The effect of aquapuncture at Pericardium 6 (PC-6) on dexmedetomidine-induced nausea and vomiting in cats.

OBJECTIVE: To determine the effect of aquapuncture at acupuncture point Pericardium 6 (PC-6) on the incidence of dexmedetomidine-induced vomiting and nausea in cats. STUDY DESIGN: Randomized, prospective, crossover study. ANIMALS: A group of 22 cats, 14 females and eight males, aged 1-12 years and weighing 3.8-5.9 kg. METHODS: Each cat was administered treatments in random order at ≥1 week intervals. For treatment (DEX-A), cats were administered PC-6 stimulation by aquapuncture (0.25 mL/250 µg vitamin B12 injection subcutaneously at PC-6). After 30 minutes, dexmedetomidine (10 µg kg-1) was administered intramuscularly (IM). For control treatment (DEX), cats were administered only dexmedetomidine (10 µg kg-1) IM. Incidence of vomiting, number of vomiting episodes and time to first vomiting were recorded by an observer unaware of treatment allocation. At 30 minutes after dexmedetomidine administration, atipamezole (0.1 mg kg-1) was injected IM. Behavior was video recorded and later scored by two observers for clinical signs of nausea. A regression model (analysis of covariance) was used to detect the influence of aquapuncture on vomiting and nausea. Significance was set at p < 0.05. RESULTS: Of 21 cats, 18 (85%) and 16 cats (76%) vomited in DEX-A and DEX, respectively. There was no significant difference in the incidence of vomiting (p = 0.55), number of vomiting episodes (p = 0.55), mean time to vomit (p = 0.88) or nausea score (p = 0.51) between DEX-A and DEX. CONCLUSIONS AND CLINICAL RELEVANCE: PC-6 aquapuncture did not reduce the incidence of dexmedetomidine-induced vomiting or severity of nausea in cats.

Sedative and cardiopulmonary effects of buccally administered detomidine gel and reversal with atipamezole in dogs.

OBJECTIVE To evaluate hemodynamic, respiratory, and sedative effects of buccally administered detomidine gel and reversal with atipamezole in dogs. ANIMALS 8 adult purpose-bred dogs. PROCEDURES Arterial and venous catheters were placed. Baseline heart rate, respiratory rate, cardiac output (determined via lithium dilution with pulse contour analysis), oxygen delivery, systemic vascular resistance, arterial blood gas values, and sedation score were obtained. Detomidine gel (2.0 mg/m2) was administered on the buccal mucosa. Cardiopulmonary data and sedation scores were obtained at predetermined times over 180 minutes. Atipamezole (0.1 mg/kg) was administered IM at 150 minutes. Reversal of sedation was timed and scored. Data were analyzed with an ANOVA. RESULTS Compared with baseline values, heart rate was lower at 45 to 150 minutes, cardiac output and oxygen delivery were lower at 30 to 150 minutes, and systemic vascular resistance was increased at 30 to 150 minutes. There were no significant changes in Paco2, Pao2, or lactate concentration at any time point, compared with baseline values, except for lactate concentration at 180 minutes. All dogs became sedated; maximum sedation was detected 75 minutes after administration of detomidine. Mean ± SD time to recovery after atipamezole administration was 7.55 ± 1.89 minutes; sedation was completely reversed in all dogs. No adverse events were detected. CONCLUSIONS AND CLINICAL RELEVANCE Buccally administered detomidine gel was associated with reliable and reversible sedation in dogs, with hemodynamic effects similar to those induced by other α2-adrenoceptor agonists. Buccally administered detomidine gel could be an alternative to injectable sedatives in healthy dogs.

Implantation of an ultrafiltration device in the ileum and spiral colon of steers to continuously collect intestinal fluid.

Collection of fluid from the lumen of the gastrointestinal tract is commonly necessary for research projects, but presents challenges including intestinal motility and potential for leakage of intestinal contents. In this study, ultrafiltration collection devices were surgically implanted in the ileum and spiral colon of 12 steers for repeated collection of intestinal fluid over 48 hours. There were no significant complications associated with surgery or during the post-operative period, nor were there any significant pathologic changes found at necropsy 3 or 4 days post-surgery. Over 48 hours, we obtained 88% of the desired 212 samples. Only two devices failed to routinely collect samples. Use of ultrafiltration probes is a novel, consistent and humane method to repeatedly sample the gastrointestinal contents.

Diode laser endoscopic cyclophotocoagulation in the normal equine eye.

OBJECTIVE: To determine the clinical and histologic effects of diode endoscopic cyclophotocoagulation (ECP) in the phakic equine eye. ANIMALS STUDIED: Phase I: 10 equine cadaver eyes. Phase II: four normal adult horses. PROCEDURES: Phase I: ECP probe angle of reach (AR) was determined. Multiple ECP energy levels: 0.75, 0.90, 1.05, 1.20, 1.35, 1.50 J, and the resulting visible and histologic ciliary process changes were evaluated. Phase II: Ocular quadrants were treated with ECP at 0.90, 1.14, 1.38 J, and a control. The contralateral eye underwent a sham operation. Tissue changes (clinical and histologic) were evaluated. RESULTS: Phase I: Mean combined AR was 162 ± 29 degrees. Mean visible tissue scores: 2.60 ± 0.58 (0.75 J) to 5.04 ± 0.30 (1.50 J) from possible total of 6. Tissue 'popping' was observed at 1.50 J. Histologic ciliary tissue damage was present at all settings. Phase II: Mean visible tissue scores: 2.90 ± 0.48 (0.90 J), 3.61 ± 0.57 (1.14 J), and 4.52 ± 0.56 (1.38 J). Tissue 'popping' was observed at 1.38 J. Histologic ciliary tissue damage was present at all settings. Clinical effects included acute inflammation, intraocular pressure reduction, cataract formation, corneal edema, corneal ulceration, and postoperative ocular hypertension. CONCLUSIONS: Diode ECP between 0.90 and 1.14 J is a potential treatment option for glaucoma in horses based on visible tissue effects and target ciliary epithelium damage. Iatrogenic cataract development may limit the use of an anterior chamber approach in phakic horses. Supported in part by an ACVO VAF grant.

Evaluation of 30- and 25-diopter intraocular lens implants in equine eyes after surgical extraction of the lens.

OBJECTIVE: To determine appropriate intraocular lens (IOL) implant strength to approximate emmetropia in horses. SAMPLE POPULATION: 16 enucleated globes and 4 adult horses. PROCEDURES: Lens diameter of 10 enucleated globes was measured. Results were used to determine the appropriate-sized IOL implant for insertion in 6 enucleated globes and 4 eyes of adult horses. Streak retinoscopy and ocular ultrasonography were performed before and after insertion of 30-diopter (D) IOL implants (enucleated globes) and insertion of 25-D IOL implants (adult horses). RESULTS: In enucleated globes, mean +/- SD lens diameter was 20.14 +/- 0.75 mm. Preoperative and postoperative refractive state of enucleated globes with 30-D IOL implants was -0.46 +/- 1.03 D and -2.47 +/- 1.03 D, respectively; preoperative and postoperative difference in refraction was 2.96 +/- 0.84 D. Preoperative anterior chamber (AC) depth, crystalline lens thickness (CLT), and axial globe length (AxL) were 712 +/- 0.82 mm, 11.32 +/- 0.81 mm, and 40.52 +/- 1.26 mm, respectively; postoperative AC depth was 10.76 +/- 1.16 mm. Mean ratio of preoperative to postoperative AC depth was 0.68. In eyes receiving 25-D IOL implants, preoperative and postoperative mean refractive error was 0.08 +/- 0.68 D and -3.94 +/- 1.88 D, respectively. Preoperative AC depth, CLT, and AxL were 6.36 +/- 0.22 mm, 10.92 +/- 1.92 mm, and 38.64 +/- 2.59 mm, respectively. Postoperative AC depth was 8.99 +/- 1.68 mm. Mean ratio of preoperative to postoperative AC depth was 0.73. CONCLUSIONS AND CLINICAL RELEVANCE: Insertion of 30-D (enucleated globes) and 25-D IOL implants (adult horses) resulted in overcorrection of refractive error.

The hemodynamic effects of medetomidine continuous rate infusions in the dog.

OBJECTIVE: To characterize the hemodynamic effects of continuous rate infusions (CRI) of medetomidine administered at doses ranging from 0 to 3 microg kg(-1) hour(-1). STUDY DESIGN: Prospective, blinded, randomized experimental trial. ANIMALS: Six adult purpose-bred mongrel dogs. METHODS: Anesthesia was induced with sevoflurane for placement of arterial and venous catheters. Dogs recovered from anesthesia after which baseline hemodynamic measurements were obtained via lithium dilution cardiac output (CO) determination, with subsequent measurements via pulse power analysis to provide continuous CO determinations. Medetomidine, 1, 2, or 3 microg kg(-1) hour(-1) or a volume equivalent placebo, was administered via CRI for 60 minutes. Systolic, mean, and diastolic arterial pressure, heart rate (HR), CO and stroke volume were measured and stroke index (SI), cardiac index (CI), total peripheral resistance (TPR), and total peripheral resistance index (TPRI) were calculated at 3, 7, 10, 20, 30, 45, 60, 90, and 120 minutes from the start of the infusion. RESULTS: Increase in dose decreased SI by 25%, 19%, and 30%, HR by 33%, 57%, and 60%, CI by 50%, 65%, 70% and increased TPRI by 109%, 235%, and 222% from baseline to the 60-minute measurement for the 1, 2, and 3 microg kg(-1) hour(-1) doses, respectively. HR, TPRI, and CI all showed significant differences over the duration of the study from the placebo treatment. CONCLUSIONS: Medetomidine CRI produces clinically relevant changes in CO, TPR, and HR. The demonstrated decrease in CO is largely because of bradycardia and the degree of cardiovascular depression appears to be dose-dependent. These findings are consistent with previously described hemodynamic changes with single bolus administration of medetomidine. CLINICAL RELEVANCE: Low-dose medetomidine CRIs produce clinically relevant hemodynamic depression at doses as low as 1 microg kg(-1) hour(-1) and should be used cautiously in dogs.

Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses.

OBJECTIVE: To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine. ANIMALS: 24 horses. PROCEDURES: Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejunal specimens were collected after the ischemic period and after euthanasia 18 hours later for histologic assessment and determination of cyclooxygenase (COX) expression (via western blot procedures). Plasma samples collected prior to (baseline) and 8 hours after the ischemic period were analyzed for prostanoid concentrations. RESULTS: Immediately after the ischemic period, COX-2 expression in horses treated with lidocaine alone was significantly less than expression in horses treated with SS or flunixin alone. Eighteen hours after the ischemic period, mucosal neutrophil counts in horses treated with flunixin alone were significantly higher than counts in other treatment groups. Compared with baseline plasma concentrations, postischemia prostaglandin E(2) metabolite and thromboxane B(2) concentrations increased in horses treated with SS and in horses treated with SS or lidocaine alone, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with ischemia-injured jejunum, lidocaine administered IV reduced plasma prostaglandin E(2) metabolite concentration and mucosal COX-2 expression. Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts.

Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum.

OBJECTIVE: To determine whether treatment of horses with firocoxib affects recovery of ischemic-injured jejunum, while providing effective analgesia. ANIMALS: 18 horses. PROCEDURES: Horses (n = 6 horses/group) received saline (0.9% NaCl) solution (1 mL/50 kg, IV), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or firocoxib (0.09 mg/kg, IV, q 24 h) before 2 hours of jejunal ischemia. Horses were monitored via pain scores and received butorphanol for analgesia. After 18 hours, ischemic-injured and control mucosa were placed in Ussing chambers for measurement of transepithelial resistance and permeability to lipopolysaccharide. Histomorphometry was used to determine denuded villus surface area. Western blots for cyclooxygenase (COX)-1 and COX-2 were performed. Plasma thromboxane B(2) and prostaglandin E(2) metabolite (PGEM) concentrations were determined. RESULTS: Pain scores did not significantly increase after surgery in horses receiving flunixin meglumine or firocoxib. Transepithelial resistance of ischemic-injured jejunum from horses treated with flunixin meglumine was significantly lower than in saline- or firocoxib-treated horses. Lipopolysaccharide permeability across ischemic-injured mucosa was significantly increased in horses treated with flunixin meglumine. Treatment did not affect epithelial restitution. Cyclooxygenase-1 was constitutively expressed and COX-2 was upregulated after 2 hours of ischemia. Thromboxane B(2) concentration decreased with flunixin meglumine treatment but increased with firocoxib or saline treatment. Flunixin meglumine and firocoxib prevented an increase in PGEM concentration after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Flunixin meglumine retarded mucosal recovery in ischemic-injured jejunum, whereas firocoxib did not. Flunixin meglumine and firocoxib were effective visceral analgesics. Firocoxib may be advantageous in horses recovering from ischemic intestinal injury.

Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum.

OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.

A novel instrumented retractor to monitor tissue-disruptive forces during lateral thoracotomy.

OBJECTIVE: Acute and chronic pain after thoracotomy, post-thoracotomy pain syndrome, is well documented. The mechanical retractors used for the thoracotomy exert significant forces on the skeletal cage. Our hypothesis was that instrumented retractors could be developed to enable real-time monitoring and control of retraction forces. This would provide equivalent exposure with significantly reduced forces and tissue damage and thus less post-thoracotomy pain. METHODS: A novel instrumented retractor was designed and fabricated to enable real-time force monitoring during surgical retraction. Eight mature sheep underwent bilateral thoracotomy. One lateral thoracotomy was retracted at a standard clinical pace of 5.93 +/- 0.80 minutes to 7.5 cm without real-time monitoring of retraction forces. The other lateral thoracotomy was retracted to the same exposure with real-time visual force feedback and a consequently more deliberate pace of 9.87 +/- 1.89 minutes (P = .006). Retraction forces, blood pressure, and heart rate were monitored throughout the procedure. RESULTS: Full lateral retraction resulted in an average force of 102.88 +/- 50.36 N at the standard clinical pace, versus 77.88 +/- 38.85 N with force feedback (a 24.3% reduction, P = .006). Standard retraction produced peak forces of 450.01 +/- 129.58 N, whereas force feedback yielded peak forces of 323.99 +/- 127.79 N (a 28.0% reduction, P = .009). Systolic blood pressure was significantly higher during standard clinical retraction (P = .0097), and rib fracture occurrences were reduced from 5 to 1 with force feedback (P = .04). CONCLUSIONS: Use of the novel instrumented retractor resulted in significantly lower average and peak retraction forces during lateral thoracotomy. Moreover, these reduced retraction forces were correlated with reductions in animal stress and tissue damage, as documented by lower systolic blood pressures and fewer rib fractures.

Tissue-disruptive forces during median sternotomy.

BACKGROUND: Acute and chronic pain after median sternotomy is common and often underestimated. The mechanical retractors used for median sternotomy exert significant forces on the skeletal cage. We hypothesized that instrumented retractors could be developed to enable real-time monitoring and control of retraction forces, functions that may provide equivalent exposure with significantly reduced forces and tissue damage, and thus, less postoperative pain. METHODS: We developed a novel instrumented retractor designed to enable real-time force monitoring during surgical retraction and then tested it by performing median sternotomies on 16 mature sheep. For 8 of these median sternotomies, retraction was performed to 7.5 cm at a standard "clinical pace" of 7.25 +/- 0.97 minutes without real-time monitoring of retraction forces. For the other 8 median sternotomies, we performed retraction to the same exposure using real-time visual force feedback and, consequently, a more deliberate pace of 12.05 +/- 1.73 minutes (P <.001). Retraction forces, blood pressure, and heart rate were monitored throughout the procedure. RESULTS: Full retraction resulted in an average force of 102.99 +/- 40.68 N at the standard clinical pace, compared to 64.68 +/- 17.60 N with force feedback (a 37.2% reduction, P = .021). Standard retraction produced peak forces of 368.79 +/- 133.61 N, whereas force feedback yielded peak forces of 254.84 +/- 75.77 N (a 30.9% reduction, P = .1152). Heart rate was significantly higher during standard clinical retraction (P = .025). CONCLUSIONS: Use of the novel instrumented retractor resulted in lower average and peak retraction forces during median sternotomy. Moreover, these reduced retraction forces correlated to a reduction in animal stress, as documented by heart rate.

Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis.

Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac with the non-selective COX inhibitor phenylbutazone in horses with lipopolysaccharide (LPS)-induced synovitis. Three groups of horses (n=6) received no treatment, phenylbutazone (4.4 mg/kg, IV, q12h), or etodolac (23 mg/kg, IV, q12h), respectively, 2-h following injection of LPS into one middle carpal joint. Synovial fluid was analyzed for white blood cell (WBC) count, and TXB2 and PGE2 levels. Phenylbutazone and etodolac significantly reduced WBC count 6 and 24-h following injection of LPS compared to untreated horses. In addition, both drugs significantly reduced PGE2 levels (P<0.05) 6-h following LPS injection, whereas the probable COX-1 prostanoid TXB2 was significantly reduced by phenylbutazone (P<0.05), but not etodolac. Etodolac may serve as a more selective anti-inflammatory agent than phenylbutazone for treatment of equine synovitis.

Physiological concentrations of bile salts inhibit recovery of ischemic-injured porcine ileum.

We have previously shown rapid in vitro recovery of barrier function in porcine ischemic-injured ileal mucosa, attributable principally to reductions in paracellular permeability. However, these experiments did not take into account the effects of luminal contents, such as bile salts. Therefore, the objective of this study was to evaluate the role of physiological concentrations of deoxycholic acid in recovery of mucosal barrier function. Porcine ileum was subjected to 45 min of ischemia, after which mucosa was mounted in Ussing chambers and exposed to varying concentrations of deoxycholic acid. The ischemic episode resulted in significant reductions in transepithelial electrical resistance (TER), which recovered to control levels of TER within 120 min, associated with significant reductions in mucosal-to-serosal (3)H-labeled mannitol flux. However, treatment of ischemic-injured tissues with 10(-5) M deoxycholic acid significantly inhibited recovery of TER with significant increases in mucosal-to-serosal (3)H-labeled mannitol flux, whereas 10(-6) M deoxycholic acid had no effect. Histological evaluation at 120 min revealed complete restitution regardless of treatment, indicating that the breakdown in barrier function was due to changes in paracellular permeability. Similar effects were noted with the application of 10(-5) M taurodeoxycholic acid, and the effects of deoxycholic acid were reversed with application of the Ca(2+)-mobilizing agent thapsigargin. Deoxycholic acid at physiological concentrations significantly impairs recovery of epithelial barrier function by an effect on paracellular pathways, and these effects appear to be Ca(2+) dependent.