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Abstract

OBJECTIVE To determine the minimum alveolar concentration that blunts adrenergic responses (MACBAR) for isoflurane and evaluate effects of fentanyl on isoflurane MACBAR in sheep.

ANIMALS 13 healthy adult Dorset-cross adult ewes.

PROCEDURES In a crossover design, each ewe was anesthetized 2 times for determination of isoflurane MACBAR. Anesthesia was induced with propofol administered IV. Sheep initially received fentanyl (5 μg/kg, IV, followed by a constant rate infusion of 5 μg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment). After a washout period of at least 8 days, the other treatment was administered. For MACBAR determination, a mechanical nociceptive stimulus (ie, sponge forceps) was applied at the coronary band for 1 minute. The MACBAR values of the 2 treatments were compared by means of a paired t test. During MACBAR determination, blood samples were collected for measurement of plasma fentanyl concentration.

RESULTS Mean ± SD isoflurane MACBAR of the fentanyl and control treatments was 1.70 ± 0.28% and 1.79 ± 0.35%, respectively; no significant difference was found between the 2 treatments. Plasma concentration of fentanyl reached a median steady-state concentration of 1.69 ng/mL (interquartile range [25th to 75th percentile], 1.47 to 1.79 ng/mL), which was maintained throughout the study.

CONCLUSIONS AND CLINICAL RELEVANCE Administration of fentanyl at 5 μg/kg, IV, followed by a constant rate infusion of the drug at 5 μg/kg/h did not decrease isoflurane MACBAR. Further studies to determine the effect of higher doses of fentanyl on inhalation anesthetic agents and their potential adverse effects are warranted. (Am J Vet Res 2016;77:119–126)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize the relative contributions of voltage-gated and capacitative Ca2+ entry to agonist-induced contractions of equine laminar arteries and veins.

Animals—16 adult mixed-breed horses.

Procedures—Laminar arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Concentration-response curves were obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine (5-HT), prostaglandin F (PGF), and endothelin-1 (ET-1) either in the absence of extracellular Ca2+ or in the presence of the voltage-gated Ca2+ channel inhibitor diltiazem or the putative inhibitor of capacitative Ca2+ entry, trifluoromethylphenylimidazole.

Results—In the absence of extracellular Ca2+, maximal responses of veins to 5-HT, phenylephrine, ET-1 and PGF were reduced by 80%, 50%, 50%, and 45%, respectively; responses of arteries to 5-HT, phenylephrine, and ET-1 were reduced by 95%, 90%, and 20%, respectively. Although diltiazem did not affect the maximal responses of veins to any agonist, responses of arteries to 5-HT, phenylephrine, and ET-1 were reduced by 40%, 50%, and 27%, respectively. Trifluoromethylphenylimidazole did not affect maximal responses of veins, but did reduce their contractile responses to low concentrations of ET-1 and PGF.

Conclusions and Clinical Relevance—Results suggested that the contribution of extracellular Ca2+ to laminar vessel contractile responses differs between arteries and veins and also between contractile agonists, voltage-gated Ca2+ entry is more predominant in laminar arteries than in veins, and capacitative Ca2+ entry has a minor role in agonist-induced contractile responses of laminar veins.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of induction of capacitative Ca2+ entry on tone in equine laminar arteries and veins.

Sample Population—Laminar arteries and veins from 6 adult mixed-breed horses.

Procedure—Arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Capacitative Ca2+ entry was induced by incubating the vessels with the specific Ca2+-ATPase inhibitor thapsigargin (100nM) in a Ca2+- free physiologic salt solution. Capacitative Ca2+ entry–associated contractile responses were determined by the subsequent addition of 2mM Ca2+ to the solution bathing the vessels; in some experiments, either the voltage-gated Ca2+ blocker diltiazem (10µM) or the putative capacitative Ca2+ entry inhibitor trifluoromethylphenylimidazole (300µM) was added to the bathing solution 15 minutes prior to a second 2mM Ca2+ exposure. The Sr2+ permeability of the capacitative Ca2+ entry pathway in laminar vessels was assessed by exposing the vessels to 4mM Sr2+ after induction of capacitative Ca2+ entry with thapsigargin.

Results—Induction of capacitative Ca2+ entry elicited robust contractile responses in laminar veins but did not increase tone in laminar arteries. In laminar veins, capacitative Ca2+ entry–induced contractile responses were unaffected by preincubation with diltiazem, attenuated by trifluoromethylphenylimidazole, and were impermeable to Sr2+.

Conclusions and Clinical Relevance—Results indicated that induction of capacitative Ca2+ entry elicits vasoconstriction in equine laminar veins but not in laminar arteries and should therefore be considered a potential mechanism by which selective venoconstriction occurs in horses during the development of acute laminitis. (Am J Vet Res 2005;66:1877–1880)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins.

Sample Population—Laminar arteries and veins obtained from 13 adult mixed-breed horses.

Procedures—Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F (PGF), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10μM), srcPTK inhibitor PP2 (10μM), or a negative control analogue for PP2 (PP3; 10μM).

Results—Responses to PE were reduced by use of Y-27632 in laminar vessels (approx inhibition, 55%). However, Y-27632 reduced responses to 5-HT to a greater degree in veins than in arteries (approx inhibition of 55% and 35%, respectively). The Y-27632 also reduced responses of laminar veins to ET-1 by approximately 40% but had no effect on maximum responses of laminar arteries to ET-1, although a rightward shift in the concentration response curve was evident. Addition of PP2 reduced responses to PE, 5-HT, and PGF in laminar veins by approximately 40%, 60%, and 65%, respectively, compared with responses after the addition of PP3; PP2 had no effect on responses to ET-1. In laminar arteries, PP2 reduced 5-HT–induced contractions by approximately 50% but did not affect responses to PE or ET-1.

Conclusions and Clinical Relevance—Results of the study were consistent with activation of Rho-kinase being important during agonist-induced constriction in laminar vessels, activation of srcPTK being an agonist-dependent event, and more prominent roles for Rhokinase and srcPTK in veins than in arteries.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of the protein kinase C (PKC) inhibitor, Ro-31-8220, on agonist-induced constriction of laminar arteries and veins obtained from horses.

Sample Population—Laminar arteries and veins obtained from 8 adult mixed-breed horses.

Procedures—Laminar arteries and veins were isolated and mounted on small vessel myographs for the measurement of isometric tension. Concentration-response curves were then obtained for the vasoconstrictor agonists phenylephrine, 5-hydroxytryptamine, prostaglandin F, and endothelin-1. All responses were measured with or without the addition of Ro-31-8220 (3μM).

Results—Laminar veins were more sensitive to vasoconstrictor agonists than laminar arteries, and incubation of laminar veins with Ro-31-8220 resulted in significantly smaller agonist-induced contractile responses for all agonists tested. In contrast, Ro-31-8220 had no effect on agonist-induced contractile responses of laminar arteries.

Conclusions and Clinical Relevance—Results of the study were consistent with activation of PKC being confined to agonist-induced contraction of laminar veins isolated from the laminar dermis of horses. Consequently, the possible involvement of PKC in the venoconstriction observed during the development of laminitis is worthy of further investigation.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To provide insights into the role of prostaglandin F (PGF) in the developmental stages of laminitis induced in horses by ingestion of black walnut heartwood extract (BWHE).

Sample Population—10 adult mixed-breed horses.

Procedures—Horses were separated into 2 groups and were euthanatized at 12 hours after placebo (water) administration (control horses) or after BWHE administration and development of Obel grade 1 laminitis. Blood samples were obtained to determine plasma PGF concentrations hourly for the first 4 hours and subsequently every 2 hours after substance administration. Laminar arteries and veins were isolated, and responses to increasing concentrations of PGF were measured before and after preincubation of blood vessels with prostanoid and thromboxane receptor antagonists SQ 29,548, SC-19220, and AH 6809.

Results—Plasma PGF concentrations increased in horses given BWHE; the WBC count decreased concurrently. In control horses, PGF was a potent contractile agonist for laminar veins but not for laminar arteries. In horses given BWHE, PGF was similarly selective for laminar veins; however, the magnitude of PGF-induced venoconstriction was less than that in control horses. After preincubation with SQ 29,548, laminar veins from control horses responded to PGF with a small degree of dilation, whereas laminar veins from horses given BWHE did not.

Conclusions and Clinical Relevance—PGF may play a role in the inflammatory and vascular dysfunction associated with the prodromal stages of laminitis. Prostanoids such as PGF may be viable targets for the prevention of acute laminitis in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare measurements of myeloperoxidase (MPO) in plasma, laminar tissues, and skin obtained from control horses and horses given black walnut heartwood extract (BWHE).

Animals—22 healthy 5- to 15-year-old horses.

Procedures—Horses were randomly assigned to 4 groups as follows: a control group given water (n = 5) and 3 experimental groups given BWHE (17) via nasogastric intubation. Experimental groups consisted of 5, 6, and 6 horses that received BWHE and were euthanatized at 1.5, 3, and 12 hours after intubation, respectively. Control horses were euthanatized at 12 hours after intubation. Plasma samples were obtained hourly for all horses. Laminar tissue and skin from the middle region of the neck were harvested at the time of euthanasia. Plasma and tissue MPO concentrations were determined via an ELISA; tissue MPO activity was measured by use of specific immunologic extraction followed by enzymatic detection.

Results—Tissues and plasma of horses receiving BWHE contained significantly higher concentrations of MPO beginning at hour 3. Laminar tissue and skin from horses in experimental groups contained significantly higher MPO activity than tissues from control horses. Concentrations and activities of MPO in skin and laminar tissues were similar over time.

Conclusions and Clinical Relevance—In horses, BWHE administration causes increases in MPO concentration and activity in laminar tissue and skin and the time of increased MPO concentration correlates with emigration of WBCs from the vasculature. These findings support the hypothesis that activation of peripheral WBCs is an early step in the pathogenesis of acute laminitis.

Full access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To investigate risk factors for the development of pasture- and endocrinopathy-associated laminitis (PEAL) in horses and ponies in North America.

DESIGN Case-control study.

ANIMALS 199 horses with incident cases of PEAL and 351 horses from 2 control populations (healthy horses [n = 198] and horses with lameness not caused by laminitis [153]) that were evaluated in North America between January 2012 and December 2015 by veterinarian members of the American Association of Equine Practitioners.

PROCEDURES North American members of the American Association of Equine Practitioners were contacted to participate in the study, and participating veterinarians provided historical data on incident cases of PEAL, each matched with a healthy control and a lameness control. Conditional logistic regression analysis was used to compare data on PEAL-affected horses with data on horses from each set of controls.

RESULTS Horses with an obese body condition (ie, body condition score ≥ 7), generalized or regional adiposity (alone or in combination), preexisting endocrinopathy, or recent (within 30 days) glucocorticoid administration had increased odds of developing PEAL, compared with horses that did not have these findings.

CONCLUSIONS AND CLINICAL RELEVANCE The present study identified several risk factors for PEAL that may assist not only in managing and preventing this form of laminitis, but also in guiding future research into its pathogenesis.

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To describe a single-portal cranial arthroscopic approach to the stifle joint in horses and to determine the clinical outcome in horses with femorotibial joint disease in which this approach was used.

Design—Retrospective study.

Animals—23 adult horses.

Procedure—Medical records were reviewed to obtain information on clinical outcome in horses in which the single-portal cranial arthroscopic approach was used.

Results—Twenty-nine stifle joints of 23 horses were examined arthroscopically, using the described approach. Subchondral bone cysts were treated in 19 medial femoral condyles of 12 horses. Unilateral cruciate ligament desmitis (4 horses), meniscal tearing (3), or both (2) were identified in 9 horses. Evidence of degenerative joint disease without cystic lesions or soft tissue trauma was found in 2 horses. Information on clinical outcome was obtained for 21 of 23 horses. A successful outcome was obtained in 15 of 21 horses and was defined as return to sound performance at a degree equal to or better than that prior to injury and lameness. Eight of 12 horses treated for medial femoral condylar cysts had a successful outcome. Four show horses treated for cruciate ligament lesions alone successfully returned to showing activity. None of the 3 horses with meniscal tearing were able to perform successfully.

Conclusions and Clinical Relevance—The femorotibial joint was evaluated through a single-portal cranial arthroscopic approach, using the femoropatellar joint as the point of access. This approach was easy to perform, allowed controlled access to the femorotibial joint, avoided accidental damage to articular structures, and required fewer access portals. (J Am Vet Med Assoc 2002;220: 1046–1052)

Full access
in Journal of the American Veterinary Medical Association