Objective-To describe neuroendocrine responses that develop in dogs subjected to prolonged periods of ventricular pacing. Animals-14 adult male hound-type dogs. Procedure-Samples were obtained and neuroendocrine responses measured before (baseline) and after 3 periods of ventricular pacing. A pacemaker was used to induce heart rates of 180, 200, and 220 beats/min (BPM). Each heart rate was maintained for 3 weeks before increasing to the next rate. Atrial natriuretic peptide, antidiuretic hormone, aldosterone, norepinephrine, epinephrine, and dopamine concentrations and plasma renin activity were measured. Severity of left ventricular compromise was estimated. Results-Shortening fraction decreased significantly with increasing heart rates (mean +/- SE, 35.5 +/- 1.4, 25.0 +/- 1.4, 19.5 +/- 1.9, and 12.2 +/- 2.3 for baseline, 180 BPM, 200 BPM, and 220 BPM, respectively). Atrial natriuretic peptide concentrations increased significantly at 180 BPM (44.1 +/- 3.0 pg/mL) and 200 BPM (54.8 +/- 5.5 pg/mL), compared with baseline concentration (36.8 +/- 2.6 pg/mL). Dopamine concentration increased significantly at 200 BPM (70.4 +/- 10.4 pg/mL), compared with baseline concentration (44.2 +/- 7.3 pg/mL). Norepinephrine concentrations increased significantly from baseline concentration (451 +/- 46.2 pg/mL) to 678 +/- 69.8, 856 +/- 99.6, and 1,003 +/- 267.6 pg/mL at 180, 200, and 220 BPM, respectively. Conclusions and Clinical Relevance-Dogs subjected to ventricular pacing for 9 weeks developed neuroendocrine responses similar to those that develop in humans with more chronic heart failure and, except for epinephrine concentrations, similar to those for dogs subjected to ventricular pacing for < 6 weeks.

Objective-To determine whether changes in amplitude of the reflex-evoked muscle action potential (REMP) elicited by noninvasive dental dolorimetry (electrical stimulation of the tooth pulp) in anesthetized dogs may be used to objectively evaluate the effectiveness of IV and intrathecal (IT) administration of morphine. Animals-6 male Beagles that were 2 to 6 years old. Procedure-Dogs were used in a crossover design with at least a 5-day washout period between treatments. Each dog received morphine, saline (0.9% NaCl) solution, and oxytocin via the IV and IT routes of administration; however, only results for morphine and saline treatments were reported here. Dogs were anesthetized and prepared for noninvasive dental dolorimetry. After IV or IT administration, electrical stimulation was applied to a tooth, and REMPs of the digastricus muscle were recorded at 5-minute intervals for 60 minutes. To determine differences in REMP amplitude between treatments, a linear regression line was fitted for each dog-treatment combination. Results-The IV administration of morphine significantly inhibited REMP amplitude, compared with IV administration of saline solution. Intrathecal administration of morphine significantly inhibited REMP amplitude, compared with IT administration of saline solution. Conclusions and Clinical Relevance-Noninvasive dental dolorimetry in anesthetized dogs has promise as a technique for use in evaluating the analgesic potential of drugs administered IV and IT through evaluation of their effect on REMP amplitude recorded for the digastricus muscle.

Objective-To evaluate whether immunosuppressive doses of cyclosporine (CsA) have an adverse effect on the liver, kidney, and pancreatic beta cells of pigs. Animals-8 juvenile 8-week-old Landrace X Large White crossbred pigs. Procedure-CsA (100 to 140 mg/kg) was administered orally to euglycemic pigs to reach whole blood trough concentrations of approximately 1500 ng/mL. To determine pancreatic beta cell function, plasma Cpeptide and insulin concentrations were measured in response to IV administration of glucose, glucagon, arginine, and oral administration of glucose. Effects on liver and kidney were determined by monitoring serum measurements of liver function and serum creatinine concentrations, respectively. Results-Plasma concentrations of C-peptide were significantly lower in euglycemic CsA-treated pigs, compared with control pigs, following IV administration of glucose, glucagon, arginine, and oral administration of glucose. Furthermore, the glucose clearance rate was decreased in euglycemic CsA-treated pigs, compared with control pigs. Serum creatinine concentrations and 4 of 7 serum measurements of liver function were not adversely affected by CsA administration. Serum concentrations of bilirubin and albumin were significantly increased, and serum alanine aminotransferase activity was significantly decreased in CsA-treated pigs, compared with control pigs. Histologic evaluation of liver and kidney sections revealed no pathologic findings in CsA-treated or control pigs. Conclusions and Clinical Relevance-In our study, immunosuppressive doses of CsA caused an impairment of porcine pancreatic beta cell function, but did not have toxic effects on the kidney. However, on the basis of changes in serum bilirubin and albumin concentrations and alanine aminotransferase activity, subclinical toxic effects on the liver did occur when immunosuppressive doses of CsA were administered.

Objective-To develop laparoscopic-assisted techniques for enterostomy feeding tube placement and full-thickness biopsy of the jejunum in dogs. Animals-15 healthy dogs. Procedure-Dogs were anesthetized, and positive pressure ventilation was provided. A trocar cannula for the laparoscope was inserted on the ventral midline caudal to the umbilicus. For enterostomy tube placement, a second trocar cannula was placed lateral to the right rectus abdominis muscle, and a Babcock forceps was used to grasp the duodenum and elevate it to the incision made for the cannula. The duodenum was sutured to the abdominal wall, and a feeding tube was inserted. For jejunal biopsy, a third trocar cannula was placed lateral to the left rectus abdominis muscle. A portion of jejunum was elevated to the incision for the second or third cannula, and a full-thickness biopsy specimen was obtained. A second specimen was obtained from another portion of jejunum, and retention sutures for the 2 biopsy sites were tied so that serosal surfaces of the biopsy sites were apposed to each other. Dogs were euthanatized 30 days after surgery. Results-The enterostomy tube was properly positioned and functional in all 8 dogs that underwent laparoscopic-assisted enterostomy tube placement, and sufficient samples for histologic examination were obtained from all 7 dogs that underwent laparoscopic-assisted jejunal biopsy. None of the dogs had any identifiable problems after surgery. Conclusion and Clinical Relevance-Results suggest that in dogs, laparoscopic-assisted procedures for enterostomy tube placement and jejunal biopsy are an acceptable alternative to procedures performed during a laparotomy.

Objective-To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. Animals-12 healthy, female, spayed cats. Procedure-Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. Results-All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. Conclusions and Clinical Relevance-Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.

Objective-To compare renal clearance of technetium Tc 99m pentetate with plasma clearance by use of a glomerular filtration rate technique in pigs from 3 to 24 weeks of age. Animals-24 female pigs. Procedure-At the time of investigation, 5 pigs were 3 weeks old, 6 pigs were 6 weeks old, 8 pigs were 12 weeks old, and 5 pigs were 24 weeks old. Plasma clearance of technetium Tc 99m pentetate was measured by the use of a single injection technique followed by collection of multiple blood samples until 5 hours after the injection. Simultaneously, urine was collected through a urinary catheter, and the renal clearance of technetium Tc 99m pentetate was calculated. Results-Plasma clearance of technetium Tc 99m pentetate was correlated with the renal clearance ( r = 0.95). Plasma clearance was higher than renal clearance at all ages (mean, 5.8%), indicating extrarenal clearance of technetium Tc 99m pentetate or methodologic errors. Volume of distribution increased with increasing age but decreased as a fraction of body weight. Conclusions-Plasma clearance of technetium Tc 99m pentetate estimates renal clearance with acceptable precision when using single injection technique and multiple blood samples in pigs from 3 to 24 weeks of age.

Objective-To determine the effects of orally administered glucosamine on concentrations of markers of bone and cartilage metabolism in Standardbred horses during race training. Animals-Twenty 16- to 20-month-old Standardbreds beginning race training. Procedure-Horses were randomly assigned to 2 groups. One group received glucosamine hydrochloride (4 g, PO, q 12 h), and the second (control) group received glucose (4 g, PO, q 12 h). Serum samples were obtained prior to onset of the study (baseline) and at regular intervals for 48 weeks for determination of concentrations of keratan sulfate (KS), osteocalcin (OC), and pyridinoline crosslinks (PYD). Results-Osteocalcin concentrations changed significantly with time; mean serum concentrations were significantly higher than baseline values for samples obtained at 24 to 48 weeks after onset of the study. Although a significant effect of time was observed for mean concentration of KS, concentrations did not differ significantly from baseline values at any time during the study when groups were analyzed separately. However, pooled analysis revealed significant increases of mean serum KS concentration at weeks 24 and 30. Significant changes in serum PYD concentrations were not detected. Oral administration of glucosamine did not significantly affect serum concentrations of any of the markers. Conclusions and Clinical Relevance-Increased serum OC in clinically normal Standardbreds during race training may reflect bone formation that accompanies adaptive remodeling of the appendicular skeleton. For these experimental conditions, glucosamine did not appear to exert a detectable influence on serum concentrations of these 3 markers of connective tissue metabolism.

Objective-To estimate pharmacokinetic variables and measure tissue fluid concentrations of meropenem after IV and SC administration in dogs. Animals-6 healthy adult dogs. Procedure-Dogs were administered a single dose of meropenem (20 mg/kg) IV and SC in a crossover design. To characterize the distribution of meropenem in dogs and to evaluate a unique tissue fluid collection method, an in vivo ultrafiltration device was used to collect interstitial fluid. Plasma, tissue fluid, and urine samples were analyzed by use of high-performance liquid chromatography. Protein binding was determined by use of an ultrafiltration device. Results-Plasma data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean +/- SD values for half-life, volume of distribution, and clearance after IV administration for plasma samples were 0.67 +/- 0.07 hours, 0.372 +/- 0.053 L/kg, and 6.53 +/- 1.51 mL/min/kg, respectively, and half-life for tissue fluid samples was 1.15 +/- 0.57 hours. Half-life after SC administration was 0.98 +/- 0.21 and 1.31 +/- 0.54 hours for plasma and tissue fluid, respectively. Protein binding was 11.87%, and bioavailability after SC administration was 84%. Conclusions and Clinical Relevance-Analysis of our data revealed that tissue fluid and plasma (unbound fraction) concentrations were similar. Because of the kinetic similarity of meropenem in the extravascular and vascular spaces, tissue fluid concentrations can be predicted from plasma concentrations. We concluded that a dosage of 8 mg/kg, SC, every 12 hours would achieve adequate tissue fluid and urine concentrations for susceptible bacteria with a minimum inhibitory concentration of 0.12 µg/mL.

In their quest for a blood meal, hematophagous arthropods must first defeat the host's hemostatic defense. Following injury as it occurs when hematophagous arthropods insert their proboscis into host skin to feed, the host will attempt to stop excessive blood loss through its hemostatic defense mechanism involving platelet aggregation, blood clotting and vasoconstriction. To acquire a full blood meal hematophagous arthropods inject an arsenal of bioactive enzymes which ultimately overpower the host's hemostatic defense. We have looked at a selected number of studies on the molecular biology of arthropod anti-hemostatic proteins and developed commentaries on the suitability of these molecules as target tick vaccine antigens.