Canine erythrocytes were loaded with the antineoplastic drug doxorubicin and then treated with 0.16% glutaraldehyde. This procedure has been previously shown to slow down the efflux of doxorubicin from erythrocytes and to result in the selective targeting of the carrier erythrocytes to liver. Three dogs were treated each with 2 different schedules of IV bolus administration of doxorubicin (0.4 mg/kg of body weight): free drug and doxorubicin encapsulated in glutaraldehyde-treated erythrocytes. The 2 treatments yielded consistent differences in the plasma pharmacokinetic properties of doxorubicin and of its only metabolite, doxorubicinol. A triphasic exponential decay of doxorubicin plasma concentrations was observed on injection of the free drug. Conversely, in the case of erythrocyte-encapsulated doxorubicin, 4 phases of plasma concentrations of doxorubicin were found. The plasma concentrations of doxorubicinol, after a steady increase during the first hour, followed patterns of decay comparable to those of the parent drug. On the basis of the kinetic variables calculated with the 2 administration schedules, area under curve concentrations of plasma doxorubicin were 136 microgram.h/L (free infusion) and 734 microgram.h/L erythrocyte-encapsulated drug). Significant alterations of hematologic and hematochemical factors were not observed in the 3 dogs during and after the 2 treatments. On the basis of our findings, doxorubicin-loaded and glutaraldehyde-treated erythrocytes may potentially be used in the treatment of systemic and hepatic tumors in dogs.

Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.

The cardiopulmonary effects of thiopental sodium were studied in hypovolemic dogs from completion of until 1 hour after administration of the drug. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. After stabilization at this pressure for 1 hour, 8 mg of thiopental/kg of body weight was administered IV to 7 dogs, and cardiopulmonary effects were measured. After blood withdrawal and prior to thiopental administration, heart rate and oxygen utilization ratio increased, whereas mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, pulmonary wedge pressure, cardiac index, oxygen delivery, mixed venous oxygen tension, and mixed venous oxygen content decreased from baseline. Three minutes after thiopental administration, heart rate, mean arterial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and mixed venous oxygen tension increased, whereas oxygen utilization ratio and arterial and mixed venous pH decreased from values measured prior to thiopental administration. Fifteen minutes after thiopental administration, heart rate was still increased; however by 60 minutes after thiopental administration, all measurements had returned to values similar to those obtained prior to thiopental administration.

Several investigators have suggested that the conventional multicompartmental exponential analysis of in vivo glucose metabolism is arbitrary and possibly not the most accurate description of glucose kinetics, especially in the large animal. In support of that hypothesis, we found that in a systematic comparison of 3 methods, blood-specific radioactivity data in single-injection studies of glucose metabolism in lactating cows was better described graphically, or by a hybrid polynomial-biexponential curve fit, than by an exclusively exponential curve fit. We hypothesized that this finding was attributable to partial failure of linearity and steady-state assumptions that underlie the exponential model. Second, using both an irreversible tracer (3H-labeled glucose) and reversible tracer (14C-labeled glucose), we found that glucose carbon recycling had no effect during the first 2 hours, but became significant in lactating cows 7 hours after injection. Finally, we determined that approximately 52 to 55% of the glucose replacement rate was being used to generate lactose.

Six calves with suppurative arthritis were given a single IM injection of sodium cephapirin at a dosage of 10 mg/kg of body weight. Cephapirin concentrations were serially measured in serum and in normal and suppurative synovial fluid over a 24-hour period. Mean peak serum concentration was 6.33 microliter/ml at 20 minutes after injection. The highest cephapirin concentrations in normal and suppurative synovial fluid were 1.68 and 1.96 microgram/ml, respectively, 30 minutes after injection. Overall mean cephapirin concentration in normal synovial fluid for the first 4 hours (1.04 +/- 0.612 microgram/ml) was not significantly different from that in suppurative synovial fluid (0.88 +/- 0.495 microgram/ml; P > 0.05). Elimination half-life was 0.60 hours and clearance was 1,593 ml/h/kg.

Analysis of hepatic enzyme activities in serum samples from 1- to 3-day-old pups revealed alkaline phosphatase (ALP) activities that were 30 times higher and gamma-glutamyltransferase (GGT) activities that were 100 times higher than activities in clinically normal adult dogs. A study was conducted to investigate high enzyme activity in pups and to determine whether there is any association between serum enzyme activity and colostrum ingestion, passive transfer of maternal serum enzyme (in colostrum or in utero), or excessive renal or hepatic tissue enzymes. Serum enzyme activity was quantified in 15 neonatal pups before and after ingestion of colostrum and in 3 colostrum-deprived neonates fed a milk substitute. Serum samples were collected on postpartum days 0, 1, 10, 15, and 30. Enzyme activity was also quantified in serum from pregnant and lactating bitches (collected on days - 2, 0, 1, 10, 30), hepatic and renal tissue from clinically normal adult dogs and 1-day-old pups, colostrum, milk (collected on days 10 and 30), and milk replacer. Significant (P < 0.01) differences in serum GGT and ALP activities between colostrum-deprived and suckling pups did not exist before initial feeding. Significant (P < 0.001) increases in serum GGT and ALP activities developed within 24 hours in suckling pups, but not in the colostrum-deprived pups. At 10 and 30 days after birth, serum GGT and ALP activities were less than values before suckling in all pups. Enzyme activities in bitches' serum remained within the normal range for adult dogs throughout whelping and lactation. Renal GGT and ALP activities were substantially greater than hepatic enzyme activities in neonates and adults. Renal tissue from adults contained 3 times greater GGT and 2 times greater ALP activities than that from neonates. Hepatic tissue from neonates contained 5 times more GGT activity than did hepatic tissues from clinically normal adults; however, hepatic ALP activity was similar in adults and neonates. Colostrum and milk bad substantially higher enzyme activities than did bitches' serum. Activities of GGT and ALP in milk were 100 times and 10 times greater, respectively, than activities in serum through day 10. By day 30, GGT and ALP activities in milk were less than before suckling. Enzyme activity was not detected in the milk substitute. These studies reveal an association between colostrum ingestion by suckling and acute, profound increases in serum GGT and ALP in 1- to 3-day-old pups. Although this phenomenon might be useful as an indicator of colostrum ingestion, it precludes the diagnostic use of either enzyme as an indicator of hepatobiliary disease in 3-day-old pups.

The central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the EEG) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution half-life. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean +/- SD, 48 +/- 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 +/- 11.3 minutes; sheep, 65.1 +/- 27.1 minutes; dogs, 58.3 +/- 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 +/- 269.0 ml/kg; sheep, 720.0 +/- 306.7 ml/kg; dogs, 597.7 +/- 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 +/- 5.3 ml/min/kg; sheep, 13.3 +/- 3.0 ml/min/kg; dogs, 18.7 +/- 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment, The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P < 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P < 0.05) with percentage of necrosis,

To assess the suitability of sheep for exercise studies, the effect of incremental exercise and conditioning on oxygen consumption 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, oxygen consumption, gas exchange ratio (R), and rectal temperatures (Tb) were recorded. All 3 protocols resulted in significant increases in oxygen consumption, R, and Tb (P < 0.05). Maximum oxygen consumption for EX-1, 49.9 +/- 5.0 ml/min/kg of body weight, was significantly greater than maximum oxygen consumption for EX-2 and EX-3, 37.8 +/- 6.5 and 42.3 +/- 6.0 ml/min/kg, respectively (P < 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 oxygen consumption increased 27% to 48.1 +/- 9.1 ml/min/kg. These data indicated that maximum oxygen consumption 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 oxygen consumption measurements are desired.

Mucosa obtained from the cecum of healthy horses and incubated in vitro with 0.1 mM cycloleucine could accumulate this amino acid against an apparent concentration gradient after 60 and 120 minutes. Accumulation by the serosal (antiluminal) surface of the tissue was 3 times greater than accumulation by the mucosal (luminal) surface after 120 minutes (P < 0.001). Cycloleucine accumulation was significantly reduced by Na deprivation after 60 minutes (P < 0.05) and 120 minutes (P < 0.01) and by anoxic conditions after 120 minutes (P < 0.05). Transmucosal flux from mucosal to serosal surface of the tissue was significantly (P < 0.05) greater than the opposing flux, but both unidirectional fluxes were small and were largely attributed to passive processes. It was concluded that the most avid transport system for cycloleucine was on the serosal surface of the horse's cecal mucosa, and an active transport system was not evident on the mucosal surface. An active transport system for amino acids on the serosal surface could be explained by the need for crypt cells, the predominant epithelial cell type in the cecum, to obtain nutrients from blood, rather than from the intestinal lumen.