Clinical evaluation of the sedative, antinociceptive and cardiorespiratory effects of intranasal dexmedetomidine combined with methadone in healthy dogs.

In this prospective, randomised, blinded clinical study, we compared the sedative, antinociceptive and cardiorespiratory effects of intranasal (IN) dexmedetomidine at 5 µg/kg (diluted with 0.03 mL/kg NaCl 0.9%, DEX) with or without methadone (0.3 mg/kg; DEXMET), through a mucosal atomization device to one nostril in twenty healthy client-owned dogs. At 5-min intervals over 45 min, sedation score, onset, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) were assessed, also ease of administration, adverse effects, and response to IV catheterization. Statistical analysis employed t-test, the Mann-Whitney U, repeated measures ANOVA and Chi-square tests as appropriate (P < 0.05). Higher sedation ocurred in DEXMET (7 [5-10]) compared to DEX (5 [2-7]) from 15 to 30 min (P < 0.01, median [interquartile range]). Heart rate was lower in DEXMET (P < 0.01; 65% reduction vs. 41% in DEX, P = 0.001). The MNTs were higher in DEXMET than DEX from 15 to 45 min (P < 0.01), peaking at T30 (17.1 ± 3.8, DEXMET and 8.5 ± 5.4 N, DEX). No differences were observed in mean arterial blood pressure and respiratory rate. Intranasal administration was considered easy for 8 dogs per group. Reverse sneezing (8 dogs; P < 0.001), sialorrhea and retching (4 and 2 dogs, respectively) occurred in DEXMET. Response to catheterisation was lower in DEXMET than DEX (P = 0.039; 2 and 7 dogs, respectively). In conclusion, intranasal methadone (0.3 mg/kg) increased the sedative and antinociceptive effects produced by dexmedetomidine (5 µg/kg) in healthy dogs and resulted in lower heart rate.

Comparison of CPAP and oxygen therapy for treatment of postoperative hypoxaemia in dogs.

OBJECTIVE: To compare 5 cmH2 O of continuous positive airway pressure with oxygen therapy in dogs recovering from general anaesthesia with low SpO2 values. continuous positive airway pressure is more effective than oxygen therapy in restoring normoxaemia (SpO2 ≥95%). MATERIALS AND METHODS: Prospectively, dogs recovering from anaesthesia, with SpO2 <95% after extubation (T0), were randomised and treated with continuous positive airway pressure (FiO2 0.21) or oxygen (O2 ; FiO2 0.35-0.40) therapy. Dogs were monitored with SpO2 every 15 minutes for 1 hour (T15, T30, T45, T60). Data from normoxaemic dogs (SpO2 >95%) were used as control (CTR). RESULTS: Of the 42 dogs enrolled, 34 completed the study. Eleven dogs were treated with O2 , 10 with continuous positive airway pressure and 13 were CTR. The SpO2 values at T0 were similar in the continuous positive airway pressure and O2 groups and were lower than in the CTR group. At T15, T30, T45 and T60, the SpO2 values in the continuous positive airway pressure group were higher than at T0; these were similar to those of the CTR group at the same time-points. In the O2 group, SpO2 values were significantly higher at T45 and T60 than at T0; 45.5% of dogs became normoxaemic at T45 and the remaining dogs became normoxaemic at T60. The average time to reach normoxaemia in the O2 group (53.1±7.3 minutes) was longer than in the continuous positive airway pressure group (15.0±0.0 minutes). CLINICAL SIGNIFICANCE: In dogs recovering from general anaesthesia with pulmonary gas exchange impairment, normoxaemia is restored more effectively and rapidly by using continuous positive airway pressure than by oxygen therapy.

Clinical comparison of the effects of isoflurane or propofol anaesthesia on mean arterial blood pressure and ventilation in dogs undergoing orthopaedic surgery receiving epidural anaesthesia.

The aim of this study was to compare the effects on mean arterial pressure (MAP) and ventilation of propofol total IV anaesthesia (TIVA) and isoflurane as anaesthetic maintenance in healthy dogs undergoing orthopaedic surgery, with epidural anaesthesia. Dogs were premedicated IM with dexmedetomidine (4µg/kg) and methadone (0.3mg/kg), induced with IV propofol (0.65-5mg/kg) and randomly assigned to be maintained with isoflurane (group I) or propofol (group P). Isoflurane end-tidal concentration (EtISO) and propofol infusion rate were adjusted during the surgery to maintain a suitable anaesthetic depth. All dogs received bupivacaine (1mg/kg) and morphine (0.1mg/kg) in the lumbosacral epidural space (total volume 0.2mL/kg). MAP was recorded every 5min during the procedure. Statistical analysis was performed using parametric (Student's t test) and nonparametric (Mann-Whitney U-test, chi-square) tests, as appropriate. Anaesthetic maintenance in groups I and P was accomplished by providing a mean EtISO of 1.12±0.15% and a mean propofol infusion rate of 15.0±4.7mg/kg/h, respectively. MAP was significantly higher in group P than in group I (92±17mmHg versus 78±10mmHg; P=0.021). Eleven dogs in group P and two dogs in group I reached an EtCO2>7.3kPa, requiring mechanical ventilation (P=0.001). In combination with epidural anaesthesia, propofol TIVA improved MAP and is a suitable alternative to isoflurane in orthopaedic surgery of the hind limb in healthy dogs. Nevertheless, since it was associated with increased respiratory depression, mechanical ventilation should be available.

Successful use of lipid emulsion to resuscitate a foal after intravenous lidocaine induced cardiovascular collapse.

BACKGROUND: Lipid emulsion has been reported to be effective for the treatment of local anaesthetic overdoses in rats, dogs and man. OBJECTIVES: To describe the successful treatment of cardiovascular lidocaine toxicity in a foal with intravenous lipid administration. STUDY DESIGN: Observational study: case report. METHODS: An 8-month-old Arabian cross foal was anaesthetised for removal of the right alar fold and nasal plate. Anaesthesia was maintained with isoflurane in oxygen and lidocaine administered with a loading dose followed by a continuous rate infusion (CRI). The anaesthetic period was uneventful and 30 min before expected termination of the procedure lidocaine infusion was stopped. A sudden drop in mean arterial blood pressure was then observed. The ECG signal was lost, the end tidal CO2 tension dropped from 40 to 10 mmHg, corneal reflex was absent and asystole diagnosed. Cardiopulmonary resuscitation manoeuvres were immediately initiated, but epinephrine and atropine were unsuccessfully administered. Lipid emulsion was administered and the heart rate and arterial blood pressure gradually returned to normal. RESULTS: The foal recovered consciousness 3 h later, regained its sternal position, was responsive and 20 h later was able to stand up alone. MAIN LIMITATIONS: It will be necessary to evaluate a greater number of cases to determine the effectiveness of lipids in foals intoxicated with lidocaine. CONCLUSION: Intravenous lipid emulsion may be helpful in the treatment of potentially lethal cardiotoxicity attributable to lidocaine overdose in the foal.

Effects of dexmedetomidine administered at acupuncture point GV20 compared to intramuscular route in dogs.

OBJECTIVE: To compare the sedative effects produced by dexmedetomidine in dogs, administered either intramuscularly or into the Governing Vessel 20 acupuncture point. MATERIALS AND METHODS: Six dogs were sedated with 125 µg/m2 dexmedetomidine injected either intramuscularly in the gluteal muscles or subcutaneously into the acupuncture point and in random order. Sedation and analgesia were assessed blindly before and after treatments at regular intervals for 90 minutes or until the dogs fully recovered. Duration and quality of sedation were assessed with a numerical sedation rating scale and a dynamic and interactive visual analogue scale. Analgesia was also assessed with a numerical rating scale. Heart and respiratory rates and rectal temperatures were recorded. RESULTS: Sedative and analgesic scores were significantly increased when dexmedetomidine was administered at the Governing Vessel 20 acupuncture point compared with the routine intramuscular route. Duration of sedation was longer in the acupuncture site injection group compared to the intramuscular group (93 ±38 and 41 ±16 minutes). Bradycardia was significantly more pronounced in the acupuncture site group than the intramuscular group, whereas respiratory rates and rectal temperatures did not differ between administration routes. CLINICAL SIGNIFICANCE: Administration at the Governing Vessel 20 acupuncture point increased the duration and degree of sedation and analgesic effects of dexmedetomidine compared with the intramuscular route.

Evaluation of an oesophageal Doppler device for monitoring cardiac output in anaesthetised healthy normotensive dogs.

OBJECTIVES: To compare cardiac output measured by oesophageal Doppler and by thermodilution monitoring and to correlate the Doppler cardiac output-generated minute distance with thermodilution cardiac output in healthy anaesthetised beagle dogs. MATERIALS AND METHODS: Prospective experimental study. Six healthy adult beagle dogs were pre-medicated with intramuscular acepromazine (0 · 05 mg/kg) and methadone (0 · 3 mg/kg). Anaesthesia was induced with intravenous propofol (dose-effect) and maintained with isoflurane in oxygen. Simultaneously, a constant rate infusion of dopamine (3 µg/kg/minute) was administered to the dogs to prevent hypotension. The minute distance, Doppler and thermodilution cardiac outputs were assessed at three different end-tidal concentrations of isoflurane (1 · 0, 1 · 3 and 2 · 0%). RESULTS: Correlation between Doppler and thermodilution cardiac output (r(2) = 0 · 582) and between minute distance and thermodilution cardiac output (r(2) = 0 · 658) were moderately good, but the limits of agreement between Doppler and thermodilution cardiac outputs were above the recommended values (±39%, for a recommended value up to 30%). CLINICAL SIGNIFICANCE: Doppler and minute distance cannot be considered as an alternative method to thermodilution to monitor cardiac output in the healthy anaesthetised dog.

Anaesthetic effects in the ferret of alfaxalone alone and in combination with medetomidine or tramadol: a pilot study.

Alfaxalone is a neurosteroid with anaesthetic effects and it has been used successfully in several animal species. However, there are no data, to our knowledge, about its efficacy and safety in ferrets (Mustela putorius furo). We evaluated a variety of anaesthetic regimens in ferrets, namely, alfaxalone at 20, 10 and 5 mg/kg (n = 1, 10 and 9, respectively; intravenously); medetomidine at 20 µg/kg (n = 3; intramuscularly); medetomidine (20 µg/kg, intramuscularly) plus alfaxalone (2.5 mg/kg, intravenously; n = 7); and tramadol (5 mg/kg, intramuscularly) plus alfaxalone (5 mg/kg, intravenously; n = 2). Two animals treated with alfaxalone at 10 mg/kg and 20 mg/kg, respectively, died. At 5 mg/kg alfaxalone produced anaesthesia with a similar onset but a shorter duration of anaesthesia and analgesia than alfaxalone at 10 mg/kg. The medetomidine-alfaxalone combination produced anaesthesia and analgesia of a longer duration than alfaxalone administered alone at 5 mg/kg (P < 0.0001 and P < 0.001, respectively). Under this anaesthetic regimen, there was a progressive decrease in pulse rate during the first 30 min before the pulse rate stabilized. Respiratory parameters were maintained at acceptable levels. When tramadol was administered, all the animals exhibited a strong excitation reaction and in no case was the toe-pinch reflex clearly abolished. Thus, alfaxalone plus medetomidine provided safe and effective anaesthesia in ferrets. Alfaxalone, alone or in combination with tramadol, did not produce satisfactory results for use as an anaesthetic for this species.

Effects of fluid load on cardiovascular function during stepwise lung recruitment manoeuvre in healthy dogs.

The aim of this study was to evaluate the effects of a stepwise lung recruitment manoeuvre (RM) on cardiac output (CO) in mechanically ventilated dogs, with or without a previous fluid load. Eight healthy adult Beagle dogs were enrolled in a prospective crossover study. Following sedation with dexmedetomidine and methadone, anaesthesia was induced with propofol and maintained with isoflurane. CO (thermodilution method) and direct arterial blood pressure were monitored. The dogs were mechanically ventilated in a volume-controlled mode (tidal volume, VT = 10 mL/kg; positive end-expiratory pressure [PEEP] = 0 cm H2O) until normocapnia was achieved (end tidal CO2 35-45 mmHg). The RM was then performed in a pressure-controlled mode, with progressive increases of the PEEP and end-inspiratory pressure of 5 cm H2O, until 15 cm H2O and 30 cm H2O were reached, respectively. After the RM, the ventilatory mode was returned to volume-control, and the PEEP was sequentially decreased to 10, 5 and 0 cm H2O. Baseline ventilation was maintained for 30 min. Next, 10 mL/kg of lactated Ringer's solution was administered within 10 min, prior to a second RM. The CO was determined before each RM (baseline) and at each pressure step. A repeated measures ANOVA test was used to compare data. Compared to baseline, CO decreased during the RM in both groups. However, there was a significantly higher CO during the second RM at the highest pressure step (P<0.05) and during all decreasing pressure steps (P<0.05). In conclusion, a previous crystalloid fluid load could reduce the impact of a RM on CO in healthy dogs.

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep.

A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12 sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 µg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150-166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P=0). Also, heart rate (P=0), cardiac index (P=0.002), stroke index (P=0) and contractility (P=0) were higher, and systemic vascular resistance (P=0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO2 between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.

Effects of a stepwise lung recruitment manoeuvre and positive end-expiratory pressure on lung compliance and arterial blood oxygenation in healthy dogs.

This study was performed to evaluate the effects of a stepwise lung recruitment manoeuvre (RM) on dynamic lung compliance (Cdyn) and gas exchange in mechanically ventilated healthy dogs. Fourteen healthy adult dogs, scheduled for elective surgery in dorsal recumbency were employed. After anaesthetic induction, dogs were mechanically ventilated in a volume-controlled mode (tidal volume, VT=10 mL/kg); positive end-expiratory pressure (PEEP)=0 cm H(2)O; oxygen inspired fraction (FiO(2))=0.4 for 30 min (baseline). The dogs were then randomly allocated into two groups, control and RM. The ventilatory mode was maintained during the whole surgical procedure in the control group without any intervention, as in general practice. The RM was performed in a pressure-controlled mode, with progressive increases of PEEP and end-inspiratory pressure of 5 cm H(2)O until 15 cm H(2)O and 30 cm H(2)O, respectively. After RM, PEEP was decreased to 4 cm H(2)O, and the ventilatory mode was returned to volume-control. Arterial blood gases and Cdyn were determined at baseline, 20 and 60 min afterwards. Student's t test and the one-way ANOVA test were employed to compare data. Cdyn increased in the RM group (183 ± 30% and 165 ± 24% at 20 and 60 min, respectively; P=0.000). The baseline partial pressure of arterial oxygen to FiO(2) ratio (PaO(2)/FiO(2) ratio) did not change in the control group, but was higher in the RM group (527 ± 41 mm Hg and 511 ± 46 mm Hg at 20 and 60 min, respectively; baseline 371 ± 34 mm Hg, P<0.001). In conclusion, a stepwise RM followed by the use of PEEP improves Cdyn and oxygenation in mechanically ventilated healthy dogs.

Gait analysis using 3D accelerometry in horses sedated with xylazine.

The aim of the present study was to verify the efficacy and sensitivity of an accelerometric device in detecting and quantifying the degree of movement alteration produced in horses sedated with xylazine. Horses (n=6) were randomly administered either xylazine or a control by intravenous injection, with at least 1 week between each treatment. A triaxial accelerometric device was used for the accelerometric gait assessment 15 min before (baseline) and 5, 15, 30, 45, 60, 75, 90, 105 and 120 min after each treatment. Eight different accelerometric parameters were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsion power, mediolateral power and total power, with the force of acceleration and the dorsoventral, mediolateral and craniocaudal (propulsive) parts of the power then calculated. Administration of xylazine decreased many of the parameters investigated, with significant differences for speed, stride frequency, dorsoventral power, propulsion power and total power at 5, 15, 30 and 45 min after injection. There were no significant differences in stride length values at any time point. Decreases in regularity values were evident with significant differences at every time point from 5 to 120 min following xylazine injection. Force values were also significantly reduced from 5 to 30 min after treatment and a redistribution of the total power was observed 5 min after injection as the mediolateral power increased significantly, while the dorsoventral power decreased. Accelerometry offers a practical, accurate, easy to use, portable and low cost method of objectively monitoring gait abnormalities at the walk in horses after sedation with xylazine.

Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses.

REASONS FOR PERFORMING STUDY: Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS: Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS: Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. RESULTS: Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.

Remifentanil and cyclooxygenase inhibitors interactions in the minimum alveolar concentration of sevoflurane in the rat.

BACKGROUND: Intraoperative opioids reduce anaesthetic requirements and thus limit the side-effects derived from high doses of the latter. Cyclooxygenase (COX) inhibitors can also be given but it remains unclear whether they further reduce the anaesthetic requirements. Our aim was to determine whether COX inhibitors potentiate the effect of remifentanil on the minimum alveolar concentration (MAC) of sevoflurane anaesthetized rats. METHODS: Male Wistar rats received remifentanil under sevoflurane anaesthesia, and the MAC was determined before and at two time intervals after, separated by 1.5 h. Rats were randomly allocated to receive paracetamol, metamizole, ketoprofen, or parecoxib just before one of the two studied time intervals. The MAC was determined from alveolar gas samples at the time of tail clamp. Data were analysed with an analysis of variance for repeated measures. RESULTS: Paracetamol potentiated the MAC reduction produced by remifentanil in rats (P=0.002), whereas metamizole, ketoprofen, and parecoxib failed to produce such an effect. Furthermore, paracetamol and remifentanil produced a maximum degree of MAC reduction [35 (10)%] even when a tolerance effect to remifentanil was observed in animals given remifentanil alone (P<0.001). A tolerance to remifentanil was not observed when metamizole, ketoprofen, or parecoxib was given once the opioid infusion has been started (P>0.05). CONCLUSIONS: COX inhibitors differentially potentiate the analgesic effect produced by remifentanil on the sevoflurane MAC, and paracetamol was the most effective drug. However, since all COX inhibitors prevented a tolerance effect to opioids once it was established, intraoperative rather than preoperative administration of these drugs is suggested.

Guidelines for the veterinary care of laboratory animals: report of the FELASA/ECLAM/ESLAV Joint Working Group on Veterinary Care.

Veterinary professionals working in partnership with other competent persons are essential for a successful animal care and use programme. A veterinarian's primary responsibilities are defined by their own professional regulatory bodies, but in this area of work there are further opportunities for contribution, which will assist in safeguarding the health and welfare of animals used in research. These guidelines are aimed not only at veterinarians to explain their duties, and outline the opportunities to improve the health and welfare of animals under their care, but also at employers and regulators to help them meet their responsibilities. They describe the desirability for postgraduate education towards specialization in laboratory animal medicine and detail the many competencies necessary to fulfil the role of the laboratory animal veterinarian. They detail the need for veterinary expertise to promote good health and good welfare of animals used in biomedical research during husbandry as well as when under experimental procedures. Regulatory and ethical aspects are covered as are the involvement of the veterinarian in education and training of others working in the animal care and use programme. Managerial aspects, including occupational health and safety, are also areas where the veterinarian's input can assist in the successful implementation of the programme.

Enriched protein diet-modified ghrelin expression and secretion in rats.

Gastrointestinal (GI) integrity and function are regulated by nutrition and growth factors. The discovery of ghrelin, a natural growth hormone (GH) secretagogue produced by the gastrointestinal (GI) tract, is a potential link between diet and growth signals. The aim of this study was to evaluate macronutrient effect on ghrelin expression and secretion in addition to some possible function in intestinal trophic status. Wistar rats were fed a high-carbohydrate, high-protein (HP), high-fat or standard (St) diet. Animals received the same daily food volume and caloric intake. After 7 days, animals were fasted for 24 h and blood and tissue samples were obtained just before feeding or at 2 or 6 h after feeding. Fasting high-protein-fed rats had higher ghrelin plasma levels than with rats fed the high-carbohydrate, high-fat or standard diets. Two-hours after refeeding, ghrelin plasma levels had decreased in all groups with a slight recovery at 6 h after refeeding, except in the high-protein group. Ghrelin plasma levels in rats fed with the high-protein diet correlated negatively with their GH and insulin-like growth factor 1 (IGF-1) plasma concentrations which were also the lowest among the study groups. In conclusion, ghrelin secretion was nutritionally manipulated because a protein-enriched diet increased its levels.

Growth hormone effects in intestinal adaptation after massive bowel resection in the suckling rat.

BACKGROUND: Massive small bowel resection provokes intestinal malabsorption that leads to diminished growth in the suckling rat. Growth hormone is one of the several factors that can enhance the adaptive response of the intestines in the adult rat; however, whether it also enhances postresection intestinal adaptation in the suckling rat, thus reducing the adverse effects of resection on growth, is still unclear. METHODS: Seventy-four 30-day-old suckling Wistar rats underwent 80% midgut bowel resection, laparotomy (sham operation), or no surgery. They were treated with either growth hormone or saline for 15 days and studied 15 or 45 days after surgery. Body weight was monitored and samples of bone and intestinal mucosa were obtained at the end of the study period for analysis. RESULTS: Resected rats lost body and bone weight regardless of growth hormone administration. Bowel resection provoked significant increases in the proliferation and size of the intestinal mucosa. Growth hormone significantly, but just barely, increased crypt height and mucosal mass at day 15 after surgery, but not at day 45. Lengthening of the intestines was the main effect of growth hormone. CONCLUSIONS: The relatively small adaptive response of intestines to growth hormone is insufficient to promote body growth after intestinal resection in the suckling rat. This response is lower than that in older rats and may reflect an age-related differential response to growth hormone.

Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines.

The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

Growth hormone plus high protein diet promotes adaptation after massive bowel resection in aged rats.

OBJECTIVE: To determine whether GH improves adaptation following massive bowel resection in the aged rat fed on a high protein-content diet. MATERIAL AND METHODS: Seventy-seven male Wistar rats aged 22+/-1 months underwent 80% bowel resection or laparotomy (sham-operation). They were randomly placed into one of eight groups, treated with either growth hormone (1mg/kg/day) or saline, and fed a liquid diet containing either a high or a normal protein content. Intestinal tissue and blood samples were taken seven days after surgery and analysed to measure intestinal mucosal proliferation and mucosal height, as well as plasma levels of IGF-1 and somatostatin. RESULTS: Resection of the small bowel in aged rats remarkably increased villous height and crypt proliferation. Growth hormone did not potentiate the increase in mucosal height and crypt proliferation observed after intestinal resection in aged rats fed a normal protein content diet, but did in those receiving a high-protein diet. Plasma levels of IGF-1 and somatostatin were not modified by surgery or treatment. CONCLUSION: Growth hormone may increase the adaptation of intestinal mucosa in aged rats undergoing massive intestinal resection, but requires an adequate nutritional support with increased amounts of high quality protein.

Somatostatin antagonism prevents elemental diet-induced intestinal atrophy in the rat.

Somatostatin is a peptide with known antiproliferative effects on the intestine. The aim of the present work was to determine whether somatostatin (SST) antagonism reduces elemental diet-induced intestinal atrophy in the rat. Male Wistar rats were fed a standard diet and treated for seven days with either continuous infusion of saline or low and high doses of a putative somatostatin antagonist; another group was given a SST antagonist in a pulsatile high dose. All these groups received an elemental diet to induce gut mucosa atrophy. Rats were killed and samples were obtained for morphometric and proliferative measurements of the intestine and for SST and insulin-like growth factor-1 (IGF-1) level determination. The elemental diet decreased mucosal length and proliferation. Pulsatile administration of SST antagonist improved or prevented both effects, whereas continuous SST antagonist delivery prevented decreased crypt proliferation induced by the elemental diet. Somatostatin plasma levels were lowest in rats receiving pulsatile administration of SST antagonist. In conclusion, somatostatin antagonism increases proliferation in the intestinal mucosa, improving elemental diet-induced intestinal atrophy; however, morphological growth is not affected.

La hormona de crecimiento y la dieta como protectores de la enteritis por metotrexato / Growth hormone and nutrition as protective agents against methotrexate induced enteritis

Objetivo: comprobar si la hormona de crecimiento, administrada exógenamente, es capaz de reducir o evitar el daño en la mucosa intestinal postquimioterapia. Los resultados esperados permitirán considerar su posible utilización clínica. Diseño: experimental de asignación aleatoria de los sujetos. Ámbito de estudio: Servicio de Cirugía Experimental del Hospital Universitario La Paz. Sujetos de estudio: ratas Wistar adultas macho de 250-300 g de peso. Material y métodos: se establece un protocolo de quimioterapia con metotrexato (120 mg/kg). El tratamiento consistirá en suero salino u hormona de crecimiento (1 mg/kg/día), 3 días antes y 4 después de la administración del quimioterápico. También recibirán una dieta líquida normoproteica o hiperproteica. Los animales serán sacrificados a los 7 días de la administración de la quimioterapia para la obtención de muestras. Resultados: la administración conjunta de hormona de crecimiento y una dieta hiperproteica produce un aumento de la proliferación de la cripta intestinal y una reducción de la apoptosis producida por la administración de metotrexato. Conclusiones : se valoró la estructura (morfometría), proliferación (Ki-67) y apoptosis (TUNEL) de la mucosa intestinal y eyunal (AU)