Intramuscular Injection Of Ketamine Research Articles

Adenosine diphosphate ribosylation factor 6 inhibition protects burn sepsis induced lung injury through preserving vascular integrity and suppressing ASC inflammasome transmission

BackgroundSevere burns are devastating injuries with significant immune dysfunction and result in substantial mortality and morbidity due to sepsis induced organ failure. Acute lung injury is the most common type of organ injury in sepsis, however, the mechanisms of which are poorly understood and effective therapeutic measures are limited. This study is aimed to investigate the effect of a small Guanosine triphosphatase (GTPase), Adenosine diphosphate ribosylation factor 6 (ARF6), on burn sepsis induced lung injury, and discuss the possible mechanisms. MethodsBurn sepsis was established in male C57BL/6 mice. Mice were anesthetised by intramuscular injection of ketamine and xylazine hydrochloride, then 30% TBSA full thickness burn followed by sub-eschar injection of lipopolysaccharide. Animals were treated with intraperitoneal injection of a small molecule inhibitor of ARF6: NAV-2729, or vehicle, right after the burn and sepsis stimuli were inflicted. Lung tissues were harvested for histopathological observation and the acute lung injury scores were calculated. Organ permeability, Vascular Endothelial Cadherin (VE-cadherin) expression, inflammatory cytokine levels and myeloperoxidase activity in lung tissues were detected. Rat pulmonary microvascular endothelial cells (PMVECs) were stimulated by burn sepsis serum with or without 10 μM NAV-2729. The ARF6 activation, VE-cadherin expression, inflammasome activity, adapter protein apoptosis speck-like protein containing a caspase recruiting domain (ASC) specks and cytokines secretion were determined. Student’s t test was used for comparison between two groups. Multiple comparisons among groups were performed by using analysis of variance, with Tukey’s test for the post hoc test. ResultsNAV-2729 treatment attenuated burn sepsis induced lung injury and promoted survival of burn septic mice by preserving VE-cadherin expression in endothelial cell adherent junction and limited vascular hyperpermeability in lung tissues. Moreover, inflammatory cytokine expression and inflammatory injury in lung tissues were alleviated. Mechanistically, NAV-2729 enhanced vascular integrity by inhibiting ARF6 activation and restoring VE-cadherin expression in PMVECs. In addition, NAV-2729 inhibited ARF6-dependent phagocytosis of ASC specks, thus preventing inflammation propagation mediated by cell-to-cell transmission of ASC specks. ConclusionsARF6 inhibition preserved vascular integrity by restoring expression of VE-cadherin and suppressed the spread of inflammation by affecting phagocytosis of ASC specks, thus protected against sepsis induced lung injury and improve survival of burn septic animals. The findings of this study implied potential therapeutics by which ARF6 inhibition can protect lung function from septic induced lung injury and improve outcomes in burn sepsis.

Randomised, prospective, blinded, clinical trial of opioid-free injectable anaesthesia with or without multimodal analgesia in kittens undergoing ovariohysterectomy.

This study compared an opioid-free injectable anaesthetic protocol with or without multimodal analgesia in kittens undergoing ovariohysterectomy. In this prospective, randomised, blinded, clinical trial, 29 healthy kittens (mean ± SD weight 1.55 ± 0.46 kg; aged 10 weeks to 6 months) were included. Anaesthesia was performed with an intramuscular injection of ketamine (4 mg/kg), dexmedetomidine (40 μg/kg) and midazolam (0.25 mg/kg). In the multimodal group (MMG), cats (n = 14) received meloxicam (0.1 mg/kg SC) and intraperitoneal bupivacaine 0.25% (2 mg/kg), whereas the same volume of saline was administered in the control group (CG; n = 15). Atipamezole (0.4 mg/kg IM) was given 15 mins after ovariohysterectomy. Postoperative pain was assessed using the UNESP-Botucatu multidimensional feline pain assessment scale - short form. Rescue analgesia (buprenorphine 0.02 mg/kg IM in MMG/CG and meloxicam 0.1 mg/kg SC in CG) was administered if pain scores were ⩾4/12. Soft food intake (after 2 and 60 mins) was evaluated at specific time points postoperatively. Statistical analyses were performed with linear models and post-hoc pairwise comparison with Benjamini-Hochberg corrections (P <0.05). The prevalence of rescue analgesia was higher in the CG (n = 15/15) than the MMG (n = 1/14; P <0.001). Pain scores at 1 h, 2 h and 4 h postoperatively were higher in the CG (4.1 ± 2.8, 4.8 ± 3.0 and 5.3 ± 1.2, respectively) than in the MMG (1.6 ± 1.0, 1.1 ± 1.0 and 0.9 ± 0.8, respectively; P <0.001). Food intake (%) at 1 h postoperatively was higher in the MMG after 2 and 60 mins (10.4 ± 9 and 71.9 ± 29, respectively) than in the CG (1.4 ± 2 and 13.9 ± 7, respectively; P <0.001). This opioid-free protocol using multimodal analgesia produced adequate postoperative pain relief, while almost eliminating the need for rescue analgesia in kittens undergoing ovariohysterectomy. Pain decreased food intake.

PECULIARITIES OF THE STRUCTURAL AND FUNCTIONAL REARRANGEMENT OF THE PARENCHYMA OF THE TESTES OF RATS WITH DOSED STENOSIS OF THE AORTO-ILIAC SEGMENT

Relevance. Abdominal ischemic disease is a general term that characterizes various clinical syndromes of damage to the organs of the digestive system when blood flow is disturbed in the abdominal part of the aorta and its branches, as a result of which there is a disparity of the blood supply of internal organs to their energy needs with the subsequent development of chronic ischemia and necrosis of cells and tissue.&#x0D; Objective. To establish the characteristic features of the dynamics of the remodeling of the blood vessel of the testicles of rats with dosed stenosis of the aorto-iliac segment.&#x0D; Materials and methods. The experiment was conducted on 48 white outbred sexually mature male rats with an average age of 3 months and a weight of 180-200 g. All animals were divided into two groups: experimental group consisted of 36 animals with simulated dosage stenosis of the aorto-iliac segment and control group (12 subjects). All operative manipulations were performed in compliance with the rules of asepsis and antisepsis. Preliminary anesthetization of the animals was carried out with the intramuscular injections of ketamine (50 mg/ml) in terms of 0.083 mg/g of body weight. After performing a laparotomy through a midsection along the white line of the abdominal wall, the abdominal aorta was isolated and compressed by 1/3 of its diameter by applying a silk ligature. The degree of narrowing was controlled using a metal probe with a cone-shaped tip according to the already known method. On the 1st, 3rd, 7th, and 14th day, the animals were taken out of the experiment and an organometric assessment of the condition of the testicles was carried out with the determination of the following parameters: the weight of the organ was determined using a torsion weight VT-500, the length and width were measured using a caliper. After that, pieces of testicular tissue were taken and fixed in a 10% solution of neutral formalin and 96% ethyl alcohol. The obtained paraffin sections with a thickness of 5-7 μm were stained with hematoxylin and eosin, and microscopic examination of a series of histological sections was carried out.&#x0D; Results. A day after the simulation of experimental stenosis of the aorto-iliac segment, a microscopic examination of the structures of the testicle revealed significant swelling of the stroma of the organ. The interstitial tissue was unevenly located between the tortuous seminiferous tubules, the lumen between which was slightly expanded. At the same time, the internal structure of the tubules remained preserved, layers of spermatogenic cells at different stages of maturation were clearly differentiated in them.&#x0D; On the third day of observation, previously identified signs of disorders of organ blood circulation in the testicles continued to increase. The swelling of the testicular interstitial tissue slightly decreased, but it was accompanied by changes in the structure of the cells of the spermatogenic epithelium, the manifestation of which was the detachment of spermatogonia from the basal membrane of the tubules and the expansion of the spaces between the rows of spermatogenic cells. The walls of the small arteries and arterioles were still significantly thickened.&#x0D; On the 7th day of observation, against the background of a significant decrease in the swelling of the space between the tortuous seminiferous tubules, dystrophic changes in the testicular tissue began to increase.&#x0D; On the 14th day of observation, even more expressed signs of organ hemodynamics violation were observed, and as a result, deviations of the trophism of testicles of experimental animals. Manifestation of such changes were prominent arterial and venous plethora. Large-caliber arteries were significantly filled with blood, and as a result, small and medium-caliber arteries, especially arterioles, had thickened walls and a markedly narrowed lumen.&#x0D; Conclusion. With dosed stenosis of the aorto-iliac segment, significant disorders of central hemodynamics occur, which are characteristic of occlusive diseases of the aorta and its branches.&#x0D; As a result, in the testes of sexually mature male rats, dystrophic changes in the cells of the spermatogenic epithelium occur and the functional activity of the organ decreases, which can form the basis for the development of infertility.

S-ketamine and intranasal application: alternatives for the castration of male suckling piglets?

BackgroundThe intramuscular injection of ketamine and azaperone was proposed as a suitable anaesthesia for male suckling piglets for surgical castration. However, this can be opposed by massive defensive movements, hypothermia and tachycardia during castration and a long recovery period. The aim of the present study was to test whether the use of S-ketamine and/or a change in the route of application from intramuscular to intranasal could reduce stress responses and the duration of recovery compared to the intramuscular route and the use of racemic ketamine. Seventy-eight healthy, five-day-old male piglets were randomized to six treatment groups in a blinded experimental study, matched by litter and weight. Experimental groups were A (15 mg kg-1 S-ketamine + 2 mg kg-1 azaperone, i.m., surgical castration), B (15 mg kg-1 R/S-ketamine racemate + 2 mg kg-1 azaperone, i.m., surgical castration), C (30 mg kg-1 S-ketamine + 2 mg kg-1 azaperone, i.n., surgical castration), D (15 mg kg-1 R/S-ketamine racemate + 2 mg kg-1 azaperone, i.m.; not castrated), E (positive control group; no anesthesia, surgical castration) and F (negative control group; no anesthesia, not castrated).ResultsS-ketamine reduced the defensive movement score during castration to a similar extent to racemic ketamine when administered intramuscularly but not via the intranasal route. However, the effects of S-ketamine (both routes) on the increase in cortisol levels and decrease in body temperature were similar to those induced by racemic ketamine. A reduction of the long recovery time known for ketamine-azaperone anaesthesia could not be achieved with S-ketamine in the given dosage, regardless of the route of application. The intranasal administration of ketamine was difficult with the available formulation as the necessary amount exceeded the capacity of the nose cavity.ConclusionsNeither the use of S-ketamine nor intranasal administration can be suitable alternatives for the anaesthesia of male suckling piglets for castration.

FIELD ANESTHESIA AND GONADAL MORPHOLOGY OF IMMATURE WESTERN SANTA CRUZ TORTOISES (CHELONOIDIS PORTERI).

Evaluation of sex ratios is a critical component of chelonian captive breeding programs and may become increasingly useful to assess the demographics of free-living populations. In many reptile species, the sex of immature animals cannot be determined based on external features. Endoscopic sex identification is an accurate and safe method to identify the sex of immature individuals of some chelonian species. A number of studies describe this technique in controlled, hospital settings and report significant interspecies variations in gonad morphology; however, there are few reports describing this technique in field conditions. In the current study, the gonadal morphology of 40 immature Western Santa Cruz tortoises (Chelonoidis porteri) on Santa Cruz Island in Galapagos, Ecuador, was assessed. A previously described endoscopic protocol was used to perform sex identification under field conditions. Tortoises were anesthetized using an intramuscular injection of ketamine (10 mg/kg) and medetomidine (0.1 mg/kg), which provided an adequate plane of anesthesia. The medetomidine was reversed with atipamezole (0.5 mg/kg). Field conditions presented challenges such as limited control over lighting, suboptimal patient positioning, and restricted power supply for endoscopy equipment. The immature testicle in Western Santa Cruz tortoises was oval, reddish pink, and tightly adhered to the coelomic membrane ventral to the kidney. The surface of the gonads resembled other species with the notable exception that the ovaries lacked a significant number of primordial follicles. These gonadal characteristics were consistent, with only one individual identified as undetermined sex of the 40 samples. This field-based endoscopic gonadal evaluation was a safe and sensitive technique for determining the sex of free-living immature Western Santa Cruz Galapagos tortoises.

Grape seed extract inhibits nucleus pulposus cell apoptosis and attenuates annular puncture induced intervertebral disc degeneration in rabbit model.

Low back pain is a musculoskeletal disorders implicated to disc degeneration. Grape seed extracts (GSEs) is a natural flavonoids rich compound with antioxidants and anti-inflammatory properties. This study is aimed at investigating the inhibitory and anabolic response of GSE on annular punctured induced disc degeneration in rabbit model. Twenty-Eight New Zealand white rabbits (weighing about 2.0–3.5 kg) were used with institutional animal care committee’s approval. The animals were divided into four groups (n=7 per group). Group A (non-punctured group) received distilled water orally for 4 weeks. Group B (punctured group) received distilled water for 4 weeks. Group C (punctured treated group) received distilled water for 4 weeks and thereafter received 500 mg/kg of GSE for another 4 weeks. Group D received 500 mg/kg of GSE immediately after puncture for 4 weeks. At the end of the experiment, the animals were sacrificed with intramuscular injection of ketamine followed by intravenous injection of sodium pentobarbital. The percentage disc height index of the punctured group showed significant decrease compared to the control and treated groups. Histological and immunohistochemical studies showed distortion in the disc morphology, decrease in chondrocyte like cells, disorganization of collagen and elastic fibers, increase Bax expression levels in the punctured group compared to control and treated groups which was attenuated after GSE administration. GSE has preventive and restorative effects on punctured induced disc preventing the degradation of collagen fibrils within the disc tissues.

Anatomical, Histological and Histochemical Investigation of Soft Palate in Cat (Felis Catus Domesticus.L)

Objectives: The aim of this study was to evaluate the normal structure and provide distribution for palatine glands in cranial and caudal part of soft palate. Also, afford information to be useful for both surgical interventions and pathological disease. Method/: Sixth healthy cats were caught in Iraq farms. All experimental animals euthanized by intramuscular injection of ketamine (0.5 cc) and xylazine (0.5 cc), Sections were stained by H&E and combined AB+PAS stain 2.5 pH. Results: The soft palate was triangular in shape, the dimensions was (2.8, 2) cm in length and width respectively. Also, had two surface; nasopharyngeal surface lined by psuedostratified columnar epithelial ciliated and oropharyngeal surface lined by stratified squamous epithelia. The palatine glands appeared magenta in color during staining by AB+PAS combined stain due to neutral secretion. Conclusion: The palatine glands variance in distribution between dorsal and ventral surface of soft palate, most of these glands constricted in oropharyngeal surface.

Intusussception Secondary to Gastrointestinal Foreign Body in an Eleven Month old Juvenile African Lion (Panthera Leo) Case Report

Abstract An eleven month old male, juvenile lion brought for rehabilitation at the Olusegun Obasanjo Presidential Library (OOPL) Wildlife Park was diagnosed with gastrointestinal foreign body and intussusception based on the history of persistent vomiting following ingestion of a cotton towel, and radiographic findings of a radiopaque gastric foreign body extending from the fundus to the pylorus and a cylindrical soft tissue mid-abdominal mass. The lion was premedicated with an intramuscular injections of ketamine (5 mg.kg−1) and midazolam (0.25 mg.kg−1), while anaesthesia was induced with an intravenous injection of propofol (2 mg.kg−1). A celiotomy followed by gastrotomy and subsequent intestinal resection and anastomosis was performed to remove the gastrointestinal foreign bodies and correct the intussus ception. The lion recovered well without any complication and was gradually introduced back into the group housing three weeks later following successful alimentation process. This report is probably the first case of intussusception in a lion that was associated with a gastrointestinal foreign body.

More effective induction of anesthesia using midazolam-butorphanol-ketamine-sevoflurane compared with ketamine-sevoflurane in the common marmoset monkey (Callithrix jacchus).

The common marmoset has been increasingly used for research in the biomedical field; however, there is little information available regarding effective methods of anesthesia in this species. This study retrospectively analyzed 2 regimens of anesthesia induction: intramuscular injection of ketamine followed by inhalation of 5% sevoflurane, and intramuscular injection of midazolam, butorphanol and ketamine followed by inhalation of 5% sevoflurane. Anesthetic depth did not reach the surgical anesthesia stage in 7 out of 99 animals receiving the former regimen, whereas there were only 2 such animals out of 273 receiving the latter regimen. The latter regimen, when followed by maintenance anesthesia with 3% sevoflurane inhalation, was successfully used in various nociceptive procedures. These results indicate that the injection of a combination of midazolam, butorphanol and ketamine followed by inhalation of a high concentration of sevoflurane is effective for anesthesia induction in marmosets.

Chemical restraint of African mole-rats (Fukomys sp.) with a combination of ketamine and xylazine

ObjectiveTo establish an accurate anaesthetic dose for chemical restraint of African mole-rats using ketamine and xylazine. Study designProspective nonrandomized laboratory study. AnimalsSixteen adult Ansell’s mole-rats (Fukomys anselli) and eight giant mole-rats (F. mechowii). MethodsFukomys anselli of different ages, sexes and reproductive status were systematically anaesthetized starting with an intramuscular injection of ketamine (2.5 mg kg−1) and increasing the doses in steps of 0.5 mg kg−1 until loss of the righting reflex (LRR) was observed. Xylazine was added to a constant dose of ketamine, starting at 0.5 mg kg−1 that was increased by 0.5 mg kg−1 in further trials. Once an effective combination was established and evaluated in F. anselli, it was also tested in F. mechowii. Heart and respiratory rates and rectal temperatures were measured during anaesthesia. anova for repeated measures and Student’s t-test were used to compare means. ResultsChemical restraint was accomplished at a dose of 6 mg kg−1 ketamine combined with 2.5 mg kg−1 xylazine. LRR lasted on average mean 56 ± SD 19 minutes (F. anselli) and 140 ± 41 minutes (F. mechowii). Loss of pedal withdrawal reflex (LPR) lasted for 20 ± 15 minutes (F. anselli) and for 29 ± 2 minutes (F. mechowii), respectively. All animals recovered satisfactorily. Heart and respiratory rates were stable during anaesthesia, but rectal temperature fell significantly in F. mechowii after losing the righting reflex (LRR) from T1 (32.6 ± 0.6 °C) to T3 (30.4 ± 0.9 °C). Conclusions and Clinical relevanceAfrican mole-rats (Bathyergidae) live in closed burrow systems under particular conditions (hypercapnia, hypoxia, stable temperature, humidity, darkness) and show several physiological adaptations. Injectable anaesthetics in the dose rates used in other rodents are not appropriate for use in these subterranean species. Here, a reliable protocol for chemical restraint is provided.

Histopathological study of the Influence of Estradiol on Liver Regeneration in Male Rabbit

This study was investigated to recognize the generative capacity of liver that influenced by administration of estradiole benzoate. Twenty four healthy local breed male rabbits weighed 1.5-2 kg were used .They were classified into two equal groups control and treated groups. Animals anaesthetized by intramuscular injection of Ketamine (35mg /kg B.W) and Xylazine (5mg\kg B.W.) In control group partial hepatectomy of liver was done, while in treated animals were subject to a same operation then received an intramuscular injection 0.1ml of estradiol benzoate 0.2% at 3rd and 5th days post operation. At 3rd days microscopic finding showed biopsy were taken at 3rd, 7th and 14 day, post operation to study the histopathological changes in liver regeneration .At 3rd day it showed early proliferation of hepatocyte character by irregular hyperchromatic multinucleated cell .While in control group it showed necrotic area of liver parenchyma surrounded by thick fibrous connective tissue infiltrated with inflammatory cells. At 7th day in treated animals still progress in proliferation of hepatocyte while, liver proliferation phase showed in control group .At 14th day in treated animals showed large cells of hepatocyte with double nuclei aggregation without central vein , while in control group showed small hyperchromatic hepatocyte with present of necrotic area. In conclusion the results of this study indicate that administration of estrogen after partial resection in male rabbits has a role in liver regeneration by early initiate or facilitate heypatocyte proliferation.

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity. Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6mg/kg/min for 30minutes. BIC (3mL/kg 8.4%), ILE (3mL/kg 20%), or LIP (24mg/kg) were infused as rescue treatments at toxicity and were repeated at 10minutes (n=5 in each group). Thirty-minute MAP was greatest in ILE-treated animals: 61mmHg ILE (interquartile range [IQR]= 49 to 64mmHg), 43mmHg LIP (IQR= 36.5 to 49mmHg), and 10mmHg BIC (IQR= 10 to 44mmHg; all p=0.02). Two of the five BIC-treated animals survived to 30minutes, compared with all five of the ILE-treated animals and all five of the LIP-treated animals (p=0.044). Both ILE and LIPs improved hemodynamic recovery compared with bicarbonate in clomipramine-induced cardiotoxicity in rabbits. Greater 30-minute MAP was observed in the ILE group.

PHYSIOLOGIC AND SERUM BIOCHEMISTRY VALUES IN FREE-RANGING HOFFMANN'S TWO-TOED (CHOLOEPUS HOFFMANNI) AND BROWN-THROATED THREE-TOED (BRADYPUS VARIEGATUS) SLOTHS IMMOBILIZED USING DEXMEDETOMIDINE AND KETAMINE

Dexmedetomidine, a highly selective alpha-2 adrenergic agonist and dextrorotary enantiomer of medetomidine, was combined with ketamine and used to immobilize 14 free-ranging Choloepus hoffmanni (Hoffmann's two-toed sloths) and 11 Bradypus variegatus (brown-throated three-toed sloths) in Upala, Costa Rica. Following intramuscular injection of ketamine (2.1 mg/kg) and dexmedetomidine (11 microg/kg), heart rate, respiratory rate, and indirect systolic blood pressure were measured every 5 min for a total of 25 min. An iStat (CG8+) was used to evaluate serum biochemical and hematologic values during anesthesia. After 30 min of anesthesia, atipamezole (0.13 mg/kg) was administered intramuscularly, which resulted in rapid and smooth recoveries. Mean heart rate and respiratory rate remained unchanged in both C. hoffmanni and B. variegatus over time. Progressive decreases in mean indirect systolic blood pressure were documented in both species. Results of this study suggest a combination of dexmedetomidne and ketamine is a safe and effective anesthetic protocol for use in free-ranging C. hoffmanni and B. variegatus. Similar to other alpha-2 adrenergic agonist-based immobilization protocols, close monitoring of cardiovascular and respiratory parameters are recommended. This study also provides serum biochemical and hematologic data in free-ranging C. hoffmanni and B. variegatus.

Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study

OBJECTIVE: To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR) and ischemia-reperfusion + tramadol (IR+T). The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively). All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v.) immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p.), the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies. RESULTS: Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both). Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group. CONCLUSIONS: On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion.

The effect of general anaesthesia on gastric myoelectric activity in experimental pigs

BackgroundSurface electrogastrography (EGG) is a non-invasive method for clinical assessment of gastric myoelectrical activity. Different forms of general anaesthesia might have various effects on porcine EGG. The aim of this study was to evaluate the impact of different anaesthetic agents on EGG in experimental pigs.MethodsFour 15-minute EGG intervals were recorded and analysed. A baseline EGG recording was started 20 minutes after intramuscular injection of ketamine and azaperone (periods A and B). Four different regimens of general anaesthesia followed immediately after the baseline EGG (5 pigs in each experimental group): thiopental, isoflurane, nitrous oxide and isoflurane plus nitrous oxide. EGG recordings followed for the next 30 minutes under general anaesthesia (periods C and D). The dominant frequencies of slow waves were compared between the baseline intervals A and B and periods C and D under general anaesthesia.ResultsThe mean dominant frequency was within the normal range (2.3 – 3.5 cycles per minute) in all animals in all regimens. Thiopental general anaesthesia did not influence any change of the dominant frequency of slow waves. Nitrous oxide general anaesthesia increased the dominant frequency of slow waves in a statistically significant manner (baseline: 2.93 ± 0.53 and 3.01 ± 0.53; under general anaesthesia: 3.25 ± 0.34 and 3.29 ± 0.38 cycles per minute; p < 0.001, p = 0.003, p < 0.001, p < 0.001). Nitrous oxide together with isoflurane induced a statistically significant decrease of dominant frequency in the last 15-minute interval (2.66 ± 0.55 cycles per minute) compared to the baseline recording (2.81 ± 0.49; p = 0.030).ConclusionsAll changes of porcine gastric myoelectric activity assessed by the dominant frequency of slow waves during EGG remained within the normal range although some of them achieved statistical significance. Thus all tested agents used for general anaesthesia can be recommended in preclinical studies with porcine models focused on gastric myoelectric activity without any risk of compromising the results. Thiopental seems to be the most suitable as it did not cause any changes at all.

Short-Term Effects of Ketamine and Isoflurane on Left Ventricular Ejection Fraction in an Experimental Swine Model

Background. General anesthesia is an essential element of experimental medical procedures. Ketamine and isoflurane are agents commonly used to induce and maintain anesthesia in animals. The cardiovascular effects of these anesthetic agents are diverse, and the response of global myocardial function is unknown. Methods. In a series of 15 swine, echocardiography measurements of left ventricular ejection fraction (LVEF) were obtained before the animals received anesthesia (baseline), after an intramuscular injection of ketamine (postketamine) and after inhaled isoflurane (postisoflurane). Results. The mean LVEF of an unanesthetized swine was 47 ± 3%. There was a significant decrease in the mean LVEF after administration of ketamine to 41 + 6.5% (P = 0.003). The addition of inhaled isoflurane did not result in further decrease in mean LVEF (mean LVEF 38 ± 7.2%, P = 0.22). Eight of the swine had an increase in their LVEF with sympathetic stimulation. Conclusions. In our experimental model the administration of ketamine was associated with decreased LV function. The decrease may be largely secondary to a blunting of sympathetic tone. The addition of isoflurane to ketamine did not significantly change LV function. A significant number of animals had returned to preanesthesia LV function with sympathetic stimulation.

Neural mechanism of activity spread in the cat motor cortex and its relation to the intrinsic connectivity

Motor cortical points are linked by intrinsic horizontal connections having a recurrent network topology. However, it is not known whether neural activity can propagate over the area covered by these intrinsic connections and whether there are spatial anisotropies of synaptic strength, as opposed to synaptic density. Moreover, the mechanisms by which activity spreads have yet to be determined. To address these issues, an 8 × 8 microelectrode array was inserted in the forelimb area of the cat motor cortex (MCx). The centre of the array had a laser etched hole ∼500 μm in diameter. A microiontophoretic pipette, with a tip diameter of 2-3 μm, containing bicuculline methiodide (BIC) was inserted in the hole and driven to a depth of 1200-1400 μm from the cortical surface. BIC was ejected for ∼2min from the tip of the micropipette with positive direct current ranging between 20 and 40 nA in different experiments. This produced spontaneous nearly periodic bursts (0.2-1.0 Hz) of multi-unit activity in a radius of about 400 μm from the tip of the micropipette. The bursts of neural activity spread at a velocity of 0.11-0.24 ms⁻¹ (mean=0.14 mm ms⁻¹, SD=0.05)with decreasing amplitude.The area activated was on average 7.22 mm² (SD=0.91 mm²), or ∼92% of the area covered by the recording array. The mode of propagation was determined to occur by progressive recruitment of cortical territory, driven by a central locus of activity of some 400 μm in radius. Thus, activity did not propagate as a wave. Transection of the connections between the thalamus and MCx did not significantly alter the propagation velocity or the size of the recruited area, demonstrating that the bursts spread along the routes of intrinsic cortical connectivity. These experiments demonstrate that neural activity initiated within a small motor cortical locus (≤ 400 μm in radius) can recruit a relatively large neighbourhood in which a variety of muscles acting at several forelimb joints are represented. These results support the hypothesis that the MCx controls the forelimb musculature in an integrated and anticipatory manner based on a recurrent network topology

Interleukin-1β Inhibition Prevents Choroidal Neovascularization and Does Not Exacerbate Photoreceptor Degeneration

The pro-inflammatory cytokine IL-1β has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1β in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1β expression significantly increased after laser injury (real time PCR) in C57BL/6 mice, in the C57BL/6 Cx3cr1(-/-) model of age-related macular degeneration (enzyme-linked immunoabsorbent assay), and in albino Wistar rats and albino BALB Cx3cr1(+/+) and Cx3cr1(-/-) mice (enzyme-linked immunoabsorbent assay) after light injury. IL-1β was localized to Ly6G-positive, Iba1-negative infiltrating neutrophils in laser-induced CNV as determined by IHC. IL-1 receptor antagonist treatment significantly inhibited CNV but did not affect Iba1-positive macrophage recruitment to the injury site. IL-1β significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1β on choroidal endothelial cell proliferation. Inhibition of IL-1β in light- and laser-induced RD models did not alter photoreceptor degeneration in Wistar rats, C57BL/6 mice, or RD-prone Cx3cr1(-/-) mice. Our results suggest that IL-1β inhibition might represent a valuable and safe alternative to inhibition of vascular endothelial growth factor in the control of CNV in the context of concomitant photoreceptor degeneration as observed in age-related macular degeneration.

Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment

Stromal cell-derived factor-1 (SDF-1) causes chemotaxis of CXCR4-expressing bone marrow-derived cells. SDF-1 is involved in the pathogenesis of various vascular diseases, including those of the eye. However, the role of SDF-1 in neuronal diseases is not completely understood. Here, we show higher SDF-1 levels in the vitreous humor of patients with retinal detachment (RD) compared with normal patients. SDF-1 correlated positively with the duration as well as the extent of RD. Furthermore, SDF-1 correlated significantly with levels of interleukin-6 and interleukin-8, but not with vascular endothelial growth factor. Western blot analysis results showed significant SDF-1 up-regulation in detached rat retinas compared with normal animals. Immunohistochemistry data showed that SDF-1 was co-localized with the glial cells of the detached retina. SDF-1 blockade with a neutralizing antibody increased photoreceptor cell loss and macrophage accumulation in the subretinal space. The retinal precursor cell line R28 expressed CXCR4. SDF-1 rescued serum starvation-induced apoptosis in R28 cells and enhanced their ability to participate in wound closure in a scratch assay. Our results indicate a surprising, protective role for SDF-1 in RD. This effect may be mediated directly or indirectly through other cell types.

Wpływ wykonania kochleostomii na zachowanie słuchu – badania na modelu zwierzęcym

To assess an effect of cochleostomy on hearing threshold in guinea pigs. The authors performed animal experiments using five 3-month-old guinea pigs. Before experiment hearing threshold were evaluated. Surgery involved access to the temporal bone by a post-auricular incision. After a wide opening of the bulla cochleostomy was created (10,000 turn/min, diamond bur of 0.8 mm diameter). Hearing threshold was identified on the basis of presence of wave V in auditory brainstem responses (ABR) for click and frequency-specific stimulation. Also morphology and latency changes for wave V for this stimulation was assessed. Hearing status was evaluated before, just after and 1-, 2-, and 4-weeks after surgery. For surgical procedure and ABR examination all animals were anesthetized with an intramuscular injection of ketamine (50 mg/kg) mixed with xylazine (9 mg/kg) in the supplemental doses. After surgery the animal was treated by antibioticoterapy for 3 days--Enrofloksacyna 0.3 ml subcutaneouly and analgesic--Tolfedine 0.05 mg in second day. Four week observation of ABR morphology and hearing thresholds for click and frequency-specific stimulation of 100 dB SPL intensity showed only temporary changes confirming that cochleostomy did not affect cochlear function. The correctly performed cochleostomy in guinea pigs did not affect persistently the cochlear function indicating that such an option of CI electrode insertion in patients is safe.