL) muscle. Through various histological techniques, robust neoangiogenesis and axonal regeneration were evidenced. Functionally, the RPNIs demonstrated the capability to discern, record, and amplify action potentials, a competence that exhibited commendable long-term stability. Different RPNI animal models have been replicated across different studies. Histological, neurophysiological, and functional analyses are summarized to be used in future studies.

Sedative and analgesic effects of two subanaesthetic doses of ketamine in combination with methadone and a low dose of dexmedetomidine in healthy dogs.

OBJECTIVE: To evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: Six healthy adult Beagles. METHODS: Dogs were randomly given three treatments: dexmedetomidine (3 µg kg-1) and methadone (0.3 mg kg-1) combined with ketamine at 1 and 2 mg kg-1 (K1 and K2, respectively) or saline (K0), intramuscularly. Sedation score, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35, and 45 minutes posttreatment. Pulse rate (PR), respiratory rate, oxygen haemoglobin saturation and noninvasive blood pressure were also recorded at baseline and every 5 minutes until 45 minutes posttreatment. Onset and duration of recumbency, response to venous catheterization and recovery quality were also assessed. Sedation and physiological variables were compared between treatments and within treatments compared to baseline (analysis of variance). Nonparametric data were analysed with the Friedman and Cochran's Q tests; p < 0.050. RESULTS: Increased sedation was found at 15 (K0 and K1), 25 (all treatments) and 35 (K1) minutes compared with baseline. Sedation score, onset (3-12 minutes) and duration of recumbency (29-51 minutes) were similar between treatments. Recovery quality was considered acceptable in all cases. Response to tail clamping was inconsistent within treatments with no differences between them. None of the dogs responded to venous catheterization. There were no differences between treatments in physiological variables, except for PR which was higher in K2 than in K0. Oxygen supplementation was required in five and three dogs administered saline and ketamine, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of 1 or 2 mg kg-1 of ketamine to methadone and dexmedetomidine combination did not enhance sedation or antinociception in healthy dogs. Recovery quality was unaffected.

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles.

OBJECTIVE: To evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: A group of six adult Beagles. METHODS: Dogs were sedated on three different occasions with IM dexmedetomidine (3 µg kg-1) and methadone (0.3 mg kg-1) combined with two doses of alfaxalone (0.5 and 1 mg kg-1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO2) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran's Q tests. Significance was p < 0.05. RESULTS: Sedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum-maximum), 43 (35-54) versus 30 (20-47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO2. CONCLUSIONS AND CLINICAL RELEVANCE: Adding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.

Anesthetic management of a dog with severe subaortic stenosis and mitral valve disease complicated with atrial fibrillation undergoing ovariohysterectomy.

The anesthetic management in patients with subaortic stenosis and mitral valve disease should involve intensive monitoring and the anesthesiologist's main concern is to ensure oxygen delivery and tissue perfusion. Since anesthetic procedures in such patients are rare, there is no previous report about the anesthetic management. A 5.5-year old, 32-kg Boxer, suffering a severe heart disease due to a final stage subaortic stenosis and mitral insufficiency, was anesthetized for an ovariohysterectomy to remove an ovarian tumor that was producing high-volume ascites. Methadone (0.3 mg kg-1) was administered intramuscularly (IM) for pre-anesthetic medication, etomidate (1.3 mg kg-1) and midazolam (0.2 mg kg-1) were used for the induction of anesthesia and after endotracheal intubation, anesthesia was maintained with sevoflurane vaporized in oxygen and air. Fentanyl (5-10 µg kg-1 h-1) and paracetamol (15 mg kg-1) were administered to improve analgesia. Previous persistent atrial fibrillation was refractory to medication (digoxin, diltiazem, and pimobendan) and continued during the anesthetic procedure. Dobutamine (1.5-5 µg kg-1 minute-1) helped to maintain mean arterial blood pressure above 60 mmHg. Epidural morphine (0.1 mg kg-1) and incisional bupivacaine (2 mg kg-1) were administered at the end of surgery to provide postoperative analgesia. Anesthesia was otherwise uneventful, and recovery was considered excellent.

Anaesthetic effects of alfaxalone administered intraperitoneally alone or combined with dexmedetomidine and fentanyl in the rat.

Alfaxalone is a neuroactive steroid used as a general anaesthetic in several species including dogs, cats, rabbits and ferrets. It has a wide margin of safety and a similar anaesthetic profile to propofol. To increase its aqueous solubility, a new formulation with cyclodextrins has been marketed recently. The objective of this study was to evaluate the anaesthetic effect of several doses of alfaxalone alone, considering differences between sexes, and alfaxalone combined with dexmedetomidine and fentanyl in the rat administered by the intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three studies, were used. Firstly, 25, 35 and 45 mg kg-1 of alfaxalone alone were tested. In a second study, alfaxalone (25 mg kg-1, females; 75 mg kg-1, males) was combined with dexmedetomidine (0.05 mg kg-1). Finally, alfaxalone (20 mg kg-1, females; 60 mg kg-1, males) was combined with dexmedetomidine (0.05 mg kg-1) and fentanyl (0.1 mg kg-1). Times of onset and duration of anaesthesia, and analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone alone produced a 2 - to 3-fold longer time of anaesthesia in females, although surgical anaesthesia was not achieved in either sex. The addition of dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone produces light anaesthesia in rats, and males required a higher dose. The combination with other sedatives or analgesics, such as dexmedetomidine or fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially suitable for invasive procedures.