Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

REASON FOR PERFORMING STUDY: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. OBJECTIVES: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. METHODS: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. RESULTS: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. CONCLUSIONS AND POTENTIAL RELEVANCE: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.

Racial differences in the incidence of gliomas: a retrospective study from Memphis, Tennessee.

This study records the incidence of glioblastoma multiforme, astrocytoma and oligodendroglioma in the white and Black patients in the Memphis Statistical Metropolitan Area (MSMA) during a 10.5-year period from 1 January 1984 through 30 June 1994. During this time, only six hospitals performed craniotomy and computer tomography (CT) scanning was routine in each of the hospitals. A total of 824 histologically confirmed first diagnoses were made at these six area hospitals. Based on the zip code listed as the home address, we determined patient's locale and identified 373 patients (232 glioblastoma multiforme, 106 astrocytomas and 35 oligodendroglioma) who resided in the area during the study interval. There were 50 black and 323 white patients. The background population for the area was obtained from the US Census Bureau's statistics for the year 1990. These statistics indicated that 40.5% of the population identified themselves as black and 57.9% as white. Age adjusted incidence rates were 1.550 (p < 0.001) for other astrocytomas, and 0.106 and 0.461 (p = 0.003) in the black and white populations, respectively. There was no significant difference in survival between the two populations. This study confirms a significant disparity in incidence rates for the three most common gliomas between the black and white populations and this disparity is higher than predicted by previous reports.

Anesthetic, cardiorespiratory, and metabolic effects of four intravenous anesthetic regimens induced in horses immediately after maximal exercise.

OBJECTIVE: To determine the anesthetic, cardiorespiratory, and metabolic effects of 4 IV anesthetic regimens in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill. Each horse ran 4 simulated races, with a minimum of 14 days between races. Races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until fatigued or for a maximum of 2 minutes. Two minutes after exercise, horses received a combination of xylazine hydrochloride (2.2 mg/kg of body weight) and acepromazine maleate (0.04 mg/kg) IV. Five minutes after exercise, horses received 1 of the following 4 IV anesthetic regimens: ketamine hydrochloride (2.2 mg/kg); ketamine (2.2 mg/kg) and diazepam (0.1 mg/kg); tiletamine hydrochloride-zolazepam hydrochloride (1 mg/kg); and guaifenesin (50 mg/kg) and thiopental sodium (5 mg/kg). Treatments were randomized. Cardiopulmonary indices were measured, and samples of blood were collected before and at specific times for 90 minutes after each race. RESULTS: Each regimen induced lateral recumbency. The quality of induction and anesthesia after ketamine administration was significantly worse than after other regimens, and the duration of anesthesia was significantly shorter. Time to lateral recumbency was significantly longer after ketamine or guaifenesin-thiopental administration than after ketaminediazepam or tilet-amine-zolazepam administration. Arterial blood pressures after guaifenesin-thiopental administration were significantly lower than after the other regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia can be safely induced in sedated horses immediately after maximal exercise. Ketamine-diazepam and tilet-amine-zolazepam induced good quality anesthesia with acceptable perturbations in cardiopulmonary and metabolic indices. Ketamine alone and guaifenesin-thiopental regimens are not recommended.

Comparison of four drug combinations for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis.

OBJECTIVE: To evaluate anesthetic effects of 4 drug combinations used for total intravenous anesthesia of horses undergoing surgical removal of an abdominal testis. DESIGN: Clinical trial. ANIMALS: 32 healthy cryptorchid horses. PROCEDURE: Horses were sedated with xylazine and butorphanol and were randomly assigned to 1 of 4 groups: induction of anesthesia with ketamine and diazepam and maintenance with bolus administration of ketamine and xylazine (KD/KX); induction and maintenance of anesthesia with bolus administration of tiletamine-zolazepam, ketamine, and detomidine (TKD); induction and maintenance of anesthesia with continuous infusion of xylazine, guaifenesin, and ketamine; and induction and maintenance of anesthesia with continuous infusion of guaifenesin and thiopental. Horses that moved 3 consecutive times in response to surgical stimulation or for which surgery time was > 60 minutes were administered an inhalant anesthetic, and data from these horses were excluded from analysis. RESULTS: Quality of induction was not significantly different among groups. Muscle relaxation and analgesia scores were lowest for horses given KD/KX, but significant differences among groups were not detected. Horses anesthetized with TKD had a significantly greater number of attempts to stand, compared with the other groups, and mean quality of recovery from anesthesia for horses in the TKD group was significantly worse than for the other groups. Anesthesia, surgery, and recovery times were not significantly different among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that all 4 drug combinations can be used to induce short-term anesthesia for abdominal cryptorchidectomy in horses. However, horses receiving TKD had a poorer recovery from anesthesia, often requiring assistance to stand.

Transarterial coil embolization of the internal and external carotid and maxillary arteries for prevention of hemorrhage from guttural pouch mycosis in horses.

OBJECTIVES: To develop a transarterial coil embolization technique for occlusion of the internal carotid artery (ICA), external carotid artery (ECA), and maxillary arteries (MA) in normal horses and to evaluate this technique for prevention of hemorrhage in horses affected with guttural pouch mycosis. ANIMALS: Ten adult, normal horses and 4 horses with guttural pouch mycosis. METHODS: All horses had transarterial coil embolization of the rostral and caudal ICA, caudal MA, and rostral ECA. In 1 affected horse, an aberrant actively bleeding branch of the ECA was also occluded. Normal horses had a premortem angiogram, and were killed either at 1 or 2 weeks or 1, 2, or 3 months after the procedure. Specimens from the ICA, ECA and MA were evaluated by light microscopy. RESULTS: No surgical complications were observed, except 1 horse that developed laryngeal hemiplegia and 1 pilot horse that had embolization of the cerebral arterial circle. In normal horses, premortem angiography confirmed complete occlusion of all vessels, and coils were positioned as intended. All normal horses had partially maturing to mature, continuous thrombi occluding at the coils. In affected horses, no further episodes of epistaxis were observed. By day 60, all mycotic plaques had resolved without further treatment. Ophthalmic complications were not observed. CONCLUSION: Transarterial embolization provided a safe, rapid, and effective method for ICA, ECA, and MA occlusion in normal and affected horses. In affected horses, the technique was possible despite active bleeding, allowing adequate identification and occlusion of all sources of hemorrhage.

Nephrosplenic entrapment in the horse: a retrospective study of 174 cases.

The clinical findings and outcome of 161 horses diagnosed with 174 episodes of nephrosplenic entrapment (NSE) were reviewed retrospectively. The median age at presentation was 5 years (9 months to 24 years), and duration of colic was 2-92 h. Nasogastric reflux was present in 49 of 113 horses (43.4%) and was significant (> or = 21) in 32 (28.3%) horses. The recurrence rate was 13/161 (8.1%). Thirteen horses (13/174, 7.5%) had other lesions including small intestinal obstruction (4), 360 degrees large colon torsion (5), gastric rupture (2), thromboembolic colic (1) and small colon infarction (1). Of 115 cases, in 107 horses treated by surgery alone, 2 horses required a large colon resection, and 8 (8/107, 7.5%) horses died or were subjected to euthanasia. Twenty-six of 35 horses (74%) were successfully corrected by rolling under general anesthesia and, of the 9 horses taken to surgery after rolling, 4 had other lesions and 2 were corrected at surgery. Phenylephrine was used in 20 of 35 horses that were rolled and 2 horses required surgery after rolling with phenylephrine. Five horses were jogged after phenylephrine administration and all were successfully corrected. Eleven horses presented with the left colon located between the spleen and the body wall were treated successfully by fasting and/or i.v. fluids. One horse had a gastric rupture after rolling. The overall success rate was 92.5%. In conclusion, NSE is a condition associated with a good prognosis for medical or surgical correction. A small number of horses may have additional gastrointestinal lesions, which may affect outcome.

Congenital atresia of the parotid duct in a horse.

Congenital anomalies of the equine salivary glands and their ductal systems are rare. In man, parotid duct atresia is thought to be due to a congenital malformation of the first branchial arch. One horse with unilateral parotid salivary duct atresia is described. Imaging modalities available for accurate diagnosis, and treatment options, are reviewed.

Prevention of epidural fibrosis with ADCON-L in presence of a durotomy during lumbar disc surgery: experiences with a pre-clinical model.

A potential complication of lumbo-sacral surgery is the inadvertent tear of the dura mater, which sometimes eludes intra-operative detection. ADCON-L, a bioabsorbable gel used in lumbosacral laminectomies or laminotomies, is a physical barrier to post-operative epidural fibrosis. Three experimental lumbar laminectomy studies were designed to assess in vivo the effects of ADCON-L when applied in presence of dural punctures in a rat model. In the first study, the durotomy was repaired with fibrin sealant, in the second experiment the dural defect was microsurgically sutured, while in a third protocol the durotomy was left unrepaired. In each study, dural healing was assessed respectively at 4, 8, or 12 weeks post-operatively. Blinded anatomical dissection and histopathology were used to compare results between treatments (sham operated control vs. ADCON-L). In the fibrin sealant experiment, an additional treatment group (fibrin sealant used together with ADCON-L) was included. The results of these studies consistently demonstrate that ADCON-L is an effective anti-fibrotic agent, and does not interfere with the normal dural healing processes following a meningeal puncture. The application of the gel may therefore be safe in presence of dural incisions, even when they are not identified during surgery, as demonstrated in these in vivo studies.

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses.

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.

Responses of human basilar and other isolated arteries to novel nitric oxide donors.

The adducts of nitric oxide (NO), diethylamine/NO (DEA/NO) and diethylenetriamine/NO (DETA/NO), are new NO donors that spontaneously release NO in aqueous solutions. These donors may have therapeutic advantages over sodium nitroprusside (SNP), which depends on metabolism to yield NO. This study was performed to define and compare the pharmacodynamic properties of these NO donors on isolated rings of human, canine, and porcine basilar arteries and further to compare canine and porcine common carotid arteries precontracted with KCl. The median effective concentration (EC50) and the basic effect of 100 microM were determined for each NO donor. On basilar arteries, DEA/NO was the most potent but the maximal dilatation produced by 100 microM did not persist for 60 min, whereas that of DETA/NO and SNP did. DETA/NO was more potent than SNP on all three species of basilar arteries but was the least potent on peripheral (carotid) arteries. Methylene blue in equimolar concentrations significantly inhibited the vasorelaxant effects of DEA/NO and DETA/NO, suggesting a common mechanism of action. Of the NO donors studied, the pharmacodynamic properties of DETA/NO seemed most relevant clinically as a cerebrovascular dilator in being more potent than SNP while producing sustained vasorelaxation.

Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor.

OBJECT: Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen++ +-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). METHODS: The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 micromol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 micromol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 micromol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-micromol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8. The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 micromol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen. CONCLUSIONS: This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

Surgical experience with an implanted artificial cervical joint.

OBJECT: To assess the effectiveness of Cummins' artificial cervical joint, the authors reviewed the cases of 20 patients in whom the joint had been placed. METHODS: A review of patients' medical records and reexamination of 18 patients were performed. The review of the surgical experience with the implantation of movable stainless-steel joints in 20 patients treated for cervical myelopathy (16 patients), cervical radiculopathy (three patients), and severe pain (one patient) indicated that the procedure is safe and well tolerated and does preserve cervical joint motion in most patients over an extended period of observation. To date, adjacent segmental symptomatic degenerative changes leading to further surgical treatment have been avoided. The joint has been placed in patients with advanced congenital and acquired cervical fusion and has been demonstrated to be stable, mobile, and biomechanically and biochemically compatible; it has shown no subsidence into adjacent bone. Wear debris has not occurred. CONCLUSIONS: The use of stainless steel in the cervical spine appears to be suitable for this joint replacement design.

Cardiorespiratory and metabolic effects of walking, standing, and standing with a splint during the recuperative period from maximal exercise in horses.

OBJECTIVE: To determine the effects of walking, standing, or standing with a splint on 1 forelimb on rate of recuperation of horses after a brief, intense bout of exercise. ANIMALS: 6 adult Thoroughbreds (435 to 542 kg). PROCEDURE: Horses were preconditioned by exercise on a treadmill to establish a uniform level of fitness. Once fit, the treadmill speed causing each horse to exercise at 120% of its maximal oxygen consumption was determined and was used in simulated races at 14-day intervals. Horses were instrumented for collection of arterial and mixed venous blood samples for measurement of acid-base status, concentrations of metabolites, and cardiopulmonary indices. The horses were exercised at a speed inducing 120% of their maximal oxygen consumption until fatigued or for a maximum of 2 minutes. Three recuperative interventions were evaluated: walking at 1.8 m/s for 30 minutes, then standing for the remainder of the 90-minute trial; standing stationary for 90 minutes; and standing stationary for 90 minutes with a splint on the right forelimb. RESULTS: Walking significantly increased cardiac output during the recuperative phase and hastened recovery of normal acid-base status and return of blood lactate concentration to baseline values. CONCLUSION: Limiting movement of horses during the recuperative period delays recovery from maximal exercise. Most measured indices returned to baseline by 60 minutes after exercise. All measured cardiopulmonary indices returned to baseline values by 90 minutes after exercise. CLINICAL RELEVANCE: Horses that are not allowed to walk during recuperation from exercise may have a prolonged recovery period.

Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L).

STUDY DESIGN: A canine lumbar laminotomy and discectomy model was used to evaluate the effects of a resorbable gel, ADCON-L (Gliatech Inc., Cleveland, OH), in reducing peridural scar formation and to assess the healing progress of immediately adjacent normal structures. OBJECTIVES: To compare peridural scar formation and anulus fibrosis healing with and without the use of ADCON-L in an animal model that closely replicates the common human surgical procedure. SUMMARY OF BACKGROUND DATA: ADCON-L has been shown to reduce the development of peridural scars in rat, rabbit, and canine laminectomy models in previous investigations; discectomies were not performed in these previous studies, however, and thus anular healing could not be assessed. METHODS: Seven adult mongrel dogs underwent a three-level unilateral lumbar hemilaminotomy and anular fenestration. In each dog, the ADCON-L was applied to two randomly assigned sites around the discectomy, the nerve roots, and the hemilaminotomy. The third site underwent surgery, but was left untreated (sham surgery only). The canines were killed 8 weeks after surgery, and a gross anatomic assessment of scar formation was done using microdissection by an observer blinded to treatment. A numerical rating system was developed to assess the relative amount and tenacity of the anterior scarring (discectomy site) and posterior scarring (hemilaminotomy site). The healing of the anular defect was assessed histologically. RESULTS: ADCON-L significantly reduced peridural fibrosis in this lumbar discectomy model compared with the sham treated sites (p < 0.05). Further, the superficial layers, the posterior longitudinal ligament, and the anulus fibrosus healed well in the ADCON-L treated sites. CONCLUSIONS: ADCON-L reduced local peridural fibrosis after lumbar laminotomy and discectomy without impacting the healing of the surrounding tissues.

Inflammatory markers in bronchoalveolar lavage fluid of standardbred racehorses with inflammatory airway disease: response to interferon-alpha.

Protein and eicosanoid concentrations and procoagulant activity were determined in bronchoalveolar lavage fluid (BALF) from 32 Standardbred racehorses with inflammatory airway disease (IAD) and 6 control horses. Total protein, albumin and immunoglobulin G (IgG) concentrations were high (P < 0.05) in the BALF from horses with IAD, a finding consistent with exudation of plasma protein into the airway. Immunoglobulin A (IgA) concentrations also were increased (P < 0.05) which may signify local immunoglobulin production. Difference was not detected in prostaglandin E2 and 6-ketoprostaglandin F1 alpha concentrations in BALF of IAD-affected and control horses. Procoagulant activity was identified in the majority (66%) of BALF samples from IAD-affected horses and was not detected in control horses. Natural human interferon-alpha (nHulFN alpha) (placebo, 50, 150, or 450 units) was administered orally for 5 days to IAD-affected horses in a double-blind, randomised block design. Total protein, IgG, and IgA concentrations in BALF were reduced (P < 0.05) 8 days after administration of 50 u and 150 u nHuIFN alpha, and 15 days after administration of 50 u nHuIFN alpha. Procoagulant activity and albumin concentrations in BALF were lower 8 days after administration of 50 u nHuIFN alpha. Oral administration of low-dose nHuIFN alpha appeared to ameliorate these parameters of lower respiratory tract inflammation in Standardbred racehorses with IAD.