The endocardial endothelium (EE) has been shown to modulate the contraction of the subjacent myocardium. Selective damage of the EE modifies the twitch of isolated cardiac muscle in a rather unique manner: an immediate and irreversible decrease in twitch duration, i.e., an earlier start of isometric relaxation which is accompanied by a decline in peak twitch tension. This phenomenon has been confirmed in different species and in vivo conditions where impairment of EE caused abbreviation of left ventricular pressure-time curve due to earlier pressure fall. An intact EE enhances myocardial performance by increasing myofilament Ca++ sensitivity. Several substances including atrial natriuretic peptides, α 1-agonists, vasopressin, serotonin and aggregating platelets exert their inotropic action on the myocardium through the EE. The mechanisms of EE modulation of myocardial performance are still under investigation and the possibilities include release of various chemical messengers (NO, prostaglandins and endothelin-1) by the EE and/or the role of EE as a physico-chemical barrier. The EE may play an important role in the compensatory mechanisms in the pathophysiology of various cardiac conditions because of its direct modulation of myocardial performance, as mediator of inotropic actions of a number of plasma hormones and by secretion of growth factors.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used frequently in avian medicine for their antipyretic, analgesic, and anti-inflammatory properties during surgery and for diseases that cause tissue damage and inflammation. NSAIDs inhibit cyclooxygenase (COX) enzymes, which are responsible for the induction of pyresis, pain, and inflammation. In our study, a lipopolysaccharide-induced (LPS) pyresis model was optimized using cockatiels (Nymphicus hollandicus) as subject birds (four males/three females) and validated in two females and one male, characterized by an intravenous bolus injection of LPS (7.5 mg/kg) administered at T0 and T24 (24 hours following the first LPS injection). To demonstrate the feasibility of the model to assess pharmacodynamic (PD) parameters of different NSAIDs, mavacoxib 4 mg/kg (four males/four females), celecoxib 10 mg/kg (four males/four females) and meloxicam 1 mg/kg (four males/four females) were evaluated in the model at dosages used frequently in practice. The PD parameters (body temperature, mentation, posture, preference of location in the cage, and prostaglandin E2 [PGE2] plasma concentrations) were determined for 10 hours following the second LPS injection. At the doses evaluated, mavacoxib and celecoxib significantly reduced LPS-induced hypothermia, but had no clear effects on other clinical signs of illness. In contrast, no effect on hypothermia or clinical appearance was observed in the LPS-challenged cockatiels treated with meloxicam. All three NSAIDs were able to inhibit the increase in LPS-induced PGE2 plasma concentrations, yet the effect was most pronounced in the birds treated with meloxicam. Consequently, the presented model opens perspectives for future dose-effect PD studies to optimize analgesic protocols in cockatiels.
OBJECTIVETo compare cutaneous wound closure with mesh and 2-octyl cyanoacrylate (MOC) vs an intradermal suture pattern (ISP) in terms of time of application and biomechanical properties.SAMPLE POPULATIONExperimental study with 12 female beagle dogs.METHODSA skin incision was created from the xiphoid to the pubis as part of an ovariohysterectomy; the linea alba and subcutaneous tissue were closed routinely. Half of the skin incision was closed with MOC, and the other half was closed with an ISP. Tissue samples were collected from both sections at days 14 and 28 and tested for ultimate strength and stiffness.RESULTSClosure with MOC (72.8 ± 14.0 s) was faster than with an ISP (398.4 ± 36.4 s; P = .001). The ultimate load and stiffness increased with time for MOC (P = .005 and P = .005, respectively) and ISP (P < .001 and P < .001, respectively). On day 14, ultimate load and stiffness were greater in wounds closed with MOC compared with ISP (P = .014 and P = .02, respectively). No difference between groups was detected at day 28.CONCLUSIONCutaneous wound closure with MOC was faster and resulted in superior strength at 14 days compared with closure with an ISP in this healthy population.CLINICAL SIGNIFICANCEMesh and 2-octyl cyanoacrylate offers an attractive alternative to ISP for skin closure after celiotomy in dogs, especially if surgical/anesthesia time is a concern.
Since the implementation of several legislations to improve pediatric drug research, more pediatric clinical trials are being performed. In order to optimize these pediatric trials, adequate preclinical data are necessary, which are usually obtained by juvenile animal models. The growing piglet has been increasingly suggested as a potential animal model due to a high degree of anatomical and physiological similarities with humans. However, physiological data in pigs on the ontogeny of major organs involved in absorption, distribution, metabolism, and excretion of drugs are largely lacking. The aim of this study was to unravel the ontogeny of porcine hepatic drug metabolizing cytochrome P450 enzyme (CYP450) activities as well as protein abundances. Liver microsomes from 16 conventional pigs (8 males and 8 females) per age group: 2 days, 4 weeks, 8 weeks, and 6-7 months were prepared. Activity measurements were performed with substrates of major human CYP450 enzymes: midazolam (CYP3A), tolbutamide (CYP2C), and chlorzoxazone (CYP2E). Next, the hepatic scaling factor, microsomal protein per gram liver (MPPGL), was determined to correct for enzyme losses during the fractionation process. Finally, protein abundance was determined using proteomics and correlated with enzyme activity. No significant sex differences within each age category were observed in enzyme activity or MPPGL. The biotransformation rate of all three substrates increased with age, comparable with human maturation of CYP450 enzymes. The MPPGL decreased from birth till 8 weeks of age followed by an increase till 6-7 months of age. Significant sex differences in protein abundance were observed for CYP1A2, CYP2A19, CYP3A22, CYP4V2, CYP2C36, CYP2E_1, and CYP2E_2. Midazolam and tolbutamide are considered good substrates to evaluate porcine CYP3A/2C enzymes, respectively. However, chlorzoxazone is not advised to evaluate porcine CYP2E enzyme activity. The increase in biotransformation rate with age can be attributed to an increase in absolute amount of CYP450 proteins. Finally, developmental changes were observed regarding the involvement of specific CYP450 enzymes in the biotransformation of the different substrates.
Reasons for performing studyRight ventricular (RV) function is scarcely described in horses. ObjectivesTo establish reliable echocardiographic measurements of right heart size and function in horses. Study designDescriptive study in healthy horses. MethodsTen healthy untrained adult trotter horses underwent repeated echocardiography performed by 2 sonographers from right and left parasternal standard and nonstandard views. Nonstandard views included a right parasternal view focused on the right atrium, left parasternal long-axis pulmonary artery view, left parasternal long-axis view focused on the right ventricle including anatomical M-mode of tricuspid annular motion and left parasternal pulsed wave Doppler recording of pulmonary flow. During off-line analysis, 2 observers performed two-dimensional, M-mode, pulsed wave Doppler, tissue Doppler imaging (TDI) and two-dimensional speckle tracking (2DST) measurements of RV size and function. Acquisition and measurement variability were assessed by calculating coefficients of variation (CV) from one-way repeated measures analyses of variance. The degree of variability was classified as low (CV<15%), moderate (CV 15-25%) or high (CV>25%). ResultsMost two-dimensional and M-mode measurements of RV, right atrial and pulmonary artery size showed low variability. The two-dimensional, M-mode and pulsed wave Doppler measurements of RV function showed a low to moderate variability. Right ventricular functional measurements by 2DST showed low variability, except for segmental strain rate. Right ventricular functional measurements by TDI showed a low to high variability, with a lower variability for timing than for peak measurements and a lower variability for velocity compared with deformation measurements. ConclusionsRight heart size and function can be assessed with low variability in horses.
Behavioural tests are often used to describe dogs' responses to a variety of stimuli. However, the expressed behaviours do not always give an accurate indication of the dogs' mental state. Cardiac measures can be recorded in parallel to the behavioural test to provide additional information about arousal level. Heart rate (HR) reflects the combination of sympathetic and parasympathetic stimulation, whereas the beat-to-beat variation in heart rate (heart rate variability: HRV) provides more details about the balance between sympathetic and parasympathetic activation. In studies validating cardiac measures typically the dog's movement is controlled or the response to only one stimulus at a time is tested. In this study, the validity and reliability of cardiac measures were tested during a behavioural test at home (N = 18 shepherd dogs). HR, HRV and behaviour were recorded in six randomised subtests, in which stimuli of different emotional valences were presented (neutral, positive, negative). Positive and negative subtests differed significantly from the neutral subtests in terms of HR and behaviour (P=0.000). Compared to the neutral subtests (77.85 +/- 21.00 bpm), HR was increased (positive: 91.67 +/- 21.64 bpm; negative: 100.29 +/- 18.54 bpm), and the dogs showed more interactions with the presented stimuli (contact/avoid, approach, look), more oral behaviours and were more active (walk, stand, less lying). However, HR only significantly correlated with activity during the neutral subtest (r = 0.511, P=0.030). Hence, activity only appeared to influence HR in the absence of significant emotional stimuli, whereas the increased HR in both the positive and negative subtests reflected arousal. This is supported by the fact that stress-related behaviours and HR were similar in dogs tested a second time (test-retest reliability; N=15 dogs), despite significant differences in activity between both test moments (Z = -2.510; P= 0.009). For the HRV variables, on the other hand, no significant differences were found between subtests of different emotional valences. This was possibly caused by errors in recording, due to poor electrode conduction caused by movement of the dogs. In conclusion, this study showed that HR can be a useful measure of arousal during behavioural tests, though it did not allow for a distinction between positive and negative emotional valences. HRV appeared more difficult to record (with the Polar (R) RS800CX with Wearlink) during constant movement of the dog. (C) 2016 Elsevier B.V. All rights reserved.
Macrolide antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to be modulators of the innate immune response, irrespectively of their antimicrobial and anti-inflammatory actions. Therefore, it was our objective to evaluate whether the macrolide gamithromycin (GAM) and the NSAID ketoprofen (KETO) attenuate the acute-phase response in calves, and whether their combined administration is beneficial due to synergistic and/or additive effects. To this end, both drugs, as well as their combination, were studied in a previously developed inflammation model, i.e., the induction of an acute-phase response by an intravenous lipopolysaccharide (LPS) challenge (0.5 mu g/kg body weight). Sixteen 4-week-old Holstein-Friesian calves were randomized into 4 groups: a positive control (+CONTR) group, receiving LPS but no pharmacological treatment (n = 4) and a GAM (n = 4), a KETO (n=4) and a GAM-KETO (n = 4) group, receiving the respective drugs 1 h prior to LPS administration. Clinical scoring and blood collection were performed at regular time points until 72 h post LPS challenge. Plasma concentrations of the selected cytokines (tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)), acute-phase protein (serum amyloid A (SAA)) and prostaglandin E-2 (PGE(2)) were subsequently quantified. Pre-treatment with GAM had no effect in the inflammation model compared to the +CONTR group. KETO, on the other hand, completely inhibited depression, anorexia and fever. This remarkable influence was associated with a significant reduction of PGE(2) synthesis by KETO, while the effect on TNF-alpha, IL-6 and SAA was not straightforward. The combined administration of GAM and KETO provided no synergistic or additive effects in this model, neither clinically nor regarding the studied inflammatory mediators. In conclusion, KETO entirely inhibited PGE(2) synthesis, fever development and depression, while GAM did not exert any effect in this model. These results promote the concomitant use of an antimicrobial drug and a NSAID in the treatment of calf diseases associated with LPS, both to enhance clinical recovery and to improve animal welfare. (C) 2016 Elsevier B.V. All rights reserved.
Introduction In order to investigate the role of roe deer in the maintenance and transmission of infectious animal and human diseases in Flanders, we conducted a serologic screening in 12 hunting areas. Materials and methods Roe deer sera collected between 2008 and 2013 (n=190) were examined for antibodies against 13 infectious agents, using indirect enzyme-linked immunosorbent assay, virus neutralisation, immunofluorescence, or microagglutination test, depending on the agent. Results and discussion High numbers of seropositives were found for Anaplasma phagocytophilum (45.8%), Toxoplasma gondii (43.2%) and Schmallenberg virus (27.9%), the latter with a distinct temporal distribution pattern following the outbreak in domestic ruminants. Lower antibody prevalence was found for Chlamydia abortus (6.7%), tick-borne encephalitis virus (5.1%), Neospora caninum (4.8%), and Mycobacterium avium subsp paratuberculosis (4.1%). The lowest prevalences were found for Leptospira (1.7%), bovine viral diarrhoea virus 1 (1.3%), and Coxiella burnetii (1.2%). No antibodies were found against Brucella sp., bovine herpesvirus 1, and bluetongue virus. A significant difference in seroprevalence between ages (higher in adults >1 year) was found for N. caninum. Four doubtful reacting sera accounted for a significant difference in seroprevalence between sexes for C. abortus (higher in females). Conclusions Despite the more intensive landscape use in Flanders, the results are consistent with other European studies. Apart from maintaining C. abortus and MAP, roe deer do not seem to play an important role in the epidemiology of the examined zoonotic and domestic animal pathogens. Nevertheless, their meaning as sentinels should not be neglected in the absence of other wild cervid species.
Background Atrial fibrillation ( AF ) cycle length ( CL ) and atrial size have been used in humans to characterize electrical and structural remodeling to predict outcome of cardioversion of AF and risk for AF recurrence ( rAF ). Hypothesis Atrial fibrillation cycle length can be determined in horses with AF , and AFCL and atrial size are related to risk for rAF . Animals Eighteen horses with naturally occurring AF that were successfully converted to sinus rhythm ( SR ) by transvenous electrical cardioversion ( TVEC ). Methods Prospective study. Horses with severe valvular regurgitation, left atrial enlargement, or that required sedation for catheter placement were excluded. In all horses intra‐atrial electrograms were recorded and estimated AF duration and echocardiographic parameters were determined before TVEC . The follow‐up time was 1 year after TVEC . Results Atrial fibrillation cycle length could be determined in all horses. The AFCL and the shortest 5th percentile (p5) AFCL in horses with rAF (n = 6 or 33%) were (mean ± SD) 157 ± 28 and 134 ± 24 milliseconds, respectively, and in those maintaining SR (n = 12 or 67%) 166 ± 13 and 141 ± 13 milliseconds, respectively. Significant parameters to predict rAF were (1) the ratios of the p5 AFCL to the left atrium ( LA ) sizes corrected to the size of aorta ( AO ) and (2) LA sizes corrected to the size of AO . Conclusions and Clinical Importance Before TVEC , assessment of LA size and atrial electrophysiologic characteristics might help to identify horses at increased risk for AF recurrence.
REASONS FOR PERFORMING STUDY:Studies on the use of atrial natriuretic peptide (ANP) as a biomarker for left atrial dilatation in horses have produced variable results. Few have been performed, and the results may have been influenced by ANP instability, differences in sampling protocol and changes in the assay over time. N-Terminal proANP (NT-proANP) is a more stable molecule and might be a good alternative for clinical use. OBJECTIVES:To compare ANP and NT-proANP in terms of the detection of left atrial dilatation and to determine the influence of sample storage at temperatures of -80 and -20°C. STUDY DESIGN:Prospective clinical study. METHODS:Atrial natriuretic peptide and NT-proANP concentrations were compared between healthy horses (Group 1, n = 20), horses with mitral valve regurgitation and a normal atrial size (Group 2, n = 11) and horses with mitral valve regurgitation associated with left atrial dilatation (Group 3, n = 16). The ANP concentration was measured with an equine enzyme-linked immunosorbent assay and the NT-proANP concentration with an enzyme-linked immunosorbent assay developed for use in human patients. Samples were stored at -20 and -80°C and analysed within 7 months. RESULTS:The NT-proANP concentrations were not significantly different between the groups. Horses in Group 3 had a significantly higher ANP concentration (median 366 pg/ml; interquartile range [IQR] 74-2000 pg/ml) compared with horses in Group 1 (median 31 pg/ml; IQR 31-333 pg/ml) or Group 2 (median 31 pg/ml; IQR 31-1152 pg/ml; P = 0.02). The ANP cut-off value for detection of left atrial dilatation was 52 pg/ml (sensitivity 81%; specificity 84%) for sample storage at -80°C, and 44 pg/ml (sensitivity 69%; specificity 84%) for storage at -20°C. A larger decrease in ANP (45 ± 126 pg/ml) than in NT-proANP (10 ± 31 pg/ml) was found associated with sample storage at -20 instead of -80°C. CONCLUSIONS:Atrial natriuretic peptide, but not NT-proANP, can be used to detect left atrial dilatation in horses. Atrial natriuretic peptide is less stable than NT-proANP when samples are stored at -20°C. Atrial natriuretic peptide is a more suitable biomarker of left atrial dilatation in horses than NT-proANP.
Cardiac troponin I (cTnI) is a marker for detection of myocardial damage in horses. Many cTnI assays exist and medical studies have shown that the clinical performance of assays differs. The aim of this study was to compare two different cTnI assays in horses. Serum samples were taken from 23 healthy horses (group 1) and 72 horses with cardiac disease (group 2). Cardiac troponin I was determined using assay 1 in laboratory A (limit of detection, LOD, 0.03 ng/mL) and assay 2 in laboratories B and C (LOD 0.01 ng/mL). In group 1, a median cTnI concentration of <0.03 (<0.03-0.04) ng/mL and <0.01 (<0.01-0.15) ng/mL was found with assays 1 and 2, respectively. A higher median value was demonstrated in group 2 for both assays (assay 1: 0.11 ng/mL, range 0.03-58.27 ng/mL, P < 0.001; assay 2: 0.02 ng/mL, range 0.01-22.87 ng/mL, P = 0.044). Although a significant correlation between assays existed, large mean differences that could be important for clinical interpretation of test results were found. A small mean difference was found between laboratories B and C. A significant optimal (P < 0.001) cut-off value for detection of cardiac disease could only be determined for assay 1 (0.035 ng/mL, sensitivity 70%, specificity 91%). Assay 1 performed better for detection of cardiac disease in horses in this study. (C) 2014 Elsevier Ltd. All rights reserved.
Vagus nerve stimulation (VNS) is an established treatment for epilepsy and depression in human patients, but in both humans and dogs, optimal stimulation parameters remain unknown. Delivering afferent bursts of stimulation may be promising as a means of increasing efficacy, but evaluation of potential effects on the heart due to unavoidable efferent stimulation is required. The present study investigated heart rate variability (HRV) in healthy Beagle dogs treated with 1 h of sham, standard or microburst left-sided VNS in a crossover design. No significant differences were found between the stimulation paradigms for any of the cardiac parameters. Short-term left-sided VNS, including a novel bursting pattern (microburst VNS), had no statistically significant effect on HRV in ambulatory healthy dogs. Studies in a larger number of animals with long-term VNS are recommended. (C) 2014 Elsevier Ltd. All rights reserved.
The current study first investigates the emulsifying potential of glycine and its N-methylated derivatives N-methylglycine (sarcosine), N,N-dimethylglycine (DMG) and N,N,N-trimethylglycine (betaine) under varying pH conditions. Subsequently, the effect of these test compounds on the membrane integrity of enterotoxigenic Escherichia coli (ETEC) was evaluated. Oil in water emulsions containing each compound show that DMG is a more potent enhancer of emulsification than glycine, sarcosine and betaine under the conditions tested. Flow cytometry was used to investigate whether the emulsifying potential is associated with an effect on ETEC membrane integrity. The bacteria were exposed to each of the test compounds under varying pH conditions and membrane integrity was assessed using the LIVE/DEAD BacLight kit. Results show a membrane deteriorating effect caused by glycine, sarcosine and DMG, but not by betaine. This effect is pH- and time-dependent and has an apparent threshold at pH 9.0. Conventional plate counts confirmed concomitant changes in culturability of the membrane comprised bacteria.
Reasons for performing study: The use of two-dimensional speckle tracking (2DST) for quantification of left ventricular (LV) function has recently been described in horses using long-axis images and short-axis images at chordal but not at papillary muscle level.Objectives: To compare the feasibility and reliability of 2DST for quantification of circumferential and radial LV function in short-axis images at papillary muscle and chordal level.Methods: Repeated echocardiographic examinations were performed on 10 healthy trotter horses by 2 observers from a right parasternal short-axis view at papillary muscle and chordal level. Segmental and averaged peak values and timing of circumferential and radial strain and strain rate, radial displacement and rotation were measured in 6 LV wall segments in each imaging plane. Global peak values were calculated for circumferential strain and strain rate. The inter- and intraobserver within- and between-day variability was assessed by calculating coefficients of variation for repeated measurements.Results: 2DST analysis was feasible in each cardiac cycle, although tracking was often inadequate during early diastole. Measurements of averaged systolic circumferential and radial strain and strain rate and radial displacement as well as global circumferential strain and strain rate could be determined with low variability. Early and late diastolic strain rate and systolic rotation showed a moderate variability. Radial segmental measurements were more reliable than circumferential measurements. The interventricular septum showed a higher circumferential and lower radial strain compared with the LV free wall. Peak timing was earlier at papillary muscle compared with chordal level.Conclusions: 2DST measurements of global and regional circumferential and radial LV wall motion are feasible both at papillary muscle and chordal level.Potential relevance: Several measurements had good reliability and should be used for evaluation of the technique in a clinical setting.
REASONS FOR PERFORMING THE STUDY:Atrial fibrillation (AF) is the most important dysrhythmia affecting performance in horses and has been associated with incoordination, collapse and sudden death. Limited information is available on ventricular response during exercise in horses with lone AF.OBJECTIVES:To investigate ventricular response in horses with lone AF during a standardised lungeing exercise test.METHODS:A modified base-apex electrocardiogram was recorded at rest and during a standardised lungeing exercise test from 43 horses diagnosed with lone AF. During the test horses walked for 7 min, trotted for 10 min, cantered for 4 min, galloped for 1 min and recovered for 7 min.RESULTS:Individual average heart rate during walk ranged from 42 to 175 beats/min, during trot from 89 to 207 beats/min, during canter from 141 to 269 beats/min, and during gallop from 191 to 311 beats/min. Individual beat-to-beat maximal heart rate ranged from 248 to 492 beats/min. Ventricular premature depolarisations were present in 81% of the horses: at rest (16%), during exercise (69%), and during recovery (2%). In 33% of the horses, broad QRS complexes with R-on-T morphology were found.CONCLUSIONS:Exercising horses with lone AF frequently develop disproportionate tachycardia. In addition, QRS broadening and even R-on-T morphology is frequently found. QRS broadening may originate from ventricular ectopic foci or from aberrant intraventricular conduction, for example due to bundle branch block. This might explain the high number of complexes currently classified as ventricular premature depolarisations.POTENTIAL RELEVANCE:Prevalence of QRS broadening and especially R-on-T was very high in horses with AF and was found at low levels of exercise. These dysrhythmias are considered risk factors for the development of ventricular tachycardia and fibrillation and they might explain signs of weakness, collapse or sudden death that have been reported in horses with AF.
The opioid and serotonergic systems are closely involved in pain processing and mood disorders. The aim of this study was to assess the influence of systemic morphine on cerebral serotonin 2A receptor (5-HT2A) binding in dogs using SPECT with the 5-HT2A radioligand 123I-5I-R91150. Methods: 5-HT2A binding was estimated with and without morphine pretreatment in 8 dogs. The 5-HT2A binding indices in the frontal, parietal, temporal, and occipital cortex and in the subcortical region were obtained by semiquantification. Results: A significantly decreased 5-HT2A binding index was found in the morphine group for the right (morphine, 1.41 ± 0.06; control, 1.52 ± 0.10) and left (morphine, 1.44 ± 0.08; control, 1.55 ± 0.11) frontal cortices, with P = 0.012 and P = 0.040, respectively. No significant differences were noted for the other regions. Conclusion: Morphine decreased the frontocortical 5-HT2A availability, confirming an interaction between the 5-HTergic and the opioid systems. Whether this interaction is caused by decreased receptor density due to direct internalization or is the result of indirect actions, such as increased endogenous serotonin release, remains to be elucidated.
BACKGROUNDHorses are extremely susceptible to ionophore intoxication. Although numerous reports are available regarding monensin, little is known about lasalocid toxicity.OBJECTIVESTo describe accidental lasalocid poisoning on a farm in Belgium.ANIMALSEighty-one horses, of which 14 demonstrated clinical signs from day 0-21 after being fed a new concentrate batch. One horse died on day 20 and another on day 27.METHODSThe most severe cases (n = 7), admitted to the clinic on day 29-46, underwent cardiac examination and blood biochemical analysis, including determination of plasma cardiac troponin I (cTnI) at admission and during follow-up. On day 57-70, cardiac examination, cTnI determination or both were undertaken on 72 remaining horses.RESULTSShort-term effects of lasalocid intoxication included inappetance, lethargy, sweating, and muscular weakness. All 7 horses admitted to the clinic demonstrated signs of myocardial degeneration such as increased cTnI, dysrhythmia and reduced myocardial contractility. Four horses developed ataxia on day 40-50. Five horses died or were euthanized on day 30-370, 2 horses recovered fully and returned to previous athletic use. None of the 72 remaining horses exhibited clinical signs between day 57-70, but 34 had dysrhythmia and 13 had increased cTnI concentrations. After a period of rest, all horses returned to their previous work. Lasalocid was detected in hepatic tissue of 2 necropsied horses.CONCLUSIONS AND CLINICAL IMPORTANCELasalocid intoxication induced myocardial and neurological damage. Although uncommon, this should be included as differential diagnosis for unexplained inappetance, signs of depression, cardiomyopathy, and ataxia in horses.