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Background: In the horse, effects of cardiovascular-active drugs on local perfusion of the gastrointestinal tract are poorly understood., Objectives: To determine the effect of drugs commonly used to support blood pressure, on local intestinal blood flow and tissue oxygenation under isoflurane anaesthesia., Study Design: In vivo randomised crossover experiment., Methods: Ten horses were anaesthetised with isoflurane. After 90 min of equilibration three doses (μg/kg bwt/min) of dobutamine (DOB 0.5/1/3), dopamine (DA 1/2/5), noradrenaline (NA 0.1/0.2/0.5) and phenylephrine (PHE 0.5/1/3) were infused for 15 min, in a randomised order, with a 45 min washout-period. Blood flow and tissue oxygenation (sO 2 ) of jejunum, colon and stomach were measured using white light remission spectrophotometry and laser doppler flowmetry; heart rate (HR), mean arterial blood pressure (MAP), cardiac output (CO) were measured and systemic vascular resistance (SVR) calculated., Results: Compared to baseline high dose dobutamine significantly increased CO, HR, MAP (P<0.001) and blood flow to the jejunum (+47 ± 26%, P = 0.001) and colon (+29 ± 15%, P<0.001) (mean ± s.d.). Dopamine (DA5) increased CO but decreased colonic blood flow (-39 ± 21% from baseline, P<0.001), as well as SVR and MAP compared to baseline (P<0.001). Noradrenaline had no significant influence on intestinal perfusion, but increased MAP and SVR from baseline (P<0.001). Phenylephrine (PHE3) caused a significant decrease in blood flow and sO 2 , most profoundly at the colon compared to baseline (flow -44 ± 21%; sO 2 -16 ± 3%, P<0.001), while MAP and SVR increased and CO and HR decreased (P<0.001)., Main Limitations: The measurement technique only allows for flow measurements in arbitrary units, which can limit comparability to other techniques., Conclusion: At the investigated doses dobutamine improved systemic and peripheral haemodynamics, while dopamine decreased MAP and peripheral perfusion. Noradrenaline increased MAP and SVR while peripheral blood flow was maintained, phenylephrine increased MAP, but reduced both local and systemic perfusion., (© 2017 EVJ Ltd.)

Reasons for Performing Study: High airway pressures, necessary to keep equine lungs open, can have a detrimental impact on central and peripheral perfusion., Objective: The aim of this study was to assess the effects of stepwise increasing airway pressure recruitment on central and intestinal perfusion and oxygenation during isoflurane anaesthesia in horses., Study Design: In vivo experimental study., Methods: Ten anaesthetised horses were ventilated using intermittent positive pressure ventilation immediately after induction. After 90 min, end-expiratory pressure (PEEP) was increased by steps of 5 cmH 2 O every 10 min up to a PEEP of 30 cmH 2 O and decreased back to zero maintaining a constant airway pressure difference of 20 cmH 2 O. Mean arterial blood pressure (MAP), heart rate, central venous pressure, pulmonary artery pressure, expiratory isoflurane concentration and cardiac output (thermodilution method) were measured. Cardiac index (CI) was calculated. Arterial blood gases were taken to measure arterial partial oxygen pressure (PaO 2 ) and calculate arterial oxygen saturation (SaO 2 ). Intestinal microperfusion and oxygenation were measured by laser Doppler flowmetry and white-light spectrophotometry. After ventral median laparotomy, a probe was placed on the stomach, jejunum and pelvic flexion of the colon. An ANOVA for repeated measurements and Tukey's post hoc test were used for statistical analysis (α = 5%)., Results: Recruitment of the lungs resulted in a significant increase in PaO 2 from 201 ± 58 mmHg (baseline) to a maximum of 495 ± 75 mmHg. The CI and MAP decreased continuously with increasing airway pressures. When CI and MAP were 37 ± 9 ml/kg/min and 52 ± 8 mmHg (at PEEP of 25 cmH 2 O), respectively, a sudden decrease in intestinal perfusion followed by a delayed decrease in oxygenation occurred., Conclusions: There was linear correlation between airway pressures and CI and MAP but not between central and gastrointestinal perfusion. Despite improvement of arterial oxygenation the decrease in CI and, therefore, in oxygen delivery PEEP resulted in a decrease in gastrointestinal oxygenation., (© 2016 EVJ Ltd.)

Reasons for Performing Study: Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin., Objectives: To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses., Methods: Two clinically healthy horses received a single i.v. bolus of 0.4 mg/kg bwt r-hirudin and 6 clinically healthy horses received the same dose subcutaneously (subcut.) q. 12 h for 3 days. Coagulation times and r-hirudin plasma concentration were determined over 720 mins and 3 days after i.v. and subcut. administration, respectively., Results: In all horses, treatment with r-hirudin was not associated with systemic or local side effects. After i.v. injection, the 2 horses showed an elimination half-life of 58 and 80 mins, respectively. After subcut. administration, maximum plasma concentration of r-hirudin occurred at 128 +/- 55 mins and declined with a terminal half-life of 561 +/- 364 mins. Maximum response of activated partial thromboplastin time (aPTT) occurred 1.5 h after administration of r-hirudin. A prolongation of 1.9 +/- 0.2 times the pretreatment value was noted., Conclusions: Pharmacokinetics of r-hirudin in healthy horses were similar to those in man and other animal species., Potential Relevance: The results of this study indicate that r-hirudin can be used in horses, but further studies should be performed in order to prove its effectiveness in diseased horses.

Twenty-four Quarter Horse and Quarter Horse-cross yearlings were experimentally infected with influenza A virus (Influenza A/equine/Saskatoon/90 [H3N8]) by nebulisation. In a double blind controlled trial the horses were randomly assigned to 3 groups of 8 animals. Group 1 received a placebo, (carrier syrup), Group 2 the labelled dose and Group 3 twice the labelled dose of clenbuterol hydrochloride. All treatments were given per os b.i.d. for 10 days and started on the day of infection. The horses were monitored for clinical signs of influenza infection for 14 days. Bronchoalveolar lavages were performed 4 days prior to, and 5 and 13 days after infection. Cell counts and concentrations of prostaglandin E2 and prostaglandin F2alpha in the lavage fluid were determined. Blood samples for haematology and serology were taken 4 days before, on the day of infection, 5, 9 and 13 days after infection. All horses experienced a typical influenza infection with fever, coughing and secondary bacterial infections with mainly Actinobacillus spp. and Streptococcus spp. There was no statistically or clinically significant effect of treatment with clenbuterol hydrochloride on measured clinical or laboratory parameters within 14 days of infection.