Objective—To assess the microcirculatory effects of IV fluid administration in healthy anesthetized dogs undergoing elective ovariohysterectomy. Animals—49 client-owned dogs. Procedures—Dogs were sedated, and anesthesia was induced with propofol and diazepam and maintained with isoflurane in oxygen. Dogs received lactated Ringer's solution (LRS) IV at rates of 0, 10, or 20 mL/kg/h. Videomicroscopy was used to assess and record effects of LRS administration on microcirculation in the buccal mucosa. Measurements of microcirculatory (total vessel density, proportion of perfused vessels, microcirculatory flow index, and perfused vessel density by vessel size [< 20 μm, ≥ 20 μm, and all diameters]) and other physiologic variables (heart rate, Doppler-measured blood pressure, oxygen saturation as measured by pulse oximetry, capillary refill time, and body temperature) were compared among groups at baseline (immediately after anesthetic induction), 30 and 60 minutes afterward, and overall. Results—Neither the proportion of perfused vessels nor microcirculatory flow index varied among treatment groups at any time point, regardless of vessel size. For vessels < 20 μm in diameter and for all vessels combined, total and perfused vessel density were similar among groups. For vessels ≥ 20 μm in diameter, total vessel density was significantly greater in the 20 mL/kg/h group than in other groups, and perfused vessel density was significantly greater in the 20 mL/kg/h group than in the 0 mL/kg/h group, when all time points were considered. Other physiologic variables were similar among groups. Conclusions and Clinical Relevance—Total and perfused vessel density of vessels ≥ 20 μm in diameter (mostly venules) were greatest in dogs that received 20 mL of LRS/kg/h. Further research is required to evaluate clinical importance of these findings.

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 mg/kg BW prazosin; or 40, 160, or 480 mg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by a2-adrenoceptors but not a1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.

Objective—To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (VA/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency. Animals—3 healthy adult Standardbreds. Procedures—Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of VA/Q matching, Qs/Qt, and Pao2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m–labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration. Results—During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in VA/Q matching, decreases in Qs/Qt, and increases in Pao2 content, all of which reverted to baseline values at 30 minutes after PiNO administration. Conclusions and Clinical Relevance—Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.

Objective-To determine whether increasing the viscosity of a standard hemoglobin-based oxygen-carrying solution (HBOC) would offset its associated vasoconstrictive effects and result in improved microvascular perfusion in healthy splenectomized dogs with experimentally induced hemorrhagic shock. Animals-12 male American Foxhounds. Procedures-Each dog underwent anesthesia and splenectomy. Shock was induced by controlled hemorrhage until a mean arterial blood pressure of 40 mm Hg was achieved and maintained for 60 minutes. Dogs were then randomly assigned to receive either a standard or hyperviscous HBOC (6 dogs/group). Sidestream dark-field microscopy was used to assess the effects of shock and HBOC administration on the microcirculation of the buccal mucosa and the jejunal serosa. Video recordings of the microcirculation were collected before shock was induced (baseline) and at intervals up to 180 minutes following HBOC administration. Vascular analysis software was used to compute microcirculatory variables. Results-Compared with baseline findings, hemorrhagic shock resulted in decreases in all microvascular variables in the buccal mucosa and the jejunal serosa. At all time points following HBOC administration, microvascular variables were similar to initial values and no significant differences between treatment groups were detected. At all time points following HBOC administration, blood and plasma viscosities in dogs treated with the hyperviscous solution were significantly higher than values in dogs receiving the standard solution. Conclusions and Clinical Relevance-In splenectomized dogs with experimentally induced hemorrhagic shock, administration of a hyperviscous HBOC did not significantly affect microvascular variables, compared with effects of a standard HBOC. Microcirculatory flow returned to baseline values in both treatment groups, suggesting that marked HBOC-associated vasoconstriction did not occur.

Objective-To characterize the pharmacokinetics of dexmedetomidine after IV administration of a bolus to conscious healthy cats. Animals-5 healthy adult spayed female cats. Procedures-Dexmedetomidine was administered IV as a bolus at 3 doses (5, 20, or 50 μg/kg) on separate days in a random order. Blood samples were collected immediately before and at various times for 8 hours after drug administration. Plasma dexmedetomidine concentrations were determined with liquid chromatography–mass spectrometry. Compartment models were fitted to the concentration-time data by means of nonlinear regression. Results-A 2-compartment model best fit the concentration-time data after administration of 5 μg/kg, whereas a 3-compartment model best fit the data after administration of 20 and 50 μg/kg. The median volume of distribution at steady-state and terminal half-life were 371 mL/kg (range, 266 to 435 mL/kg) and 31.8 minutes (range, 30.3 to 39.7 minutes), respectively, after administration of 5 μg/kg; 545 mL/kg (range, 445 to 998 mL/kg) and 56.3 minutes (range, 39.3 to 68.9 minutes), respectively, after administration of 20 μg/kg; and 750 mL/kg (range, 514 to 938 mL/kg) and 75.3 minutes (range, 52.2 to 223.3 minutes), respectively, after administration of 50 μg/kg. Conclusions and Clinical Relevance-The pharmacokinetics of dexmedetomidine was characterized by a small volume of distribution and moderate clearance and had minimal dose dependence within the range of doses evaluated. These data will help clinicians design dosing regimens once effective plasma concentrations are established.

Objective- To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in American kestrels (Falco sparverius). Animals-12 healthy adult American kestrels. Procedures- A single dose of hydromorphone (0.6 mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the time between IM and IV administration experiments was 1 month. Blood samples were collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours (4); and 0.5, 2, and 6 hours (4) after drug administration. Results- Plasma hydromorphone concentrations were determined by means of liquid chromatography with mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Mean plasma hydromorphone concentration for each time was determined with naïve averaged pharmacokinetic analysis.Plasma hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM and IV administration, respectively, but not at 9 hours after administration. The fraction of the hydromorphone dose absorbed after IM administration was 0.75. The maximum observed plasma concentration was 112.1 ng/mL (5 minutes after administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM administration, respectively. Conclusion and Clinical Relevance- Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated..

Objective—To determine renal arterial resistive index (RI) and pulsatility index (PI) and clinical signs of overhydration induced by IV administration of saline (0.9% NaCl) solution and to assess RI and PI as variables for monitoring of dogs to detect overhydration. Animals—10 clinically normal Beagles. Procedures—Each dog received saline solution at a maintenance rate (2.5 mL/kg/h) and a rate 3 times that of the maintenance rate (overhydration rate; 7. 5 mL/kg/h). Values of RI and PI were determined with pulsed-wave Doppler ultrasonographic examination of renal interlobar or arcuate arteries before saline solution administration, every hour during 5 hours of administration, and 1 hour after administration was stopped. Results—No significant changes in RI or PI were detected during administration of saline solution at the maintenance rate. However, RI (starting 1 hour after the beginning of fluid administration [mean ± SD value, 0.589 ± 0.012]) and PI (starting 2 hours after the beginning of fluid administration [value, 0.867 ± 0.052]) were significantly lower during administration at the overhydration rate than they were during administration at the maintenance rate. Clinical signs of overhydration were observed in all dogs starting 4 hours after the beginning of fluid administration at the overhydration rate. Conclusions and Clinical Relevance--Results indicated overhydration of dogs caused significant decreases in RI and PI prior to detection of clinical signs of overhydration. Ultrasonographic determination of renal arterial RI and PI seemed to be a noninvasive and sensitive method for evaluation of overhydration in dogs.

This study aimed to investigate and compare the antagonistic effects of atipamezole, yohimbine, and prazosin on xylazine-induced diuresis in clinically normal cats. Five cats were repeatedly used in each of the 9 groups. One group was not medicated. Cats in the other groups received 2 mg/kg BW xylazine intramuscularly, and saline (as the control); 160 μg/kg BW prazosin; or 40, 160, or 480 μg/kg BW atipamezole or yohimbine intravenously 0.5 h later. Urine and blood samples were collected 10 times over 8 h. Urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine, osmolality, and electrolyte values in both urine and plasma were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis, but prazosin did not. The antidiuretic effect of atipamezole was more potent than that of yohimbine but not dose-dependent, in contrast to the effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed xylazine-induced decreases in both urine specific gravity and osmolality, and the increase in free water clearance. Glomerular filtration rate, osmolar clearance, and plasma electrolyte concentrations were not significantly altered. Antidiuresis of either atipamezole or yohimbine was not related to the area under the curve for AVP concentration, although the highest dose of both atipamezole and yohimbine increased plasma AVP concentration initially and temporarily, suggesting that this may in part influence antidiuretic effects of both agents. The diuretic effect of xylazine in cats may be mediated by α2-adrenoceptors but not α1-adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents against xylazine-induced diuresis in clinically normal cats.

Objective-To determine cellular changes associated with secondary epidermal laminae (SEL) in forefeet and hind feet of ponies with insulin-induced laminitis. Animals-8 ponies. Procedures-Laminitis was induced in 4 ponies by IV administration of insulin and glucose; 4 control ponies received saline (0.9% NaCl) solution IV. Laminar tissue samples obtained from the dorsal aspects of the hooves were histologically evaluated. Primary epidermal lamina (PEL) length and width and SEL length, width, and angle were determined. Numbers of epidermal cell nuclei per micrometer and per total length of SEL and numbers of apoptotic and proliferative cells in axial, middle, and abaxial laminar regions were determined. Results-SEL in treatment group ponies were significantly longer, were significantly narrower, and had a smaller angle relative to PEL in all laminar regions versus control ponies. In treatment group ponies, the number of epidermal cell nuclei per SEL was typically higher and the number of cells per micrometer of SEL was lower in laminar regions, apoptotic cell numbers were higher in abaxial and middle regions in forefeet and hind feet, and proliferating cell numbers were higher in axial laminar regions in forefeet and all laminar regions in hind feet, versus control ponies. Conclusions and Clinical Relevance-Results indicated SEL elongation, narrowing, and alteration in orientation developed in all feet of ponies with insulin-induced laminitis. This was primarily attributable to cell stretching that developed at the same time as an accelerated cell death-proliferation cycle; differences in cell cycle responses among laminar regions between forefeet and hind feet may have been attributable to differences in load bearing.

Objective-To assess effects of body position on direct measurements of intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) in horses anesthetized with total intravenous anesthesia (TIVA). Animals-9 healthy adult horses. Procedures-Instrumentation in unsedated standing horses involved insertion of an arterial catheter for blood pressure measurements and 3 intraperitoneal cannulas (left flank, right flank, and ventral abdomen) for IAP measurements. Baseline values were measured for heart rate, respiratory rate, systolic arterial blood pressure, mean arterial blood pressure (MAP), diastolic arterial blood pressure, and IAP. Horses were medicated with xylazine, and pressures were measured again. Anesthesia was induced with ketamine-diazepam and maintained with a ketamine-guaifenesin infusion. Horses were positioned twice into left lateral recumbency, right lateral recumbency, or dorsal recumbency. Hemodynamic pressures and accessible abdominal pressures were measured for each recumbency position. The APP was calculated as MAP - IAP. Differences in IAP, MAP, APP and sedation (standing horses) or body position (anesthetized horses) were compared by means of repeated-measures ANOVA or paired t tests. Results-Baseline hemodynamic and IAPs were not different after xylazine administration. Ventral abdomen IAP and MAP were lower for horses in dorsal recumbency than in right or left lateral recumbency. Ventral abdomen APP remained unchanged. For lateral recumbencies, flank IAP was lower and APP was higher than pressure measurements at the same sites during dorsal recumbency. Conclusions and Clinical Relevance-Body position affected IAP and APP in healthy anesthetized horses. These effects should be considered when developing IAP acquisition methods for use in horses with abdominal disease.