Reduction of isoflurane MAC with buprenorphine and morphine in rats

Preoperative analgesics are being increasingly used to provide analgesia in the intraoperative and postoperative period. Opioids reduce anaesthetic requirements, although the effect varies with the different drug and species. The aim of this work was to determine whether buprenorphine reduces the minimum alveolar concentration (MAC) of isoflurane in a dose-related fashion, and whether this effect is similar to morphine when clinical doses of both drugs are used in the rat. Thirty-six male Wistar rats were anaesthetized with isoflurane, and MAC was determined before and after the administration of either buprenorphine or morphine. MAC of isoflurane was determined from alveolar gas samples when a standard noxious stimulus, in the form of a tail clamp, was applied. The duration and degree of reduction of the MAC of isoflurane were recorded. Basic cardiovascular and respiratory measurements were also recorded. Buprenorphine (10, 30 and 100 microg/kg) and morphine (1, 3 and 10 mg/kg) reduced in a dose-dependent fashion the MAC of isoflurane by 15%, 30% and 50%, respectively. Buprenorphine resulted in less cardiovascular and respiratory depression and had a longer-lasting action than morphine. In conclusion, buprenorphine has a dose-related isoflurane sparing effect in the rat similar to that caused by morphine at clinical doses of both drugs.     

Immobilization of wild ocelots with tiletamine and zolazepam in southern Texas

Telazol was used to immobilize nine wild ocelots (Leopardus pardalis) captured in box-traps in southern Texas (USA) between May 1997 and April 1998. Mean (+/- SD) intramuscular dosage rate of 5.05 (+/- 0.76) mg/kg produced an induction time of 3.7 +/- 1.8 min. Duration of cataleptic anesthesia was 67.4 +/- 19.8 min and ocelots stood 50.0 +/- 30.7 min after emergence from cataleptic anesthesia. Ocelots recovered to their preinjection condition 129.7 +/- 28.8 min after first standing and 250.8 +/- 55.1 min after initial injection. We observed no adverse reactions to Telazol aside from minor loss of thermoregulatory control. Telazol administered at 5 mg/kg was an effective and safe immobilizing agent for wild ocelots.     

Total intravenous anesthesia with midazolam, ketamine, and xylazine or detomidine following induction with tiletamine, zolazepam, and xylazine in red deer (Cervus elaphus hippelaphus) undergoing surgery

Sixteen captive female red deer were successfully anesthetized to surgically implant a telemetry system. The deer were immobilized with (mean±SD) 1.79±0.29 mg/kg xylazine and 1.79±0.29 mg/kg tiletamine/zolazepam given intramuscularly with a dart gun. Anesthesia was maintained for 69±2 min using a total intravenous protocol with a catheter placed in the jugular vein. Group X received xylazine (0.5±0.055 mg/kg/hr) and group D, detomidine (2±0.22 μg/kg/hr), both in combination with ketamine (2±0.02 mg/kg/hr) and midazolam (0.03±0.0033 mg/kg/hr), as a constant rate infusion. Anesthesia was reversed with 0.09±0.01 mg/kg atipamezole and 8.7±1.21 μg/kg sarmazenil given intravenously in both groups. These drug combinations provided smooth induction, stable anesthesia for surgery, and rapid recovery. Respiratory depression and mild hypoxemia were seen, and we, therefore, recommend using supplemental intranasal oxygen.     

Estimation of minimum alveolar concentration (MAC) for halothane, enflurane and isoflurane in spontaneously breathing guinea pigs

MAC for halothane, enflurane and isoflurane was determined in guinea pigs (Cavia porcellus) exposed to constant anesthetic concentrations (2.5 hours each) in a flow-through glass chamber. The following values were obtained (N = 8 for each anesthetic): 1.01 +/- 0.03 vol% for halothane, 2.17 +/- 0.04 vol% for enflurane, and 1.15 +/- 0.05 vol% for isoflurane. In guinea pigs, MAC for halothane and enflurane are similar to those reported for other rodents, while MAC for isoflurane is lower. The data indicate that guinea pigs possibly are more susceptible to isoflurane's anesthetic actions than other rodents.     

Effects of repeated anaesthesia with ketamine/medetomidine and of pre-anaesthetic administration of buprenorphine in rats

Two groups of rats were anaesthetized at weekly intervals for 6 weeks with either ketamine/medetomidine alone (60 mg/0.4 mg/kg i.p.) or ketamine/medetomidine (45 mg/0.3 mg/kg i.p.) one hour following buprenorphine (0.05 mg/kg s.c.). Animals that received buprenorphine had longer periods of surgical anaesthesia (P = 0.04) and a greater depression of both mean pedal withdrawal score (P < 0.01) and mean respiratory rate (P = 0.014). Mean total duration of anaesthesia was also greater in the buprenorphine group on day 1. Sleep times reduced with successive doses of anaesthetic in the buprenorphine group (P = 0.024). Two animals in the buprenorphine group died. Repeated anaesthesia with ketamine/medetomidine alone was not associated with anaesthetic mortality. These results indicate that although buprenorphine has a clear anaesthetic-sparing effect, its use with ketamine/medetomidine may be associated with an increased risk of anaesthetic-related mortality.     

Chemical immobilization of adult female Weddell seals with tiletamine and zolazepam: effects of age, condition and stage of lactation

Background

Postweaning diarrhoea (PWD) in pigs is usually the main infectious problem of large-scale farms and is responsible for significant losses worldwide. The disease is caused mainly by enterotoxigenic E. coli (ETEC) and Shiga-toxin producing E. coli (STEC). In this study a total of 101 E. coli isolated from pigs with PWD in Slovakia were characterized using phenotypic and genotypic methods.

Results

These 101 isolates belonged to 40 O:H serotypes. However, 57% of the isolates belonged to only six serotypes (O9:H51, O147:H-, O149:H10, O163:H-, ONT:H-, and ONT:H4), including two new serotypes (O163:H- and ONT:H4) not previously found among porcine ETEC and STEC isolated in other countries. Genes for EAST1, STb, STa, LT and Stx2e toxins were identified in 64%, 46%, 26%, 20%, and 5% of isolates, respectively. PCR showed that 35% of isolates carried genes for F18 colonization factor, and further analyzed by restriction endonuclease revealed that all of them were F18ac. Genes for F4 (K88), F6 (P987), F17, F5 (K99), F41, and intimin (eae gene) adhesins were detected in 19 %, 5%, 3%, 0.9%, 0.9%, and 0.9% of the isolates, respectively. The study of genetic diversity, carried out by PFGE of 46 representative ETEC and STEC isolates, revealed 36 distinct restriction profiles clustered in eight groups. Isolates of the same serotype were placed together in the dendrogram, but high degree of polymorphism among certain serotypes was detected.

Conclusion

Seropathotype O149:H10 LT/STb/EAST1/F4 (14 isolates) was the most commonly detected followed by O163:H- EAST1/F18 (six isolates), and ONT:H4 STa/STb/Stx2e/F18 (five isolates). Interestingly, this study shows that two new serotypes (O163:H- and ONT:H4) have emerged as pig pathogens in Slovakia. Furthermore, our results show that there is a high genetic variation mainly among ETEC of O149:H10 serotype.     

Immobilization of wild dogs (Lycaon pictus) with a tiletamine hydrochloride/zolazepam hydrochloride combination and subsequent evaluation of selected blood chemistry parameters

A tiletamine hydrochloride/zolazepam hydrochloride combination was used successfully to immobilize captive untamed wild dogs (Lycaon pictus) (n = 16) at dosage rates ranging from 2.3 to 32.3 mg/kg. Animals remained immobilized for periods ranging from 35 min to 24 hr 14 min. There was a significant positive correlation (r = 0.85, P less than 0.01) between dosage rate and the time immobilized. Profuse salivation and intermittent mild myoclonal contractions were observed in some wild dogs. Mildly reduced partial oxygen and carbon dioxide pressures as well as reduced concentrations of bicarbonate were observed in arterial blood at 10 and 20 min after administration of the drug. Serum concentrations of sodium, potassium, chloride, phosphorus, calcium, magnesium, urea, creatinine, glucose, proteins, albumin, gammaglutamyltransferase, creatinine kinase, aspartate transaminase, alkaline phosphatase, lactate dehydrogenase, insulin, cortisol and thyroxine are presented. These concentrations were found to be in agreement with values previously reported for wild dogs.     

Hemodynamic and electroencephalographic effects of epidural buprenorphine during orthopedic hindlimb surgery in sheep: A comparison with intramuscular buprenorphine and epidural saline

Epidural opioids exert segmentally limited spinal analgesia by acting at dorsal horn neurons. While the spinal cord may be the predominant site of action for hydrophilic opioids such as morphine, initial supraspinal effects have been suggested for lipophilic opioids such as buprenorphine. In view of significant systemic effects, the value of epidural administration of lipophilic opioids in human patients has been questioned. Since epidural buprenorphine may be beneficial for hindlimb surgeries in sheep, intraoperative hemodynamic and central nervous effects were evaluated. In a prospective, randomized, and placebo-controlled study, 15 adult sheep anesthetized for cranial cruciate ligament reconstruction were treated with either epidural buprenorphine (5 μg/kg, n = 5), intramuscular buprenorphine (5 μg/kg, n = 5), or epidural saline (0.15 ml/kg, n = 5) preoperatively. Heart rate, arterial blood pressures and the electroencephalographic variables /δ ratio, α/δ ratio, β/δ ratio, median power frequency (MED), and 80% spectral edge frequency were recorded before and immediately after skin incision and during drilling a tunnel through the tibia bone. Arterial pressures after epidural buprenorphine were significantly lower compared with epidural saline but were quite similar to intramuscular buprenorphine before skin incision. Mean EEG /δ ratios and MED values following epidural and intramuscular buprenorphine were significantly lower compared with epidural saline but quite similar for the two buprenorphine groups during drilling. In conclusion, similar hemodynamic and electroencephalographic effects of epidural and intramuscular buprenorphine suggest systemic effects of epidural buprenorphine in sheep.     

Reduction of the sevoflurane minimum alveolar concentration induced by methadone, tramadol, butorphanol and morphine in rats

This study aimed to estimate the reduction in the minimum alveolar concentration (MAC) of sevoflurane induced by low and high doses of methadone (5 and 10 mg/kg), tramadol (25 and 50 mg/kg), butorphanol (5 and 10 mg/kg) or morphine (5 and 10 mg/kg) in the rat. A control group received normal saline. Sixty-three adult male Sprague-Dawley rats were anaesthetized with sevoflurane (n = 7 per group). Sevoflurane MAC was then determined before and after intraperitoneal administration of the opioids or saline. The duration of the sevoflurane MAC reduction and basic cardiovascular and respiratory measurements were also recorded. The baseline MAC was 2.5 (0.3) vol%. Methadone, tramadol and morphine reduced the sevoflurane MAC (low dose: 31 ± 10, 38 ± 15 and 30 ± 13% respectively; high dose: 100 ± 0, 83 ± 17 and 77 ± 25%, respectively) in a dose-dependent manner. The low and high doses of butorphanol reduced the sevoflurane MAC to a similar extent (33 ± 7 and 31 ± 4%, low and high doses, respectively). Two rats developed apnoea following administration of high-dose butorphanol and methadone. These anaesthetic-sparing effects are clinically relevant and may reduce the adverse effects associated with higher doses of inhalational anaesthetics.     

Enhancement of tolerance development to morphine in rats prenatally exposed to morphine,methadone, and buprenorphine

Background  

Abuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.     

Changes in RANKL/OPG/RANK gene expression in peripheral mononuclear cells following treatment with estrogen or raloxifene

The RANKL/OPG/RANK pathway is the key mediator of osteoclastogenesis. Mononuclear cells may be implicated in post-menopausal osteoporosis. The effect of estrogen or raloxifene on bone resorption and the expression of RANKL/OPG/RANK in peripheral blood mononuclear cells (PBMCs) was examined. Twenty-nine women with post-menopausal osteoporosis were treated with estrogen (HRT) or raloxifene for 12 months. Bone mineral density (BMD) was measured at baseline and at 12 months at the spine and hip. Serum C-terminal telopeptide (CTX) and OPG were measured at baseline and at 1, 3, 6 and 12 months. PBMCs were isolated from 17 women and changes in RANKL, OPG and RANK mRNA were determined. The effects of estrogen or raloxifene in PBMCs in vitro were also assessed. BMD increased following treatment (lumbar spine % change mean [S.E.M.]: 4.3% [0.9], p<0.001). Serum CTX decreased (6 months: -43.7% [6.0], p<0.0001). Serum OPG declined gradually (12 months: -26.4% [4.4], p<0.001). RANKL, OPG and RANK gene expression decreased (6 months: RANKL 50.0% [24.8] p<0.001, OPG: 21.7% [28] p<0.001, RANK: 76.6% [10.2] p=0.015). Changes in OPG mRNA correlated with changes in BMD (r=-0.53, p=0.027) and CTX (r=0.7, p=0.0044). Down-regulation in RANKL, OPG, RANK mRNA and reduction in bone resorption was also seen in vitro. These results suggest that the expression of RANKL/OPG/RANK in PBMCs are responsive to the slowing in bone turnover/remodeling associated with treatment with estrogen or raloxifene. Further confirmatory studies are needed.     

Effects of epidural morphine and transdermal fentanyl analgesia on physiology and behaviour after abdominal surgery in pigs

The objective of this work was to evaluate the physiological and behavioural effects of opioid analgesic treatment in pigs subjected to abdominal surgery. Ten Swedish Landrace x Yorkshire pigs (20 +/- 4 kg b.w.) were submitted for intestinal cannulation. The pigs were allocated into two groups during one preoperative, one surgical and two postoperative days. All pigs were anaesthetized with medetomidine, tiletamine and zolazepam. One group was treated with epidural morphine (0.1 mg/kg) preoperatively, and transdermal fentanyl patches (50 microg/kg/h) were applied behind the ear immediately after surgery. The other group received epidural saline (equivalent volume) and placebo patches. All pigs were regularly weighed and clinically examined and repeated blood samples were analysed for serum concentrations of cortisol, beta-endorphin and fentanyl. Pre- and postoperative behaviours were evaluated by a swine specialist blinded to the treatment, three times a day, and were also videotape recorded for a total of 84 h per pig. No differences in behaviour were noted by the observer. During the first postoperative 12 h, treated pigs did not differ in activity compared with preoperative recordings, while untreated pigs were found to be less active. The treated group started to show interest in eating immediately after anaesthesia recovery, whereas the placebo group did not. During the 12-60 h postoperative period, the treated group had lower activity levels compared with the preoperative levels, which were similar to those in the placebo group. Treated pigs gained 0.5 +/- 0.2 kg during the subsequent two postoperative days, whereas the untreated pigs lost weight throughout the experiment. Cortisol concentration differed immediately after the surgery: Group P had 325 +/- 120 nmol/L and Group M 159 +/- 49 nmol/L. beta-endorphin concentration did not differ between groups. The highest serum fentanyl concentration (0.37 +/- 0.3 ng/mL) was measured 24 h postoperatively. Preoperative epidural morphine in combination with postoperative transdermal fentanyl resulted in earlier return to normal activity levels and an immediate weight gain after surgery.     

Plasma and cerebrospinal fluid concentration of neuropeptide Y, serotonin, and catecholamines in patients under propofol or isoflurane anesthesia

Propofol is a widely used anesthetic for both induction and maintenance of anesthesia during surgery. A strong feeling of hunger has been reported during the early recovery period after propofol anesthesia. We have investigated the effect of propofol on appetite in 10 patients undergoing a craniotomy and in parallel measured neuropeptide Y (NPY), catecholamines, and serotonin levels in the cerebrospinal fluid and plasma during anesthesia. Ten patients anesthetized with a volatile agent (isoflurane) served as a control group. Plasma NPY and catecholamines levels were not affected by surgery at any time. We observed a strong increase in NPY concentrations in the cerebrospinal fluid independently of the anesthetic technique agent used, whereas catecholamines were unchanged. We found that serotonin concentrations decreased significantly in the plasma (but not in the cerebrospinal fluid) of patients treated by propofol when compared with the control group; this decrease was associated with an increase of hunger early postoperatively. We concluded that the proappetite effect of propofol is mediated through a decrease of serotonin at the peripheral level.