Morphologic changes and xanthine oxidase activity in the equine jejunum during low flow ischemia and reperfusion.

OBJECTIVE: To determine whether xanthine oxidase and dehydrogenase activities are altered during low flow ischemia and reperfusion of the small intestine of horses. ANIMALS: 5 clinically normal horses without histories of abdominal problems. PROCEDURE: With the horse under general anesthesia, a laparotomy was performed and blood flow to a segment of the distal jejunum was reduced to 20% of baseline for 120 minutes and was then reperfused for 120 minutes. Biopsy specimens were obtained before, during, and after ischemia for determination of xanthine oxidase and dehydrogenase activities, and for histologic and morphometric analyses. RESULTS: Percentage of xanthine oxidase activity (as a percentage of xanthine oxidase and dehydrogenase activity) was not altered during ischemia and reperfusion. An inflammatory response developed and progressed during ischemia and reperfusion. Mucosal lesions increased in severity after ischemia and reperfusion. Mucosal surface area and volume decreased during ischemia and continued to decrease during reperfusion. Submucosal volume increased slightly during ischemia, and continued to increase during reperfusion. CONCLUSIONS AND CLINICAL RELEVANCE: Evidence for conversion of xanthine dehydrogenase to xanthine oxidase during ischemia was not found. Factors other than production of reactive oxygen metabolites may be responsible for progressive epithelial loss, decrease in mucosal surface area and volume, and increase in submucosal volume observed in this study. Other methods of determining xanthine oxidase activity that detect the enzyme in sloughed epithelial cells should be used to better define the importance of this pathway in jejunal reperfusion injury in horses.

Effects of U-74389G, a novel 21-aminosteroid, on small intestinal ischemia and reperfusion injury in horses.

OBJECTIVE: To determine the effects of the 21-aminosteroid, U-74389G, on reperfusion of the equine jejunum, using total (TVO) and partial (PVO) vascular occlusion during the ischemic period. DESIGN: TVO: 16 healthy horses were randomly allotted to 3 groups-4 horses received the vehicle alone, 6 horses received a low dosage (3 mg/kg o body weight), and 6 horses a high dosage (10 mg/kg) of U-7438G. PVO: 10 healthy horses were randomly allotted to 2 groups--5 horses received the vehicle alone, and 5 horses received the low dosage (3 mg/kg) of U-74389G. PROCEDURES: TVO was induced for 1 hour followed by 2 hours of reperfusion. During PVO, blood flow was reduced to 20% of baseline for 2 hours, followed by 2 hours of reperfusion. For both models, either the vehicle alone or the drug was given 15 minutes prior to reperfusion. Samples were obtained before, during, and after ischemia for determination of myeloperoxidase (MPO) activity, malondealdehyde (MDA) concentration, concentration of conjugated dienes (PVO experiment only), and morphometric analysis. RESULTS: TVO: tissue concentration of MDA and MPO activity were not altered in any group by ischemia or reperfusion. During ischemia, mucosal volume and surface area were reduced. After reperfusion, no further reduction occurred. After initial decrease in submucosal volume during ischemia, there was a significant increase after reperfusion in the vehicle-only group (P < 0.05). PVO: there were no alterations in the concentration of either MDA or conjugated dienes. There was significant increase in the activity of MPO during ischemia and reperfusion (P < 0.05). These effects were similar for the vehicle-only and drug groups. During ischemia, there was a significant decrease in mucosal surface area and volume (P < 0.05), that was continued during reperfusion for the vehicle-only (P < 0.05). Submucosal volume increased during ischemia and reperfusion. CONCLUSIONS AND CLINICAL RELEVANCE: Reduced blood flow during ischemia (PVO group) caused continued loss in mucosal volume and surface area during reperfusion. At the dosage given, the 21-aminosteroid, U-74389G, was not effective in preventing continued reduction in mucosal volume and surface area after restoration of blood supply in the horses subjected to reduced blood flow.

Allometry of pharmacokinetics and pharmacodynamics of the muscle relaxant metocurine in mammals.

We investigated the effects of body size on the pharmacokinetics and pharmacodynamics of the renally cleared muscle relaxant metocurine. We hypothesized that pharmacokinetics of the drug would change allometrically in proportion to physiological time [infinity Mb0.25, where Mb is body mass] and that pharmacodynamics would be independent of size because of the highly conserved structure of the acetylcholine receptor. Metocurine effects during general anesthesia were examined in 17 rats, 8 cats, 6 dogs, 5 pigs, 7 sheep, and 12 horses. Allometric analysis demonstrated size dependence for pharmacokinetics, which were affected by physiological time (Mb0.25). Pharmacodynamics were size independent, except for the value for effect compartment concentration associated with 50% twitch paralysis (IC50). Data from individual species had a bimodal distribution that was significant: pigs and sheep were more sensitive than other large species, and their IC50 appeared size independent. IC50 was size dependent in more active species (horse, dog, cat, rat). Although the mechanism is unknown, we speculate that this trend might relate to receptor density within the end plate. Thus pharmacokinetics changed in proportion to physiological time, and pharmacodynamics were in part size independent.

Interaction of gentamycin and atracurium in anaesthetised horses.

Evoked hind limb digital extensor tension (hoof twitch) was maintained at 40% of baseline for 1 h by atracurium infusion in 7 horses anaesthetised with halothane. After 1 h, atracurium was discontinued and hoof twitch allowed to recover to 75%. Atracurium was again given by infusion to maintain 40% twitch for a second hour, then 2 mg gentamycin/kg bwt were given i.v. Atracurium infusion was continued for a third hour, and then hoof twitch was again allowed to recover spontaneously to 75%. Gentamycin reduced twitch strength from 40 +/- 1% (mean +/- sem) to 29 +/- 4% within 7.0 +/- 1.5 min (P = 0.02). Twitch gradually returned to pre-gentamycin strength over the course of the next hour. Recovery of hoof twitch from 50% to 75% took 7.7 +/- 0.7 min for atracurium alone and 11.5 +/- 2.7 min for atracurium plus gentamycin (P = 0.03). Recovery from 50% twitch to 75% fade recovery took 13.8 +/- 0.8 min for atracurium alone and 13.7 +/- 1.2 min for atracurium plus gentamycin. At 75% recovery of fade, hoof twitch was 87 +/- 3% for atracurium alone and 82 +/- 4% for atracurium plus gentamycin. Reversal of the block with edrophonium and subsequent recovery of the horses from anaesthesia were uneventful. It was concluded that, although gentamycin did augment the neuromuscular blockade of atracurium, the effect was minimal.

Effects of the 21-aminosteroid U-74389G on ischemia and reperfusion injury of the ascending colon in horses.

Sixteen horses were allotted at random to 3 groups: vehicle only; low dosage (vehicle and 3 mg of U-74389G/kg of body weight); high dosage (vehicle and 10 mg of U-74389G/kg). These solutions were given prior to reperfusion. The ascending colon was subjected to 2 hours of ischemia followed by 2 hours of reperfusion. Before, during, and after ischemia, full-thickness colonic tissue biopsy specimens were obtained for measurement of malondealdehyde (MDA) concentration and myeloperoxidase activity and for morphologic evaluation. Although increases were not significant, MDA concentration and myeloperoxidase activity increased during ischemia and reperfusion. Administration of U-74389G did not have significant effects on MDA concentration and myeloperoxidase activity. However, the lower dosage tended (P = 0.08) to reduce myeloperoxidase activity at 30 and 60 minutes of reperfusion. In horses of the vehicle-only group, ischemia induced a decrease in mucosal surface area that was continued into the reperfusion period (P < or = 0.05). Administration of U-74389G at both dosages (3 and 10 mg/kg) prevented the reperfusion-induced reduction in mucosal surface area, which was significant at 60 minutes (high dosage; P = 0.05) and 90 minutes (low and high dosages; P = 0.02). After initial reduction in horses of all groups, mucosal volume increased for the initial 60 minutes of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular blockade by use of atracurium in anesthetized llamas.

Anesthesia was induced in 8 healthy llamas by administration of guaifenesin and ketamine, and was maintained with halothane in oxygen. On 2 separate experimental days, atracurium was given to induce 95 to 99% reduction of evoked hind limb digital extensor tension (twitch). For the first part of the study, atracurium was given IV as repeat boluses, with muscle twitch strength being allowed to return without intervention to 75% of baseline after each bolus before the subsequent bolus was given. A total of 5 bolus doses of atracurium was given. For the first bolus, 0.15 mg/kg of body weight IV, and for subsequent boluses, 0.08 mg/kg, induced desired relaxation. Onset of relaxation was slightly more rapid for repeat, compared with initial, bolus. Duration of relaxation and recovery time were similar to initial and repeat doses. Maximal twitch reduction was observed in 4 +/- 0.2 minutes (mean +/- SEM). Duration from maximal twitch reduction to 10% recovery was 6.3 +/- 0.4 minutes. Twitch recovery from 10 to 50% of baseline took 11.6 +/- 0.6 minutes. Twitch recovery from 10 to 75% recovery took 19.5 +/- 1.1 minutes. Recovery from 10% twitch to 50% fade took 12.8 +/- 0.5 minutes. Fade at 50% recovery of twitch was 39 +/- 0.02%. Significant (P < 0.05) animal-to-animal variation was observed in twitch recovery times. For the second part of the study, atracurium was initially given IV as a 0.15-mg/kg bolus, followed by infusion for 1 to 2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of sensitivity to metocurine in exercised horses.

On the basis of results in dogs, conditioning exercise may increase sensitivity to nondepolarizing muscle relaxants. Five Thoroughbreds were exercised/conditioned 3 times weekly on a treadmill for 8 months. Increasing maximal rate of O2 consumption verified that the horses were responding to exercise conditioning. Six nonexercised Thoroughbreds served as the control group. Studies were done with horses under general anesthesia by use of halothane during partial paralysis by a brief constant-rate infusion with the muscle relaxant, metocurine iodide. Quantification of degree of paralysis of the hoof twitch (eg, digital extensor) occurred with simultaneous quantification of blood values of metocurine. Pharmacokinetic and pharmacodynamic analyses of the data were done by a nonlinear regression program, using the Hill equation. There were no differences in findings between exercised and nonexercised horses. The mean blood concentration for the 50% paralyzing dose of metocurine was 0.44 +/- 0.11 (SD) microgram/ml in exercised horses, and 0.58 +/- 0.22 microgram/ml in nonexercised horses. Despite evidence for a response to conditioning, a significant change in the sensitivity of the neuromuscular junction to metocurine was not found.

Clinical investigations of halothane and isoflurane for induction and maintenance of foal anesthesia.

Fifty-eight foals were divided into two groups for study of aspects of the clinical anesthetic management of foals and to characterize effects of halothane (n = 30) and isoflurane (n = 28) in foals. There were no significant differences (P greater than 0.05) in the demographics of the two groups. Results of hemograms and biochemical analysis of venous blood samples before and after anesthesia were either not influenced or only mildly (clinically unimportant) affected by either agent. Like adult horses, foals have an increased PaCO2 when anesthetized with inhaled anesthetics. We could detect no difference in the magnitude of increase in PaCO2 with either anesthetic. Anesthetic induction and recovery was most rapid with isoflurane. The quality of induction and recovery was similarly acceptable with either agent. Heart rate during isoflurane was not significantly different from conscious conditions but during halothane, heart rate was significantly less than control except at 91-120 min when statistical significance was not detected. These results support the clinical impression that foals can be safely and reliably anesthetized with either agent.

A comparison of xylazine-diazepam-ketamine and xylazine-guaifenesin-ketamine in equine anesthesia.

After sedation with xylazine (0.3 mg/kg intravenously [IV]), anesthesia was induced in six healthy horses with ketamine (2.0 mg/kg IV) and guaifenesin (100 mg/kg IV), diazepam (0.05 mg/kg IV), or diazepam (0.10 mg/kg IV). Anesthesia was maintained with halothane for 30 minutes. Heart rate, respiratory rate, direct arterial blood pressure, arterial blood gas, and pH measurements were made before, and at set intervals after, induction of anesthesia. Quality and characteristics of induction and recovery were evaluated objectively by an independent observer unaware of the protocol used. There were no significant differences among the three protocols from pre-induction values for arterial blood pressure, blood gas values, and pH. There was significantly greater ataxia at induction with the use of guaifenesin. The nature of induction, transition to and recovery from general anesthesia were comparable between guaifenesin and the higher dose of diazepam. Because of movements and difficulty with intubation, the lower dose of diazepam was considered unsatisfactory. It was concluded that diazepam (0.10 mg/kg) could be substituted for guaifenesin (100 mg/kg) to produce comparable quality of anesthesia in horses.

Effect of gentamicin administration on the neuromuscular blockade induced by atracurium in cats.

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four (T4 ratio) to increase from 50% to 75%. After recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered IV, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded. Within 1 minute of gentamicin administration, the mean +/- SD T1 response decreased from 49 +/- 5% to 33 +/- 8% of baseline and the T4 ratio decreased from 28 +/- 19% to 14 +/- 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 +/- 6% of baseline and a T4 ratio of 13 +/- 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 +/- 7% of baseline and the T4 ratio had increased to 21 +/- 13%. The time for recovery significantly (P less than 0.03) increased from 9.9 +/- 3.4 minutes during the control study to 18.1 +/- 10.7 minutes during the gentamicin study. In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium.

Contracture test and histologic and histochemical analyses of muscle biopsy specimens from horses with exertional rhabdomyolysis.

Biopsy specimens of the cutaneous omobrachialis muscle were obtained from 10 horses with a problem of myositis from mild exercise. One horse had been evaluated previously and malignant hyperthermia-like contractures developed in its muscle biopsy specimen during the contracture test. In this study, the halothane-caffeine contracture test and histologic and histochemical evaluations were performed on muscle biopsy specimens. In the contracture test, no muscle biopsy specimen developed contracture in the presence of 2 or 4% halothane alone. The mean (+/- SEM) caffeine-specific concentration in the presence of halothane was 5.23 +/- 0.5 mM for 2% halothane, and 4.46 +/- 0.6 mM for 4% halothane. The caffeine-specific concentration values were not significantly different. Contracture response for any muscle specimen did not resemble contracture associated with malignant hyperthermia. The cutaneous omobrachialis muscle was composed of type-II fibers, with type-I fibers seldom seen. For 9 of the 10 horses, overall fiber morphology was normal; 1 horse had necrotic fibers. Of the 10 muscle specimens, 9 had fibers that had positive reaction for alkaline phosphatase activity; 3 muscle specimens contained ringed myofibers. Three horses of this study were administered general anesthesia; 2 were research horses, anesthetized with halothane and succinylcholine, and 1 was a clinical case given halothane anesthesia plus a non-depolarizing muscle relaxant. One research horse developed a malignant hyperthermia-like reaction to anesthesia, with severe rhabdomyolysis evident after anesthesia, and an episode of muscle cramping in its stall 2 days after anesthesia. The other 2 horses had unremarkable postanesthetic periods.

Effects of atracurium administered by continuous intravenous infusion in halothane-anesthetized horses.

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.

Blood pressure response to tourniquet use in anesthetized horses.

Blood pressure during anesthesia and surgery was compared for 2 groups of horses. Group A, consisting of 23 horses, had a tourniquet placed on the distal portion of a limb. The other group of 20 horses (group B) had surgery of comparable nature and duration as did group-A horses, but a tourniquet was not used. There was a statistical difference (P less than 0.05) in the peak systolic arterial blood pressure between the groups; group-A horses had a mean (+/- SEM) peak of 151 +/- 6 mm of Hg and group-B horses had a peak of 118 +/- 4 mm of Hg. In addition, group-A horses had immediate decrease in blood pressure, coincident with tourniquet deflation. The blood pressure decrease of 23 +/- 3 mm of Hg represented 16% of immediate predeflation blood pressure. Comparable blood pressure decrease was not observed at the end of surgery in group-B horses. Significant difference was not found when other factors that could affect blood pressure were considered. These factors included preanesthetic medication, anesthetic agents, mode of ventilation, pretourniquet inflation blood pressure, and duration of tourniquet inflation. Significant (P less than 0.05) difference in peak blood pressure was observed when the tourniquet was placed on the dependent, compared with the uppermost, limb, with changes more pronounced when the tourniquet was placed on the dependent limb. Tourniquet placement was associated with hypertension, and tourniquet deflation was associated with blood pressure decrease in these anesthetized horses.

The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses.

To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental days (P less than 0.05), despite Day 7 cholinesterase activity that was 16% of pre-trichlorfon values. For atracurium Injections 1 and 2-5, 85 and 43 micrograms/kg of atracurium, respectively, were required to produce a 95-99% reduction in hoof twitch. The time from injection to maximum twitch reduction was approximately 9 min after Injection 1 and 5 min after subsequent injections. Time from injection to maximum twitch reduction was significantly longer for Injection 1 than Injections 2-5 on both experimental days. The time from maximum twitch reduction until 10% recovery was approximately 8 min, with no significant difference between experimental days. The time for twitch recovery from 10 to 75% was approximately 17 min for all injections. Antagonism of atracurium with edrophonium caused the twitch height to return to pre-atracurium strength in approximately 7 min. Edrophonium caused a significant increase in arterial blood pressure. Heart rate change was variable after edrophonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical use of the neuromuscular blocking agents atracurium and pancuronium for equine anesthesia.

Neuromuscular blocking agents (muscle relaxants) are useful and common adjuncts to general anesthesia for human beings, but have not been used extensively during anesthesia of large animal species. Over a 3-year period, atracurium or pancuronium were used as adjuncts to general anesthesia for 89 anesthetic procedures in 88 equids (of 18 breeds and age ranging in age from 5 weeks to 25 years) at the teaching hospital. Forty-one of the anesthetic procedures were for abdominal surgery, and orthopedic (n = 19), ophthalmologic (n = 17), thoracotomy (n = 1), and soft tissue (n = 14) procedures composed the rest. Most equids were given atracurium because it was less expensive than pancuronium. Initial dosage of either relaxant ranged from 0.12 to 0.2 mg/kg of body weight IV, and repeat doses ranged from 10 to 30 mg. Relaxants were used for as long as 205 minutes. Muscles of the face or hind limb digital extensor muscles were used to monitor relaxation. Muscles of the hind limb were more sensitive to the effects of relaxants than were muscles of the face. At the end of a surgical procedure, just prior to being taken to the recovery stall, a relaxant antagonist, edrophonium (0.5 to 1 mg/kg), was administered IV to each equid. Edrophonium caused blood pressure to increase in most of the equids. Heart rate change was variable, with approximately half the equids having no change or increased heart rate and the remainder having decreased heart rate. Recovery to standing after anesthesia was rated excellent or good for 72 equids, fair for 11, and poor for 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular and cardiovascular effects of atracurium administered to healthy horses anesthetized with halothane.

Neuromuscular and cardiovascular effects of atracurium, a nondepolarizing neuromuscular blocking agent, were evaluated in 10 halothane-anesthetized adult horses. Hind limb digital extensor tension (hoof twitch) was measured with a strain gauge to quantitate the muscle relaxant effects of atracurium. Response of facial muscles was compared with hoof twitch. Five injections of atracurium were given. Initial mean (+/- SEM) dosage of 0.07 +/- 0.01 mg of atracurium/kg of body weight caused 98.6 +/- 0.8% reduction of the preinjection hoof twitch. Subsequent dosages of 0.04 +/- 0.003 mg/kg induced a degree of relaxation similar to that induced by the initial dose. Duration of paralysis from maximal effect to 10% recovery of twitch was 12.2 +/- 1.5 minutes for the first injection. This was significantly (P less than 0.05) different from subsequent paralysis periods, which lasted approximately 7 minutes. The 10% to 75% recovery time after all injections was similar-approximately 16 minutes. The facial muscles were less affected objectively by atracurium than was the hind limb. Atracurium did not cause cardiovascular changes. When the hoof twitch had recovered to 95% of its tension before atracurium administration, 0.5 mg of edrophonium/kg, was given to antagonize neuromuscular blockade. Within 5 minutes of edrophonium administration, twitch tension exceeded that measured before atracurium administrations. Within 2 minutes of edrophonium administration, blood pressure began to increase and continued to increase approximately 10 mm of Hg above the value measured before edrophonium administration. Heart rate was not affected by edrophonium. Other muscarinic side effects of edrophonium were not observed. Of the 10 horses, 9 had good, unremarkable recovery to standing position. One horse had a violent recovery period.

Neuromuscular and cardiovascular effects of atracurium in ponies anesthetized with halothane.

Atracurium besylate, a recently developed, intermediate-duration acting, neuromuscular-blocking agent, was given to 15 halothane-anesthetized ponies to produce surgical relaxation (95% to 99% reduction of hoof twitch). All 15 ponies were given 3 injections; 8 of the 15 ponies were given 2 additional injections. Initial dosage of 0.11 +/- 0.01 mg/kg (mean +/- SD) and all subsequent injections of 0.052 mg/kg produced desired relaxation. Paralysis phase (maximum twitch reduction to 10% twitch recovery) lasted 24 +/- 5 minutes for the initial injection. Paralysis from subsequent injections lasted for a slightly shorter time. Recovery phase (10% to 75% twitch recovery) was similar for all injections (initial and repeated) and lasted approximately 11 minutes. Cardiovascular side effects were not seen. Reversal of effects of atracurium with administration of 0.5 mg of edrophonium/kg was achieved when the evoked digital extensor tension (twitch height) had returned to 95% of base line after the last atracurium injection. Edrophonium caused systolic blood pressure to increase 121% +/- 7% of base-line pressure, which was 133 +/- 18 mm of Hg. Heart rate changed to 93% +/- 9% of base line after edrophonium was given, which was 49 +/- 7 beat/min, but this change did not occur until after the blood pressure increased. Recovery to standing was smooth and strong. Five ponies stood on their first attempt to rise, 5 on the 2nd attempt, 2 on the 3rd, and 1 on the 4th. Seven ponies stood within 30 minutes after transportation to the recovery stall, 7 within an hour.(ABSTRACT TRUNCATED AT 250 WORDS)