In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses

OBJECTIVE: To determine effects of cisapride and 5-hydroxytryptamine (5-HT) on the jejunum of horses. SAMPLE POPULATION: Jejunal muscle strips from 8 horses. PROCEDURE: Muscle strips were suspended in isolated muscle baths. Isometric stress responses to 5-HT and cisapride, with and without specific antagonists, were determined. RESULTS: Muscle strips incubated with atropine and tetrodotoxin responded to 5-HT and cisapride with an increase in contractile force. The 5-HT caused a concentration-dependent increase in contractile amplitude, with a maximum response (Emax) of 1,151+/-214 g/cm2 and a molar concentration that induces contractile force equal to 50% of maximum response (EC50) of 0.028+/-0.002 microM. Prior incubation with the 5-HT2 antagonist ketanserin decreased the Emax (626 +/-147 g/cm2) and potency (EC50, 0.307+/-0.105 microM) of 5-HT Prior incubation with the 5-HT3 antagonist tropisetron decreased the efficacy (Emax, 894+/-184 g/cm2) to 5-HT Cisapride also caused a concentration-dependent increase in contractile amplitude, with an Emax of 331+/-82 g/cm2 and an EC50 of 0.302+/-0.122 microM. Prior incubation with ketanserin decreased the Emax (55+/-17 g/cm2) and potency (EC50, 0.520+/-0.274 microM) of cisapride. CONCLUSION AND CLINICAL RELEVANCE: Stimulatory effects of 5-HT and cisapride on circular smooth muscle of equine jejunum are mediated primarily through a noncholinergic effect. The effects of 5-HT are mediated, at least partially, by 5-HT2 and 5-HT3 receptors, whereas the effects of cisapride are mediated primarily by 5-HT2 receptors. This may impact treatment of horses with postoperative ileus.     

Plasma lidocaine concentrations in conscious horses after cervicothoracic (stellate) ganglion block with 1% lidocaine HCl solution

Arterial and/or central venous plasma concentrations of lidocaine were determined in 12 nonmedicated adult horses (422 +/- 59 kg of body weight, mean +/- SD) after injecting a 1% lidocaine HCl solution into the cervicothoracic ganglion (CTG). A mean dosage of 2.9 +/- 0.5 mg of lidocaine/kg of body weight was used to induce unilateral CTG blockade in 8 horses and 4.8 +/- 0.8 mg was used to induce bilateral CTG blockade in 4 horses. Blood samples were collected before and at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after injection. The plasma lidocaine concentrations were determined by use of gas chromatography (sensitivity less than 0.01 microgram/ml). Cervicothoracic sympathetic blockade was characterized by Horner's syndrome and by profuse sweating over the face, neck, and thoracic limbs. Mean maximal venous concentrations of lidocaine were 0.86 +/- 0.33 microgram/ml at 26.3 +/- 6.9 minutes after unilateral CTG blockade, and 1.14 +/- 0.25 micrograms/ml at 31.2 +/- 18.9 minutes after bilateral CTG blockade. The mean venous and arterial concentrations of lidocaine were not significantly different at 45 and 120 minutes after injection. Venous concentrations of lidocaine were consistently higher than were concentrations in simultaneously collected arterial blood samples in 2 horses in which the right CTG and brachial plexus were temporarily anesthetized after repeated administration of 100 ml of lidocaine into the right CTG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intratesticular injection of lidocaine on cardiovascular responses to castration in isoflurane-anesthetized stallions

OBJECTIVE: To evaluate the effect of intratesticular administration of lidocaine on cardiovascular responses and cremaster muscle tension during castration of isoflurane-anesthetized stallions. ANIMALS: 28 healthy stallions (mean +/- SD age, 4.2 +/- 2.8 years) with no testicular abnormalities that were scheduled for castration. PROCEDURE: Each horse was given acepromazine (20 microg/kg, IM), romifidine (50 microg/kg, IV), and butorphanol (20 microg/kg, IV). Anesthesia was induced with ketamine (2.5 mg/kg, IV) and midazolam (50 microg/kg, IV) and maintained with isoflurane (1.7% end-tidal concentration). After 10 minutes at a stable anesthetic plane, a needle was placed in each testicle and either no fluid or 15 mL of 2% lidocaine was injected; 10 minutes after needle placement, surgery was commenced. Pulse rate and arterial blood pressures were measured invasively at intervals from 5 minutes prior to castration (baseline) until 5 minutes after the left spermatic cord was clamped. The surgeon subjectively scored the degree of cremaster muscle tension. In 2 horses, lidocaine labeled with radioactive carbon (C(14)) was used and testicular autoradiograms were obtained. RESULTS: Compared with baseline values, castration significantly increased blood pressure measurements; intratesticular injection of lidocaine decreased this blood pressure response and cremaster muscle tension. In 2 horses, autoradiography revealed diffuse distribution of lidocaine into the spermatic cord but poor distribution into the cremaster muscle. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized stallions, intratesticular injection of lidocaine prior to castration appeared to decrease intraoperative blood pressure responses and cremaster muscle tension and may be a beneficial supplement to isoflurane anesthesia.     

Prokinetic effects of erythromycin on the ileum, cecum, and pelvic flexure of horses during the postoperative period

OBJECTIVE: To evaluate the effect of erythromycin on motility of the ileum, cecum, and pelvic flexure of horses during the postoperative and post-recovery periods. ANIMALS: 8 healthy adult horses. PROCEDURE: Horses were anesthetized and bipolar electrodes were implanted in smooth muscle of the ileum, cecum, and pelvic flexure. Approximately 4, 16, and 24 hours (postoperative recording sessions) and at least 8 days (post-recovery recording session) after surgery, myoelectric activity was recorded before and after administration of erythromycin (0.5 mg/kg). RESULTS: Following erythromycin administration, myoelectric activity was increased in the ileum during all postoperative recording sessions but not during the post-recovery recording session. Myoelectric activity was increased in the cecum following erythromycin administration only during the post-recovery recording session. Myoelectric activity was increased in the pelvic flexure following erythromycin administration during all recording sessions. During several recording sessions, there were short periods during which myoelectric activity was significantly decreased following erythromycin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that erythromycin has an effect on myoelectric activity of the ileum, cecum, and pelvic flexure in horses; however, prokinetic effects of erythromycin administered during the postoperative period were not always the same as effects obtained when the drug was administered after horses had recovered from the effects of surgical implantation of recording devices. Therefore, caution must be exercised when extrapolating results of prokinetic studies in healthy animals to animals with abnormal gastrointestinal tract motility.     

Cystometrography and urethral pressure profiles in healthy horse and pony mares

Cystometrography and urethral pressure evaluations were performed in 7 horse mares and 5 pony mares before and after sedation with xylazine. Before sedation, mean (+/- SD) maximal bladder contraction pressure was 91.4 +/- 16.5 cm of H2O in horses and was 86.0 +/- 14.4 cm of H2O in ponies, and maximal urethral closure pressure was 49.1 +/- 19.4 cm of H2O in horses and 37.7 +/- 14.4 cm of H2O in ponies. A significant difference was not found between values of nonsedated vs sedated animals. Only values for threshold volume were significantly different (P less than 0.05) between nonsedated horses (1,982 +/- 1,241 ml) and ponies (825 +/- 412 ml).     

Use of an extracorporeal circuit to evaluate effects of intraluminal distention and decompression on the equine jejunum

OBJECTIVE: To use an extracorporeal circuit to evaluate effects of intraluminal distention on the jejunum of healthy horses. SAMPLE POPULATION: 2 jejunal segments from each of 5 horses. PROCEDURE: Jejunal segments were harvested and maintained in an extracorporeal circuit. One segment was subjected to distention (intraluminal pressure, 25 cm H2O) followed by decompression, and 1 segment was maintained without distention. The influence of distention-decompression on vascular resistance was calculated. Mucosal permeability was evaluated by measuring the clearance of albumin from blood to lumen. After distention and decompression, tissue specimens were collected for histomorphologic evaluation. In addition, the contractile response of the circular smooth muscle layer was determined following incubation with 3 prokinetic agents. RESULTS: Intestinal vascular resistance increased during intraluminal distention and returned to baseline values after decompression. Albumin clearance rate increased after distention, compared with baseline and control values. Histologic examination of the distended segments revealed grade-1 and -2 lesions of the mucosal villus. Edema and hemorrhage were evident in the submucosa and muscular layers. Mesothelial cell loss, edema, and hemorrhage were also evident in the serosa. Mucosal surface area and villus tip height decreased and submucosal volume increased in the distended tissue. Compared with responses in control specimens, distention decreased the contractile response induced by cisapride, erythromycin, and metoclopramide. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal distention of the jejunum followed by decompression increased mucosal permeability and injury and decreased responses to prokinetic agents. Horses with intraluminal intestinal distention may have a decreased response to prokinetic agents.     

Measurement of erythrocyte carbonic anhydrase isozymes (CA-I and CA-II) in racehorses and riding horses

Equine carbonic anhydrase isozymes (CA-I and CA-II) were purified from erythrocytes by several column chromatography. Polyclonal anti-CA-I and anti-CA-II sera were produced in rabbits. Sensitive competitive enzyme-linked immunosorbent assays (ELISA) were established to determine the developmental changes in CA-I and CA-II levels in equine erythrocytes. Concentrations of CA-I and CA-II in erythrocytes from 150 clinically normal thoroughbreds (123 racehorses and 27 riding horses) were determined by ELISA. Mean (+/- SD) concentrations of CA-I and CA-II in racehorses were 1.70 +/- 0.48 and 0.94 +/- 0.13 mg/g hemoglobin (Hb), respectively. Mean concentrations of CA-I and CA-II in riding horses were 2.34 +/- 0.52 and 0.76 +/- 0.08 mg/g Hb, respectively. When the CA levels in racehorses and riding horses were compared, the CA-I level in riding horses was higher than that in racehorses (p=0.01). The CA-II level in racehorses was higher than that in riding horses (p=0.02). These data suggest that the levels of CA isozymes in erythrocytes of racehorses were influenced by chronic physical stress. The CA-I concentration in erythrocytes of 2-month-old horses was approximately 0.25 mg/g Hb. The CA-I level noticeably increased during the first year of life and approached normal adult levels by 2 years. The CA-II level decreased slightly with age, indicating different regulation of CA-I and CA-II expression during development.     

The disposition of lidocaine during a 12-hour intravenous infusion to postoperative horses

Lidocaine is administered as an intravenous infusion to horses for a variety of reasons, but no study has assessed plasma lidocaine concentrations during a 12-h infusion to horses. The purpose of this study was to evaluate the plasma concentrations and pharmacokinetics of lidocaine during a 12-h infusion to postoperative horses. A second purpose of the study was to evaluate the in vitro plasma protein binding of lidocaine in equine plasma. Lidocaine hydrochloride was administered as a loading dose, 1.3 mg/kg over 15 min, then by a constant rate IV infusion, 50 microg/kg/min to six postoperative horses. Lidocaine plasma concentrations were measured by a validated high-pressure liquid chromatography method. One horse experienced tremors and collapsed 5.5 h into the study. The range of plasma concentrations during the infusion was 1.21-3.13 microg/mL. Lidocaine plasma concentrations were significantly increased at 0.5, 4, 6, 8, 10 and 12 h compared with 1, 2 and 3 h. The in vitro protein binding of lidocaine in equine plasma at 2 microg/mL was 53.06+/-10.28% and decreased to 27.33+/-9.72% and 29.52+/-6.44% when in combination with ceftiofur or the combination of ceftiofur and flunixin, respectively. In conclusion, a lower lidocaine infusion rate may need to be administered to horses on long-term lidocaine infusions. The in vitro protein binding of lidocaine is moderate in equine plasma, but highly protein bound drugs may displace lidocaine increasing unbound concentrations and the risk of lidocaine toxicity.     

Effect of atropine-dobutamine stress test on left ventricular echocardiographic parameters in untrained warmblood horses

The aim of this study was to investigate the effect of combined atropine low-dose dobutamine stress test on left ventricular parameters in adult warmblood horses, to establish a potential protocol for pharmacological stress echocardiography. Seven healthy untrained warmblood horses aged 9 to 22 years were used. Heart rate (HR) and left ventricular B- and M-mode dimensions were recorded at baseline and during stress testing with 35 microg/kg atropine IV followed by incremental dobutamine infusion of 2 to 6 microg/kg/min. HR increased significantly (P < .05) during the pharmacological challenge, and a maximal HR of 156.6 +/- 12.5 bpm was reached at maximal dobutamine infusion rate. Systolic and diastolic interventricular septum thickness, systolic and diastolic left ventricular free wall thickness, and fractional shortening increased significantly and reached a maximum at the highest infusion rate (mean +/- SD: 4.51 +/- 0.27 versus 5.65 +/- 0.31 cm, 2.89 +/- 0.19 versus 3.78 +/- 0.10 cm, 3.72 +/- 0.34 versus 4.77 +/- 0.18 cm, 2.44 +/- 0.28 versus 3.11 +/- 0.34 cm, 34.98 +/- 3.82 versus 50.56 +/- 3.42%, respectively). Systolic and diastolic left ventricular internal diameter decreased significantly during dobutamine infusion. Left ventricular external and internal area were significantly lower at a dobutamine infusion rate of 2 microg/kg/min but no further decrease was observed during the subsequent steps. Systolic and diastolic myocardial area was significantly lower after the administration of dobutamine but not significantly different during dobutamine infusion, when compared to baseline values. This pharmacological stress test induced significant changes in left ventricular echocardiographic parameters in adult warmblood horses. Additional research should evaluate the value of this stress test in horses suffering from cardiac disease.     

Assessment of the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in calves

OBJECTIVE: To determine and compare the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in suckling calves. ANIMALS: 6 male Holstein calves (15 to 40 days of age). PROCEDURE: Calves were monitored for 1 hour before being fed milk replacer (60 mL/kg; time, 0 minutes) and then were monitored for another 3 hours. Calves received 6 treatments in randomized order: erythromycin (8.8 mg/kg, IM) at -30 minutes; low-dose erythromycin (0.88 mg/kg, IM) at -30 minutes; erythromycin (8.8 mg/kg, IM) at -30 minutes and neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; metoclopramide (0.1 mg/kg, IM) at-30 and 90 minutes; and placebo (2 mL of saline [0.9% NaCl] solution, SC) at -30 minutes. Abomasal volume was calculated from ultrasonographic measurements of abomasal width, length, and height. Abomasal motility and emptying rate were assessed by measuring luminal pressure and change in abomasal volume over time. RESULTS: Administration of erythromycin (8.8 mg/kg) increased the frequency of abomasal luminal pressure waves and the mean abomasal luminal pressure and decreased the half-time of abomasal emptying by 37%. Administration of metoclopramide, neostigmine, and low-dose erythromycin (0.88 mg/kg) did not alter abomasal motility, mean luminal pressure, or emptying rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of erythromycin at the labeled antimicrobial dose (8.8 mg/kg, IM) exerted an immediate, marked prokinetic effect in healthy suckling calves, whereas administration of metoclopramide or neostigmine did not alter abomasal motility or emptying rate.     

Effects of ground surface deformability, trimming, and shoeing on quasistatic hoof loading patterns in horses

OBJECTIVE: To determine whether solar load distribution pattern on a solid nondeformable ground surface is the product of contact erosion and is the mirror image of load distribution on a deformable surface in horses. ANIMALS: 30 clinically normal horses. PROCEDURES: Solar load distribution was compared among 25 clinically normal horses during quasistatic loading on a solid nondeformable surface and on a highly deformable surface. Changes in solar load distribution patterns were evaluated in 5 previously pasture-maintained horses housed on a flat nondeformable surface. Changes in solar load distribution created by traditional trimming and shoeing were recorded. RESULTS: Unshod untrimmed horses had a 4-point (12/25, 48%) or a 3-point (13/25, 52%) wall load distribution pattern on a flat solid surface. Load distribution on a deformable ground surface was principally solar and located transversely across the central region of the foot. Ground surface contact areas on solid (24.2 +/- 8.62 cm2) and deformable (69.4 +/- 22.55 cm2) surfaces were significantly different. Maintaining unshod horses on a flat nondeformable surface resulted in a loss of the 3- and 4-point loading pattern and an increase in ground surface contact area (17.9 +/- 2.77 to 39.9 +/- 12.77 cm2). Trimming increased ground surface contact area (24.2 +/- 8.60 to 45.7 +/- 14.89 cm2). CONCLUSION AND CLINICAL RELEVANCE: In horses, the solar surface is the primary weight-loading surface, and deformability of ground surface may have a role in foot expansion during loading. Increased surface area induced by loading on deformable surfaces, trimming, and shoeing protects the foot.     

An in vitro comparison of cordopexy, cordopexy and laryngoplasty, and laryngoplasty for treatment of equine laryngeal hemiplegia

OBJECTIVE: To examine the effect of cordopexy, laryngoplasty, and cordopexy combined with a modified laryngoplasty on airway mechanics. STUDY DESIGN: Experimental airway mechanics were determined by subjecting equine cadaveric larynges to airflows similar to inspiratory airflow of exercising horses. ANIMALS OR SAMPLE POPULATION: Twenty equine larynges. METHODS: Using cadaveric larynges, we developed and tested a new technique of arytenoid cartilage abduction. All larynges had the right arytenoid cartilage abducted to mimic the degree of arytenoid abduction that occurs at maximal exertion in live horses. Three surgical techniques were used to stabilize the left arytenoid cartilage of treated larynges; the left arytenoid cartilage was not stabilized in control larynges. Technique 1: Cordopexy--a suture was placed between the vocal ligament and the lamina of the thyroid cartilage. Technique 2: Standard laryngoplasty--a suture was placed between the muscular process of the arytenoid cartilage and the caudomedial aspect of the cricoid cartilage. Technique 3: Cordopexy plus modified laryngoplasty--the cordopexy suture was placed with a second suture between the horizontal ridge rostral to the muscular process of the left arytenoid cartilage and the lamina of the thyroid cartilage. Translaryngeal impedances (TI) were determined for each surgical technique by subjecting the larynges to increasing airflows and measuring the translaryngeal pressure differences. The arytenoid right to left angle quotient (RLQ) and the glottic cross-sectional area (CSA) were also measured. RESULTS: At maximal airflow, the adjusted means for the arytenoid RLQ and the TI for the cordopexy plus modified laryngoplasty (1.48 +/- 0.04, 0.69 +/- 0.05 cm H2O/L/s) and the standard laryngoplasty (1.39 +/- 0.04, 0.78 cm H2O/L/s) were different (P < .05) from values obtained after cordopexy alone (2.74 +/- 0.37, 1.76 +/- 0.48 cm H2O/L/s) or in control larynges (3.66 +/- 0.54, 4.16 +/- 0.96 cm H2O/L/s). Overall, a cordopexy plus modified laryngoplasty (9.69 cm2), a standard laryngoplasty (9.34 cm2), and a cordopexy alone (9 cm2) resulted in an increased glottic CSA greater than that for control larynges (6.94 cm2; P = .0001). CONCLUSIONS: Cordopexy alone did not improve airflow in a left laryngeal hemiplegic model. Cordopexy plus modified laryngoplasty was as efficacious as the standard laryngoplasty in alleviating the effects of left laryngeal hemiplegia on TI, glottic CSA, and arytenoid RLQ. CLINICAL RELEVANCE: Fixation of the vocal cord (cordopexy) in addition to a laryngoplasty procedure may prove useful in the surgical treatment of equine laryngeal hemiplegia.     

Comparison of lidocaine, xylazine, and xylazine/lidocaine for caudal epidural analgesia in horses.

Caudal epidural analgesia was achieved in 6 adult horses on 3 successive occasions at weekly intervals by injection of lidocaine, xylazine, and a combination of lidocaine/xylazine through indwelling epidural catheters. Analgesia was defined as a lack of response to pinprick and hemostat pressure in the skin of the perineal area. A significant (P < 0.05) difference was not found for time of onset of analgesia between lidocaine (4.3 +/- 0.8 minutes, mean +/- SEM) and the lidocaine/xylazine combination (5.3 +/- 1.3 minutes). Time to onset of analgesia after administration of xylazine was significantly (P < 0.05) longer (32.0 +/- 3.4 minutes) than that for either of the other 2 treatments. Duration of analgesia was significantly (P < 0.05) longer for the combination (329.8 +/- 6.2 minutes) than for either drug used alone (lidocaine, 87.2 +/- 7.5 minutes; xylazine, 204.2 +/- 12.9 minutes). Pulse and respiratory rates were not significantly altered by any of the drugs. Neurologic sequelae were not clinically apparent after administration of the drugs or after chronic epidural catheterization.     

Influence of gastrointestinal tract disease on pharmacokinetics of lidocaine after intravenous infusion in anesthetized horses

OBJECTIVE: To determine the disposition of lidocaine after IV infusion in anesthetized horses undergoing exploratory laparotomy because of gastrointestinal tract disease. ANIMALS: 11 horses (mean +/- SD, 10.3 +/- 7.4 years; 526 +/- 40 kg). PROCEDURE: Lidocaine hydrochloride (loading infusion, 1.3 mg/kg during a 15-minute period [87.5 microg/kg/min]; maintenance infusion, 50 microg/kg/min for 60 to 90 minutes) was administered IV to dorsally recumbent anesthetized horses. Blood samples were collected before and at fixed time points during and after lidocaine infusion for analysis of serum drug concentrations by use of liquid chromatography-mass spectrometry. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. Selected cardiopulmonary variables, including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2, were recorded. Recovery quality was assessed and recorded. RESULTS: Serum lidocaine concentrations paralleled administration, increasing rapidly with the initiation of the loading infusion and decreasing rapidly following discontinuation of the maintenance infusion. Mean +/- SD volume of distribution at steady state, total body clearance, and terminal half-life were 0.70 +/- 0.39 L/kg, 25 +/- 3 mL/kg/min, and 65 +/- 33 minutes, respectively. Cardiopulmonary variables were within reference ranges for horses anesthetized with inhalation anesthetics. Mean HR ranged from 36 +/- 1 beats/min to 43 +/- 9 beats/min, and mean MAP ranged from 74 +/- 18 mm Hg to 89 +/- 10 mm Hg. Recovery quality ranged from poor to excellent. CONCLUSIONS AND CLINICAL RELEVANCE: Availability of pharmacokinetic data for horses with gastrointestinal tract disease will facilitate appropriate clinical dosing of lidocaine.     

Distribution of innervation and circulation in porcine cervical trachea

The circulation and innervation to porcine cervical trachea were studied in 54 animals in situ. The antemortem response of porcine tracheal muscle was measured isometrically during selective injection of acetylcholine into the cranial thyroid arterial circulation. A predominantly unilateral (70.4%), rather than bilateral (3.7%), arterial circulation was identified; a cranial thyroid artery was not demonstrated in 25.9% of swine, suggesting dominant perfusion from the caudal thyroid circulation. After animals were killed, dye injection through the dominant cranial thyroid trunk demonstrated homogeneous perfusion of the muscle in all instances. In 20 of these animals, the distribution of parasympathetic innervation to porcine tracheal muscle was studied by selective electrical stimulation of the vagus nerves in situ. Tracheal smooth muscle response was measured isometrically, using settings (20 v, 20 Hz) causing maximal contractile force. Bilateral electrical stimulation caused active tracheal tension of 23.2 +/- 1.9 g/cm. Unilateral stimulation of the left vagus nerve caused 17.8 +/- 1.5 g/cm contraction, which was significantly greater than the response caused by selective stimulation of the right vagus nerve (12.1 +/- 1.6 g/cm; P less than 0.001). Innervation to porcine cervical trachea, although bilateral, is derived predominantly from the left vagus nerve; circulation is derived almost always from the left cranial thyroid artery.     

Metoclopramide modifies oral cephalexin pharmacokinetics in dogs

The purpose of this study was to investigate whether previous administration of metoclopramide affects cephalexin pharmacokinetics after its oral administration in dogs as well as whether these changes impair its predicted clinical efficacy. Six healthy beagle dogs were included in this study. Oral 25 mg/kg cephalexin monohydrate and intravenous 0.5 mg/kg metoclopramide HCl single doses were administered. Each dog received cephalexin or cephalexin following metoclopramide, with a 2-week washout period. Plasma concentrations of cephalexin were determined by microbiological assay. Cephalexin peak plasma concentration and area under the curve from 0 to infinity significantly increased from 18.77+/-2.8 microg/mL and 82.65+/-10.4 microg.h/mL to 21.88+/-0.8 microg/mL and 113.10+/-20.9 microg.h/mL, respectively, after pretreatment with metoclopramide. No differences between treatments were found for other pharmacokinetic parameters. Pharmacokinetic/pharmacodynamic indices calculated for highly susceptible staphylococci were similar for both experiences. Metoclopramide pretreatment may have increased cephalexin absorption by affecting its delivery to the intestine, and/or enhancing intestinal transporter PEPT1 function. Neither difference in the efficacy of cephalexin nor an increase in toxicity is expected as a result of this modification. Consequently, no dose adjustment is required in cephalexin-treated patients pretreated with metoclopramide.     

In vitro effects of lidocaine on the contractility of equine jejunal smooth muscle challenged by ischaemia‐reperfusion injury

Reasons for performing study: Post operative ileus (POI) in horses is a severe complication after colic surgery. A commonly used prokinetic drug is lidocaine, which has been shown to have stimulatory effects on intestinal motility. The cellular mechanisms through which lidocaine affects smooth muscle activity are not yet known. Objectives: To examine the effects of lidocaine on smooth muscle in vitro and identify mechanisms by which it may affect the contractility of intestinal smooth muscle. Hypothesis: Ischaemia and reperfusion associated with intestinal strangulation can cause smooth muscle injury. Consequently, muscle cell functionality and contractile performance is decreased. Lidocaine can improve basic cell functions and thereby muscle cell contractility especially in ischaemia‐reperfusion‐challenged smooth muscle. Methods: To examine the effects of lidocaine on smooth muscle function directly, isometric force performance was measured in vitro in noninjured and in vivo ischaemia‐reperfusion injured smooth muscle tissues. Dose‐dependent response of lidocaine was measured in both samples. To assess membrane permeability as a marker of basic cell function, release of creatine kinase (CK) was measured by in vitro incubations. Results: Lidocaine‐stimulated contractility of ischaemia‐reperfusion injured smooth muscle was more pronounced than that of noninjured smooth muscle. A 3‐phasic dose‐dependency was observed with an initial recovery of contractility especially in ischaemia‐reperfusion injured smooth muscle followed by a plateau phase where contractility was maintained over a broad concentration range. CK release was decreased by lidocaine. Conclusion: Lidocaine may improve smooth muscle contractility and basic cell function by cellular repair mechanisms which are still unknown. Improving contractility of smooth muscle after ischaemia‐reperfusion injury is essential in recovery of propulsive intestinal motility. Potential relevance: Characterisation of the cellular mechanisms of effects of lidocaine, especially on ischaemia‐reperfusion injured smooth muscle, may lead to improved treatment strategies for horses with POI.     

Influence of general anesthesia on pharmacokinetics of intravenous lidocaine infusion in horses

OBJECTIVE: To compare the disposition of lidocaine administered IV in awake and anesthetized horses. ANIMALS: 16 horses. PROCEDURE: After instrumentation and collection of baseline data, lidocaine (loading infusion, 1.3 mg/kg administered during 15 minutes (87 microg/kg/min); constant rate infusion, 50 microg/kg/min) was administered IV to awake or anesthetized horses for a total of 105 minutes. Blood samples were collected at fixed times during the loading and maintenance infusion periods and after the infusion period for analysis of serum lidocaine concentrations by use of liquid chromatography with mass spectral detection. Selected cardiopulmonary parameters including heart rate (HR), mean arterial pressure (MAP), arterial pH, PaCO2, and PaO2 were also recorded at fixed time points during lidocaine administration. Serum lidocaine concentrations were evaluated by use of standard noncompartmental analysis. RESULTS: Serum lidocaine concentrations were higher in anesthetized than awake horses at all time points during lidocaine administration. Serum lidocaine concentrations reached peak values during the loading infusion in both groups (1,849 +/- 385 ng/mL and 3,348 +/- 602 ng/mL in awake and anesthetized horses, respectively). Most lidocaine pharmacokinetic variables also differed between groups. Differences in cardiopulmonary variables were predictable; for example, HR and MAP were lower and PaO2 was higher in anesthetized than awake horses but within reference ranges reported for horses under similar conditions. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia has an influence on the disposition of lidocaine in horses, and a change in dosing during anesthesia should be considered.     

Effect of butorphanol, pentazocine, meperidine, or metoclopramide on intestinal motility in female ponies

Effect of butorphanol, pentazocine, meperidine, and metoclopramide on jejunal and pelvic flexure myoelectric and mechanical activity in 4 female ponies was investigated. The agent to be tested or saline solution was administered IV at the start of a 6-hour recording trial. In the jejunum, duration between activity fronts of regular spiking activity, defined as the length of the migrating myoelectric complex (MMC), was measured. The average duration of the MMC during control trials was 150 +/- 46 minutes. The average duration of the MMC after meperidine, butorphanol, pentazocine, and metoclopramide administration was 295 +/- 70 minutes, 260 +/- 60 minutes, 275 +/- 60 minutes, and 163 +/- 64 minutes, respectively. Meperidine, butorphanol, or pentazocine significantly increased the MMC duration (P less than 0.05), and did not significantly alter the pelvic flexure activity. Seemingly, meperidine, butorphanol, and pentazocine inhibited cyclic myoelectric activity in the jejunum. Metoclopramide had no effect on jejunal or pelvic flexure motility.     

Effects of intravenous lidocaine on isoflurane concentration,physiological parameters,metabolic parameters and stress-related hormones in horses undergoing surgery

Physiological parameters, metabolic parameters and stress-related hormones are evaluated in horses anaesthetized with isoflurane in oxygen combined with lidocaine intravenously. Two groups of horses anaesthetized with isoflurane (six horses in each group) were studied: a lidocaine group (IL), which received intravenous lidocaine and a control group (C), which received intravenous saline. Horses in both groups were premedicated with detomidine (i.v.), and anaesthesia was induced with midazolam-ketamine (i.v.). The lidocaine group received intravenous lidocaine as a loading dose of 2.5 mg kg(-1) at 15 min after induction of anaesthesia directly followed by a maintenance dosage of 50 microg kg(-1) min(-1), while the control group received saline (i.v.) following the same regime. End-tidal isoflurane and standard physiological parameters were measured. Blood was sampled for measurement of lidocaine, stress hormones and metabolic parameters. The end-tidal isoflurane concentration in the lidocaine group was 0.96 +/- 0.06% versus 1.28 +/- 0.06% (mean +/- SD) in the control group, a significant (P < 0.05) reduction of 25%. No significant differences were found regarding stress-related hormones, metabolic and physiological parameters. This study suggests that the use of lidocaine to decrease the concentration of isoflurane to obtain a sufficient surgical anaesthesia has no subsequent effects on physiological and metabolic parameters or stress-related hormones.