Nonsteroidal anti-inflammatory drugs (NSAID) are widely used for treatment of people and animals. Their use is limited by frequent side effects commonly involving the gastrointestinal tract, most important of which is development of ulcerating lesions principally in the stomach. Unfortunately, presence of such lesions is often unsuspected because clinical signs may be overlooked until a complication develops. We reported that such damage can be detected by measuring the increase in gastric permeability that is a hallmark of this condition. Sucrose is a novel probe molecule for determination of site-specific gastric permeability. As a disaccharide, it is large enough to be effectively excluded by the intact gastric epithelium, and because it is rapidly digested within the small intestine, absorption of the intact molecule implies damage proximal to this site. Recently, we found that increased sucrose permeability is useful in predicting presence of endoscopically relevant gastric damage in people. We extended these results to the detection of NSAID-induced gastropathy in dogs. Dogs treated with aspirin developed NSAID-induced gastropathy (including gastric ulceration), and the degree of endoscopically detectable damage correlated well with sucrose permeability. Furthermore, healing of these lesions could also be monitored by sequential measurements of sucrose permeability. Sucrose permeability decreased more rapidly than the disappearance of gastric ulcers, suggesting that this technique is more sensitive to generalized mucosal damage than is the presence of discrete, endoscopically visible ulceration. This was confirmed by creating artificial ulcers in the antrum and observing that sucrose permeability was not increased in this setting. We conclude that determination of increased sucrose permeability is a useful, noninvasive means of predicting presence of gastric damage in dogs treated with NSAID.

Six horses were subjected to 3 hours of low-flow ischemia and 3 hours of reperfusion of the large colon. After induction of anesthesia, the large colon was exteriorized through a ventral midline celiotomy. Colonic blood flow was measured continuously, using Doppler ultrasonic flow probes placed on the colonic arteries supplying the dorsal and ventral colons and was allowed to stabilize for 15 to 30 minutes after instrumentation. Low-flow ischemia was induced by reducing colonic arterial blood flow to 20% of baseline (BL) flow. Colonic mucosal, seromuscular, and full-thickness blood flow were determined on a tissue-weight basis by injecting colored microspheres proximally into the colonic artery supplying the ventral colon. Reference blood samples were obtained at a known flow rate from the colonic artery and vein at a site more distal to the site of injection. Left ventral colon biopsy specimens were harvested at BL, 3 hours of ischemia, and 15 minutes of reperfusion. Blood and tissue samples were digested and filtered to collect the microspheres, and dimethylformamide was added to release the colored dyes. Dye concentration in blood and tissue samples was measured by use of spectrophotometry, and tissue-blood flow was calculated. Data were analyzed, using two-way ANOVA for repeated measures; statistical significance was set at P < 0.05. Doppler blood flow decreased to approximately 20% of BL, whereas microsphere blood flow ranged between 13.7 and 15.5% of BL at 3 hours of ischemia. Doppler-determined blood flow increased immediately on restoration of blood flow, reached 183% of BL at 15 minutes of reperfusion, and remained at or above BL throughout 3 hours of reperfusion. This reactive hyperemia was also detected, using the colored microspheres; blood flow increased to 242 and 327% of BL at 15 minutes of reperfusion in the mucosal and seromuscular layers, respectively. Mucosal blood flow was not different from seromuscular blood flow at any time, indicating relatively equal distribution of blood flow between these 2 layers. As determined from the venous reference samples, there was no evidence of arteriovenous anastomoses.

The minimal inhibitory concentration (MIC) of cefixime, a new third-generation orally administered caphalosporin, was determined for reference and clinical isolates from dogs. The MIC of the drug for all but 1 of the 18 Enterobacteriaceae isolates tested, 1 Pasteurella canis, 1 Rhodococcus equi, 1 Streptococcus canis, and 1 Streptococcus group G isolate, was less than 1.0 micrograms/ml. The MIC for 9 Staphylococcus intermedius isolates ranged from 1.56 to 6.25 micrograms/ml and, for 8 Sta aureus isolates, the MIC values ranged from 1.56 to 12.5 micrograms/ml. Pseudomonas aeruginosa, Actinomyces sp, and a single Bordetella bronchiseptica isolate were considered resistant to cefixime. Cefixime was administered orally in 2 phases at a standard dosage of 5 mg/kg of body weight to clinically normal adult male and female dogs. In the first phase, the drug was given once as a capsule and once as a suspension. In the second phase, it was administered once per day for 6 consecutive days in capsule form. Serum drug concentration was determined by use of a microbiological assay, and the following kinetic values were estimated for each dog: area under the concentration-time curve, peak serum drug concentration (Cmax), time of Cmax, absorption half-life, and elimination half-life (t1/2el). The kinetic profile of the drug in serum after oral administration of a single dose of cefixime was similar, with mean Cmax values of 3.36 and 4.76 micrograms/ml after treatment with the capsule and suspension, respectively. Quick oral absorption is characteristic for cefixime in dogs; mean absorption half-life values of 1.3 and 0.58 hours for the capsule and suspension, respectively, were calculated. Drug elimination from serum was biphasic, with an initial mean t1/2el of 8.1 to 8.6 hours and a secondary mean t1/2el of 11.7 to 14.5 hours. In the trial involving once daily treatment for 6 days, serum drug concentration after the sixth dose was significantly (P < 0.05) higher than that after the first dose. indicating drug accumulation. Cefixime is extensively bound to canine serum proteins (82 to 92% at concentration ranging between 7.5 and 1.5 micrograms/ml). Concentration of cefixime was determined in the uterus, ovaries, and abdominal fat tissues 24 hours after single-dose treatment and 24 hours after the sixth treatment. Tissue drug distribution was limited after administration of the single dose, but improved after the sixth dose. The in vitro antibacterial activity of the drug and its pharmacokinetic properties warrant assessing its clinical and bacteriologic efficacy as a longterm once-daily orally administered treatment for common bacterial infections in dogs.

Effects of temperature and storage time on canine bone-transfixation pin specimens were tested by comparing pin pull-out forces. A total of 16 femurs from 8 mature dogs were tested. Five nonthreaded Steinmann pins were placed through both cortices in the diaphysis of each femur. The femurs were then sectioned transversely between each pin, with a bonepin specimen placed evenly into each of 5 groups prior to biomechanical testing. Four bone-pin specimen groups were stored at -20 or -70 C for 14 or 28 days, while 1 specimen group was immediately tested. Pull-out forces for frozen groups were compared with pull-out forces for the fresh group. Using two-way ANOVA, there was no statistical difference in mean axial-extraction forces among bonepin specimen in any of the tested groups. It is concluded that acute pin pull-out forces are not significantly affected by freezing temperature or time. However, specimens stored at -20 C for as few as 14 days had a trend for increased pull-out forces, compared with freshly harvested specimens. Therefore, the authors recommend storage of bone-pin specimens at -70 C when possible.

Cardiovascular effects of epidurally administered morphine, a morphine-xylazine combination, and saline solution (control) during isoflurane-maintained anesthesia were assessed in 6 healthy dogs. Anesthesia was induced with isoflurane in O2 and was maintained at 2.0% end-tidal isoflurane concentration. Ventilation was controlled to maintain PaCO2 at 35 to 45 mm of Hg. The dorsal pedal artery was cannulated for measurement of systolic, mean, and diastolic pressures, and for blood sample collection. Arterial blood pH and gas tensions were determined every 30 minutes. Cardiac output was determined by thermodilution. The ECG, heart rate, body temperature, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal isoflurane concentration, and CO2 tension were monitored. Systemic and pulmonary vascular resistance, arterial HCO3(-) concentration, base excess, and cardiac index were calculated. After baseline measurements were taken, morphine (0.1 mg/kg of body weight) in 5 ml of isotonic saline solution, morphine and xylazine (0.1 mg of morphine and 0.09 mg of xylazine/kg) in 5 ml of isotonic saline solution, or 5 ml of isotonic saline solution was injected into the lumbosacral epidural space. Data were recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Statistical analysis included ANOVA for repeated measures. Significance was set at P < 0.05. None of the measured variables was significantly different among the 3 treatments at any time. Results of the study indicated that epidural administration of morphine or morphine and xylazine is not associated with significant cardiovascular side effects during isoflurane-maintained anesthesia in dogs.

Effects of a single IV administered therapeutic dose of vincristine sulfate on platelet numbers and function were evaluated in 16 clinically normal dogs over the 2 weeks after drug administration. Results were statistically compared with those of a previous control study in which the same 16 dogs were administered saline solution (IV), instead of vincristine. Of the 16 dogs, 8 were orally administered daily immunosuppressive doses of prednisone concurrently throughout the saline-control and vincristine study periods. Platelet numbers and mean platelet volume were measured, using an automated hematology analyzer. Platelet function was evaluated by turbidimetric measurement of platelet aggregation in response to collagen, platelet-activating factor, and adenosine diphosphate (ADP), and by clot retraction (diluted whole-blood method) and buccal mucosa bleeding time. Vincristine had a significant (P < 0.05) effect on circulating platelet numbers. Vincristine induced a transient mild decrease in platelet numbers, followed by a moderate increase in numbers, with peak platelet count observed 8 days after drug administration. Mean platelet volume was not significantly affected by administration of vincristine. Vincristine had no significant effects on platelet aggregation in response to collagen, low or high doses of platelet-activating factor, and a high dose of ADP. The maximal degree of platelet aggregation attained in response to a low dose of ADP was not significantly affected by prior administration of vincristine. The maximal rate of platelet aggregation induced by a low dose of ADP after vincristine administration, however, was significantly (P < 0.05) lower than the rate of aggregation induced by a similar dose of ADP in the previous control study. Vincristine had no significant effects on clot retraction and bleeding time. Prednisone did not significantly affect platelet numbers and function, and did not modify vincristine's effects on the same variables.

Objective: To determine whether standard manual frequency filters in the ON and OFF settings affected P-QRS-T voltages, discover whether recorded P-QRS-T voltages vary between commercial electrocardiographs, assess effects of frequency filters on base-line artifact, and evaluate ECG frequency content by high-fidelity recordings subjected to digital filters with variable frequencies. Design: Sequential 10-lead ECG were recorded in 30 cats, using 3 commercial electrocardiographs to assess effects of manual frequency filters on the P-QRS-T wave forms. Three clinically normal cats were evaluated for ECG frequency content. Animals: Thirty cats (13 with hypertrophic cardiomyopathy; 4 with restrictive cardiomyopathy; 3 hyperthyroid; 1 with ventricular septal defect; 1 with aortic stenosis; and 8 with no detectible cardiovascular disease). Three additional clinically normal cats were studied for effects of frequency filters on the ECG frequency content. Procedure: Ten-lead ECG were recorded on each cat by use of 3 commercial electrocardiographs sequentially. For each machine, a recording was made with manual filters ON, immediately followed by a recording with manual filters OFF. High-fidelity lead-II ECG recordings were made with filters set with their rolloff frequency at 0.1 Hz and 3.0 kHz; output voltage (0.2 mV/V) was fed to an analog-to-digital converter, then to attendant software, which sampled the signal at 6 kHz with a 12-bit sampler, and were digitally filtered at various corner frequencies. Results: Voltages recorded by all 3 electrocardiographs were greatest when filters were OFF (most prominent on R- and S-wave voltages). In all recorded leads, it-wave voltage was significantly greater when filters were OFF than ON. Comparison of voltages indicated significant (P < 0.05) differences between R-wave voltages recorded in all leads with manual filters ON, but not with filters OFF. With filters ON, each electrocardiograph produced a smaller percentage of recordings with moderate to severe baseline artifact than with filters OFF. R-Wave amplitudes of high-fidelity lead-II ECG were significantly decreased with digital filters set at corner frequencies < 150 Hz. Conclusion: Significant (P < 0.05) voltage attenuation was recorded by each of the 3 commercial electrocardiographs when frequency filters were ON, compared with OFF. Comparison of waveform voltages among electrocardiographs with filters ON indicated significant variation in R-wave amplitudes in all leads. With manual filters ON, each electrocardiograph recorded a smaller percentage of recordings with baseline artifact than with filters OFF. Substantial frequency components greater than or equal to 150 Hz are present in the feline ECG waveform. Thus, filters with frequencies < 150 Hz markedly attenuate the feline R wave. Clinical Relevance: Attenuation of feline ECG signals occurs with use of commercial electrocardiographs and varies greatly between manufacturers. This is attributable largely to internal manual frequency filters. These consequences may be important when applying standard feline reference values or when equivocal voltage measurements are recorded.

The effects of 3 occlusive dressing materials and a standard, nonadherent dressing material on healing of full-thickness skin defects were evaluated in dogs. Two wounds measuring 2 X 2 cm were created bilaterally (4 wounds/dog) on the dorsolateral aspect of the trunk of 12 Beagles. Wound treatments were evenly distributed between 4 sites, using a Latin square design. Treatments evaluated were: equine amnion (group A), biosynthetic hydrogel dressing (group B), transparent polyethylene sheeting (group T), and a semi-occlusive rayon/polyethylene, nonadherent dressing (group C). Rates of contraction and epithelialization of group-A wounds were significantly greater than those of wounds of groups C, B, and T. On days 14, 21, and 28, mean percentage of wound contraction and mean percentage of total wound healed in group A exceeded those wounds in groups C, B, and T. On day 28, wounds in group A were significantly smaller than wounds in groups B and T, but were not significantly smaller than wounds in group C. All wounds in group A achieved 100% healing during the 28-day study period. Mean time for complete healing of group-A wounds was 21 days. The percentages of wounds completely healed by day 28 for groups B, C, and T were 25, 67, and 25%, respectively. Results indicate that use of equine amnion as an occlusive biological dressing on full-thickness wounds in dogs increases rate of healing.

Adhesion of equine spermatozoa to homologous oviduct epithelial cells (OEC) in vitro results in specific changes in spermatozoa and OEC function. To test the hypothesis that adhesion of spermatozoa affects protein synthesis and secretion by OEC, the following treatment groups were established in culture: OEC with culture medium only; control spermatozoa in culture medium only; OEC in coculture with spermatozoa; and OEC and spermatozoa in coculture, but physically separated by a microporous membrane. The experiment was replicated within each of 4 ejaculates from 3 stallions. De novo protein secretion by OEC was measured and compared by incorporation of [35S]methionine, and evaluated, using two-dimensional polyacrylamide gel electrophoresis and fluorography. Monolayers of OEC secreted a large number of proteins of molecular mass ranging from 14 to 205 kd. Adhesion of spermatozoa consistently caused reduced synthesis of 2 OEC secretory proteins and new or increased synthesis of 6 proteins. When spermatozoa and OEC were separated by a microporous membrane, some but not all of these changes were duplicated. Synthesis of 3 OEC secretory proteins, unaffected by binding of spermatozoa, was reduced when spermatozoa were prevented from contact with OEC by a microporous membrane. Adhesion of equine spermatozoa to homologous OEC monolayers and presence of equine spermatozoa resulted in qualitative and quantitative changes in synthesis and secretion of proteins by OEC. These changes have implications for storage, longevity, and maturation of spermatozoa.

The effects of the skeletal muscle-relaxing drug dantrolene sodium alone, and in combination with the alpha 1-adrenergic antagonist prazosin, on the urethral pressure profile were investigated in male cats with obstructive lower urinary tract disease. Decreases in mean segmental intraurethral pressure induced by dantrolene (n = 3) or dantrolene in combination with prazosin (n = 3) were evaluated statistically, using a paired design. Statistical analysis was applied to absolute (mm of Hg) pressure values. Intravenous administration of dantrolene alone (1 mg/kg of body weight, n = 3) significantly decreased pressure in the postprostatic/penile urethral segment, but did not decrease prostatic urethral pressures. Dantrolene in combination with prazosin (0.03 mg/kg IV) caused a 20% pressure decrease in the prostatic segment (P = 0.060). Preprostatic urethral pressure was not significantly affected by either treatment regimen in the small pool of cats studied. There was no difference in baseline pressures (mm of Hg) in the 3 intraurethral segments of these 6 recently obstructed male cats, compared with historic baseline pressures (mm of Hg) in the 3 intraurethral segments of 28 healthy male cats. These results indicate that dantrolene and prazosin may be effective in relaxing intraurethral skeletal and smooth musculature in male cats clinically afflicted with obstructive lower urinary tract disease. However, it is not certain that administration of muscle relaxants would facilitate urethral catheterization and removal of the obstruction in male cats with blockage of the lower urinary tract. Strikingly, results of this study suggest that urethral muscle spasm had a minor role in these cats.