Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses.

This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and 3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2) and 5% CO(2), and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M), pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When competitive antagonism was characterized, the affinity constant (pA(2)) was calculated by Schild plots. A parallel rightward shift in the concentration-response curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentration-response curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (E(max)), while the highest concentration increased slope of the concentration-response curve and increased E(max). The pA(2) for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3) receptors. The complex role of M(2) receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.

Evaluation of accuracy and reliability of indirect calorimetry for the measurement of resting energy expenditure in healthy dogs.

OBJECTIVE: To assess accuracy and reliability of open-flow indirect calorimetry in dogs. ANIMALS: 13 clinically normal dogs. PROCEDURE: In phase 1, oxygen consumption per kilogram of body weight (VO2/kg) was determined in 6 anesthetized dogs by use of open-flow indirect calorimetry before and after determination of VO2/kg by use of closed-circuit spirometry. In phase 2, four serial measurements of VO2 and carbon dioxide production (VCO2) were obtained in 7 awake dogs by use of indirect calorimetry on 2 consecutive days. Resting energy expenditure (REE) was calculated. RESULTS: Level of clinical agreement was acceptable between results of indirect calorimetry and spirometry. Mean VO2/kg determined by use of calorimetry before spirometry was significantly greater than that obtained after spirometry. In phase 2, intraclass correlation coefficients (ICC) for REE and VO2 were 0.779 and 0.786, respectively, when data from all 4 series were combined. When the first series was discounted, ICC increased to 0.904 and 0.894 for REE and VO2, respectively. The most reliable and least variable measures of REE and VO2 were obtained when the first 2 series were discounted. CONCLUSIONS AND CLINICAL RELEVANCE: Open-flow indirect calorimetry may be used clinically to obtain a measure of VO2 and an estimate of REE in dogs. Serial measurements of REE and VO2 in clinically normal dogs are reliable, but a 10-minute adaption period should be allowed, the first series of observations should be discounted, multiple serial measurements should be obtained, and REE.

Pharmacokinetics and toxic effects of lithium chloride after intravenous adminstration in conscious horses.

OBJECTIVE: To determine the pharmacokinetics and toxic effects associated with IV administration of lithium chloride (LiCl) to conscious healthy horses. ANIMALS: 6 healthy Standardbred horses. PROCEDURE: Twenty 3-mmol boluses of LiCl (0.15 mmol/L) were injected IV at 3-minute intervals (total dose, 60 mmol) during a 1-hour period. Blood samples for measurement of serum lithium concentrations were collected before injection and up to 24 hours after injection. Behavioral and systemic toxic effects of LiCl were also assessed. RESULTS: Lithium elimination could best be described by a 3-compartment model for 5 of the 6 horses. Mean peak serum concentration was 0.561 mmol/L (range, 0.529 to 0.613 mmol/L), with actual measured mean serum value of 0.575 mmol/L (range, 0.52 to 0.67 mmol/L) at 2.5 minutes after administration of the last bolus. Half-life was 43.5 hours (range, 32 to 84 hours), and after 24 hours, mean serum lithium concentration was 0.13+/-0.05 mmol/L (range, 0.07 to 0.21 mmol/L). The 60-mmol dose of LiCl did not produce significant differences in any measured hematologic or biochemical variables, gastrointestinal motility, or ECG variables evaluated during the study period. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of lithium best fit a 3-compartment model, and clearance of the electrolyte was slow. Healthy horses remained unaffected by LiCl at doses that exceeded those required for determination of cardiac output. Peak serum concentrations were less than steady-state serum concentrations that reportedly cause toxic effects in other species.

Cardiopulmonary effects of the alpha2-adrenoceptor agonists medetomidine and ST-91 in anesthetized sheep.

To test the hypothesis that pulmonary alterations are more important than hemodynamic changes in alpha2-agonist-induced hypoxemia in ruminants, the cardiopulmonary effects of incremental doses of (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imadazole) hydrochloride (medetomidine; 0.5, 1.0, 2.0, and 4 micrograms/kg) and 2-(2, 6-diethylphenylamino)-2-imidazol (ST-91; 1.5, 3.0, 6.0, and 12 micrograms/kg) were compared in five halothane-anesthetized, ventilated sheep using a placebo-controlled randomized crossover design. Pulmonary resistance (RL), dynamic compliance, and tidal volume changes in transpulmonary pressure (DeltaPpl) were determined by pneumotachography, whereas cardiac index (CI), mean pulmonary artery pressure (Ppa), and pulmonary artery wedge pressure (Ppaw) were determined using thermodilution and a Swan-Ganz catheter. The most important finding was the fall in partial pressure of oxygen in arterial blood (PaO2) after administration of medetomidine at a dose (0.5 micrograms/kg) 20 times less than the sedative dose. The PaO2 levels decreased to 214 mm Hg as compared with 510 mm Hg in the placebo-treated group. This decrease in PaO2 was associated with a decrease in dynamic compliance and an increase in RL, DeltaPpl, and the intrapulmonary shunt fraction without changes in heart rate, CI, mean arterial pressure, pulmonary vascular resistance, Ppa, or Ppaw. On the other hand, ST-91 only produced significant changes in PaO2 at the highest dose. After this dose of ST-91, the decrease in PaO2 was accompanied by a 50% decrease in CI and an increase in mean arterial pressure, Ppa, Ppaw, and the intrapulmonary shunt fraction without significant alterations of RL and DeltaPpl. The study suggests that the mechanism(s) by which medetomidine and ST-91 produce lower PaO2 are different and that drug-induced alterations in the pulmonary system are mainly responsible for the oxygen-lowering effect of medetomidine.

Histopathologic alterations induced in the lungs of sheep by use of alpha2-adrenergic receptor agonists.

OBJECTIVE: To study effects of central- and peripheral-acting alpha2-adrenergic receptor agonists on lung parenchyma, platelets, and pulmonary intravascular macrophages (PIM) of sheep. ANIMALS: 12 healthy mature female sheep. PROCEDURE: Group-1 (control, n = 2) sheep received 5 ml of physiologic saline solution IV and were euthanatized 3 minutes later. Sheep of group 2 (n = 8) received xylazine (150 microg/kg of body weight, IV), then 2 sheep each were euthanatized 3, 10, or 60 minutes, or 12 hours later. Sheep (n = 2) of group 3 were given ST-91 (30 microg/kg, IV), then were euthanatized 3 minutes later. Immediately after euthanasia, the lungs were fixed intratracheally and tissue was obtained for light and electron microscopy after 1 hour. RESULTS: Pulmonary parenchymal damage or morphologic alterations in PIM and platelets were not evident in control sheep. Three minutes after xylazine administration, morphologic changes in PIM were appreciable. After 10 minutes, extensive damage to the capillary endothelium and alveolar type-I cells, intra-alveolar hemorrhage, and interstitial and alveolar edema were evident. Most PIM had complete internalization of the surface coat. Similar changes were seen 60 minutes after xylazine administration; however, by 12 hours, morphologic features of PIM and lung parenchyma were almost completely restored. Evidence of PIM activation, obvious damage to capillary endothelium, and extensive pulmonary edema also were evident 3 minutes after ST-91 administration. CONCLUSIONS: XYLAZINE induces severe pulmonary parenchymal damage when administered at clinical sedative doses in sheep; morphologic changes in PIM within 3 minutes after administration of these drugs are substantial; and platelet aggregation is not apparent.

Effects of intravenously administered glycopyrrolate in anesthetized horses.

The purpose of this study was to determine the heart rate (HR) and blood pressure (BP) effect of glycopyrrolate in anesthetized horses with low HR (< or = 30 beats/min). The horses were randomly treated with glycopyrrolate (2.5 micrograms/kg body weight (BW)) or saline, intravenously (i.v.) (n = 17). If HR failed to increase (by > 5 beats/min within 10 min), glycopyrrolate (same dose) was administered. Heart rate increased by > 5 beats/min in 3 out of 9 horses following the initial glycopyrrolate treatment. Overall changes in HR and mean BP were not significantly different, while systolic and diastolic BP increased significantly (P < 0.025 using a Bonferroni corrected paired t-test). On the 2nd treatment, 3 out of 7 horses given 2.5 micrograms/kg BW glycopyrrolate, and 4 out of 5 horses given 5.0 micrograms/kg BW (total dose) showed an increase in heart rate of > 5 beats/min, which was significant. A significant increase in BP was produced following treatment with 2.5 micrograms/kg BW, but not following 5.0 micrograms/kg BW. A final increase in HR, of > 5 beats/min, was associated with a significant rise in BP (P < 0.05 using an unpaired t-test). In conclusion, an increase in HR can occur with 2.5 to 5.0 micrograms of glycopyrrolate/kg BW, i.v., and results in improvement in BP in anesthetized horses.

Plasma concentrations and cardiovascular influence of lidocaine infusions during isoflurane anesthesia in healthy dogs and dogs with subaortic stenosis.

OBJECTIVE: To determine the plasma concentrations and cardiovascular changes that occur in healthy dogs and dogs with aortic stenosis that are given an infusion of lidocaine during isoflurane anesthesia. STUDY DESIGN: Phase 1, controlled randomized cross-over trial; Phase 2, before and after trial ANIMALS: Phase 1, 6 healthy dogs (4 female, 2 male) weighing 23.8 +/- 7.4 kg; Phase 2, 7 dogs (4 female, 3 male) with moderate to severe subaortic stenosis (confirmed by Doppler echocardiography) weighing 31.1 +/- 14.5 kg. METHODS: After mask induction, intubation, and institution of positive pressure ventilation, instrumentation was performed to measure hemodynamic variables. After baseline, measurement at an end-tidal isoflurane concentration of 1.9% (phase 1) or 1.85% (phase 2), a loading dose infusion of lidocaine at 400 microg/kg/min was given. Phase 1: Maintenance doses of lidocaine were administered consecutively (40, 120, and 200 microg/kg/min) after the loading dose (given for 10, 10, and 5 minutes, respectively) in advance of each maintenance concentrations. Measurements were taken at the end of each loading dose and at 25 and 35 minutes during each maintenance level. The same animals on a different day were given dextrose 5% and acted as the control. Phase 2: Dogs were studied on a single occasion during an infusion of lidocaine at 120 microg/kg/ min given after the loading dose (10 minutes). Measurements occurred after the loading dose and at 25 and 35 minutes. A blood sample for lidocaine concentration was taken at 70 minutes. Data were compared using a one-way ANOVA for phase 1, and between phase 1 and 2. Statistical analysis for phase 2 was performed using a paired t-test with a Bonferroni correction. A P value < or = .05 was considered significant. RESULTS: Phase 1: Plasma lidocaine concentrations achieved with 40, 120, and 200 microg of lidocaine/kg/min were 2.70, 5.27, and 7.17 microg/mL, respectively. A significant increase in heart rate (HR) (all concentrations), central venous pressure (CVP), mean pulmonary arterial pressure (PAP), and a decrease in stroke index (SI) (200 microg/kg/min) were observed. An increase in systemic vascular resistance (SVR) and mean PAP, and a decrease in SI also followed the loading dose given before the 200 microg/kg/min infusion. No other significant differences from the control measurements, during dextrose 5% infusion alone, were detected. Phase 2: Plasma lidocaine concentrations achieved were 5.35, 4.23, 4.23, and 5.60 microg/mL at 10, 25, 35, and 70 minutes, respectively. They were not significantly different from concentrations found in our healthy dogs at the same infusions. A significant but small increase in CVP compared with baseline was noted after the loading dose. There were no significant differences from baseline shown in all other cardiovascular data. There were no statistically significant differences in any measurements taken during the lidocaine infusion between the dogs in phase 1 and phase 2. Dogs with aortic stenosis tended to have a lower cardiac index than healthy dogs at baseline (88 v 121 mL/kg/min) and during lidocaine infusion (81 v 111 mL/kg/min). A small, statistically significant difference in systolic PAP was present at baseline. CONCLUSIONS: There does not appear to be any detrimental cardiovascular effects related to an infusion of lidocaine at 120 microg/kg/min during isoflurane anesthesia in healthy dogs or dogs with aortic stenosis. The technique used in this study resulted in therapeutic plasma concentrations of lidocaine. CLINICAL RELEVANCE: Methods shown in the study can be used in clinical cases to achieve therapeutic lidocaine levels without significant cardiovascular depression during isoflurane anesthesia.

Modification of cardiopulmonary and intestinal motility effects of xylazine with glycopyrrolate in horses.

Xylazine (XYL) administration in horses is accompanied by significant cardiovascular depression characterized by a 25-35% decrease in cardiac output (CO) which is likely to compromise tissue oxygen delivery (DO2), and usually vagally mediated bradycardia is an important cause of this reduced cardiovascular performance. To examine the possible benefit of preventing the bradycardiac response, 6 healthy horses were treated with intravenous (IV) saline (SAL) or 2.5 micrograms/kg glycopyrrolate (GLY) in a blinded, randomized, crossover trial. Fifteen minutes later, 1 mg/kg XYL was administered IV and systolic, diastolic and mean blood pressures (SBP, DBP, and MBP, respectively), central venous pressure (CVP), mean pulmonary artery pressure, heart rate (HR), CO, and arterial and mixed venous blood gases were measured at the following times: baseline, 2, 5, and 10 min post-SAL or GLY; and 2, 5, 10, 15, 30, 45 and 60 min post-XYL. Determination of cardiac index (CI), stroke index (SI), left ventricular work, systemic vascular resistance (SVR), DO2, oxygen uptake, and oxygen extraction ratio were made at the same time. Gastrointestinal (GI) motility was evaluated by four-quadrant auscultation for 24 h post-XYL. Statistical analysis of continuous variables was carried out using ANOVA for repeated measures and Wilcoxon's rank-sum test for non-parametric data. In GLY treated horses, HR, SBP, MBP, DBP, CI, DO2 and mixed venous oxygen tension were significantly higher up to 30 min after XYL (P < or = 0.02) while CVP and SI were significantly lower 2 and 5 min post-XYL, respectively. In both groups, GI motility as assessed by auscultation was virtually abolished for an hour, with a non-significant tendency for the decrease in motility to last longer in the GLY/XYL group. None of the treated horses developed abdominal discomfort. No significant difference was observed in the other variables. The study shows that 2.5 micrograms/kg GLY premedication reduces the cardiovascular depression caused by 1 mg/kg XYL, without adversely affecting GI motility.

The comparative hypoxaemic effect of four alpha 2 adrenoceptor agonists (xylazine, romifidine, detomidine and medetomidine) in sheep.

In the present study, the hypoxaemic potential of four alpha 2 agonists possessing different selectivity for alpha 2 adrenoceptors and of a saline placebo was studied in five clinically healthy sheep using a randomized Latin square design and equipotent sedative doses. Baseline values for heart rate (HR), mean arterial pressure (MAP), arterial oxygen (PaO2)f and carbon dioxide (PaCO2) tensions, respiration rate and maximum change in pleural pressure (delta Ppl) were obtained, followed by the intravenous administration of either: xylazine (150 micrograms/kg); romifidine (50 micrograms/kg); detomidine (30 micrograms/kg); medetomidine (10 micrograms/kg) or placebo. Subsequent recordings were made up to 60 min after drug administration. No significant (P < or = 0.05) alterations in any variable occurred with placebo. All the alpha 2 agonists significantly (P < or = 0.05) decreased PaO2 levels without a significant (P < or = 0.05) change in PaCO2. The lowest PaO2 values were 29-42 mm Hg (3.9-5.5 kPa) with no significant difference between drugs. Respiratory rate and delta Ppl increased significantly within 2 min of drug administration; the duration of this effect varied with the alpha 2 agonist, lasting longest with romifidine. As compared to the saline treated group, a significant increase in MAP was observed up to 10 min after administration of romifidine and detomidine, however, a significant decrease was seen at 10 and 45 min after xylazine and medetomidine, respectively. The alpha 2 agonists studied induced a similar change in PaO2 at peak effect, despite their reported variable selectivity for alpha 2 vs. alpha 1 adrenoceptors.

Cardiopulmonary effects of clonidine, diazepam and the peripheral alpha 2 adrenoceptor agonist ST-91 in conscious sheep.

The cardiopulmonary effects of the intravenous administration of clonidine (15 micrograms/kg), ST-91 (30 micrograms/kg) and diazepam (0.4 mg/kg) were compared in five healthy sheep using a randomized cross-over design, to determine whether the hypoxaemic effects of alpha 2 adrenoceptor agonists are due to sedation, or to peripheral alpha 2 adrenoceptor stimulation. All three drugs significantly lowered arterial oxygen tension (PaO2) levels within 2 min of their administration; however, clonidine and ST-91 produced long lasting and severe hypoxaemia with mean PaO2 levels of approximately equal to 40 mm Hg and 50 mm Hg (5.3 kPa and 6.6 kPa), respectively. The fall in PaO2 was considerably less with diazepam (63 mm Hg or 8.4 kPa at 2 min) and by 15 min the values did not differ from placebo treated animals. None of the drugs increased arterial carbon dioxide tension (PaCO2) levels when compared to saline treatment and the acid base variables did not show any significant change. A significant increase was recorded in the packed cell volume of the ST-91 treated group throughout the study. Within 2 min of their administration, all drugs caused a significant increase in mean arterial pressure (MAP) as compared to the placebo treated group. The MAP remained significantly increased for 5 and 60 min after clonidine and ST-91 treatment, respectively. The study shows that ST-91 and clonidine produce a greater degree of hypoxaemia than occurs with diazepam sedation, and that the hypoxaemic effect of alpha 2 adrenoceptor agonists in sheep are mainly mediated by peripheral alpha 2 adrenoceptors.

Cardiopulmonary and gastrointestinal motility effects of xylazine/ketamine-induced anesthesia in horses previously treated with glycopyrrolate.

OBJECTIVE: To assess the usefulness of glycopyrrolate (GLY) in preventing the decrease in cardiac index (CI) usually caused by xylazine (XYL)/ketamine (KET)-induced anesthesia in horses. ANIMALS: 6 healthy horses. PROCEDURE: Horses were treated with saline solution or 2.5 micrograms of GLY/kg of body weight, administered i.v. 15 minutes later, XYL (1 mg/kg) was administered i.v., followed 5 minutes later by KET (2 mg/kg) administration. The horses were positioned in left lateral recumbency, insufflated with 15 L of oxygen/min, and maintained for 30 minutes on the infusion of 0.05 mg of XYL and 0.1 mg of KET/kg/min. Mean, systolic, and diastolic arterial blood pressures, mean pulmonary arterial and central venous pressures, heart rate, CI, and arterial and mixed venous blood gas tensions were recorded up to 40 minutes after anesthesia induction. Intestinal motility was assessed by auscultation of 4 abdominal quadrants for 24 hours after induction. Data were analyzed by Wilcoxon's rank-sum test for nonparametric observations, and by ANOVA for repeated measures and Scheffé's test for continuous parametric variables. RESULTS: Horses given GLY had significantly higher heart rate; mean, systolic, and diastolic arterial blood pressures; CI; oxygen delivery; and mixed venous oxygen tensions, with significantly less tissue oxygen extraction, compared with saline-treated horses. Both groups had complete loss of intestinal motility associated with general anesthesia. CONCLUSIONS: GLY significantly reduced the cardiovascular dysfunction attributable to general anesthesia with XYL and KET. The return of intestinal motility was delayed by 3 to 6 hours without causing any serious side effects.

A comparison of romifidine and xylazine when used with diazepam/ketamine for short duration anesthesia in the horse.

The purpose of this study was to compare and evaluate sedation with intravenous xylazine (1.1 mg/kg bodyweight [BW]) versus intravenous romifidine (100 micrograms/kg BW) followed by induction of anesthesia with intravenous diazepam (0.04 mg/kg BW) and ketamine (2.2 mg/kg BW). Twelve healthy horses were used in a blinded, randomized, cross-over design. Heart rate, presence of 2nd degree atrioventricular heart blocks (2 degrees AVB), respiratory rate, arterial blood pressures, blood gases, packed cell volume, total serum proteins, and duration of anesthesia and recumbency were recorded. Induction and recovery quality was evaluated using a 0 to 4 score. Response to stimulation with noise, pressure, and cutaneous electrical stimulation was assessed at 5 minute intervals during recumbency to evaluate the depth of anesthesia. Heart rate was lower and 2 degrees AVB more frequent in the romifidine group, while blood pressure was lower in the xylazine group. Duration of anesthesia was longer in the romifidine group (mean 20.8, s mean 2.3 min) versus the xylazine group (mean 15.8, s mean 1.6 min), while induction and recovery were excellent in both groups. Respiratory rates, blood gas values, packed cell volumes, and total protein levels did not differ between groups. The results indicate that romifidine premedication followed by diazepam and ketamine is a very satisfactory regime for short duration intravenous anesthesia in horses.

Pulmonary function measurements during repeated environmental challenge of horses with recurrent airway obstruction (heaves).

OBJECTIVES: To evaluate the degree of reproducibility in clinical variables, blood gas measurements, and lung function variables, and the changes in these variables caused by exposure to moldy hay in naturally sensitized and control horses. PROCEDURE: The magnitude of variation in arterial blood gas and pulmonary function measurements were evaluated in a model of naturally acquired heaves. Horses with heaves and similarly aged control horses were studied prior to moldy hay challenge and again after the horses with heaves manifested clinical signs of airway obstruction. This cycle of testing was repeated 3 times to determine the variation of the before and after challenge measurements. Variables evaluated for repeatability included: clinical score; arterial O2 and CO2 tensions; pulmonary function variables, such as breathing rate (f), tidal volumes, and flow rates; lung resistance (RL); dynamic compliance; and work of breathing (Wb). RESULTS: Before challenge, significant differences observed between control horses and horses with heaves included clinical score, expiratory flow rate at near-end expiration, RL, and Wb. After exposure to moldy hay, variables measured in control horses were largely unchanged. However, in the afflicted horses, significant changes were observed for clinical score, arterial O2 and CO2 tensions, breathing rate, peak tidal inspiratory and expiratory flow rates, dynamic compliance, RL, and Wb, compared with prechallenge values and with control horses' postchallenge values. Analysis of the data revealed few statistically significant differences between repeats of challenges. CONCLUSION: Horses afflicted with heaves manifest airway obstruction that can be measured in repeatable fashion.

The relationship between respiratory exchange ratio, plasma lactate and muscle lactate concentrations in exercising horses using a valved gas collection system.

A valved gas collection system for horses was validated, then used to examine the relationship between the respiratory exchange ratio (RER), and plasma and muscle lactate in exercising horses. Four healthy Standardbred horses were trained to breathe through the apparatus while exercising on a treadmill. Comparisons of arterial blood gas tensions were made at 3 work levels for each horse, without (control), and with the gas collection system present. At the highest work level, the arterial oxygen tension (PaO2) was significantly lower (P < 0.05), and the arterial carbon dioxide tension (PaCO2) was significantly higher (P < 0.05), than control levels when the apparatus was present; however arterial oxygen content remained unchanged. The horses completed a standardized incremental treadmill test on 4 occasions to determine the repeatability of measurements of oxygen consumption (VO2), carbon dioxide production (VCO2), inspired minute ventilation (VI), respiratory exchange ratio (RER), ventilatory equivalent for oxygen (VI/VO2), tidal volume (VT), and ventilatory frequency (VF). All gas exchange and respiratory measurements showed good reproducibility with the mean coefficient of variation of the 4 horses ranging from 3.8 to 12%. We examined the relationship between 3 indices of energy metabolism in horses performing treadmill exercise: respiratory exchange ratio (RER), central venous plasma and muscle lactate concentrations. A relationship between RER and plasma lactate concentration was established. To compare muscle and plasma lactate concentrations, the horses completed a discontinuous exercise test without the gas collection apparatus present. Significant relationships (P < 0.05), between plasma lactate concentration and RER, and between plasma and muscle lactate concentration, were described for each horse. The valved gas collection system produced a measurable but tolerable degree of interference to respiration, and provided reproducible measurements of gas exchange and ventilatory measurements. It was concluded that measurements of both gas exchange and blood lactate may be used to indicate increased glycolytic activity within exercising skeletal muscle.

Cardiorespiratory effects of a 5HT2 antagonist (R51703) in awake and anesthetized dogs.

To investigate cardiorespiratory effects of an experimental 5-hydroxytryptamine receptor antagonist (R51703) with sedative properties, intramuscular doses of the drug were studied in 6 awake dogs of mixed breed, and in 6 anesthetized beagles. Two doses (0.2 and 0.4 mg/kg) of R51703 and a saline control were studied in the awake dogs using a randomized crossover trial. Subsequently, the higher dose of R51703 was included as a component of halothane anesthesia to determine whether the halothane sparing effect of R51703 produced a beneficial alteration of hemodynamic function. Data were obtained at equipotent halothane/R51703 (H/R) and halothane/saline (H/S) doses equivalent to 1.0, 1.5 and 2.0 MAC. In awake dogs, heart rates tended to be lower in dogs sedated with R51703, significantly so at 30 min for both doses, and at 90 and 120 min for the 0.2 and 0.4 mg/kg doses, respectively (P < 0.05). The cardiac index (CI) was lower at 60 min with both doses compared to the saline control group. Both doses of R51703 reduced mean blood pressure at 30, 90 and 120 min, and diastolic pressure at 30 and 90 min after administration; however, systolic blood pressure (SBP) was not altered. Overall, the cardiovascular alterations were minimal in conscious dogs and there was no evidence of respiratory depression. In the anesthetized dogs, at equipotent MAC, CI tended to be lower with H/R than with H/S, though the difference was not significant. Heart rate and stroke volume index also tended to be lower in the dogs treated with R51703, while systemic vascular resistance tended to be higher: these changes were not significant. Mean and SBP were higher at each MAC multiple in the H/R group. It was concluded that the halothane sparing effect of R51703 did not substantially improve hemodynamic function compared to the use of halothane alone at equipotent doses.