The partitioning of total pulmonary resistance (RL) into upper airway resistance and lower airway resistance (Rl) was studied in 8 Thoroughbred geldings. In addition, the phase shift and amplitude distortion of 3 catheters used for pressure measurements in this study were evaluated under static and dynamic conditions. Flow rate was obtained from a heated pneumotachograph attached to a tight-fitting mask placed over the nose. Electronic integration of the flow signal gave tidal volume. Transpulmonary pressure (PL) was obtained from calculation of the difference between the esophageal balloon catheter pressure and mask pressure. Lateral tracheal pressure was measured from a polyethylene catheter placed percutaneously in the middle portion of the trachea. Lower airway pressure (Pl) was calculated as the difference between esophageal pressure and lateral tracheal pressure. Similarly, upper airway pressure was defined as the difference between lateral tracheal pressure and mask pressure. Pressures are reported as the difference between the maximal and the minimal pressures recorded during a respiratory cycle. Airway resistance was calculated, using the isovolume method, at 50% of tidal volume. There were individual and group variations in Pl and Pl/PL, although P1 accounted for more than 60% of PL in all horses. In 6 horses, Rl was more than 50% of RL whereas in 2 horses, Rl was only 30 and 34% of RL. Amplitude distortion was minimal for the 3 catheters under static conditions in the in vitro study. Under dynamic conditions, amplitude distortion varied according to the catheter studied, the frequency, and the resistance of the system. There were no phase differences under static conditions at low frequency. However, phase discrepancy, which was variable through the cycle, was observed for some catheters at high frequency under static and dynamic conditions. It was concluded that, until measuring techniques are standardized in horses, variations in the partitioning of RL are likely to be obtained between studies and between animals within studies. However, phase discrepancy, which was variable through the cycle, was observed for some catheters at high frequency under static and dynamic conditions. It was concluded that, until measuring techniques are standardized in horses, variations in the partitioning of RL are likely to be obtained between studies and between animals within studies.

Eight Holstein cows, 4 inoculated intracisternally in 1 quarter of the mammary gland with Escherichia coli and 4 noninfected controls, were administered ceftiofur sodium (3 mg/kg of body weight, IV, q 12 hours) for 24 hours, beginning at 14 hours after inoculation of infected cows. All challenge-exposed cows became infected, with mean +/- SEM peak log10 bacterial concentration in milk of 5.03 +/- 0.69 colony-forming units/ml. The infection resulted in systemic signs (mean peak rectal temperature, 41.5 +/- 0.3 C; anorexia; signs of depression) and local inflammation (mean peak albumin concentration in milk, 7.89 +/- 1.71 mg/ml). Ceftiofur was detectable in milk from all challenge-exposed cows, compared with only 1 of 4 noninfected cows, and the mean period after inoculation that ceftiofur was detectable in milk was longer (P < 0.05) in infected (147.7 +/- 27.5 hours) than noninfected cows (1.3 +/- 1.3 hours). However, maximal ceftiofur concentration attained in milk for all cows was 0.28 micrograms/ml, and was 0.20 micrograms/ml or less for all but 2 milk samples collected for 10 days after challenge exposure. Mean serum concentration of ceftiofur peaked at 1.0 +/- 0.3 micrograms/ml and 0.7 +/- 0.1 micrograms/ml for infected and noninfected COWS, respectively. After each ceftiofur dose, mean peak and trough concentrations of ceftiofur in serum did not differ between groups; however, concentration of ceftiofur in serum was higher at 7 hours after each dose in noninfected cows, suggesting more rapid clearance of the drug in infected cows. Ceftiofur was not detected in serum (< 0.05 micrograms/ml) of any cow at or after 120 hours following inoculation of infected cows. Storage of serum samples at -20 C for 3 weeks resulted in a 98.8% decrease in ceftiofur activity, compared with that in fresh serum samples. Eighty-seven percent of this loss occurred 30 minutes after mixing serum and ceftiofur; thus, about 13% of the original activity was lost in storage. Storage of milk samples under similar conditions did not result in loss of ceftiofur activity. Despite acute inflammation, the dosage of ceftiofur used in this trial would not result in drug concentrations in milk above FDA safe concentrations, or above the reported minimum inhibitory concentration for coliform bacteria.

To determine whether abnormal airway pressures have a role in development of dorsal displacement of the soft palate (DDSP), measurements of tracheal and pharyngeal pressures were correlated with nasopharyngeal morphology in exercising horses. Exercising videoendoscopy and measurement of tracheal and pharyngeal pressures were used in 14 clinically normal horses and 19 horses with intermittent DDSP. The pressure signals were superimposed on the videoendoscope image, and both images were saved simultaneously on a videocassette for slow motion analysis to determine the instant displacement occurred in the respiratory cycle. Horses were submitted to an escalating 8-minute high-speed test with a maximal speed of 14 m/s. Compared with clinically normal horses, horses with intermittent DDSP did not have excessively negative inspiratory pressures during exercise. Eight horses displaced the soft palate during inspiration, 4 horses displaced it during expiration, and 7 displaced it by swallowing. Some horses displaced the soft palate at the beginning of the exercise trial, before reaching maximal speed, some horses displaced it at the peak speed, and some horses displaced it when slowing down. Epiglottic size in horses with DDSP was within normal limits, ruling out epiglottic hypoplasia as a cause of DDSP during exercise. Airway pressures were significantly (P < 0.002) altered after DDSP. Pharyngeal and tracheal inspiratory pressures were less negative, whereas pharyngeal expiratory pressure became less positive and tracheal expiratory pressure became more positive after displacement, suggesting a decrease in airflow and an increase in expiratory resistance in the upper airway.

A repeated-measures study was conducted on 5 dogs to clinically, radiographically, and echocardiographically characterize the actions of the angiotensin-converting enzyme inhibitor, enalapril, before and after development of experimentally induced heart failure. Heart failure was artificially induced, using a surgically implanted programmable ventricular pacemaker, which stimulated the heart at a rate of 245 beats/min until a low-output cardiomyopathic a state developed. This condition was then stabilized by decreasing the pacing rate to 190 beats/min. Pacing-induced heart failure was successfully induced in a mean +/- SD 4.2 +/- 1.95 weeks. The condition closely resembled the clinical, radiographic, and echocardiographic features of naturally acquired idiopathic dilated cardiomyopathy in dogs. Enalapril was well tolerated by dogs, and clinical adverse reactions did not develop. Results of echocardiographic studies indicated that enalapril treatment during the control period resulted in a significant (P < 0.05) increase in velocity of circumferential fiber shortening and a significant (P < 0.05) decrease in left ventricular ejection time. Therapeutic responses to enalapril were evident after development of heart failure. These included reduced severity of clinical signs of disease, evidence of decreased radiographically determined cardiac size (2 of 5 dogs), radiographic evidence of a reduction in pulmonary edema and congestion (4 of 5 dogs), significant (P < 0.05) reductions in left atrial and ventricular chamber dimensions (left atrial dimension, diastolic left ventricular internal dimension as determined echocardiographically), and improvement in some echocardiographic indices of left ventricular performance (velocity of circumferential fiber shortening and left ventricular ejection time).

Activities of diagnostically important enzymes were measured in serum and lysates of liver, kidney, skeletal muscle, heart, intestine, lung, and pancreatic tissues from wild-caught yellow rat snakes, Elaphe obsoleta quadrivitatta. All samples were analyzed for alkaline phosphatase, lactate dehydrogenase (LD), aspartate transaminase (AST), alanine transaminase, gamma-glutamyltransferase, and creatine kinase (CK) activities. The major enzyme activities found in the liver were LD and AST. The kidney had moderate activities of LD, AST, alanine transaminase, and CK. Skeletal muscle and heart contained high CK activity. Intestine, lung, and pancreas had low activities for most enzymes analyzed. Little to no gamma-glutamyltransferase activity was found in serum or tissues analyzed. Serum enzyme activities in yellow rat snakes were similar to those described for other reptile species, except for serum CK activity, which was increased in rat snakes.

A surgical technique was developed for implanting a flexible polyurethane cannula in a lateral ventricle in the brain of calves. Initially, measurements were made on 25 calves at necropsy to develop equations for calculating coordinates for cannula placement. The distance (cm) caudal, in the sagittal plane, from the coronal suture line to the center of a hole to be drilled in the parietal bone of the skull was: 0.73 + (0.00925 X body weight [kg]). The distance (cm) lateral from the midline to the center of the hole to be drilled was: 0.018 + (0.6464 X distance caudal). The depth (cm) from the surface of the skull to the dorsal surface of the lateral ventricle was: 2.29 + (0.0159 X body weight [kg]). Surgery was subsequently performed on 17 calves. A 5-mm-diameter hole was drilled through the skull with a hand trephine at coordinates derived from the aforementioned regression equations. A polyurethane cannula (total length, 30 cm; 1 mm ID; 2 mm OD) covering a stainless-steel 20-gauge blunt-tipped needle (stylet) was lowered through the brain and into a lateral ventricle at an angle of 20.5 degrees relative to the frontal bones of the skull. The blunt-tipped needle was then removed, and CSF was allowed to drip from the cannula to verify placement. One stainless-steel screw was inserted 0.6 cm medial, and another was inserted 0.6 cm caudal to the hole in the skull. The area around the cannula, bone screws, and hole in the skull was covered with dental acrylic (approx 2 cm in diameter) to stabilize the cannula. With minimal restraint of calves, injection of substances into and withdrawal of CSF from a lateral ventricle of the brain were possible in most calves for at least 6 weeks after surgery was performed.

The concentration of carbonic anhydrase III isoenzyme (cA-III) in serum samples from 216 clinically normal Thoroughbreds was determined by use of an enzyme immunoassay. The concentration range of cA-III was from 16.0 to 254.5 ng/ml (mean, 56.5 +/- 11.9 ng/ml). Significant differences were not detected according to age or sex. To confirm whether serum cA-III concentration was high in horses with muscle disease, serum samples of 11 horses with exertional rhabdomyolysis were analyzed by enzyme immunoassay. Their serum cA-III concentration was about 56 times (3,136 +/- 2,610 ng/ml) that of healthy Thoroughbreds. Concentration of cA-III was higher in horses with rhabdomyolysis that had been transiently recumbent than in horses with mild disease that were reluctant to move. Blood samples obtained serially from 6 horses with exertional rhabdomyolysis were studied. Serum activities of aldolase, creatine kinase, aspartate transaminase, and lactate dehydrogenase were high. Increases and decreases in concentration of cA-III were more rapid than that for aldolase, creatine kinase, aspartate transaminase, and lactate dehydrogenase activities; thus, cA-III may be clinically applicable as a diagnostic marker for muscle disease in horses.

Serum alpha-mannosidase activity and swainsonine concentration were determined in 4 cattle and 15 sheep (3 groups of 5 each) that were administered ground locoweed (Oxytropis sericea or Astragalus lentiginosus) containing swainsonine at dosages of approximately 0.8 mg/kg of body weight/d (cows, 30 days each) and 0, 1.0, and 1.5 mg/kg/d (sheep, 11 days each). The cattle developed mild clinical signs of locoism, including signs of depression, lethargy, and slight intention tremors. Clinical signs of toxicosis were not observed in the sheep. Within 24 hours of initial treatment, serum alpha-mannosidase activity in cows and sheep, measured by the release of 4-methylumbelliferone from an artificial substrate, was markedly decreased to 28 and 40 micromoles of 4-methylumbelliferone/L, respectively. Mean serum alpha-mannosidase activity of control cows and sheep was 400 +/- 94 and 422 +/- 42 (mean +/- SD), respectively. In the treated animals, decreased serum alpha-mannosidase activities returned to normal or higher activities within 6 days after treatment was discontinued. Using a jack bean alpha-mannosidase assay, increased swainsonine activity (153, 209, and 381 ng/ml, respectively) was detected in the serum of cattle and of sheep in the high- and low-dose groups within 24 hours after treatment with locoweed. Swainsonine concentration remained high, with mean concentrations of 204, 432, and 395 ng/ml (cows and 2 sheep groups, respectively) during the treatment period. After treatment, swainsonine was rapidly cleared, with estimated serum half-life of 16.4, 17.6, and 20.3 hours (cows, and high- and low-dose sheep groups, respectively). Significant differences in either alpha-mannosidase activity or swainsonine concentration were not detected between the 2 groups of treated sheep. These results suggest that serum alpha-mannosidase and swainsonine values are sensitive indicators of locoweed intoxication in cattle and sheep. Furthermore, it suggests that swainsonine is rapidly absorbed, resulting in rapid inhibition of serum alpha-mannosidase activity, leading to high serum swainsonine concentration. After exposure is eliminated, swainsonine is rapidly cleared from the serum, with serum alpha-mannosidase activity returning to normal values shortly thereafter.

Microcystin and related toxic peptides produced by cyanobacteria (blue-green algae) are potent and selective inhibitors of protein phosphatases 1 and 2A. We adapted existing enzymatic techniques to analyze the liver of rainbow trout after oral administration of hepatotoxic cyanobacteria. Liver tissue was removed 3 and 12 hours after treatment, and phosphatase activity was determined in liver extracts, using a specific phosphoprotein substrate. In all samples from fish exposed to toxic cyanobacteria, phosphatase activity was suppressed, whereas the control enzyme, lactate dehydrogenase, present in the same liver extract, was not affected by cyanobacteria. Thus, experimental poisoning by hepatotoxic cyanobacteria resulted in an abnormally low ratio of phosphatase to lactate dehydrogenase activity in the liver extracts. These results indicate that specific inhibition of phosphatases 1 and 2A may provide a useful diagnostic tool to determine the early effects of cyanobacteria toxic peptides directly in liver samples from poisoned animals. Although this test was developed with rainbow trout, it should be possible to extend the analysis of liver phosphatase activity to other species, including sheep and cattle, which are frequently affected by hepatotoxic cyanobacteria.

We evaluated the pharmacokinetics of IV administered sodium heparin and the pharmacodynamic effect of heparin on lipoprotein lipase (LPL) activity Horses were allotted to 3 groups. Plasma samples were obtained from each horse before and at various times for 6 hours after heparin administration for determination of heparin concentration, LPL activity, and activated partial thromboplastin time (APTT). The disposition of heparin was dose dependent. The area under the plasma heparin concentration vs time curve (AUC) increased more than proportionally with dose, indicating that heparin elimination was nonlinear. Total clearance of heparin was similar after the 40 and 80 IU/kg of body weight dosages, averaging 0.45 and 0.36 IU/kg/min, respectively. However, after administration of the 120 IU/kg dose, clearance was significantly less than that after the 40 IU/kg dose. The half-life of heparin averaged 53, 70, and 136 minutes after 40, 80, and 120 IU/kg, respectively, with significant differences observed between the low and high doses. In contrast to heparin, the area under the plasma concentration vs time curve for LPL activity increased less than proportionally with dose. Maximal LPL activity observed was independent of dose, averaging 4.8 micromole of free fatty acids/ml/h. The APTT was significantly prolonged for 120 minutes after administration of the 40 IU/kg dose. Correlation coefficients for LPL activity vs either plasma heparin concentration or APTT were less than 0.7, indicating that neither laboratory measure can be used to accurately predict plasma LPL activity.