The effects of furosemide on the racing times of 79 horses without exercise-induced pulmonary hemorrhage (EIPH) and 52 horses with EIPH were investigated. Racing times were adjusted to 1-mile equivalent racing times by 2 speed handicapping methods, and analysis of covariance was used to adjust actual racing times by winning time and distance for each race. All 3 methods of determining racing time indicated that geldings without EIPH had significantly faster racing times (P < 0.05) when given furosemide before racing than when furosemide was not given before racing. Females and colts without EIPH were determined to have faster racing times when furosemide was given before racing, but the difference was not significant. Geldings with EIPH had significantly faster racing times (P = 0.0231) when given furosemide before racing, as determined by one of the speed handicapping methods. There was a strong correlation (range 0.9314 to 0.9751) between the 1-mile equivalent racing times, as determined by the 2 speed handicapping methods for horses with and without EIPH. Furosemide failed to prevent the development of EIPH in many horses that were previously considered to be EIPH-negative. When given furosemide, 62 (25.3%) of 235 EIPH-negative horses were EIPH-positive after racing. Furosemide had questionable efficacy for prevention of EIPH in known EIPH-positive horses. Thirty-two (61.5%) of 52 EIPH-positive horses given furosemide before a race remained EIPH-positive after that race.

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four ratio (T4 ratio) to increase from 50% to 75%. After recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered IV, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded. Within 1 minute of gentamicin administration, the mean +/= SD T1 response decreased from 49 +/- 5% to 33 +/- 8% of baseline and the T4 ratio decreased from 28 +/- 19% to 14 +/- 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 +/- 6% of baseline and a T4 ratio of 13 +/- 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 +/- 7% of baseline and the T4 ratio had increased to 21 +/- 13%. The time for recovery significantly (P less than 0.03) increased from 9.9 +/- 3.4 minutes during the control study to 18.1 +/- 10.7 minutes during the gentamicin study. In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium.

Latency and reactivation of pseudorabies virus in swine was studied. Thirty-one pigs were assigned to 5 groups and were given 1 of 4 vaccines; 10 remained unvaccinated controls. All pigs were then challenge exposed with a sublethal dose of virulent pseudorabies virus. One hundred one days after challenge exposure, all pigs were treated with dexamethasone to reactivate the virus. Virus-positive tonsil and nasal mucus isolates were recovered from 29 of the 31 pigs over a 12-day period. Frequency and duration of virus-positivity were significantly (P < 0.05) and consistently lower among vaccinated pigs than among the unvaccinated controls. It was concluded that vaccination before challenge exposure had little or no effect on the rate of establishment of virus latency, but that vaccination reduced shedding after subsequent reactivation of the virus.

A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP after treatment with thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that thelambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected.

Absorption rate and plasma and fat disposition oflindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 microgram/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 microgram/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 microgram/g (ie, lower than the generally accepted tolerance level of 2 microgram/g).

The size of the liver, as well as the situation and diameter of vessels in cattle were determined by use of ultrasonography. Ultrasonographic examinations of the liver were performed on 10 cows 10 times within 2 weeks, using a 3.5-MHz linear transducer on the right side in the 12th, 11th, and 10th intercostal spaces. Dorsal and ventral margin of the liver as well as localization and diameter of the caudal vena cava and the portal vein were determined in each intercostal space. Furthermore, the angle of the liver in the ventral area between the visceral surface and the diaphragmatic surface, the dorsal margin, and the circumference of the gall bladder were determined. The ultrasonographic values of liver size and localization in healthy cows can be used as reference values for the diagnosis of changes in liver size attributable to illness.

Excretion of creatinine, sodium sulfanilate (SS), and phenolsulfonphthalein (PSP) was studied in healthy goats. In conscious goats, mean (+/- SEM) inulin clearance was 2.26 +/- 0.08 ml/min/kg of body weight. Endogenous creatinine clearance, 1.97 +/- 0.09 ml/min/kg, underestimated inulin clearance (P < 0.01), probably because of the presence of noncreatinine chromogens in caprine plasma. The estimated renal clearance of PSP was 6.88 +/- 0.39 ml/min/kg, whereas the estimated renal clearance of SS was 3.71 +/- 0.39 ml/min/kg. Both exceeded inulin clearance (P < 0.01), confirming renal tubular secretion of both compounds. In 6 anesthetized goats, exogenous creatinine clearance and SS clearance exceeded inulin clearance (P < 0.05). Results of stop-flow experiments documented secretion of creatinine and ss by the peoximal portion of the caprine nephron. Plasma half-life of PSP in uninephrectomized goats exceeded that in intact goats (20.2 +/- 1.5 min vs 11.9 +/- 0.7 min; P < 0.01). Similarly, plasma half-life of SS was greater in goats after uninephrectomy (58.2 +/- 6.2 min vs 30.4 1.2 min; p < 0.01).

Concentration of hyaluronate (HA) in equine serum was determined by a recently developed specific radioassay. The mean +/- SD HA concentration in equine serum was 288 +/- 145 micrograms/L, was age dependent, and varied widely between horses (range, 190 to 760 micrograms/L). Light or moderate exercise increased serum HA concentration from baseline values by 1.5- to 3-fold. In all horses, serum HA concentration returned to or below the original resting values 1 and 2 hours after exercise.

L-lactic acid and D,L-lactic acid infusion in ponies resulted in metabolic acidosis with high anion gap (AG). Increased AG was explained entirely by increased blood L- and D-lactate concentrations. Hydrochloric acid infusion caused metabolic acidosis with decreased AG. Saline (NaCl) infusion caused mild metabolic acidosis, with no significant change in AG. Plasma K+ concentration was decreased by all types of infusions, with a maximum of 0.50, 0.25, 0.40, 0.50 mmol/L below baseline at the end of infusion in the L-lactic acid-, D,L-lactic acid-, HCl-, and NaCl-infused ponies, respectively. Only hydrochloric acid had a tendency to increase plasma K+ concentration. Hypophosphatemia developed in NaCl- and HCl-infused ponies, but not in the D,L-lactic acid-infused ponies. Serum inorganic phosphate concentration in L-lactic acid-infused ponies increased initially, but was significantly (P < 0.05) lower than values in the other ponies at 4 hours after onset of infusion. In ponies, the effect of acidemia on plasma K+ and serum inorganic phosphate concentrations was similar to that reported for other species. Changes were small in magnitude and depended on the nature of the acid anion. Results indicate that large changes in plasma K+ and serum inorganic phosphate concentrations during acidosis are probably not a direct result of acidemia.

The feasibility of renal arterial infusion of nonbiodegradable microspheres as a model of chronic renal disease in dogs was evaluated. Resin-coated, styrene-divinyl benzene copolymer microspheres were infused into the kidneys of healthy adult Beagles by direct injections of both renal arteries in a single surgical procedure. Injections of 25-micrometer diameter microspheres had minimal effect on either the clinical status or serum values of the dogs. Histologic examination revealed the majority of the microspheres lodged within the capillary beds of the glomeruli, and little change to the kidneys. However, injections of 50-micrometer diameter microspheres caused significant increases in serum concentrations of urea nitrogen and creatinine. Histologically, the larger microspheres obstructed afferent arterioles and small arteries, which caused diffuse glomerular necrosis and nephron damage. With doses ranging from 1 to 3 million microspheres/dog, a correlation between the quantity of microspheres injected and severity of renal damage was observed. The optimal dose for producing a model of moderate renal disease was determined to be 1.8 million microspheres/dog (0.9 million microspheres/kidney). During long-term studies, microsphere-injected dogs fed a moderately restricted protein ration remained relatively azotemic, compared with control dogs on the identical ration. During the 5-month postsurgical period, the serum urea nitrogen concentration averaged 18.41 +/- 1.59 mg/dl (mean +/- SE) for the microsphere-injected dogs vs 9.31 +/- 0.38 for the control dogs (P < 0.001). Similarly, the mean serum creatinine value was significantly higher (P = 0.020) for the microsphere-injected dogs, compared with the controls (1.23 +/- 0.12 mg/dl vs 0.94 +/- 0.03). In addition, the difference in mean endogenous creatinine clearance rates was statistically significant (microsphere-injected 1.02 0.05 ml/min/kg, vs control 1.53 +/- 0.06, P < 0.001).