Development of a three-dimensional computer model of the equine heart using a polyurethane casting technique and in vivo contrast-enhanced computed tomography.

INTRODUCTION/OBJECTIVES: Insight into the three-dimensional (3D) anatomy of the equine heart is essential in veterinary education and to develop minimally invasive intracardiac procedures. The aim was to create a 3D computer model simulating the in vivo anatomy of the adult equine heart. ANIMALS: Ten horses and five ponies. MATERIALS AND METHODS: Ten horses, euthanized for non-cardiovascular reasons, were used for in situ cardiac casting with polyurethane foam and subsequent computed tomography (CT) of the excised heart. In five anaesthetized ponies, a contrast-enhanced electrocardiogram-gated CT protocol was optimized to image the entire heart. Dedicated image processing software was used to create 3D models of all CT scans derived from both methods. Resulting models were compared regarding relative proportions, detail and ease of segmentation. RESULTS: The casting protocol produced high detail, but compliant structures such as the pulmonary trunk were disproportionally expanded by the foam. Optimization of the contrast-enhanced CT protocol, especially adding a delayed phase for visualization of the cardiac veins, resulted in sufficiently detailed CT images to create an anatomically correct 3D model of the pony heart. Rescaling was needed to obtain a horse-sized model. CONCLUSIONS: Three-dimensional computer models based on contrast-enhanced CT images appeared superior to those based on casted hearts to represent the in vivo situation and are preferred to obtain an anatomically correct heart model useful for education, client communication and research purposes. Scaling was, however, necessary to obtain an approximation of an adult horse heart as cardiac CT imaging is restricted by thoracic size.

Endocardial electro-anatomic mapping in healthy horses: Normal sinus impulse propagation in the left and right atrium and the ventricles.

Understanding the depolarisation pattern of the equine heart under normal physiologic conditions, and its relationship to the surface electrocardiogram (ECG), is of uppermost importance before any further research can be done about the pathophysiology of complex arrhythmias. In the present study, a 3D electro-anatomical mapping system was used to evaluate the qualitative and quantitative depolarisation patterns and correlation to the surface ECG of both the atrial and ventricular endocardium in seven healthy horses in sinus rhythm under general anaesthesia. Bipolar activation maps of the endocardium were analysed. The first atrial activation was located at the height of the terminal crest. Only one interatrial conduction pathway was recognised. The first and second P wave deflections represent the right and left atrial depolarisation, respectively. Bundle of His electrograms could be recorded in 5/7 horses. Left ventricular activation started at the mid septum and right ventricular activation started apically from the supraventricular crest. This was followed by separate depolarisations at the height of the mid free wall. Further ventricular depolarisation occurred in an explosive pattern. Electrically active tissue could be found in all pulmonary veins. In contrast to findings of previous studies, all parts of the ventricular depolarisation contributed to the surface ECG QRS complex. This study provides a reference for the normal sinus impulse endocardial propagation pattern and for conduction velocities in equine atria and ventricles.

Percutaneous transcatheter closure of an aorto-cardiac fistula in a six-year-old Warmblood mare with atrial fibrillation.

This report describes a rare case of an aorto-cardiac fistula in a six-year-old French Warmblood mare presented with atrial fibrillation, decreased performance, ventral oedema, bounding arterial pulsation and pathological jugular venous pulse. A 2.7-cm-diameter fistula connected the right aortic sinus of Valsalva to the right atrium. Atrial fibrillation was likely due to volume overload of the right heart due to left-to-right shunting. The horse was treated by percutaneous transcatheter closure of the fistula delivered under general anaesthesia using a transarterial approach. The operation was initially successful, and clinical signs of congestive heart failure improved immediately. However, the device dislodged six days after procedure, and the general condition of the horse deteriorated quickly. A second closure attempt to deliver the occluder using a transvenous approach in the standing horse failed, and the horse was eventually euthanized. Procedural aspects and several possible risk factors for device dislodgement are discussed.

Foramen epiploicum mesh closure (FEMC) through a ventral midline laparotomy.

BACKGROUND: Preventive laparoscopic closure of the epiploic foramen (EF) has previously been described, but methods for EF closure during laparotomy for treatment of colic are lacking. OBJECTIVES: To describe the foramen epiploicum mesh closure (FEMC) technique through a ventral midline laparotomy in horses under general anaesthesia and its outcome. STUDY DESIGN: Terminal surgical experiment and in vivo study. METHODS: In a pilot study, a standard ventral midline laparotomy was performed under general anaesthesia in 10 experimental horses and a three-dimensional expandable diabolo-shaped mesh construct was manually introduced through the EF into the omental vestibule. The laparotomy incision was routinely closed after which the horses were subjected to euthanasia. Subsequently, the cadavers were extensively manipulated and finally mesh position was verified during necropsy. Thereafter, a ventral midline laparotomy, with simulation of abdominal manipulations during colic surgery was performed on six experimental horses. A three-dimensional expandable diabolo-shaped mesh with a radiological marker was introduced as in the pilot study. Clinical and laboratory parameters were recorded during the post-operative period. Four weeks after the intervention, abdominal radiography and laparoscopy were performed in all six horses. RESULTS: Insertion of all 16 diabolo-shaped mesh constructs during laparotomy was uneventful. The 10 mesh constructs of the pilot study were positioned correctly at necropsy. No post-operative clinical or laboratory parameter alterations were noticed in the other six horses, apart from a transient leucocytosis and an increase in serum amyloid A. Abdominal radiography at 4 weeks revealed consistent positioning of the mesh marker. Laparoscopy confirmed that all six EFs were closed, without intestinal adhesions. MAIN LIMITATIONS: Mesh insertion in clinical cases and during clean contaminated surgery was not investigated. CONCLUSION: The FEMC technique via laparotomy provides a fast, simple and reliable procedure to obliterate the EF and may be useful during EFE surgery to prevent recurrence of the disease, avoiding a subsequent laparoscopic procedure.

Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A systematic review (2005-2017).

The objective of this review was to perform a literature compilation of all the equine publications that used dexmedetomidine as the first article on this topic was published, in 2005. We also aimed to answer the question whether the use of dexmedetomidine can currently be justified. For that, we compiled information from databases, such as PubMed, Google Scholar and Web of Science and the proceedings of the last veterinary anaesthesiology meetings. Dexmedetomidine is an attractive drug to be used in horses, mainly due to its pharmacokinetic profile and pharmacodynamics that favour its use as intravenous constant rate infusion (CRI). Nowadays, its clinical use is popular for sedation in prolonged standing procedures and during partial intravenous anaesthesia (PIVA) and total intravenous anaesthesia (TIVA). However, legal requirements for its use should be taken into account.

The Influence of the Size, Age and Sex on the Computed Tomographic Measured Size of the Pituitary Gland in Normal Horses.

The objective of this study was to examine the influence of the size, age and sex of the horse on the size of the pituitary gland and determine the possibility of using the pituitary gland height-to-brain area ratio (P:B ratio) to allow comparison of different sized and aged horses. Thirty-two horses without pituitary pars inter-media dysfunction that underwent a contrast-enhanced computed tomographic (CT) examination were included in a cross-sectional study. On the CT images, the pituitary gland height was measured and the P:B ratio was calculated. These measurements were correlated to the size, age and sex of the horses. The pituitary gland height was significantly associated with the size (P < 0.001) and the age (P < 0.001), but not with the sex (P = 0.40), of the horses. No significant association was found between the P:B ratio and the size (P = 0.25), the age (P = 0.06) or the sex (P = 0.25) of the horses. In conclusion, the pituitary gland size varies between different sized and aged horses. The use of the P:B ratio is a valuable metric for making comparisons between the pituitary glands of these horses.

The effects of intravenous lidocaine before propofol induction in premedicated dogs.

OBJECTIVE: The effects of lidocaine, administered before induction of anaesthesia with propofol, on arterial blood pressure, heart rate, respiratory rate, cough reflex, ease of intubation, extrapyramidal signs and required dose of propofol in healthy premedicated dogs were evaluated. METHODS: Twenty-four client-owned dogs were premedicated intramuscularly with 1 µg/kg dexmedetomidine and 0·2 mg/kg methadone, and randomly allocated to receive 2 mg/kg lidocaine (group L) or saline (group P) 120 seconds before induction of anaesthesia with propofol. Heart rate, non-invasive arterial blood pressure and respiratory rate were assessed at pre-established intervals. Quality of intubation, cough reflex and the occurrence of adverse effects were scored according to predefined scales. The total amount of propofol administered was also recorded. RESULTS: Cardiovascular and respiratory variables changed over time but were not significantly different between treatments. No significant differences between groups were found for the incidence of coughing, quality of intubation, adverse effects and propofol intubation dose. CLINICAL SIGNIFICANCE: Intravenous administration of lidocaine 2 mg/kg before propofol induction was not associated with significant cardiovascular and respiratory benefits compared to standard induction and did not result in a propofol dose-sparing effect or improvement of the quality of intubation in dogs premedicated with dexmedetomidine and methadone.

lesion development in a new intestinal loop model indicates the involvement of a shared Clostridium perfringens virulence factor in haemorrhagic enteritis in calves.

Clostridium perfringens-associated enterotoxaemia is a fatal disease in fast growing suckler and veal calves. An intestinal loop model was developed to study the pathogenesis of the disease. Loops were injected with stationary and logarithmic C. perfringens cultures with or without, a milk protein-based commercial milk replacer for calves. Isolates tested were from cases of bovine enterotoxaemia and from calves without signs of enterotoxaemia, in addition to netB-positive and -negative isolates from poultry, a type C isolate from piglets and the human isolate JIR325. All isolates induced necrohaemorrhagic lesions in combination with milk replacer, while all control loops (i.e. medium plus milk replacer) remained histologically normal. In addition, time-course experiments were conducted using an isolate from an outbreak of bovine enterotoxaemia. Histological examination showed that the earliest lesion was congestion of the capillaries, starting within 30 min of inoculation. Haemorrhage and mucosal necrosis began at the tips of the villi 3-4 h after bacterial inoculation. These lesions are similar to those observed in natural cases of bovine enterotoxaemia. Therefore, in this model, necrohaemorrhagic lesions can be induced by C. perfringens isolates from diverse origins, suggesting that the lesions may be caused by one or more virulence factors that are shared by these isolates.

Effects of a constant-rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies.

REASONS FOR PERFORMING STUDY: Dexmedetomidine has been administered in the equine as a constant-rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. OBJECTIVES: To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. METHODS: Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10-T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant-current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05). RESULTS: An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%). CONCLUSIONS AND POTENTIAL RELEVANCE: A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane.

Expression of P-glycoprotein in the intestinal epithelium of dogs with lymphoplasmacytic enteritis.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory disease of the stomach, the small intestine and/or the large intestine. Loss of integrity of the intestinal barrier may be an important factor in the pathogenesis of IBD. In dogs, lymphoplasmacytic enteritis (LPE) is one of the recognized forms of IBD. P-glycoprotein (P-gp) is a membrane-bound efflux pump constituting an important component of the intestinal barrier. Changes in P-gp expression at the level of the intestinal barrier may be important in the pathogenesis of canine LPE, as this may lead to variable protection against xenobiotics and bacterial products in the intestine. The aim of the present study was to evaluate the expression of epithelial P-gp in the intestine in dogs with LPE compared with disease-free animals. Formalin-fixed intestinal biopsy samples from 57 dogs with histopathological evidence of LPE were immunolabelled with anti-P-gp antibodies (C494 and C219). Endoscopic biopsy samples of the duodenum and colon from 16 healthy beagles were used as controls. None of the control dogs had P-gp expression in the apical membrane of duodenal enterocytes, but all had P-gp labelling at the colonic epithelial surface. Twenty out of 57 dogs with LPE had P-gp expression at the apical surface membrane of villus epithelial cells in the duodenum, jejunum and/or ileum. Six out of 16 colonic samples from dogs with LPE had decreased P-gp expression at the epithelial surface compared with controls. It is unclear whether these changes in P-gp expression in dogs with LPE are a cause or a consequence of the inflammation. The observed changes could affect bioavailability of therapeutic drugs used in LPE.

The influence of modulation of P-glycoprotein and /or cytochrome P450 3A on the pharmacokinetics and pharmacodynamics of orally administered morphine in dogs.

The influence of pretreatment with ketoconazole [cytochrome P450 3A (CYP3A) + P-glycoprotein (P-gp) inhibitor], elacridar (selective P-gp inhibitor) and rifampicin (CYP3A + P-gp inducer) on oral morphine pharmacokinetics and pharmacodynamics was investigated in experimental dogs. Seven beagles were used in a four-way crossover design. Morphine hydrochloride was administered orally (2.5 mg/kg) alone (control group CON) or after pretreatment with ketoconazole (group KETO), elacridar (group ELA) or rifampicin (group RIF). Morphine plasma concentrations were analysed by liquid chromatography-tandem mass spectrometry. Sedation scores (none, mild, moderate or severe) were evaluated subjectively. Dogs were significantly (P < 0.05) more sedated after ketoconazole pretreatment. There were no significant differences between group CON and the other pretreatment groups in pharmacokinetic parameters taking both sexes into account. Sex differences were apparent in some pharmacokinetic parameters of morphine. The area under the plasma concentration time curve (AUC(0-∞) ) was significantly higher, and the total body clearance was significantly lower in male compared to female dogs in all treatment groups. Ketoconazole, rifampicin and elacridar pretreatment had no significant effects on morphine pharmacokinetics, although dogs in the ketoconazole group showed higher sedation scores.

Influence of administration route on the biotransformation of amoxicillin in the pig.

A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine-2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration (P > 0.05). After p.o. administration, the half-life of elimination (t(1/2(el))) for AMA is at least two or three times the t(1/2(el)) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open beta-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis.

Transsplenic portal catheterization combined with a jugular double-lumen catheter for pharmacokinetic and presystemic metabolization studies in pigs.

The reliability of a silicone double-lumen catheter implanted into the external jugular vein and tunnelled towards the neck region was investigated in eight pigs. Surgery was uneventful without interference with the normal homoeostasis during 8 days. After injection of amoxicillin/clavulanic acid through the distal port of the catheter, analysis of drug components in the simultaneous blood samples obtained by the proximal port and a Venoject system were comparable in one pig. Histological control of the catheterized jugular veins pointed to an acceptable tissue reaction while bacteriological examination of the tip of the catheters was negative in only three animals. A moulding of the intestinal veins was made in a pig cadaver to determine the optimal length of insertion of a silicone portal catheter from the splenic vein towards the portal vein. Surgery was straightforward in four pigs whereby the catheter was exteriorized towards the back region. No complications were encountered during and after surgery for 9 days. The technique of a double-lumen catheter placed into the jugular vein and a transsplenic portal catheter is a useful tool for the study of the pharmacokinetics and also the first-pass effect of drugs in experimental pigs.

Cardiorespiratory effects of enoximone in anaesthetised colic horses.

REASONS FOR PERFORMING STUDY: No studies have been reported on the effects of enoximone in anaesthetised colic horses. OBJECTIVE: To examine whether enoximone improves cardiovascular function and reduces dobutamine requirement in anaesthetised colic horses. METHODS: Forty-eight mature colic horses were enrolled in this prospective, randomised clinical trial. After sedation (xylazine 0.7 mg/kg bwt) and induction (midazolam 0.06 mg/kg bwt, ketamine 2.2 mg/kg bwt), anaesthesia was maintained with isoflurane in oxygen and a lidocaine constant rate infusion (15 mg/kg bwt, 2 mg/kg/h). Horses were ventilated (PaCO2 < 8.00 kPa). If hypotension occurred, dobutamine and/or colloids were administered. Ten minutes after skin incision, horses randomly received an i.v. bolus of enoximone (0.5 mg/kg bwt) or saline. Monitoring included respiratory and arterial blood gases, heart rate (HR), arterial pressure and cardiac index (CI). Systemic vascular resistance (SVR), stroke index (SI) and oxygen delivery index (DO2I) were calculated. For each variable, changes between baseline and T10 within each treatment group and/or colic type (small intestines, large intestines or mixed) were analysed and compared between treatments in a fixed effects model. Differences between treatments until T30 were investigated using a mixed model (a = 0.05). RESULTS: Ten minutes after enoximone treatment, CI (P = 0.0010), HR (P = 0.0033) and DO2I (P = 0.0007) were higher and SVR lower (P = 0.0043) than at baseline. The changes in CI, HR and SVR were significantly different from those after saline treatment. During the first 30 min after enoximone treatment, DO2I (P = 0.0224) and HR (P = 0.0003) were higher than after saline administration. Because the difference in HR between treatments was much clearer in large intestine colic cases, an interaction was detected between treatment and colic type in both analyses (P = 0.0076 and 0.0038, respectively). CONCLUSIONS: Enoximone produced significant, but short lasting, cardiovascular effects in colic horses. POTENTIAL RELEVANCE: Enoximone's cardiovascular effects in colic horses were of shorter duration than in healthy ponies.

Laryngeal rhinosporidiosis in a Belgian warmblood horse.

In Belgium and even in northern Europe Rhinosporidium seeberi has not been reported in autochtonous people or animals. In this paper, the authors report the first observation of laryngeal masses, caused by Rhinosporidium seeberi, in a Belgian Warmblood horse. Moreover, laryngeal rhinosporidiosis is extremely rare since this localisation is only described in four human cases.

Disposition and oral bioavailability of amoxicillin and clavulanic acid in pigs.

The pharmacokinetic properties of amoxicillin and clavulanic acid were studied in healthy, fasted pigs after single intravenous (i.v.) and oral (p.o.) dosage of 20 mg/kg of amoxicillin and 5 mg/kg of clavulanic acid. The plasma concentrations of the drugs were determined by validated high-performance liquid chromatographic methods and the pharmacokinetic parameters were calculated by compartmental and noncompartmental analyses. After i.v. administration of the two drugs, plasma concentration-time curves were best described by a three-compartmental open model for amoxicillin and a two-compartmental open model for clavulanic acid. Amoxicillin (with a t(1/2 gamma) = 1.03 h and a clearance of 0.58 L/h.kg) and clavulanic acid (with a t(1/2 beta) of 0.74 h and a clearance of 0.41 L/h.kg) were both rapidly eliminated from plasma. Both drugs had apparently the same volume of distribution of 0.34 L/kg. After p.o. administration of the two drugs, a noncompartmental model was used. Elimination half-lives of amoxicillin and clavulanic acid were not significantly different, i.e. 0.73 and 0.67 h respectively. The mean maximal plasma concentrations of amoxicillin and clavulanic acid were 3.14 and 2.42 mg/L, and these were reached after 1.19 and 0.88 h respectively. The mean p.o. bioavailability was found to be 22.8% for amoxicillin and 44.7% for clavulanic acid.

Refined anaesthesia for implantation of engineered experimental aortic valves in the pulmonary artery using a right heart bypass in sheep.

The feasibility of an anaesthetic protocol developed for surgery during right heart bypass in sheep is reported. Seven female Suffolk sheep, weighing 25-35 kg, were selected for the study. Premedication consisted of midazolam and methadone (both 0.1 mg kg(-1) intravenously). Anaesthesia was induced with propofol (2-4 mg kg(-1)) and maintained with isoflurane in oxygen and continuous rate infusions of propofol (5-7 mg kg(-1 )h(-1)) and fentanyl (5 microg kg(-1) bolus, 5 microg kg(-1) h(-1)). Cisatracurium (0.2 mg kg(-1)) provided muscle relaxation. A standard roller pump was used for the extracorporeal circulation. Drugs administered to maintain blood pressure and heart rate within acceptable levels included phenylephrine (3-4 microg kg(-1)), ephedrine (0.1-0.2 mg kg(-1)), nitroglycerine (50-150 microg kg(-1) h(-1)) and metoprolol succinate (30-80 microg kg(-1)). Electrolytes were infused as needed. Postoperative analgesia was provided by an intercostal block (15 mL 0.5% bupivacaine + epinephrine), carprofen (4 mg kg(-1)) and an opioid (methadone 0.1 mg kg(-1) or buprenorphine 0.01 mg kg(-1)). One sheep became hypoxic during the bypass (PaO(2) 47.7 mmHg). Irregularities of the electrocardiogram were observed during manipulation of the heart in all animals. During the initial phase of the bypass, blood pressure decreased in all sheep, accompanied by dilatation of the heart and large intrathoracic veins in five sheep. With appropriate treatment, blood pressure was restored and easily maintained until the end of the bypass. Weaning from the bypass, using an infusion of nitrates, was smooth. One sheep required a blood transfusion because of severe blood loss and another sheep died postoperatively from respiratory complications. Minor irregularities of the electrocardiogram observed during manipulation of the heart were not life threatening and required no treatment. Decreases in blood pressure at the beginning of the bypass can be expected and require treatment. Nitrates are useful in avoiding volume overload during weaning. The anaesthetic protocol is acceptable for surgery under right heart bypass in sheep.

Surgical repair of a tibial fracture in a Belgian Landrace pig.

This paper reports the surgical treatment of a tibial fracture in a castrated adult male Belgian Landrace pig of 180 kg. The fracture was repaired using an intramedullary Steinmann pin, combined with cerclage wire and external transfixation. In contrast to other animal species, the fracture repair in the pig was hindered by the short and curved bones, the thick subcutaneous fat layer and the pronounced musculature. Postoperatively, the pig developed an osteomyelitis of the tibia due to pin tract contamination. Despite this complication, the fracture healed acceptably when all fixation material was removed two months after surgery. The infection resolved quickly and a satisfactory clinical result was obtained.