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Background: There are no known treatments that halt or reverse chronic kidney disease (CKD) in cats. In rodent models, stem cell treatment has been associated with improvement in renal function parameters, especially when stem cells were delivered intra-arterially to the kidney. To date, only IV and intrarenal stem cell infusions have been studied in cats with CKD with no clinically relevant improvement noted., Objective: To assess the safety and feasibility of intra-arterial delivery of autologous mesenchymal stem cells (MSC) in stromal vascular fraction (SVF) to the kidney in cats with CKD., Animals: Five client-owned domestic cats with International Renal Interest Society stage III CKD., Methods: Prospective cohort study (phase I clinical trial). Adipose tissue was harvested from study animals on day 0. On days 2 and 14, an infusion of MSC in SVF was administered into the renal artery via the femoral or carotid artery using fluoroscopic guidance. Serum creatinine and blood urea nitrogen concentration, plasma iohexol clearance, and quality of life assessments were monitored between days 0 and 90., Results: The procedure was performed successfully in all cats. No severe adverse events were observed in any cat during the study period., Conclusions and Clinical Importance: Intra-arterial infusion of MSC into the renal artery in CKD cats was feasible and safe within a 3-month postoperative period. Efficacy and long-term safety have yet to be established. This procedure requires careful technique and training., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Alfaxalone is becoming a popular anesthetic for nonmammalian vertebrates, but the physiological effects of its administration remain largely unknown in these taxa. Therefore, the cardiovascular responses to a clinically relevant dose of alfaxalone (10 mg/kg) are reported in the bullfrog ( Lithobates catesbeianus), following intramuscular (IM) and intravascular (IV) administration (via a femoral artery catheter) and compared with an IV dose of propofol, another parenteral GABA (γ-aminobutyric acid) agonist in common veterinary use as an induction agent. Heart rate (HR) and mean arterial blood pressure (MAP) (assessed by direct measurement from the catheter) are reported from under undisturbed conditions to assess both the direct effects of the drugs and the interaction with the stress of handling associated with IM injection of alfaxalone where IM administration is possible. Alfaxalone caused HR to increase significantly for over 45 min in both groups from a baseline of approximately 30 beats/min. This was significantly different from the lack of significant HR response on the IV administration of propofol. MAP increased in the peri-injection period with both routes of administration for alfaxalone but after IV use decreased significantly from 10 min following administration. Propofol did not affect blood pressure after 5 min from injection. Assessment of immobilization following intramuscular injection of alfaxalone in a pilot study was in accordance with the literature, as it provided no antinociception as a sole agent but did produce sedation and loss of righting reflex.

Background: Survival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered., Objective: To describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC)., Animals: Client-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11)., Methods: Retrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically., Results: Intraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024)., Conclusion and Clinical Importance: This study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Reasons for Performing Study: Intra-arterial (i.a.) and intravenous (i.v.) regional limb perfusions (RLP) through the median artery and cephalic vein, respectively, have been previously investigated for administration of mesenchymal stem cells (MSCs) to the equine distal limb. Limitations due to thrombosis of the arteries after i.a. RLP and poor distribution of MSCs to the foot with i.v. RLP were observed. These techniques need to be modified for clinical use., Objectives: Evaluate the distribution, uptake and persistence of radiolabelled MSCs after i.a. injection through the median artery without a tourniquet and after i.v. RLP through the lateral palmar digital vein., Study Design: In vivo experimental study., Methods: (99m) Tc-HMPAO-labelled MSCs were injected through the median artery of one limb and the lateral palmar digital vein of the other limb of 6 horses under general anaesthesia. No tourniquet was used for the i.a. injection. A pneumatic tourniquet was placed on the metacarpus for i.v. injection. Scintigraphic images were obtained up to 24 h after injection., Results: Intra-arterial injection resulted in MSCs retention within the limb despite the absence of a tourniquet and no thrombosis was observed. Both i.a. injection and i.v. RLP led to distribution of MSCs to the foot. The i.a. injection resulted in a more homogeneous distribution. The MSC uptake was higher with i.v. RLP at the initial timepoints, but no significant difference was present at 24 h., Conclusions: Both i.a. injection through the median artery without a tourniquet and i.v. RLP performed through the lateral palmar digital vein under general anaesthesia are safe and reliable methods for administration of MSCs to the equine foot. The i.a. technique is preferred owing to the better distribution, but is technically more challenging. The feasibility of performing these techniques on standing horses remains to be investigated., (© 2013 EVJ Ltd.)

The aim of the present study was to investigate changes in blood glucose concentration ([Glu]B), acid-base status and electrolyte concentrations during constant rate infusions (CRI) of two alpha2-adrenergic agonists in seven horses treated in a blinded, randomised, crossover design with xylazine or romifidine. An intravenous (IV) bolus of xylazine (1mg/kg) or romifidine (80 μg/kg) was administered followed by an IV CRI of xylazine (0.69 mg/kg/h) or romifidine (30 μg/kg/h) for 2h. Blood samples were collected from the pulmonary artery before and after loading doses, during the CRI, and for 1h after discontinuing drugs. Blood glucose, base excess (BE), pH, partial pressure of carbon dioxide (Pv¯CO2), strong ion difference (SIDest) and bicarbonate concentration ( [Formula: see text] ) increased significantly during the CRI with both alpha2-adrenergic agonists. Chloride concentration ([Cl(-)]B) and anion-gap (AG) decreased significantly compared to baseline. The decrease in sodium concentration ([Na(+)]B) was only significant with xylazine. From 1h after starting the CRI onwards, [Glu]B was significantly higher with romifidine compared to xylazine. Except [Glu]B, SIDest, and Pv¯CO2, all variables returned to normal values 1h after discontinuing xylazine. After stopping romifidine, all variables except pH remained altered for at least 1h. It was concluded that loading doses of alpha2-adrenergic agonists followed by CRIs produce [Glu]B, acid-base and electrolyte changes. The clinical significance of the reported changes remains to be investigated and absolute values should be interpreted with caution, as fluid boli were used for cardiac output measurements, but may become important during prolonged infusion and in critically ill patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The present study was undertaken to evaluate the effect of L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor on serum nitric oxide, progesterone, estradiol profiles and estrous cycle length in buffaloes. Murrah buffaloes (n = 16) exhibiting regular estrous cycles were randomly allocated to two groups of eight animals. In the treatment group, buffaloes were administered 400 mg/h L-NAME over 2 h (total dose = 800 mg) via the coccygeal artery and the aorta abdominalis on day 15 of the estrous cycle. In the control group, normal saline was infused on the same day of the cycle by the same route. Blood samples were collected every 4 h on days 15 and 16, and once daily from days 17 to 21 of the estrous cycle for the assay of progesterone, estradiol and nitric oxide. L-NAME treatment significantly (p < 0.05) reduced serum nitric oxide concentration from 4 h of day 15 until day 20 of the cycle. Serum progesterone concentration increased significantly (p < 0.05) between 0 and 20 h post treatment on day 15. The estrous cycle length was 19.8 ± 0.36 and 23.6 ± 0.17 days for control and treated group buffalo (p < 0.05), respectively. It was concluded that treatment of buffalo with L-NAME in the late luteal phase of the estrous cycle inhibited serum nitric oxide concentration resulting in increased progesterone production and extension of the effective life of the corpus luteum, thus prolonging the estrous cycle length.

The purpose of this report was to evaluate the frequency and type of reactions to intraarterial iodinated contrast medium injection in horses. Ninety-seven received an intraarterial injection of ionic, iodinated contrast medium for computed tomographic assessment of the distal limb. Nine (9.0%) horses developed a reaction attributable to the contrast medium administration. Of those, 4/97 (4.0%) developed a skin response (three with urticaria, one with facial edema) within 20 min. Five (5.0%) developed elevation of heart rate and/or blood pressure immediately upon administration of the contrast medium. No horse developed a severe reaction such as shock, cardiac, or respiratory arrest. No treatment was necessary in any horse., (© 2011 Veterinary Radiology & Ultrasound.)

A 5-year old neutered male cat was admitted to our hospital in the early morning with sudden onset of bilateral hindlimbs paralysis. Conservative anticoagulant therapy using heparin, warfarin, and dipyridamole, and thrombolytic therapy with urokinase administered by intravenous infusion were started. However, no improvement was noted even after 2 days of treatment, and the cat was started on local intra-arterial administration of urokinase via a catheter on disease day 3. Successful thrombolysis could be accomplished by this approach, and the motor function of both hindlimbs recovered on disease day 5. The cat could be discharged on disease day 9. Complications such as hemorrhage and hyperkalemia were not observed during the thrombolytic therapy. These results suggest that local intra-arterial administration of urokinase may be an effective approach for the treatment of FATE.

Reasons for Performing Study: Ileus and peritoneal adhesions are the most common complications following surgery for small intestinal obstruction. Carolina Rinse (CR) has been shown to decrease reperfusion injury in intestine and other organs., Hypothesis: CR decreases intestinal inflammation and subsequent scarring associated with reperfusion injury., Methods: CR was infused intra-arterially and applied topically just prior to reperfusion in jejunum exposed to experimental ischemia. Vascular permeability, neutrophil accumulation and serosal scarring were compared in treated and untreated intestine., Results: CR maintained a normal osmotic reflection coefficient and decreased migration of neutrophils into the serosa during reperfusion. After 10 days, treated intestine was normal in appearance with a trend toward less serosal scarring and fibroblast proliferation. There was a significant decrease in fibroplasia at biopsy sites in treated intestine., Conclusions: Arterial perfusion combined with topical application of CR during jejunal ischaemia decreases immediate reperfusion injury and limits post operative scarring., Potential Relevance: CR should be used as a local perfusate rather than a systemic treatment; it may best be applied topically and intraluminally to avoid damaging mesenteric arteries. CR should be considered an adjunct treatment as part of overall surgical management and post operative care.

It is suspected that prolactin may affect mohair growth; therefore, effects of infusing prolactin on mohair growth were investigated using a skin perfusion technique. Seven Angora wethers (average body weight, 30 +/- 3 kg) were implanted bilaterally with silicon catheters into the superficial branches of the deep circumflex iliac artery and vein. For the first 14 d of the experiment, animals were infused (2.4 mL/h) with prolactin (one side) or control (other side) into the deep circumflex iliac arteries. The infusion rate of prolactin was 2.21 mg/d and was calculated to triple prolactin blood concentration in the perfused region. The area of skin supplied by the deep circumflex iliac artery was approximately 240 cm2. Two weeks after the cessation of infusions, 100-cm2 areas within the perfused regions were shorn to determine mohair growth. Greasy and clean mohair production was decreased (P < 0.05) by prolactin compared with control (3.79 vs 4.62 and 3.02 vs 3.67 g/[100 cm2 x 28 d], respectively). Oxygen satura tion in blood hemoglobin from the deep circumflex iliac veins was greater (P < 0.02) on the side infused with prolactin than on the control side (75.1 vs 68.2%). Higher concentrations of methionine, lysine, valine, isoleucine, and leucine were observed in blood of the deep circumflex iliac vein on the side infused with prolactin vs that infused with control (P < 0.05). In conclusion, direct skin infusion with prolactin decreased mohair fiber synthesis by the skin and may have concomitantly lessened oxygen consumption. Thus, effects of increasing prolactin concentration approximately two-fold in the skin on mohair fiber growth may not be limited to simple competition for nutrients between skin and other tissues such as the mammary gland.

Grain-finished, high-percentage Charolais steers (n = 36) were selected for uniformity. Immediately after jugular vein exsanguination, 27 steers were infused at 10% of live weight via the carotid artery with a solution developed by MPSC, Inc. (St. Paul, MN) consisting of 98.52% water, 0.97% saccharides, 0.23% sodium chloride, and 0.28% phosphate blend plus either 500 ppm vitamin C (MPSC+C; n = 9), 500 ppm vitamin E (MPSC+E; n = 9), or 500 ppm vitamin C + 500 ppm vitamin E (MPSC+C+E; n = 9). Uninfused controls (CON) were exsanguinated conventionally. Carcasses were fabricated at 48 h postmortem. Longissimus thoracis (LT), psoas major (PM), and semimembranosus (SM) muscles were removed, vacuum-packaged, and stored at 2 degrees C until 14 d postmortem. Then, steaks 2.54 cm thick were sliced from the three muscles, placed on foam trays, and overwrapped with polyvinyl chloride film. Ground beef (GB) was formulated from the quadriceps femoris to contain 20% fat, mounded into 0.45-kg portions, placed on styrofoam trays, and wrapped with polyvinyl chloride film. Steaks were visually evaluated for uniformity and initial color on display d 0. Instrumental color measurements of L*, a*, b* and trained sensory panel color evaluations were obtained daily for 4 d (PM and GB) or 5 d (LT and SM) of display. No display time x treatment interaction existed for L*, a*, or b* values. The LT from CON cattle had more uniform color (P < 0.05) and was more cherry red than that from all infused cattle on d 0. Visual scores indicated that GB from MPSC+E cattle was more red (P < 0.05) than that from MPSC+C infused cattle throughout display, and GB from MPSC+E cattle was more red (P < 0.05) than that from CON cattle for the last 3 d of display. The vascular infusion solutions generally did not improve color or display-color stability of steaks, but the infusion solution with vitamin E did improve display-color stability of GB.

To evaluate a close mammary infusion technique for the study of milk protein responses to blood amino acid profile, five early-lactation, multiparous Holstein cows were surgically fitted with catheters in both external iliac arteries. Animals were infused into one arterial catheter with five different solutions on 5 consecutive days in a Latin square design. Infusions began at 0800 h and continued until 1800 h. The five infusates were a 3% saline control, 15 g/h of complete amino acid mix, 15 g/h of imbalanced amino acid mix (minus His), 30 g/h of complete amino acid mix, and 30 g/h of imbalanced amino acid mix (minus His). Cows were fed a total mixed ration twice daily containing 16% crude protein and 1.7 Mcal/kg of net energy for lactation. Infusion of the complete amino acid mix elevated amino acid concentrations in arterial plasma two- to threefold but caused only a small dose-dependent increase in milk protein content and yield. Fat percentage in milk was decreased from 4.08 to 3.35% by the complete amino acid infusions so that the protein:fat ratio climbed from 0.76 on the control to 0.99 with 30 g/h of amino acid. Removal of His from the infusate caused plasma His concentrations to drop but had no effect on any other circulating amino acids. Milk composition was restored to control levels by removal of the single amino acid. A short-term circulating amino acid imbalance depresses milk protein percentage and increases milk fat content in dairy cows.

14C-methyltestosterone pharmacokinetics after intraarterial (2 and 20 mg/kg) and oral (30 mg/kg) administration were investigated in rainbow trout at 15 degrees C. Plasma concentrations of methyltestosterone were determined by reverse phase high performance liquid chromatography (HPLC) in combination with reverse isotope dilution for up to 6 and 12 days after oral and intraarterial administration, respectively. Methyltestosterone pharmacokinetic parameter values after intraarterial administration were determined using a two compartment model (WinNonlin). For the 2 and 20 mg/kg doses, respectively, the parameter values were, area under the plasma concentration-time curve (11.2 and 82.3 micromol h/l), total body clearance (0.640 and 0.903 l/h per kg), distribution half-life (4.13 and 8.23 h), elimination half-life (54.9 and 58.6 h), volume of the central compartment (3.83 and 13.9 l/kg), volume of distribution at steady state (6.06 and 26.8 l/kg), and the mean residence time (9.57 and 22.7 h). After oral administration, the following parameter values were assessed using a model-independent method, peak concentration (3.03 micromol/l), time of concentration peak (8.80 h), mean absorption time (13.8 h), and area under curve (AUC)(0-->infinity) (90.2 micromol h/l). A two compartment model analysis of the average plasma concentration-time profile after oral administration showed that absorption followed first-order kinetics with a half-life of 4.7 h. The oral bioavailability of methyltestosterone from food was about 70%.

The effects of close intra-arterial infusion of acetylcholine and adrenalin on ovarian secretion of progesterone and oxytocin were examined on Day 10 of the estrous cycle in goats (estrus = Day 0). Acetylcholine (15 micrograms/min) was without effect, but adrenalin (10 micrograms/min) significantly (P < 0.001) raised both progesterone and oxytocin concentrations in ovarian vein plasma. These results show that luteal hormone secretion is enhanced in the goat by beta-adrenergic stimulation and suggest that, as in the sheep and cow, there may be neuroendocrine involvement in the regulation of caprine luteal function.

Dose-dependent effects of cimaterol (CIM) on hindlimb metabolism were determined in six steers (247 +/- 22 kg BW) using a close arterial infusion. The external iliac vessels of both hindlimbs were catheterized to accommodate measurement of blood flow, circulating concentrations, and net flux of NEFA, lactate, and alpha-amino nitrogen (AAN) during infusion of CIM at 0, .05, .1, .3, .7, 1 and 3 micrograms/ min. Close arterial infusion of CIM in the hindlimb of steers can be used to achieve a local concentration elevation that is required to differentiate local and systemic effects in vivo. Calculated plasma threshold CIM concentration required to initiate cardiovascular responses was 21 pg/mL, which resulted from an infusion rate of .3 microgram/min. Threshold concentrations of CIM for stimulation of NEFA and lactate net flux in the hindlimb were 38 and 34 pg/mL, respectively, and would be achieved with an infusion rate of .7 microgram/min. All measured responses except AAN net flux exhibited significant linear and quadratic dose effects, and responses in the treated hindlimb were always severalfold greater than in the contralateral control hindlimb. Maximal differences between treated and control hindlimb blood flow occurred with a CIM infusion rate of .7 microgram/min, but the highest infusion rate (3 micrograms/min) was required to maximize differences in NEFA and lactate flux. Therefore, to minimize cardiovascular and other systemic responses and optimize direct hindlimb responses, an infusion rate of .5 microgram of CIM/ min should cause significant stimulation of beta-adrenergic receptors only in the CIM-infused hindlimb of young, growing steers.

The effect of mimosine on a perfused area of skin tissue was studied using an isolated perfusion technique. Four mature Angora wethers (body weight 35 (SE 2.3) kg) were cannulated bilaterally with indwelling silicone catheters in the superficial branches of the deep circumflex iliac artery and vein. Mimosine (40 mg/kg metabolic weight (W)0.75) per d) was infused intra-arterially into one iliac artery of each goat for 3 d and saline was infused in the contralateral (control) iliac artery. Iliac venous blood samples were taken from both sides along with arterial samples from the carotid artery. Mimosine infusion elevated plasma mimosine in the carotid artery (52.6 (SEM 19.21) mumol/l) and iliac vein on the saline-treated side to 54.1 (SEM 16.31) mumol/l and in the iliac vein on the mimosine-treated side to 191.3 (SEM 19.14) mumol/l (P < 0.01). Mimosine decreased feed intake (2.3 v. 0.6 kg/d, SEM 0.29; P < 0.001) and water consumption (5.2 v. 1.3 litres/d, SEM 0.67; P < 0.001). Mimosine did not cause defleecing in the area of infusion and was cleared from the bloodstream within 12 h of cessation of infusion. The following effects were also observed during mimosine infusion: decrease in plasma amino acids to half pre-infusion values (methionine 22.7 v. 13.1 mumol/l, SEM 1.41; lysine 95.9 v. 37.4 mumol/l, SEM 4.28; P < 0.001); decreases in plasma triiodothyronine (1495 v. 695 ng/l, SEM 43.1; P < 0.001), thyroxine (61.5 v. 19.5 micrograms/l, SEM 1.8; P < 0.001) and insulin (28.7 v. 17.3 microIU/ml, SEM 1.89; P < 0.01) concentrations; increase in plasma cortisol (14 v. 62 micrograms/l, SEM 0.35; P < 0.001) concentration; decreases in levels of plasma Zn and Mg (0.97 v. 0.49 mg/l, SEM 0.063; P < 0.001 and 21.4 v. 14.6 mg/l, SEM 1.74; P < 0.001 respectively). All reported variables returned to their normal values 24 h after cessation of mimosine infusion except feed intake which was affected for a longer period. Mohair length and diameter were not affected by mimosine infusion. The toxicity of mimosine may be due to the drastic depletion of Zn and Mg in the blood as mimosine possesses very strong chelating properties and is excreted in the urine as a chelate.

Strenuously exercising Thoroughbreds exhibit a dramatic increase in pulmonary capillary blood pressure, which contributes to stress failure of pulmonary capillaries resulting in exercise induced pulmonary haemorrhage (EIPH). One strategy to prevent EIPH is, therefore, to lower the pulmonary capillary blood pressure of exercising horses. Recent work in several species suggests that nitric oxide plays a significant role in maintaining low vascular resistance in the pulmonary circulation; however, the effects of nitrovasodilators (which work via the same mechanism as nitric oxide) on equine pulmonary circulation have not been examined. The present study examined the effects of glyceryl trinitrate (nitroglycerin) on right atrial and pulmonary vascular pressures in 7 healthy sound Thoroughbred horses. Freshly prepared nitroglycerin solution was infused for 240 s into the right atrium of quietly standing Thoroughbreds at dose rates of 350, 700, 1400 and 2100 g/min in a randomised manner. All infusions were performed in duplicate. Heart rate, right atrial, pulmonary artery, pulmonary capillary and pulmonary artery wedge pressures were determined preinfusion, at 30 s intervals during nitroglycerin infusions and at 60 s post infusion. Measurements were made using catheter mounted manometers whose in vivo signals had been matched with fluid-filled systems referenced at the level of the point of the shoulder. It was observed that nitroglycerin infusions caused a dose related increase in heart rate while dose related reductions occurred in the mean right atrial, pulmonary artery, pulmonary artery wedge and pulmonary capillary pressures. At 2100 micrograms/min, nitroglycerin induced reduction in pulmonary artery wedge pressure was significantly greater than that in the pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo oxidation rate of arterially infused D-(-)-3-hydroxybutyrate (3HB) was measured in 1-2-d-old-piglets. Twelve piglets (1.4 kg) were randomly assigned to a 12 h continuous infusion of 3HB at 19.5, 37.8, 55.8 or 74.5 mumol/min along with -31 kBq/h of [3-14C]3HB. Piglets were housed in respiration chambers allowing collection of total expired CO2 over 20-min intervals for the 12 h infusion and 6 h washout. Oxidation of 3HB was calculated from the quantity and specific radioactivity of expired CO2 for 20-min collection periods at 6, 9 and 12 h for each piglet and collectively plotted against plasma 3HB concentration measured in blood drawn during those 20-min periods. A Lineweaver-Burk plot of these data yielded a Km of 0.62 +/- 0.07 mmol/L and Vmax of 0.74 +/- 0.02 mmol ATP equivalents/(min.kg 0.75) (parameter estimate +/- SD), which could account for 32% of the piglet mean total ATP turnover of 2.3 mmol/(min.kg 0.75). These data show that 3HB oxidation is a linear function of plasma concentration in the physiologic range measured in piglets (0.006 mmol/L to 0.1 mmol/L) and within this range would account for 0.3% to 4.5% of piglet energy requirement. Oxidation of 3HB can meet a maximum of 30 to 40% of piglet energy requirement at unphysiologically high 3HB concentrations (> 3 mmol/L).

Cardiopulmonary and behavioral responses to detomidine, a potent alpha 2-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 2), 19.1 +/- 5.1. (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused concentration-dependent sedation and somnolence. These effects were profound during infusions 3 and 4, in which marked head ptosis developed and all horses leaned heavily on the bars of the restraining stocks. Heart rate and cardiac index decreased from baseline measurements (42 +/- 7 beats/min, 65 +/- 11 ml.kg of body weight-1.min-1) in linear relationship with the logarithm of plasma detomidine concentration (ie, heart rate = -4.7 [loge detomidine concentration] + 44.3, P < 0.01; cardiac index = -10.5 [loge detomidine concentration] + 73.6, P < 0.01). Second-degree atrioventricular block developed in 5 of 7 horses during infusion 3, and in 6 of 7 horses during infusion 4. Mean arterial blood pressure increased significantly from 118 +/- 11 mm of Hg at baseline to 146 +/- 27 mm of Hg at infusion 4. Similar responses were observed for mean pulmonary artery and right atrial pressures. Systemic vascular resistance (baseline, 182 +/- 28 mm of Hg.ml-1.min-1.kg-1) increased significantly during infusions 3 and 4 (to 294 +/- 79 and 380 +/- 58, respectively). (ABSTRACT TRUNCATED AT 250 WORDS)

The cardiovascular effects of serial increasing infusions of dopexamine HCl were investigated in six conscious (1, 2, 4, 6, 10 micrograms/kg bodyweight [bwt]/min) and eight (0.5, 1, 5, 10, 20 micrograms/kg bwt/min) halothane-anaesthetised horses. Dopexamine produced dose-dependent increases in heart rate, +dP/dtmax' -dP/dtmax and cardiac output, and a decrease in systemic vascular resistance in conscious and halothane-anaesthetised horses. Mean arterial blood pressure did not change in conscious horses but increased to a maximum value at 10 micrograms/kg bwt/min in halothane-anaesthetised horses. Thereafter, median artery blood flow decreased. Ventricular arrhythmias occurred in two conscious horses during the infusion of 10 micrograms/kg bwt/min dopexamine HCl. No cardiac arrhythmias other than sinus tachycardia were observed in halothane-anaesthetised horses. The administration of propanolol eliminated the haemodynamic response to the infusion of 5 and 10 micrograms/kg bwt/min dopexamine HCl in halothane-anaesthetised horses. The haemodynamic effects of dopexamine HCl offer specific advantages over dopamine and dobutamine for the treatment of low cardiac output states in horses.

Twelve dogs with appendicular osteosarcoma were treated with 24-40 Gy of cobalt 60 radiation and two doses of intraarterial cisplatin. Improvement in limb function occurred in four dogs, and three dogs, which had only mild initial lameness, had no worsening of their lameness post-treatment. In nine dogs in which local control was evaluable, eight had local failure, with the median (95% CI) duration of local control being 5.9 (4.6, 6.7) months. Two dogs had metastatic disease before therapy, and an additional nine dogs had metastatic disease at a median time of 6.4 months. Pathologic fracture was present in four dogs; two fractures occurred before treatment and two were documented at the time of tumor recurrence. Median (95% CI) survival time for all 12 dogs was 4.9 (3.4, 6.8) months. Excluding the two dogs with preexisting metastatic disease, median survival time was 6.7 months. Three dogs survived longer than 1 year. This mode of therapy was well tolerated and may be considered an alternative to amputation or limb-sparing surgical procedures in selected dogs with appendicular osteosarcoma.

Four lactating dairy cows received arterial infusions of insulin (1.41 U/h), an AA mixture (threonine, methionine, leucine, phenylalanine, and lysine at 5.87, 1.90, 3.55, 2.17, and 4.21 mmol/h, respectively), and a combination of the two in a 4 x 4 Latin square. The infusions were performed over a 3-d period directly into the extra pudic artery on both sides of the mammary gland, and samples were taken simultaneously of the downstream extra pudic arterial blood and also of subcutaneous abdominal venous blood. Blood flow was measured by dye dilution using p-amino-hippuric acid and was increased by 37% by infusion of insulin plus AA (P less than .05). Infusions of AA tended to increase the arteriovenous difference and uptake of the infused AA (P less than .05 for phenylalanine) and had varying effects on the uninfused AA. Inclusion of insulin in the AA infusion tended to increase uptake of infused AA, whereas infusions of insulin alone tended to decrease uptake. There were no significant effects of infusion on milk yield or composition.

Using a pump-perfused extracorporeal isolated digital preparation, the effects of a 30-minute infusion of either saline solution (control) or endotoxin on equine digital hemodynamics and microvascular function were determined. Digital blood flow and arterial, venous, and capillary pressures were recorded at 15-minute intervals for 150 minutes. From these data, total vascular resistance and pre- and postcapillary resistances were calculated. Isogravimetric capillary filtration coefficient, vascular compliance, and the osmotic reflection coefficient were determined after the last hemodynamic measurements were taken. Changes in hemodynamic values of control equine digits were not observed. During the 120 minutes after infusion of endotoxin, digital blood flow decreased 43%, and total vascular resistance increased 89%. Precapillary resistance increased 122%, but postcapillary resistance did not change significantly. Changes in vascular compliance or the capillary filtration coefficient were not observed in response to either treatment. The osmotic reflection coefficient, an index of permeability, did not differ significantly between digits of the endotoxin-treated and control groups. These data indicate that the increase in vascular resistance during endotoxemia may have been attributable to arterial/arteriolar constriction and that neither the permeability nor the surface area of the exchange vasculature within the digit was significantly affected by endotoxin. Although marked alterations in vascular function are seen after administration of endotoxin, these changes do not parallel those documented in association with experimentally induced laminitis.

In 6 adult horses anesthetized with pentobarbital, the hemodynamic responses of the equine digit to infusion of dopamine were evaluated by use of an isolated extra corporeal pump perfused digital preparation. Digital blood flow was maintained at a constant rate that was independent of systemic hemodynamic changes. Three sequential experiments were performed on each horse. In the first experiment (n = 6), dopamine was infused IV at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. For the second experiment (n = 5), dopamine (400 micrograms/ml) was infused into the digital artery at the rates of 0.07, 0.7, and 1.2 ml/min. The third experiment (n = 5) consisted of a 5-minute intra-arterial infusion of phentolamine followed by the intra-arterial infusion of dopamine while continuing the infusion of phentolamine. Digital venous, arterial, and capillary pressures, total digital vascular resistance, and precapillary to postcapillary resistance ratios were determined in each experiment. Systemic infusion of dopamine did not induce changes in the hemodynamics of the digital vasculature. Digital arterial infusion of dopamine alone resulted in a dose-dependent increase in arterial pressure, total digital vascular resistance, and an increase in the precapillary to postcapillary resistance ratio. Phentolamine attenuated the vasoconstrictive response elicited by intra-arterial infusion of dopamine.

A study was conducted to determine the effect of pulses of naloxone on plasma LH concentration in prepubertal ewes and to see if this treatment affects the pituitary response to subsequent LHRH pulses. Prepubertal ewes (n = 5) received three intracarotidal pulses of naloxone (NAL, 1 mg/kg BW) and four pulses of Luteinizing Hormone Releasing Hormone (LHRH, 1 micrograms/pulse) at hourly intervals. Control ewes (n = 5) received saline instead of NAL followed by the LHRH pulses at the same frequency. Blood samples were collected from one hour before the first pulse of saline or NAL at 15 min intervals for four hours and at 30 min intervals for another four hours. Plasma LH concentration was measured by radioimmunoassay. The first pulse of NAL increased plasma LH levels compared to the basal levels and compared to control animals (P less than 0.01). The succeeding pulses were ineffective. LHRH provoked an increase in plasma LH concentration in control as well as in treated animals but the amplitude of the net peak height increased progressively up to the third pulse in NAL treated animals, while there was no increase in pituitary responsiveness to LHRH in control prepubertal ewes. Also, the area under the LHRH response curve was greater (P less than 0.05) in animals pretreated with NAL than in lambs pretreated with saline. The results suggest that there is an inhibitory opioid tone over LH secretion in female lambs. NAL increases the responsiveness to exogenous LHRH pulses, probably as a result of endogenous LHRH release.

A technique for long-term infusion into the inferior mesenteric artery was developed which allows simple and reliable regional infusion into the colorectal segment of unrestrained rats. The cannulation system consists of an injection port 'In Stoppers' as a flow swivel, connected to an injection needle, which is inserted into a polyethylene tube protected by a steel spiral. During infusion the animals are free to move in the cage with access to food and water ad libitum. The method is suitable for regional chemotherapy as well as for studies of colorectal tumours in rats. In this study 73% of the cannulae remained functional for continuous infusion over a 15 day period.

Cured were 59 cows, affected by puerperal catarrhal suppurative endometritis, by intra-aortic and uterine infusion of procaine and antibiotic solutions. A good curative and biological effect was reached. The aortic-treated animals were fertilized at average independence and service periods--accordingly 43.52 and 57.31 days, for the uterine treatment--accordingly 51.67 and 78 days.

The construction of a double channel swivel for infusing two fluids separately into an unrestrained animal is described. The swivel is constructed of readily available, inexpensive materials and does not require any machining of parts. These swivels have been found to last for 720 hr without leakage.

Twenty dogs with spontaneously developing osteosarcoma of the extremities were treated with 1 of 3 multimodality limb-sparing procedures. Excision of the tumor was preceded by intra-arterial (IA) administration of cisplatin (cis-diamminedichloroplatinum) alone directed to the affected extremity, irradiation plus IA administration of cisplatin, or irradiation plus IV administration of cisplatin. All dogs were free of apparent metastatic disease at the time of initial treatment. After diagnosis, dogs administered cisplatin IA had selective angiography performed on arteries supplying the tumor, and 70 mg of cisplatin/m2 of body surface was administered over 2 hours. This protocol was repeated 3 weeks later. Dogs that were irradiated received 25 or 40 Gy in 10 fractions over a 22-day period. The first and last radiation doses were immediately preceded by IA administration of cisplatin. Dogs given IV treatment received 10 mg of cisplatin/m2 2 hours before each radiation fraction was administered. Three weeks after the last treatment, tumors were excised and the limb underwent orthopedic reconstruction, generally using cortical allografting and bone plating. Limb function, allograft healing, local tumor control, and metastatic dissemination were monitored. Limb function was good to excellent in 69% (11/16) of dogs evaluated. Forelimb-sparing procedures were generally associated with better function than were limb-sparing procedures performed on hind limbs. Local tumor control was obtained in 79% (11/14) of dogs thoroughly evaluated, with local recurrences in 3 dogs at 3, 4, and 7 months after treatment. Fifteen dogs developed metastatic disease at a median time of 8 months from the time of diagnosis. Mean and median survival times for all dogs, regardless of cause of death, were 11.7 and 8 months, respectively. Tumor necrosis greater than 80% was statistically associated with lack of recurrence. Of 16 dogs, 5 (31%) developed infections at the surgical site. Multimodality limb-sparing treatment is believed to be a viable alternative for appropriately selected dogs with osteosarcoma. The optimal method of treatment prior to or after tumor excision has not yet been established.

A technique for the catheterization and intra-arterial infusion of the common carotid artery of the rabbit utilized a simple swivel apparatus, an acrylic head mount, and a silicone rubber sleeve. This method was used for continuous intra-arterial infusion in 29 unrestrained rabbits for periods up to 61 days.

Previous reports indicate that intravenous infusion of HCl can alter breathing and blood pressure even if reductions in systemic arterial pH are prevented. To extend these findings, as well as to determine whether other acids elicit comparable results, this report compares the cardiopulmonary response between right atrial infusion of lactic acid and HCl in awake ponies. Lactic acid, infused at a dose of 1.5 mmol/kg over 18 min, lowered systemic and pulmonary arterial pH 0.062 and 0.092 U, respectively, and increased pulmonary arterial pressure (delta Ppa, 4 mmHg), heart rate (HR, 4/min), and tidal volume (delta VT, 190 ml/m2). HCl, infused at a reduced dose of 0.5 mmol/kg over 18 min, lowered systemic and pulmonary arterial pH 0.024 and 0.047 U, respectively, but produced increases in Ppa (delta 23 mmHg), HR (delta 42/min), and VT (delta 321 ml/m2) that were significantly greater than from the larger dose of lactic acid. These results indicate that cardiopulmonary responses to infusion acidosis differ between the type of acid infused. It is suggested that, in the unanesthetized pony, HCl-induced infusion acidosis has a unique cardiopulmonary-stimulating action unrelated to the pH changes imparted to the circulating arterial blood and that this response is absent during the infusion of lactic acid.

This study was conducted to determine whether the increase in serum glucose observed in pigs treated chronically with pGH is due to an increase in hepatic glucose output or to an impairment in glucose clearance. Barrows (n = 4 per treatment) were treated with pituitary derived pGH (ppGH), recombinant pGH analog (rpGH) or vehicle. Pigs were treated for 28 d by daily i.m. injections. Insulin tolerance and glucose tolerance tests (GTT) were performed on d 19 and 21, respectively, following treatment with pGH. Glucose turnover was quantified on d 28 using [6-3H]glucose. Chronically treating pigs with pGH resulted in a significant decrease (26%; P less than .05) in glucose clearance, as determined by the GTT. Glucose clearance was affected similarly by ppGH and rpGH. Intra-arterial glucose infusion markedly increased plasma insulin concentration in pGH-treated pigs. Peak plasma insulin response was 87% and 58%, respectively, higher (P less than .05) in ppGH- and rpGH-treated than in control pigs. Insulin infusion elicited a marked hypoglycemia in pigs; however, the extent and duration of hypoglycemia were significantly less in pGH-treated pigs (ppGH or rpGH). Glucose production rates were 23% higher (P = .085) in ppGH-treated than in control pigs. These results establish that the hyperglycemia induced by pGH is the result of an increase in hepatic glucose output and a concurrent impairment in glucose clearance.

We evaluated the hemodynamic effects of IV and intraaortic (aortic root) administration of 7.5% NaCl solution on hemodynamics in anesthetized cats with severe hypovolemia. Hypovolemic shock was induced by exsanguinating cats to a mean arterial blood pressure of 50 mm of Hg, which was maintained for 30 minutes prior to treatment. Shed blood volume was 38.4 +/- 2.1 ml/kg of body weight. The cats were treated with a small volume (4 ml/kg) of 0.9% NaCl solution IV, 7.5% NaCl solution IV, or 7.5% NaCl solution administered into the aortic root. The IV administration of 0.9% NaCl solution did not improve hemodynamics. The IV administration of 7.5% NaCl solution induced rapid restoration of arterial blood pressure, aortic blood flow, and cardiac contractility. Total peripheral vascular resistance decreased. The administration of 7.5% NaCl solution into the aortic root induced a further deterioration in hemodynamics resulting in death in 3 cats and a marked improvement in hemodynamics similar to that observed after IV administration of 7.5% NaCl solution in 2 cats. The duration of the beneficial hemodynamic effects after IV or intra-aortic administration of 7.5% NaCl solution did not exceed 60 minutes. Results of these studies suggested that either the IV or intra-aortic administration of 7.5% NaCl solution in cats can induce beneficial hemodynamic effects that may be of value in the field resuscitation of hypovolemic patients.

The acute and chronic effects of porcine growth hormone (pGH) administration on glucose homeostasis of pigs were investigated in the present study. Twelve Yorkshire barrows (average BW = 65 kg) fitted with femoral artery catheters were allotted to three groups. Pigs received acute, intra-arterial injections of either pituitary pGH, a recombinantly derived pGH analog (ppGH or rpGH, 100 micrograms/kg BW) or saline. Acute injection of pGH did not affect fasting plasma glucose or insulin status. Pigs then were treated daily by i.m. injection for 24 d with 70 micrograms ppGH/kg BW. Serum glucose and insulin concentrations during the fed and fasted states were higher in pGH-treated than in control pigs. On d 25, an acute intra-arterial injection of ppGH (100 micrograms/kg BW) elicited increases in plasma glucose and insulin in pigs chronically treated with pGH. The area circumscribed by the glucose and insulin response curves 5 min to 7 h postinjection was 40% (P less than .005) and 177% (P less than .001), respectively, higher in ppGH-treated than in control pigs. These data indicate that pGH does increase plasma glucose and insulin in the fed and fasted states; however, this response is only observed after chronic pGH administration. In addition, pGH is capable of increasing plasma glucose and insulin acutely in the pig. This effect, however, only is observed in pigs treated chronically with pGH. The mechanisms by which pGH elicit these effects on glucose homeostasis are not known.