Effects of distention and neostigmine on jejunal vascular resistance, oxygen uptake, and intraluminal pressure changes in ponies

The influence of distention (high baseline intraluminal pressure) and neostigmine methylsulfate on intestinal vascular resistance, oxygen uptake, and intraluminal pressure changes (rhythmic contractions) was studied in terminal jejunal segments, which were perfused at a constant rate, in 16 anesthetized ponies. When baseline intraluminal pressure was increased to 10 mm of Hg, the intestinal vascular resistance and amplitude of rhythmic contractions were increased. Neostigmine induced cyclic increases in amplitude of rhythmic contractions whether intraluminal pressure was 0 or 10 mm of Hg. Neostigmine also increased intestinal oxygen uptake at intraluminal pressures of 0 mm of Hg, but not at 10 mm of Hg, and vascular resistance was not altered at either intraluminal pressure. The results indicate that intestinal hemodynamics are adversely affected by distention. Further, neostigmine did not adversely affect intestinal hemodynamics while increasing rhythmic contractions, suggesting that neostigmine may be useful in the treatment of ileus in equids.     

Effects of xylazine on equine intestinal vascular resistance, motility, compliance, and oxygen consumption

Isolated jejunal segments were perfused at a constant blood flow rate to determine simultaneously the effects of xylazine on intestinal vascular resistance, motility, compliance, and oxygen consumption in 12 anesthetized ponies. Xylazine was infused into the artery perfusing the intestinal segment (group 1), or into the jugular vein as a single IV bolus (group 2), or 3 times as IV boluses repeated at 10-minute intervals (group 3). Dose-response curves in group 1 indicated a biphasic response to the drug with vasoconstriction, increased motility, and increased oxygen consumption at lower doses followed by a return toward base-line values at higher doses. Intestinal compliance decreased at lower doses, but increased at higher doses. A single IV bolus of xylazine (group 2) induced systemic hypotension for 30 minutes, and increased intestinal vascular resistance for 10 minutes accompanied by increased motility, and repeatedly administered IV boluses of xylazine (group 3) increased and prolonged these effects. The results indicated that xylazine, especially in repeated doses, may decrease bowel viability by simultaneously increasing intestinal vascular resistance, motility, and oxygen consumption.     

Morphologic and ultrastructural evaluation of effect of ischemia and dimethyl sulfoxide on equine jejunum

Morphologic changes in equine jejunal segments subjected to 1 hour of ischemia and 1 hour of reperfusion, and protective effects of systemic administration of dimethyl sulfoxide (DMSO; 1 g/kg of body weight) were investigated in 18 ponies, using light microscopy and scanning and transmission electron microscopy. Ponies were allotted to 4 groups: group 1--control (n = 3); group 2--DMSO (n = 3); group 3--ischemia (n = 6); and group 4--ischemia and DMSO (n = 6). In each pony, 2 jejunal sections were evaluated. The first section was obtained prior to induction of ischemia, and the second was obtained 2 hours later after reperfusion. Mucosal lesions were graded from 0 (normal) to 5 (most severe). Combined ischemia and reperfusion of 2 hours' duration induced moderately severe mucosal injury to the equine jejunum (group 3; grade 1.5 to 2.5), characterized principally by disruption of enterocyte attachment from the basement membrane and lamina propria. Fluid accumulation disrupted enterocyte cell-to-cell adhesion toward cell bases, while apical tight junctions and desmosomal junctions toward the luminal surface remained intact. Intracytoplasmic organellar changes within enterocytes were not a prominent feature of the injury. The aforementioned processes were marked at the villus tip and progressed down the villus sides. These findings support the importance of mechanisms leading to early subepithelial fluid accumulation rather than that of direct severe enterocyte injury. Further, fluid accumulation does not appear to arise from intercellular migration from the luminal surface. In this model, a pathomechanical effect caused by vigorous villus retraction appears to exacerbate epithelial lifting toward the villus tip.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histopathologic effects of dimethyl sulfoxide on equine endometrium

Endometrial fibrosis is a major cause of infertility in broodmares. Because of the proven anti-inflammatory effects of dimethyl sulfoxide (DMSO) and its influence on collagen, the effect of DMSO on the endometrium was investigated in mares. Solutions of DMSO (25%, 50%, or 75%) were infused into the uterus of clinically normal mares. Examination of serially obtained biopsy specimens revealed epithelial ulceration and stromal inflammation that were proportional to the DMSO concentration infused, but vasodilatation was not observed. In all mares, the endometrium had returned to normal by day 21 after DMSO infusion.     

Effects of Carolina rinse solution, dimethyl sulfoxide, and the 21-aminosteroid, U-74389G, on microvascular permeability and morphology of the equine jejunum after low-flow ischemia and reperfusion

OBJECTIVE: To evaluate effects of Carolina rinse solution, dimethyl sulfoxide (DMSO), and 21-aminosteroid, U-74389G, on microvascular permeability and morphology of the equine jejunum after low-flow ischemia and reperfusion. ANIMALS: 20 healthy adult horses. PROCEDURE: Under anesthesia, full-thickness biopsy specimens of a distal portion of the jejunum were obtained for baseline measurements. In addition to a control segment, 2 jejunal segments were identified as sham-operated or experimental segments. Experimental segments underwent 60 minutes of low-flow ischemia and 3.5 hours of reperfusion. Treatments were as follows: U-74389G (3 mg/kg, IV; 6 horses), DMSO (20 mg/kg, IV; 6) diluted in 1 L of saline (0.9% NaCl) solution, local perfusion (via jejunal artery) of Carolina rinse solution (0.5 mL/kg; 4), and local perfusion of lactated Ringer's solution (0.5 mL/kg; 4). RESULTS: Jejunal microvascular permeability was significantly lower after treatment with Carolina rinse solution or DMSO, compared with U-74389G or lactated Ringer's solution treatments. After DMSO treatment, serosal- and submucosal-layer edema was significantly increased in experimental segments, compared with control or sham-operated segments; however, edema increases were significantly less than for lactated Ringer's solution or U-74389G treatments. Significant decreases in intestinal wet weight-to-dry weight ratio were found following Carolina rinse solution or DMSO treatments, compared with lactated Ringer's solution or U-74389G treatments. Edema formation and leukocyte infiltration in jejunal segments of horses treated with lactated Ringer's solution or U-74389G were increased, compared with Carolina rinse solution or DMSO treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Carolina rinse solution and DMSO may be protective against ischemia-reperfusion injury in the equine jejunum.     

In vitro evaluation of the effect of dimethyl sulfoxide on equine articular cartilage matrix metabolism

OBJECTIVE: To evaluate the effects of dimethyl sulfoxide (DMSO) on equine articular cartilage matrix metabolism. STUDY DESIGN: Using a cartilage explant culture system, proteoglycan (PG) synthesis, PG release, lactate metabolism, chondrocyte viability, and metabolism recovery were determined after cartilage exposure to DMSO. SAMPLE POPULATION: Cartilage harvested from metacarpophalangeal and metatarsophalangeal joints of 12 horses (age range, 1 to 10 years). METHODS: Explants were exposed to concentrations of DMSO (1% to 20%) for variable times (3 to 72 hours). PG synthesis and release were determined by a radiolabel incorporation assay and dimethylmethylene blue (DMMB) dye assay, respectively. Lactate released into culture media was measured, and chondrocyte viability was assessed using the Formizan Conversion Assay and a paravital staining protocol. Metabolism recovery was assessed in explants that were allowed to recover in maintenance media after exposure to DMSO. RESULTS: PG synthesis and lactate metabolism were inhibited in a dose- and time-dependent manner after exposure to DMSO concentrations > or = 5%; there was no significant alteration in PG release. No change in chondrocyte viability was detected after incubation with DMSO. PG synthesis and lactate metabolism returned to baseline rates when allowed a recovery period after exposure to DMSO. CONCLUSIONS: DMSO concentrations > or = 5% suppress equine articular cartilage matrix metabolism. Suppression of PG synthesis and lactate metabolism is reversible and does not appear to be the result of chondrocyte death. CLINICAL RELEVANCE: Equine clinicians adding DMSO to intraarticular lavage solutions should be aware that DMSO may have deleterious effects on equine articular cartilage matrix metabolism.     

Effect of intraluminal distension or ischemic strangulation obstruction of the equine jejunum on jejunal motilin receptors and binding of erythromycin lactobionate

OBJECTIVE: To determine whether inflammation of the jejunum of horses decreases the number of motilin receptors and amounts of motilin receptor mRNA and alters erythromycin lactobionate binding affinity to the motilin receptor in jejunal tissues. SAMPLE POPULATION: Jejunal segments in 6 adult horses. PROCEDURE: Each horse was anesthetized, and a ventral median celiotomy was performed; 2 segments of jejunum underwent a sham operation, 2 segments underwent ischemic strangulation obstruction (ISO), and 2 segments underwent intraluminal distension (ILD). Treatments were maintained for 120 minutes. From each segment, full-thickness biopsy samples were collected and smooth-muscle homogenates were prepared. Affinity and distribution of motilin binding to these preparations were determined by use of iodine 125 (125I)-labeled synthetic porcine motilin. Via displacement experiments, competition between 125I-labeled motilin and erythromycin lactobionate for binding to motilin receptors in the different segments was investigated. A quantitative real-time PCR technique was used to assess motilin receptor mRNA content in the muscle preparations. RESULTS: Compared with the ISO or ILD segments, the number of motilin receptors was significantly higher in the sham-operated segments; ILD segments contained the lowest number of motilin receptors. The expression of motilin receptor mRNA was significantly decreased in ILD segments but not in ISO segments. Erythromycin lactobionate displacement of 125I-labeled motilin from motilin receptors did not differ significantly among the jejunal segments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that downregulation and decreased production of motilin receptors in inflamed jejunal tissue contribute to the altered prokinetic response to erythromycin in horses with gastrointestinal disease.     

Effects of intraluminal distention and decompression on microvascular permeability and hemodynamics of the equine jejunum

OBJECTIVE: To determine whether intraluminal distention and subsequent decompression of the equine jejunum affects intestinal blood flow, hemodynamics, and microvascular permeability. ANIMALS: 5 healthy adu t horses. PROCEDURES: Horses were anesthestized and underwent exploratory laparotomy. Two jejunal segments were identified as sham-operated or instrumented segments. After baseline values were obtained, intraluminal distention was created in the experimental segment to induce an ntraluminal pressure of 18 cm H2O. After 120 minutes of distention, the intestine was decompressed for 120 minutes. Mesenteric blood flow, oxygen delivery, oxygen consumption, microvascular permeability, wet weight-to-dry weight ratio, neutrophil infiltration, and vascular resistance were determined and comparisons made among control, sham-operated, and experimental segments. RESULTS: Mean jejunal blood flow was 21.4 ml/min per kg. There was a significant decrease in mesenteric bood flow to the distended intestine (13.4 ml/min per kg). Blood flow increased significantly during the decompression period (340% of baseline blood flow). Intraluminal distention and subsequent decompression resulted in a significant increase in microvascular permeability, as determined by the osmotic reflection coefficient. Oxygen delivery and oxygen content decreased significantly during the distention period and increased during decompression. Morphologic evaluation revealed a significant increase in edema and neutrophil infiltration after distention and decompression, compared with results for the sham-operated or control segments. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal distention and decompression of the equine jejunum results in low-flow ischemia and edema, which may contribute to adhesions and ileus in the postoperative period after surgery for obstructions of the small intestines.     

Inhibitory effects of combinations of oxytetracycline, dimethyl sulfoxide, and EDTA-tromethamine on Escherichia coli

Antibacterial activity against Escherichia coli was obtained with subminimal inhibitory concentrations of oxytetracycline (OTC) and EDTA-tromethamine. Inhibitory effects were not observed using combinations of dimethyl sulfoxide and OTC or dimethyl sulfoxide and EDTA-tromethamine. Neither EDTA-tromethamine nor OTC used alone was capable of the same degree of inhibition. Using a 2-dimensional Microtiter checkerboard technique, the inhibitory activity of these combinations was studied and isobolograms were plotted. A synergistic effect was seen with combinations of OTC and EDTA-tromethamine. Kinetic studies of microbial death, using subminimal inhibitory concentrations of these agents, confirmed these findings.     

Effects of intravenous administration of dimethyl sulfoxide on cardiopulmonary and clinicopathologic variables in awake or halothane-anesthetized horses

OBJECTIVE: To evaluate the cardiopulmonary and clinicopathologic effects of rapid IV administration of dimethyl sulfoxide (DMSO) in awake and halothane-anesthetized horses. DESIGN: Prospective study. ANIMALS: 6 adult horses. PROCEDURES: Horses received IV infusion of 5 L of a balanced electrolyte solution with and without 1 g/kg (0.45 g/lb) of 10% DMSO solution when they were awake and anesthetized with halothane (4 treatments/horse). Arterial and venous blood samples were collected immediately before and at intervals during or after fluid administration and analyzed for blood gases and hematologic and serum biochemical variables, respectively. Heart rate, respiratory rate, and arterial blood pressure variables were recorded prior to, during, and after fluid administration. RESULTS: After administration of fluid with or without DMSO, changes in measured variables were detected immediately, but most variables returned to baseline values within 4 hours. One awake control horse had signs of anxiety; agitation and tachycardia were detected in 2 awake horses administered DMSO. These clinical signs disappeared when the rate of infusion was reduced. In anesthetized horses, increased concentrations of WBCs and plasma fibrinogen and serum creatine kinase activity persisted for 24 hours, which was related to the stress of anesthesia more than the effects of fluid administration. CONCLUSIONS AND CLINICAL RELEVANCE: Infusion of 5 L of balanced electrolyte solution with or without 10% DMSO induced minimal changes in cardiopulmonary function and clinicopathologic variables in either awake or halothane-anesthetized horses. Stress associated with anesthesia and recovery had a greater influence on measured variables in anesthetized horses than fluid administration.     

Effects of training on maximum oxygen consumption of ponies

OBJECTIVES: To establish maximum oxygen consumption VO2max) in ponies of different body weights, characterize the effects of training of short duration on VO2max, and compare these effects to those of similarly trained Thoroughbreds. ANIMALS: 5 small ponies, 4 mid-sized ponies, and 6 Thoroughbreds. PROCEDURE: All horses were trained for 4 weeks. Horses were trained every other day for 10 minutes on a 10% incline at a combination of speeds equated with 40, 60, 80, and 100% of VO2max. At the beginning and end of the training program, each horse performed a standard incremental exercise test in which VO2max was determined. Cardiac output (Q), stroke volume (SV), and arteriovenous oxygen content difference (C [a-v] O2) were measured in the 2 groups of ponies but not in the Thoroughbreds. RESULTS: Prior to training, mean VO2max for each group was 82.6 = 2.9, 97.4 +/- 13.2, and 130.6 +/- 10.4 ml/kg/min, respectively. Following training, mean VO2max increased to 92.3 +/- 6.0, 107.8 +/- 12.8, and 142.9 +/- 10.7 ml/kg/min. Improvement in VO2max was significant in all 3 groups. For the 2 groups of ponies, this improvement was mediated by an increase in Q; this variable was not measured in the Thoroughbreds. Body weight decreased significantly in the Thoroughbreds but not in the ponies. CONCLUSIONS AND CLINICAL RELEVANCE: Ponies have a lower VO2max than Thoroughbreds, and larger ponies have a greater VO2max than smaller ponies. Although mass-specific VO2max changed similarly in all groups, response to training may have differed between Thoroughbreds and ponies, because there were different effects on body weight.     

Antibacterial action of combinations of oxytetracycline, dimethyl sulfoxide, and EDTA-tromethamine on Proteus, Salmonella, and Aeromonas

Antibacterial effects against Proteus mirabilis, Salmonella typhimurium, and Aeromonas hydrophila were obtained with subminimal inhibitory concentrations of oxytetracycline and EDTA-tromethamine. Antibacterial effects were not observed with subminimal inhibitory concentrations of dimethyl sulfoxide plus oxytetracycline or with dimethyl sulfoxide plus EDTA-tromethamine. Using a 2-dimensional Microtiter checkerboard technique, inhibitory activities of the various combinations of solutions were studied, and isobolograms were plotted. A synergistic effect was seen with combinations of oxytetracycline and EDTA-tromethamine. The greatest synergistic effect was observed when the mixture was caused to react with P mirabilis. These findings were confirmed by kinetic studies of microbial death, using one-fourth minimal inhibitory concentrations of these preparations.     

Effects of inhibition of nitric oxide synthase on systemic arterial pressure and renal vascular resistance in cats

These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg⁻¹ bodyweight min⁻¹ resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml⁻¹ to 6·83 ± 1·15 mmHg min ml⁻¹. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min⁻¹, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min⁻¹, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.     

Effects of conditioning and maximal incremental exercise on oxygen consumption in sheep

To assess the suitability of sheep for exercise studies, the effect of incremental exercise and conditioning on oxygen consumption (VO2) was studied. Six sheep were adapted to a treadmill and subsequently trained 8 weeks. The sheep were then studied, in random order, using 3 incremental exercise protocols (EX-1, EX-2, and EX-3). The protocols were chosen to approximate high (EX-1), moderate (EX-2), and low (EX-3) intensity exercise by varying treadmill speed and incline. The sheep were then conditioned for an additional 12 weeks and retested on the EX-2 protocol. During exercise, VO2, gas exchange ratio (R), and rectal temperatures (Tb) were recorded. All 3 protocols resulted in significant increases in VO2, R, and Tb (P less than 0.05). Maximum VO2 for EX-1, 49.9 +/- 5.0 ml/min/kg of body weight, was significantly greater than maximum VO2 for EX-2 and EX-3, 37.8 +/- 6.5 and 42.3 +/- 6.0 ml/min/kg, respectively (P less than 0.05), whereas maximum R and maximum Tb were similar. After the additional 12-week conditioning, time on the treadmill increased 40% from 9.58 +/- 0.87 to 13.4 +/- 0.44 minutes, and maximum VO2 increased 27% to 48.1 +/- 9.1 ml/min/kg. These data indicated that maximum VO2 varied with intensity of the exercise, 12 weeks of maximal exercise conditioning was sufficient to produce a measurable training effect (ie, increase endurance and maximum oxygen consumption) and sheep are suitable for maximal exercise studies where VO2 measurements are desired.     

Effects of thiopentone on the equine electroencephalogram during anaesthesia with halothane in oxygen

Objective To characterise the effects of thiopentone on the equine electroencephalogram during halothane anaesthesia. Study design Prospective controlled study. Animals Eight healthy Welsh mountain pony geldings between 5 and 9 years old and weighing between 270 and 330 kg (mean 301 kg). Methods Anaesthesia was induced with thiopentone and maintained using halothane in oxygen. End tidal halothane was maintained above 0.75 and below 0.85%. EEG was recorded continuously and a binaural broad band click stimulus was provided throughout the experiment at 6.1224 Hz. An infusion of 500 mg thiopentone was given over 5 minutes. Samples were taken for blood gas analysis and plasma thiopentone assay (HPLC) 5 minutes prior to the start of the infusion and at 3, 5, 7, 10, 15, 20, 30, 45 and 60 minutes. The median and 95th percentile of the EEG were calculated using standard statistical techniques and the mid‐latency of the auditory evoked response was generated. The values of EEG variables at each time point were compared to the average value for the 15 minute period before the infusion was started. Arterial blood gas values and plasma thiopentone concentration were compared to the baseline sample taken prior to the start of the infusion. Comparisons were made using analysis of variance for repeated measures followed by Dunnett's test if a significant difference was detected. Results The peak serum plasma concentration was 14.5 ± 2.4 µg mL^?1 (mean ± SD) occurring 5 minutes after the start of the infusion. The 95% spectral edge frequency of the EEG decreased by a maximum of 27.4 ± 18.4% 7 minutes after the start of the thiopentone infusion. No changes were seen in median frequency of the EEG or the second differential of the middle latency auditory evoked response. Conclusions These results, coupled with the lack of antinociceptive action of thiopentone, support the hypothesis that median frequency of the EEG may be a useful indicator of nociception in anaesthetized animals. Clinical relevance If the EEG is to become a useful monitoring technique then it is important to understand the relative contribution of changing plasma concentrations of the agents used in anaesthesia.     

Effects of guaiphenesin on the equine electroencephalogram during anaesthesia with halothane in oxygen

Objective To identify and characterize the effects of guaiphenesin (GGE) on the electroencephalogram during halothane anaesthesia. Study design Prospective controlled study. Animals Eight healthy Welsh mountain pony geldings between 5 and 9 years old and weighing between 270 and 330 kg (mean 301 kg). Methods Anaesthesia was induced with thiopentone and maintained using halothane in oxygen. End tidal halothane was maintained above 0.75 and below 0.85%. The EEG was recorded continuously and a binaural broad band click stimulus was provided throughout the experiment at 6.1224 Hz. An infusion of 1500 mg GGE was given over 5 minutes. Samples were taken for blood gas analysis and plasma GGE assay (HPLC) 5 minutes prior to the start of the infusion and at 3, 5, 7, 10, 15, 20, 30, 45 and 60 minutes thereafter. The median and 95th percentile of the EEG were calculated using standard statistical techniques and the mid‐latency of the auditory evoked response was generated. The values of EEG variables at each time point were compared to the average value for the 15 minute period before the infusion was started. Arterial blood gas values and plasma GGE concentration were compared to the baseline sample taken prior to the start of the infusion. Comparisons were made using analysis of variance for repeated measures followed by Dunnett's test if a significant difference was detected. Results The peak serum plasma concentration was 49.6 ± 7.8 μg mL^?1 (mean ± SD) occurring five minutes after the start of the infusion. The 95% spectral edge frequency (F95) of the EEG decreased by a maximum of 5.2 ± 14.3% 5 minutes after the start of the GGE infusion. This change did not reach statistical significance (p= 0.07). When three nonresponders were excluded, the depression in F95 at 5 minutes in the remaining five animals became 13.0 ± 12.0% and was statistically significant (p= 0.02). No changes were seen in median frequency of the EEG or the second differential of the middle latency auditory evoked potential. Conclusions These results did not demonstrate any statistically significant GGE‐induced changes in the EEG. However, there was some visible depression of F95 in five of the animals studied even though the dose of GGE used was considerably less than that used in most clinical circumstances. Clinical relevance The EEG effects seen in this study concur with the commonly held view that while GGE has some sedative effects, it is not a reliable anaesthetic agent.