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Effetto degli oppioidi sulle cellule di tubulo renale prossimale: studio in vitro e possibili applicazioni
Full text linkOpioid are the most commonly used analgesics drugs in medicine. Beside their effect on the nervous system additional peripheral properties are also being discovered. Recently, opioid pre-conditioning and anti-apoptotic functions are some of the most studied secondary effects of these drugs. Ischemia and reperfusion injury are unavoidable insults occurring to the graft as a consequence of transplantation. As opioid receptors are expressed in the kidney, the aim of this study is to assess the effect of this class of analgesics on viability, apoptosis and necrosis in a kidney proximal tubular cell line before and after undergoes an ischemic event.
OK cells (Opossum Kidney tubular cells) expressing κ opioid receptor were exposed to 4 different opioid analgesic solutions (morphine, fentanyl, butorphanol and buprenorphine) containing 10-10, 10-8 and 10-5 M of each drug. Cells were tested in different conditions: 1) opioids were added to culture medium for 48 hours; 2) cells were pre-treated and recovered with an opioid or were exposed before or 2 hours after a simulated ischemia (SI) which was performed by ATP depletion with antimycin A and 2-deoxi-D-glucose. Colorimetric cell viability assay, luminescent ATP assay and caspase-3 and -7 activity were performed. Apoptosis and necrosis were also evaluated by annexine-V/propidium iodide staining and flow cytometric analysis.
At a high concentration fentanyl and buprenorphine decreased OK cells survival after 48 hours of exposure but the effect was limited and not significant. In ATP depletion studies, morphine and fentanyl exhibited a positive effects in preserving celluar ATP content and in decreasing caspases activities and apoptotic and necrotic ratios. Fentanyl preserved the ATP content also when administered before the SI. The present study showed no effect by butorphanol and buprenorphine on improving theATP content nor decreasing caspases activity or apoptosis.
Pure agonists of κ opioid receptors decrease the cellular damage due to ischemia/reperfusion injury mainly by maintaining intracellular ATP content but by also suppressing apoptosis. Therefore this class of drugs should be as prefered analgesics during kidney transplantation surgery.Gli analgesici oppioidi sono ampiamente usati in medicina. Questa classe di farmaci, oltre ad una azione sul sistema nervoso, ha effetti anche a livello di tessuti periferici dove i recettori oppioidi vengono espressi. Negli ultimi anni diversi studi mostrano come il precondizionamento con oppioidi abbia effetti protettivi contro i danni dovuti a ischemia e riperfusione che si presentano inevitabilmente durante un trapianto d’organo. Lo scopo del lavoro è quello di valutare l’effetto su una linea cellulare derivante da tubulo renale prossimale che esprime i recettori κ degli oppioidi, sottoposta o meno ad un evento ischemico.
Le cellule OK (Opossum Kidney tubular cells) sono state esposte a 4 oppioidi (morfina, fentanyl, butorfanolo e buprenorfina) alle concentrazioni di 10-10, 10-8, 10-5 M. Le cellule erano: 1) esposte ai farmaci per 48 ore; 2) esposte agli analgesici prima e dopo un evento ischemico indotto con antimicina A e 2-Deossi-D-glucosio od ancora trattate con i farmaci solo prima o solamente dopo. Sono state eseguite prove colorimetriche e di luminescenza per valutare la vitalità cellulare, il contenuto di ATP e attivazione delle caspasi-3 e -7. Prove citofluorimetriche erano impiegate per valutare l’apoptosi e la necrosi.
Ad alte dosi fentanyl e buprenorfina dimiuiscono la sopravvivenza delle cellule OK dopo 48 ore di esposizione ma l’effetto è limitato e non rilevante. La morfina e il fentanyl hanno un effetto positivo nel preservare il contenuto di ATP e nel diminuire l’attivazione delle caspasi e l’apoptosi. anche la necrosi diminuisce quando le cellule sono esposte a questi oppioidi prima e dopo l’evento ischemico. Il fentanyl mantiene elevato l’ATP anche quando somministrato prima dell’evento ischemico. Butorfanolo e buprenorfina non mostrano alcun effetto positivo sul contenuto di ATP o sull’apoptosi.
Gli agonisti puri dei recettori degli oppioidi κ prevengono la comparsa di apoptosi e necrosi preservando il contenuto cellulare di ATP dopo ischemia. Il loro impiego potrebbe dimostrare dei vantaggi nel prevenire i danni da ischemia e riperfusione durante interventi di trapianto renale
Effect of three opioid-based analgesic protocols on the perioperative autonomic-mediated cardiovascular response in sheep.
No full textFew reports evaluate the clinical effects of opioids in sheep during experimental surgical procedures. Catecholamine-mediated haemodynamic changes resulting from surgical noxious stimulation are blunted by opioids. The aim of this study was to evaluate the efficacy of three opioid-based analgesic protocols in avoiding a 20% increase in heart rate (HR) and/or mean arterial blood pressure (MAP) during experimental intervertebral disk nucleotomy in sheep. Eighteen female Brogna sheep were anaesthetized with propofol and maintained with a fixed end-tidal isoflurane concentration of 1.5 0.1%. Sheep were assigned to one of three groups that intravenously received methadone 0.3 mg/kg (group M), fentanyl 2 mg/kg followed by 10 mg/kg/h (group F), or buprenorphine 10 mg/kg and 30 minutes later ketamine 1 mg/kg followed by 5 mg/kg/h (group BK). Intravenous fentanyl at 2 mg/kg would have been used for rescue analgesia in case HR and/or MAP had increased. During surgery, HR and MAP values did not increase over 20% in all groups. All animals main- tained the percentage change between -4 and 7% for both variables; only one sheep in group BK had an increase in MAP superior to 20% after ketamine administration before surgical stimulation. In group M, HR decreased over time and in group BK, MAP tended to increase during surgery. All the opioid-based protocols tested were able to control the cardiovascular response to noxious stimulation in sheep undergoing spinal surgery, although ketamine may have represented a confounding factor
Effect of perfusion index on oxygen reserve index accuracy in estimating arterial oxygen tension in anesthetized dogs: Data reanalysis
Full text linkMulti-wave CO-oximetry, utilizing the oxygen reserve index (ORi), estimates arterial partial pressure of oxygen (PaO2) in mild hyperoxemia, between 100 and 200 mmHg, and concurrently quantifies local perfusion at the measurement site using the perfusion index (PI). This study explores how variations in PI influence the accuracy of ORi in estimating PaO2 in anesthetized dogs. Data from 37 mechanically ventilated dogs were retrospectively reanalyzed using a different approach. ORi and PI values were collected using a CO-oximeter. The data were categorized into four groups based on PI quartiles. In each group, the relationship between ORi and PaO2 was assessed using linear regression analysis, and the area under the receiver operating characteristic curve (AUROC) investigated the diagnostic performance of ORi in detecting PaO2 > 150 mmHg. Strong relationships between ORi and PaO2 were observed in groups with PI values 150 mmHg decre..
Effect of intraoperative constant rate infusion of lidocaine on short-term survival of dogs with septic peritonitis: 75 cases (2007-2011)
Full text linkOBJECTIVE To investigate whether intraoperative administration of a lidocaine infusion to dogs with septic peritonitis was associated with short-term (48 hours) survival after surgery. DESIGN Retrospective case series. ANIMALS 75 dogs with septic peritonitis. PROCEDURES Medical records of dogs with septic peritonitis that underwent laparotomy between January 2007 and December 2011 at the Royal Veterinary College were reviewed. Select variables during the preoperative, intraoperative, and postoperative periods and short-term survival after surgery were compared between dogs that received an opioid only (group O; n = 33) and dogs that received lidocaine (50 μg/kg/min [22.7 μg/kg/min], IV; group L; 42) in addition to an opioid during surgery. RESULTS The proportion of dogs that survived for 48 hours after surgery was significantly greater for group L (35/42) than for group O (20/33). Intraoperative infusion of lidocaine increased the odds of short-term survival (OR, 8.77; 95% CI, 1.94 to 39.57). No significant differences were observed between the 2 treatment groups for variables assessed during the preoperative and postoperative periods. During the intraoperative period, more dogs in group L received an IV bolus of a synthetic colloid than did dogs in group O, but the number of IV boluses administered was not associated with short-term survival. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IV infusion of lidocaine might improve the short-term survival of dogs with septic peritonitis. Prospective clinical trials are necessary to determine the efficacy of lidocaine as a supportive treatment for dogs with septic peritonitis
Two-Dimensional and Doppler Echocardiographic findings in healthy non-sedated red-eared slider terrapins (Trachemys scripta elegans)
No full textEchocardiographic evaluation was performed in six healthy young adult non-sedated terrapins (Trachemys scripta elegans). The best imaging quality was obtained through the right cervical window. Base-apex inflow and outflow views were recorded, ventricular size, ventricular wall thickness and ventricular outflow tract were measured, and fractional shortening was calculated. Pulsed-wave Doppler interrogation enabled the diastolic biphasic atrio-ventricular flow and the systolic ventricular outflow patterns to be recorded. The following Doppler-derived functional parameters were calculated: early diastolic (E) and late diastolic (A) wave peak velocities, E/A ratio, ventricular outflow systolic peak and mean velocities and gradients, Velocity-Time Integral, acceleration and deceleration times, and Ejection Time. For each parameter the mean, standard deviation and 95% confidence interval were calculated. Echocardiography resulted as a useful and easy-to-perform diagnostic tool in this poorly known species that presents difficulties during evaluation
Intraoperative end-tidal concentration of isoflurane in cats undergoing ovariectomy that received tramadol, buprenorphine or a combination of both
No full textThe aim of the study was to evaluate the end-tidal concentration of isoflurane required to maintain heart and respiratory rate within ± 20% of basal measurement in cats undergoing ovariectomy that received buprenorphine, tramadol or a combination of both
Evaluation of three-medetomidine based protocols for chemical restraint and sedation for non painful procedures in companion rats (Rattus norvegicus)
No full textThree medetomidine-based protocols were evaluated for sedation in companion rats undergoing diagnostic
procedures. Group Me received medetomidine at 150 μg/kg intramuscularly (IM); group Me-Bu
received medetomidine 100 μg/kg IM and butorphanol 2 mg/kg IM, and group Me-Bu-Mi received
medetomidine 50 μg/kg IM, butorphanol 2mg/kg IM and midazolam 1mg/kg IM.
The righting reflex disappeared more quickly in the Me-Bu-Mi group, but recovery after atipamezole
was longer. In group Me, a palpebral reflex was present throughout sedation in more rats than in the other
two groups. Pulse and respiratory rates were higher when lower doses of medetomidine were used, although
arterial haemoglobin O2 saturation was similar among groups. All protocols tested produced adequate
sedation lasting 25 min
Evaluation of a chemical immobilization protocol in Cape porcupine (Hystrix africaeustralis) undergoing surgical gonadectomy
No full textChemical immobilization of porcupine is often required for wildlife studies or specific clinical needs, but details and clinical effect of general anaesthesia for surgical procedures in this specie is not reported in literature. The aim of this preliminary study was to investigate the use of a novel balanced anaesthesia protocol in Cape porcupines (Hystrix africaeustralis). The primary objectives were to evaluate the quality of sedation, intubation, maintenance and recovery from anaesthesia and the impact of the combination of drugs used on the physiological parameters. The secondary objective was to assess the ease of orotracheal intubation using a traditional laryngoscope versus video-assisted intubation by means of a smartphone otoscope.
The study was conducted at the Valcorba Zoological Park, following approval from the Institutional Ethical Committee of the University of Padova. Six porcupines received a combination of dexmedetomidine (0.008 mg/kg), butorphanol (0.3 mg/kg), ketamine (5 mg/kg) and midazolam (0.2 mg/kg) intramuscularly. All the animals achieved recumbency within 5 minutes of injection and lost palpebral reflex within 10 minutes.
Intubation was firstly attempted using a video-otoscope and then achieved within 12 minutes from injection in all porcupines after 1 to 4 attempts using a laryngoscope with a Miller blade and a urinary catheter as guidewire inserted into the endotracheal uncuffed tube.
All animals underwent volatile anaesthesia with isoflurane in oxygen by spontaneous ventilation. Echocardiography and abdominal ultrasound were performed on all porcupines, surgical orchiectomy on 5 subjects. Physiological parameters such as heart rate, respiratory rate, pulse-oximetry, arterial blood pressure, end-tidal CO2 and temperature were stable in all animals during the procedures. Intratesticular administration of lidocaine 2 mg/kg contributed to preventing any pain-response to surgical stimuli. Extubation was feasible in less than a minute after the isoflurane was turned off and all porcupines were able to walk within 12 minutes of intramuscular administration of atipamezole (0.08 mg/kg).
Sedation, intubation, maintenance, and recovery quality were assessed as good in all animals, ensuring safe and effective immobilization during procedures. Moreover, recovery was predictable, and smooth in all animals. No complications occurred during the procedure nor in the follow-up. The studied drug combination might be a valid alternative in porcupine chemical immobilization and offers the possibility to perform a safe and stable anaesthesia allowing surgical orchiectomy. Moreover, the drug combination used allowed intubation, nevertheless some technical difficulties were encountered. Larynx visualization was challenging due to the anatomical features of porcupines and laryngoscope provided acceptable larynx visualization, but many attempts were often required to perform intubation. In contrast, otoscope laryngoscopy was unsuccessful in this study, although it has been reported as a simple and effective in small laboratory rodents. Other investigations are needed to optimize intubation technique, as correct airway management is fundamental to safe anaesthetic practice
Exploring oxygen reserve index for timely detection of deoxygenation in canine patients recovering from anesthesia
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