Effects of xylazine hydrochloride during isoflurane-induced anesthesia in horses.

OBJECTIVE: To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose concentrations, and urinary output also were measured during the anesthetic studies. RESULTS: Isoflurane MAC (mean +/- SEM) was reduced by 24.8 +/- 0.5 and 34.2 +/- 1.9% at 42 +/- 7 and 67 +/- 10 minutes, respectively, after administration of XYL at 0.5 and 1 mg/kg. Amount of MAC reduction by XYL was dose- and time-dependent. Overall, cardiovascular and respiratory values varied little among treatments. Administration of XYL increased blood glucose concentration; the magnitude of change was dose- and time-dependent. Urine volume increased but not significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of XYL reduced the anesthetic requirement for isoflurane in horses. The magnitude of the decrease is dose- and time-dependent. Administration of XYL increases blood glucose concentration in anesthetized horses in a dose-related manner.

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.

The effect of doxapram-induced hyperventilation on respiratory mechanics in horses.

To investigate the influence of increased respiratory frequency on respiratory mechanics in the horse, measurements were made in two groups of seven tracheostomized horses before and after the administration of doxapram. The horses in group I had normal base line values for respiratory mechanics, whereas the horses in group II had significantly lower values of dynamic compliance (Cdyn), higher respiratory resistance (R), and a higher total change in pleural pressure (delta P). The administration of 0.3 mg kg-1 doxapram intravenously resulted in a significant increase in respiratory frequency (fR), R, delta P, tidal volume (VT), and peak to peak respiratory flow (V), and a decrease in Cdyn in both groups of horses. The group II horses had significantly greater increases in R and delta P than the horses in group I.

Involvement of nitric oxide in inhibitory neuromuscular transmission in equine jejunum.

OBJECTIVES: To evaluate the role of nitric oxide (NO), vasoactive intestinal peptide (VIP), and a transmitter acting through an apamin-sensitive mechanism in mediating inhibitory transmission in the equine jejunal circular muscle, and to determine the distribution of VIP-and NO-producing nerve fibers in the myenteric plexus and circular muscle. PROCEDURE: Circular muscle strips were suspended in tissue baths containing an oxygenated modified Krebs solution and attached to isometric force transducers. Responses to electrical field stimulation (EFS), tetrodotoxin, the NO antagonists L-N-nitro-arginine-methyl-ester (L-NAME) and N-nitro-L-arginine, apamin, VIP, authentic NO, and the NO donar sodium nitroprusside were tested. Immunostaining for VIP-like and NADPH diaphorase histochemical staining were performed on paraformaldehyde fixed tissue. RESULTS: Subpopulations of myenteric neurons and nerve fibers in the circular muscle were positive for NADPH diaphorase and VIP-like staining. EFS caused a frequency-dependent inhibition of contratile activity. Tetrodotoxin prevented the EFS-induced inhibition of contractions. L-NAME (200 microM) and apamin (0.3 microM) significantly (P < 0.01) reduced EFS-stimulated inhibition of contractile activity at most frequencies tested. The effects of L-NAME and apamin were additive. In their combined presence, EFS induced excitation instead of inhibition (196.7% increase at 5 Hz, n = 28, P < 0.01). Inhibition of contractile activity by EFS was mimicked by sodium nitroprusside. Authentic NO (3-6 microM) abolished contractile activity. VIP induced a dose-dependent inhibition of contractile activity (89.1 +/- 6.3% reduction at approximately 0.3 microM, n = 16). Antagonism of NO synthesis did not alter the response to VIP. CONCLUSION: NO, VIP, and a substance acting through an apamin-sensitive mechanism appear to comediate inhibitory transmission in the equine jejunal circular muscle. CLINICAL RELEVANCE: These findings may suggest new therapeutic targets for motility disorders, such as agents that inhibit the synthesis or actions of NO.

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.

Effects of inhalation anesthetic agents on response of horses to three hours of hypoxemia.

OBJECTIVE: To study the effects of inhalation anesthetic agents on the response of horses to 3 hours of hypoxemia. DESIGN: Controlled crossover study. ANIMALS: Five healthy adult horses. PROCEDURE: Horses were anesthetized twice: once with halothane, and once with isoflurane in O2. Anesthetized horses were positioned in left lateral recumbency. Constant conditions for the study began at 2 hours of anesthesia. A constant agent dose of 1.2 minimum alveolar concentration, PaO2 of 50 +/- 5 mm of Hg, and PaCO2 of 45 +/- 5 mm of Hg were maintained for 3 hours. Circulatory measurements were made at 0.5, 1, 2, and 3 hours of hypoxemia (anesthesia hours 2.5, 3, 4, and 5). Blood was collected from horses for biochemical analyses before anesthesia, within a few minutes after standing, and at 1, 2, 4, and 7 days after anesthesia. RESULTS: Cardiac index was greater (P = 0.018) during isoflurane than halothane anesthesia. Cardiac index remained constant during the 3 hours of hypoxemia during halothane anesthesia, whereas it decreased from the baseline during isoflurane anesthesia. Marginally nonsignificant P values for an agent difference were detected for arterial O2 content (P = 0.051), and oxygen delivery (P = 0.057). Serum activities of aspartate transaminase (P = 0.050) and sorbitol dehydrogenase (P = 0.017) were higher in halothane-anesthetized horses than in isoflurane-anesthetized horses. Circulatory function was better in hypoxemic horses anesthetized with isoflurane than with halothane. Isoflurane resulted in less muscular injury in hypoxemia horses than did halothane anesthesia. Halothane anesthesia and hypoxemia were associated with hepatic insult. CONCLUSION: Isoflurane is better than halothane for hypoxemic horses.

Microvascular permeability and endothelial cell morphology associated with low-flow ischemia/reperfusion injury in the equine jejunum.

Microvascular permeability of the jejunum of clinically normal equids and microvascular permeability associated with 60 minutes of ischemia (25% baseline blood flow) and subsequent reperfusion were investigated. Eight adult horses were randomly allotted to 2 equal groups: normal and ischemic/reperfusion injury. Lymphatic flow rates, mesenteric blood flow, and lymph and plasma protein concentrations were determined at 15-minute intervals throughout the study. Microvascular permeability was determined by estimates of the osmotic reflection coefficient, which was determined when the ratio of lymphatic protein to plasma protein concentration reached a constant minimal value as lymph flow rate increased (filtration-independent lymph flow rate), which occurred at venous pressure of 30 mm of Hg. Full-thickness jejunal biopsy specimens were obtained at the beginning and end of each experiment, and were prepared for light microscopy to estimate tissue volume (edema) and for transmission electron microscopy to evaluate capillary endothelial cell morphology. The osmotic reflection coefficient for normal equine jejunum was 0.19 +/- 0.06, and increased significantly (P < or = 0.0001) to 0.48 +/- 0.05 after the ischemia/reperfusion period. Microscopic evaluation revealed a significant increase (P < or = 0.0001) in submucosal and serosal volume and capillary endothelial cell damage in horses that underwent ischemia/reperfusion injury. Results indicate that ischemia/reperfusion of the equine jejunum caused a significant increase in microvascular permeability.

Autologous blood instillation alters respiratory mechanics in horses.

To investigate physiological consequences of autologous blood instillation in the lungs of healthy horses, respiratory mechanics and bronchial response to histamine were studied in 8 Thoroughbreds before and after introducing autologous blood (n = 5) and sterile saline solution (n = 3) into their lungs. Blood instillation resulted in a decrease in dynamic compliance (Cdyn) and increased respiratory resistance (R). Bronchial sensitivity and reactivity were unchanged after blood introduction. There were no significant changes in pulmonary mechanics or bronchial response after saline instillation.

Evaluation of a technique for detection of pulmonary hemorrhage in horses, using carbon monoxide uptake.

The diffusing capacity for carbon monoxide (DLCO) and the functional residual capacity (FRC) of the lung were measured in 5 healthy Thoroughbreds before and after instillation of autologous blood into their lungs, in an attempt to develop a method to quantitate extravascular blood in the lungs of horses with exercise-induced pulmonary hemorrhage. Mean (+/- SD) baseline values of DLCO and FRC were 333.8 +/- 61.9 ml/min/mm of Hg and 21.464 +/- 4.156 L, respectively. Blood instillation resulted in decreases in DLCO and FRC. The paradoxic decrease in DLCO (we were expecting to find an increase owing to blood in the airspaces, as has been reported in people) appears to be associated with the bronchoscopic procedure and with presence of blood in the airways. We concluded that rebreathing DLCO measurements were not effective for detecting blood introduced bronchoscopically into the lungs of horses.

Morphine-isoflurane interaction in dogs, swine and rhesus monkeys.

In monkeys, dogs and swine (six each) we tested the reduction of the isoflurane MAC (minimal alveolar concentration) produced by 2 mg.kg-1 morphine intravenously (i.v.) and the concurrent effect on PCO2 with spontaneous ventilation. MAC fell to a minimum of 55% of control at 53 min in monkeys, 50% at 38 min in dogs and 13% at 33 min in swine. PaCO2 rose at constant MAC with morphine to 55-60 mmHg, but did not fall over the next several hours despite the decline of plasma morphine concentration, and the resulting needed rise in isoflurane concentration to keep the anaesthesia depth at 1 MAC. After isoflurane concentration had returned to pre-morphine control levels, naloxone immediately reduced PaCO2 to or below control level. Morphine pharmacokinetics in the three species studied conformed to a two-compartment model.

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)

Recovery of horses from inhalation anesthesia.

To study behavioral and cardiopulmonary characteristics of horses recovering from inhalation anesthesia, 6 nonmedicated horses were anesthetized under laboratory conditions on 3 different days, with either halothane or isoflurane in O2. Anesthesia was maintained at constant dose (1.5 times the minimum alveolar concentration [MAC]) of halothane in O2 for 1 hour (H1), halothane in O2 for 3 hours (H3), or isoflurane in O2 for 3 hours (I3). The order of exposure was set up as a pair of Latin squares to account for horse and trial effects. Circulatory (arterial blood pressure and heart rate) and respiratory (frequency, PaCO2, PaO2, pHa) variables were monitored during anesthesia and for as long as possible during the recovery period. End-tidal percentage of the inhaled agent was measured every 15 seconds by automated mass spectrometry, then by hand-sampling after horses started moving. Times of recovery events, including movement of the eyelids, ears, head, and limbs, head lift, chewing, swallowing, first sternal posture and stand attempts, and the number of sternal posture and stand attempts, were recorded. The washout curve or the ET ratio (end-tidal percentage of the inhaled agent at time t to end-tidal percentage of the inhaled agent at the time the anesthesia circuit was disconnected from the tracheal tube) plotted against time was similar for H1 and H3. The slower, then faster (compared with halothane groups) washout curve of isoflurane was explainable by changes in respiratory frequency as horses awakened and by lower blood/gas solubility of isoflurane. The respiratory depressant effects of isoflurane were marked and were more progressive than those for halothane at the same 1.5 MAC dose. During the first 15 minutes of recovery, respiratory frequency for group-I3 horses increased significantly (P < 0.05), compared with that for the halothane groups. For all groups, arterial blood pressure increased throughout the early recovery period and heart rate remained constant. Preanesthesia temperament of horses and the inhalation agent used did not influence the time of the early recovery events (movement of eyelids, ears, head, and limbs), except for head lift. For events that occurred at anesthetic end-tidal percentage < 0.20, or when horses were awake, temperament was the only factor that significantly influenced the nature of the recovery (chewing P = 0.04, extubation P = 0.001, first stand attempt P = 0.008, and standing P = 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Modulation of bronchial responsiveness in horses by phenylbutazone and furosemide.

Effects of phenylbutazone (PBZ) and furosemide (FUR) on the respiratory tract of horses were evaluated, focusing on bronchial responsiveness. Four healthy Thoroughbreds were used and data were analyzed by use of a Latin square design. Histamine provocation tests (0.5, 1, 2, and 4 micrograms/min, i.v.) were done: (1) without prior treatment with PBZ or FUR, (2) 30 minutes after administration of PBZ (8 mg/kg, i.v.), (3) 1 hour after administration of FUR (1 mg/kg, i.v.), and (4) after administration of PBZ plus FUR. Pulmonary function tests (dynamic compliance, resistance, respiratory frequency, and tidal volume) and heart rate were monitored throughout the experiments. Phenylbutazone did not influence basal pulmonary function test results, whereas FUR caused a significant (P < 0.05) increase in dynamic compliance and decrease in resistance. Histamine infusion resulted in a dose-dependent decrease in dynamic compliance and a dose-dependent increase in resistance, respiratory frequency, and heart rate. Phenylbutazone administration significantly (P < 0.05) attenuated most of the changes induced by histamine, whereas FUR had less protective action. Administration of PBZ plus FUR before administration of histamine was less effective than administration of PBZ alone.

Measurement of pulmonary diffusing capacity for carbon monoxide and functional residual capacity during rebreathing in conscious thoroughbreds.

A rebreathing method for measurement of pulmonary diffusing capacity for carbon monoxide (DLCO) and functional residual capacity (FRC) was evaluated in conscious horses. Horses were manually ventilated through an endotracheal tube, using a custom-made syringe filled with a gas mixture containing 18-carbon monoxide (18CO) and helium (He). The 18CO and He concentrations were continuously monitored by use of a mass spectrometer connected to the rebreathing circuit. Values for DLCO and FRC were calculated from changes in the concentration of these 2 gases. In 11 Thoroughbreds, mean (+/- SD) DLCO was 330.3 +/- 56.9 ml.min-1 x mm of Hg-1, and FRC was 20.21 +/- 3.35 L. Body weight normalization yielded mean (+/- SD) values of 0.652 +/- 0.114 ml.min-1 x mm of Hg-1 x kg-1 for DLCO, and 39.9 +/- 6.4 ml.kg-1 for FRC.

Evaluation of the effect of alfentanil on the minimum alveolar concentration of halothane in horses.

The effect of 3 plasma concentrations of alfentanil on the minimum alveolar concentration (MAC) of halothane in horses was evaluated. Five healthy geldings were anesthetized on 3 occasions, using halothane in oxygen administered through a mask. After induction of anesthesia, horses were instrumented for measurement of blood pressure, airway pressure, and end-tidal halothane concentrations. Blood samples, for measurement of pH and blood gas tensions, were taken from the facial artery. Positive pressure ventilation was begun, maintaining PaCO2 at 49.1 +/- 3.3 mm of Hg and airway pressure at 20 +/- 2 cm of H2O. The MAC was determined in triplicate, using a supramaximal electrical stimulus of the oral mucous membranes. Alfentanil infusion was then begun, using a computer-driven infusion pump to achieve and maintain 1 of 3 plasma concentrations of alfentanil. Starting at 30 minutes after the beginning of the infusion, MAC was redetermined in duplicate. Mean +/- SD measured plasma alfentanil concentration during the infusions were 94.8 +/- 29.0, 170.7 +/- 29.2 and 390.9 +/- 107.4 ng/ml. Significant changes in MAC were not observed for any concentration of alfentanil. Blood pressure was increased by infusion of alfentanil and was dose-related, but heart rate did not change. Pharmacokinetic variables of alfentanil were determined after its infusion and were not significantly different among the 3 doses.

Influence of inhaled anesthetics on the pharmacokinetics and pharmacodynamics of morphine.

We determined the magnitude and duration of the effect of morphine (1.0 mg/kg intravenous bolus) on isoflurane and halothane minimum alveolar concentration (MAC) in six dogs anesthetized on two occasions in cross-over fashion. Plasma morphine concentration-time profiles and changes in PaCO2 were determined after morphine injection. After morphine injection, the end-tidal anesthetic dose was manipulated over the course of a 4-h observation period to account for the decline in plasma morphine concentration and to maintain an anesthetic level equivalent to 1.0 MAC isoflurane or halothane alone. Morphine decreased the MAC of halothane and isoflurane. The magnitude of MAC decrease was related to time after morphine injection and was similar for a given time with both halothane and isoflurane. For example, at 28.8 +/- 3.6 (mean +/- SE) and 34.8 +/- 6.3 min after morphine injection, the MAC for halothane and isoflurane were reduced by 35.7% +/- 4.5% and 39.3% +/- 3.4%, respectively. By 4 h after morphine injection, the MAC reduction for both anesthetics was less than 10% in most of the animals. Except for systemic clearance of morphine during halothane and isoflurane (40.1 +/- 6.1 and 53.7 +/- 5.6 mL.min-1.kg-1, respectively), there were no differences in disposition kinetics of free morphine associated with the two inhaled anesthetics. Morphine increased PaCO2 to a similar degree with both halothane (from 42.2 +/- 2.1 mm Hg to 55.6 +/- 2.3 mm Hg) and isoflurane (46.2 +/- 2.4 mm Hg to 55.3 +/- 2.1 mm Hg). Respiratory depression was abolished by noxious stimulation (tail clamp) and naloxone in all animals with both anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Circulatory and respiratory responses of spontaneously breathing, laterally recumbent horses to 12 hours of halothane anesthesia.

Cardiovascular and respiratory changes that accompany markedly long periods (12 hours) of halothane anesthesia were characterized. Eight spontaneously breathing horses were studied while they were positioned in left lateral recumbency and anesthetized only with halothane in oxygen maintained at a constant end-tidal concentration of 1.06% (equivalent to 1.2 times the minimal alveolar concentration for horses). Results of circulatory and respiratory measurements during the first 5 hours of constant conditions were similar to those previously reported from this laboratory (ie, a time-related significant increase in systemic arterial blood pressure, cardiac output, stroke volume, left ventricular work, PCV, plasma total solids concentration, and little change in respiratory system function). Beyond 5 hours of anesthesia, arterial blood pressure did not further increase, but remained above baseline. Cardiac output continued to increase, because heart rate significantly (P < 0.05) increased. Peak inspiratory gas flow increased significantly (P < 0.05) in later stages of anesthesia. There was a significant decrease in inspiratory time beginning at 4 hours. Although PaO2 and PaCO2 did not significantly change during the 12 hours of study, PVO2 increased significantly (P < 0.05) and progressively with time, beginning 6 hours after the beginning of constant conditions. Metabolic acidosis increased with time (significantly [P < 0.05] starting at 9 hours), despite supplemental IV administered NaHCO3. Plasma concentrations of eicosanoids: 6-keto-prostaglandin F1 alpha (PGF1 alpha, a stable metabolite of PGI2), PGF2 alpha, PGE, and thromboxane (TxB2, a stable metabolite of TxA2) were measured in 5 of the 8 horses before and during anesthesia. Significant changes from preanesthetic values were not detected. Dynamic thoracic wall and lung compliances decreased with time.

Effects of five hours of constant 1.2 MAC halothane in sternally recumbent, spontaneously breathing horses.

Circulatory and respiratory effects of five h of constant 1.06 per cent alveolar halothane in oxygen were identified in eight healthy horses, which breathed spontaneously, were otherwise unmedicated and positioned in sternal recumbency. Only a few important significant (P less than 0.05) changes occurred with time. Total peripheral resistance was about 15 per cent lower after two hours of constant dose halothane than after 30 mins of constant dose (P less than 0.05) and accounted for the significant 10 per cent reduction in mean carotid arterial blood pressure. By 5 h, the reduction in resistance and arterial blood pressure was 20 and 25 per cent respectively. Heart rate increased progressively with time and the increase became significant at 5 h (15 per cent increase). However, the heart rate change was not large enough to alter cardiac output. There were no major time-related changes in PaO2 or PaCO2. Three of four horses recovered from anaesthesia had markedly elevated serum creatine kinase levels and clinical signs of severe post anaesthetic myopathy.

Effect of high PaCO2 and time on cerebrospinal fluid and intraocular pressure in halothane-anesthetized horses.

The effects of different arterial carbon dioxide tensions (PaCO2) on cerebrospinal fluid pressure (CSFP) and intraocular pressure (IOP) were studied in 6 male halothane-anesthetized horses positioned in left lateral recumbency. Steady-state anesthetic conditions (1.06% end-tidal halothane concentration) commenced 60 minutes following anesthetic induction with only halothane in oxygen. During atracurium neuromuscular blockade, horses were ventilated, and respiratory rate and peak inspiratory airway pressure were maintained within narrow limits. The CSFP and IOP were measured at 3 different levels of PaCO2 (approx 40, 60, and 80 mm of Hg). The PaCO2 sequence in each horse was determined from a type of switchback design with the initial PaCO2 (period 1), established 30 minutes after the commencement of steady-state anesthesia, being repeated in the middle (period 3) and again at the end (period 5) of the experiment. Measurements taken from the middle 3 periods (2, 3, and 4) would form a Latin square design replicated twice. The interval between each period was approximately 45 minutes. Data from periods 2, 3, and 4 indicated that CSFP (P less than 0.05) and mean systemic arterial pressure increased significantly (P less than 0.05) with high PaCO2. Mean central venous pressure, heart rate, and IOP did not change significantly during these same conditions. Measurements taken during periods 1, 3, and 5 were compared to assess the time-related responses to anesthesia and showed a significant increase in CSFP, a significant decrease in mean central venous pressure, and a small (but not statistically significant) increase in mean systemic arterial pressure.