Cardiac arrhythmias in poorly performing Standardbred and Norwegian-Swedish Coldblooded trotters undergoing high-speed treadmill testing.

The significance of cardiac arrhythmias and their possible association with upper airway obstruction are frequently considered in the clinical investigation of poor performance. The specific aims of this retrospective study of a group of poorly performing Standardbred and Norwegian-Swedish Coldblooded trotters were to: (1) describe the overall frequency and frequency distributions of arrhythmias; (2) describe arrhythmia characteristics including percent prematurity, relative recovery cycle lengths and QRS morphology; (3) describe variability of normal RR intervals; and (4) explore possible associations between upper airway abnormalities and arrhythmia categories during peak exercise and recovery. The records of 103 trotters presented to the Norwegian University of Life Sciences for high-speed treadmill testing were reviewed. The occurrence of at least one arrhythmic event was high (77-78%) when considering all exercise periods and 6-10% prematurity criteria. Triplets, salvos, and/or paroxysmal tachyarrhythmias occurred in 8% of horses during peak exercise. Complex ventricular arrhythmias occurred in 15% of horses in the first 2 min of recovery. Evaluation of QRS morphology and return cycle lengths demonstrated areas of overlap in characteristics typically attributed to either supraventricular or ventricular arrhythmias. There was no association between airway diagnosis and arrhythmias during any exercise period. The maximum average HR during peak exercise was an excellent predicter for complex ventricular arrhythmias during recovery. Because perfect categorization of arrhythmias is not possible, future studies should report descriptive arrhythmia information. Prospective studies that evaluate various degrees of upper airway obstruction and the effect on known initiators of arrhythmogenesis are needed.

Hypercapnia and hyperlactatemia were positively associated with higher-grade arrhythmias during peak exercise in horses during poor performance evaluation on a high-speed treadmill.

Cardiac arrhythmias are common in horses during exercise, especially immediately post-exercise. The objectives of this study were to: (1) describe the frequency and type of cardiac arrhythmias detected in horses during incremental high-speed treadmill exercise testing (ITET); (2) determine if arterial blood gas (ABG) changes at peak and immediately post-exercise were associated with arrhythmias; and (3) determine whether upper or lower airway disease was associated with exercising cardiac arrhythmias. Horses (n = 368) presenting for an ITET underwent resting and exercising upper airway endoscopy, resting, exercising and post-exercise electrocardiography, resting and post-exercise echocardiography and exercising ABG. Arrhythmias were graded by the most severe arrhythmia present. Grade 1 arrhythmias were defined as one or two atrial (APCs) or ventricular premature complexes (VPCs), or one APC and one VPC, detected in 6.9% at peak and 16% at 0-2 min post exercise.. Grade 2 arrhythmias were >2 APCs or VPCs, or both, detected in 5.8% at peak and 16.6% at 0-2 min post exercise. Grade 3 included complex arrhythmias (couplets, triplets, R on T, multiform complexes or paroxysmal atrial or ventricular tachycardia), detected in 4.4% at peak and 7.3% at 0-2 min post exercise. Both partial pressure of arterial CO2 (PaCO2; P = 0.008) and lactate (P = 0.031) were significantly associated with arrhythmias occurring at peak exercise, but not immediately post-exercise. As PaCO2 and lactate increased, arrhythmia severity increased. Blood pH was significantly associated with grades 2 and 3 arrhythmias at 0-2 min post ITET (OR = 0.0002; P < 0.001). There was no significant association between grades 2 and 3 cardiac arrhythmias, inflammatory airway disease (IAD), or exercise-induced pulmonary hemorrhage (EIPH). When adjusted for lactate concentration (P = 0.06), higher PaCO2 concentrations in horses with and without exercising upper respiratory tract (URT) obstruction were associated with higher likelihood of grades 2 and 3 arrhythmias (P < 0.01). This study demonstrated that at peak exercise, with severe hypercapnia and hyperlactatemia, there was increased risk for grades 2 or 3 cardiac arrhythmias and, as the PaCO2 and lactate values increased further, the severity of those arrhythmias increased.

Two-dimensional, M-mode and left atrial velocity echocardiographic measurements in healthy Norwegian-Swedish Coldblooded Trotters.

INTRODUCTION: The Norwegian-Swedish Coldblooded Trotter (NSCT) is an important breed in Norwegian and Swedish harness racing. In spite of this, little is known about its cardiac measurements and factors that may influence these. The aims of this study were to establish reference intervals (RI) for a series of conventional echocardiographic variables, primarily of the left heart, in NSCTs in race training and to evaluate any effects age, gender, estimated body weight (EBW), number of starts and racing performance may have on these. ANIMALS: Sixty-three apparently healthy NSCTs in race training. METHODS: Observational study, convenience sampling. All horses were examined unsedated in their normal stabling environment. Auscultatory and echocardiographic examinations were performed. Means, standard deviations, medians and confidence intervals of the RI limits were used to summarize the data. The relationship between selected echocardiographic variables and age, gender, EBW, racing performance and number of starts were explored using linear regression analyses. RESULTS: Reference intervals were determined for routinely used echocardiographic variables. Data for left atrial velocity were also obtained. Increasing age, number of starts and money earned significantly increased all cardiac measurements. Males had significantly higher ventricular measurements than females. Great vessel measurements increased with increasing EBW. Horses with faster recorded racing times had generally significantly increased cardiac measurements. Clinically insignificant valvular regurgitation was a common finding, particularly at the tricuspid and pulmonary valves. CONCLUSIONS: The RIs described and the factors that may affect these will assist clinicians in interpreting echocardiograms of NSCTs with suspected cardiac disease or poor performance.

Association of hematopoietic cell transplantation-specific comorbidity index with resource utilization after allogeneic transplantation.

Comorbidities affect clinical outcomes and costs in medicine. The hematopoietic cell transplantation (HCT)-specific comorbidity index (HCT-CI) predicts mortality risk after HCT. Its association with resource utilization (RU) is unknown. In this single-center, retrospective study, we examined the association of HCT-CI with RU (readmissions, length of hospital stay (LOS) and days out of hospital alive (DOHA)) in first 100 days (n=328) and 1 year (n=226) in allogeneic HCT patients from January 2010 to June 2014. Age, disease risk, conditioning and use of antithymocyte globulin were significantly different in the four groups with HCT-CI 0 to1 (n=138), 2 (n=56), 3 (n=55) or ⩾4 (n=79). Although the readmissions were higher in the first 100 days for patients with HCT-CI >0-1 (P=0.03), they were not significantly different in patients over 1 year (P=0.13). In the multivariable analysis, patients with HCT-CI score of >0 to 1 had increased LOS and fewer DOHA in both 100 days and 1 year after HCT. In this exploratory analysis, we found that HCT-CI >0 to 1 is associated with increased RU after allogeneic HCT. Recognizing predictors of RU can identify patients at risk of high utilization and help understand what drives health-care costs.

Third-Degree Atrioventricular Block and Collapse Associated with Eosinophilic Myocarditis in a Horse.

Third-degree atrioventricular block (AVB) and primary inflammatory myocarditis are uncommon findings in horses. The horse of this report presented for collapse at rest and was found to have multiple cardiac arrhythmias, most notably 3rd-degree AVB. The horse was subsequently diagnosed with eosinophilic myocarditis on necropsy, a rare form of myocarditis not previously reported in horses. Despite extensive testing, an etiologic agent could not be identified, illustrating the difficulty in identifying a specific cause of myocarditis in horses.

Occurrence of cardiac arrhythmias in Standardbred racehorses.

REASONS FOR PERFORMING STUDY: Cardiac arrhythmias are a recognised but poorly characterised problem in the Standardbred racehorse. Frequency data could aid the development of cardiac arrhythmia screening programmes. OBJECTIVES: To characterise the occurrence of cardiac arrhythmias in Standardbreds prior to racing and in the late post race period using a handheld, noncontinuous recording device. STUDY DESIGN: Prospective, observational study, convenience sampling. METHODS: Noncontinuous electrocardiographic recordings were obtained over a 12 week period from Standardbred horses competing at a single racetrack. Electrocardiograms were obtained before racing and between 6 and 29 min after the race using a handheld recording device. Prevalence of arrhythmias was calculated for all horses and overall frequency of arrhythmias was calculated for race starts and poor performers. Univariate logistic regression analysis was used to identify risk factors for cardiac arrhythmias. RESULTS: A total of 8657 electrocardiogram recordings were obtained from 1816 horses. Six horses had atrial fibrillation after racing (prevalence = 0.11%, frequency = 0.14%), one horse had supraventricular tachycardia before racing (prevalence = 0.06%, frequency = 0.02%), and 2 horses had ventricular tachyarrhythmias after racing (prevalence = 0.06%, frequency = 0.05%). The frequency of atrial fibrillation among race starts with poor performance was 1.3-2.0%. Increasing age was a significant risk factor for the presence of atrial premature contractions before racing and atrial fibrillation and ventricular ectopy after racing. CONCLUSIONS: Both physiological and pathological cardiac arrhythmias can be detected in apparently healthy Standardbred horses in the prerace and late post race period using noncontinuous recording methods. Future studies should examine cumulative training or racing hours as a risk factor for cardiac arrhythmia. The prevalence and frequency information may be useful for track veterinarians and regulatory personnel following trends in cardiac arrhythmias.

Stable insulin-secreting ducts formed by reprogramming of cells in the liver using a three-gene cocktail and a PPAR agonist.

With the long-term aim of developing a new type of therapy for diabetes, we have investigated the reprogramming of liver cells in normal mice toward a pancreatic phenotype using the gene combination Pdx1, Ngn3, MafA. CD1 mice were rendered diabetic with streptozotocin and given a single dose of Ad-PNM, an adenoviral vector containing all three genes. Ad-PNM induced hepatocytes of the liver to produce insulin, and the blood glucose became normalized. But over several weeks, the insulin-positive cells were lost and the blood glucose rose back to diabetic levels. Simultaneous administration of a peroxisome-proliferator-activated receptor agonist, WY14643, caused remission of diabetes at a lower dose of Ad-PNM and also caused the appearance of a population of insulin-secreting ductal structures in the liver. The insulin-positive ducts were stable and were able to relieve diabetes in the long term. We show that the effect of WY14643 is associated with the promotion of cell division of the ductal cells, which may increase their susceptibility to being reprogrammed toward a beta cell fate.

Comparison of a rebound tonometer with an applanation tonometer in dogs with glaucoma.

Eighteen dogs which presented to the Purdue University Ophthalmology Service with a final diagnosis of primary or secondary glaucoma, and 5 dogs with normal eye examinations, were evaluated. Each dog underwent a complete ophthalmic examination. An eye was categorised as glaucomatous if an intraocular pressure (IOP) measurement ≥25 mm Hg was obtained, and clinical signs consistent with glaucoma were present. Readings with the TonoVet were always performed first without topical anaesthesia. After obtaining readings with the TonoVet, one drop of proparacaine was applied to each eye, followed by IOP measurement with the Tono-Pen XL. As IOP increased, the difference between measurements obtained with the two tonometers was statistically significant. The TonoVet consistently gave higher IOP values compared with the Tono-Pen XL in glaucomatous eyes with Tono-Pen XL IOP readings ≥25 mm Hg. IOP readings were not significantly different between tonometers for normotensive eyes. Based on the results of the current study, the same device should be used for monitoring of IOP in individual patients.

Cardiac troponin I in racing standardbreds.

BACKGROUND: Upper reference limits for cTnI have not been established for healthy Standardbred racehorses. OBJECTIVES: To establish cTnI upper reference limits for Standardbred racehorses and determine if increases in plasma cTnI concentration can be detected in 1-2 hours after a race. ANIMALS: Samples were obtained from 586 apparently healthy Standardbreds aged 2-14 years before racing and from the winners of 144 races 1-2 hours after the end of the race. METHODS: Prospective, observational study; convenience sampling; assay validation; and reference limits determinations were performed according to ASCVP guidelines. Plasma cardiac troponin I concentrations before racing were determined, potential outliers identified, and the 95th and 99th percentile upper reference limits calculated using nonparametric methods. The correlation between cTnI concentration and age, differences in median cTnI concentrations by subgroups and differences between cTnI concentrations before and after racing in winning horses were determined. RESULTS: The 95th and 99 th percentile upper reference limits for all horses excluding outliers were < 0.04 ng/mL and 0.06 ng/mL. There were no significant differences in cTnI concentrations based on age (P = .06), sex (P = .35), gait (P = .55), or race classification (P = .65) and a weak correlation of cTnI with age (ρ = 0.09, P = .03). There were no significant differences between cTnI concentrations before and after racing in winning horses (P = .70). CONCLUSIONS AND CLINICAL IMPORTANCE: Because of lack of standardization across cTnI assays, the reference limits apply only to the Stratus CS immunoassay. Future studies looking at the effects of high intensity, short duration exercise on cTnI should consider sampling more than 2 hours after racing or using an ultrasensitive assay.

Intraoperator, intraobserver and interoperator variability of echocardiographic measurements in healthy foals.

REASON FOR PERFORMING STUDY: The repeatability of various echocardiographic measurements is unknown. OBJECTIVES: To determine the intraoperator, intraobserver and interoperator variability of echocardiographic measures in healthy foals. METHODS: Echocardiographic examinations were carried out on 6 healthy foals by 3 experienced echocardiographers. Intraoperator variability was determined by having a single echocardiographer obtain and measure images from 6 foals scanned on 3 consecutive days. Interoperator and intraobserver variability were determined by having 3 echocardiographers each obtain images from an additional 6 sedated foals. Within-day interoperator variability was determined by having each echocardiographer measure their own images. Intraobserver variability was determined by having a single echocardiographer measure images obtained by all 3 echocardiographers. The coefficient of variation (CV) and standard error were calculated for each measure. RESULTS: The variability for most measurements was either very low (CV < 5%) or low (CV = 5-15%). Measurements of right ventricular internal diameter (RVID) in systole and E-point to septal separation (EPSS) showed moderate (CV 15-25%) to high variability (CV > 25%) in all 3 categories. Measurements of the left ventricular ejection time (LVET) and velocity time integral from the right parasternal long axis view of right outflow tract in the fourth intercostal space showed moderate intraoperator variability. Measurements of the LVET, RVID in diastole and left atrial appendage (LAA) showed moderate interoperator variability and measurements of the RVID in diastole and acceleration time from the short axis view of the right outflow tract in the right third intercostal space showed moderate interobserver variability. CONCLUSION: The intraoperator, intraobserver and interoperatorvariabilities for most echocardiographic measurements in foals are low. POTENTIAL RELEVANCE: Most standard transthoracic echocardiographic measurements in foals have a low enough variability to warrant their use in serial clinical evaluations or experimental studies. Repeated measurements of RVID, EPSS, LVET and LAA should be interpreted with caution.

Repeatability, reproducibility, and effect of head position on central venous pressure measurement in standing adult horses.

BACKGROUND: Central venous pressure (CVP) is a used as an estimation of intravascular volume status in various species. Techniques for measuring CVP in horses have been described, but the repeatability of these readings at a single time point or over time has not been established. HYPOTHESIS: That CVP measurements in healthy adult horses would be repeatable at each time point, that these readings would be reproducible over time, and that alteration in head position relative to the heart would alter CVP. ANIMALS: Ten healthy adult research horses. METHODS: In an experimental study, horses were instrumented with a central venous catheter. Readings were taken in triplicate q6h for 2 days by water manometry, and twice daily with the head in neutral, elevated, and lowered positions by electronic manometry. RESULTS: Variation in the "neutral" measurements obtained at each time point was <0.1 ± 1.0 cmH(2)O (P = .718). There was a significant decrease in CVP over time (P = .015), which was eliminated when results were controlled for acute decrease in body weight of -1.35% (presumed hypohydration because of lack of acclimatization and decreased water intake). Head height had a significant and directional effect on CVP in that the elevated head position decreased CVP -2.0 ± 6.5 cmH(2)O (P < .001) while the lowered head position increased CVP by 3.7 ± 5.5 cmH(2)O (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: CVP values obtained by water manometry were repeatable in adult horses, but were reproducible only when controlled for changes in hydration. Care should be taken to maintain consistency in head position to prevent erroneous readings.

Comparison of water manometry to 2 commercial electronic pressure monitors for central venous pressure measurement in horses.

BACKGROUND: Central venous pressure (CVP) customarily has been measured in veterinary patients with water manometry. However, many institutions are now using stallside electronic monitors in both anesthesia and intensive care units for many aspects of patient monitoring. HYPOTHESIS: Electronic stall side monitoring devices will agree with water manometry for measurement of CVP in horses. ANIMALS: Ten healthy adult horses from the university research herd. METHODS: Central venous catheters were placed routinely, and measurements were obtained in triplicate with each of the 3 methods every 12 hours for 3 days. Data were analyzed by a Lin concordance correlation coefficient and modified Bland-Altman limits of agreement, with all devices compared pairwise. RESULTS: Compared with water manometry, agreement (bias) of the Passport was -1.94 cmH2O (95% limits of agreement, -8.54 to 4.66 cmH2O) and of the Medtronic was -1.83 cmH2O (95% limits of agreement, -8.60 to 4.94 cmH2O). When compared with the Passport, agreement of the data obtained with the Medtronic was 0.27 cmH2O (95% limits of agreement, -4.39 to 4.93 cmH2O). CONCLUSIONS AND CLINICAL IMPORTANCE: These data show that both electronic monitors systematically provide measurements that are approximately 2 cmH2O lower than water manometry, but differences between the 2 electronic devices are small enough (< 0.5 cmH2O) to be considered clinically unimportant. This discrepancy should be taken into account when interpreting data obtained with these monitoring devices.

Echocardiographic changes in heart size in hypohydrated horses.

BACKGROUND: Hypohydration causes transient echocardiographic changes in pigs, dogs, humans, and cats. These changes mask the diagnosis of some cardiac diseases (valvular regurgitation, dilated cardiomyopathy) and promote the diagnosis of others (hypertropic cardiomyopathy and infiltrative disease), thus inhibiting accurate echocardiographic evaluation. OBJECTIVES: To describe the echocardiographic changes associated with hypohydration in normal horses. ANIMALS: Ten adult horses without detectable cardiac disease. METHODS: Experimental study. Echocardiographic examinations were performed on horses in the euhydrated and hypohydrated states. Horses were hypohydrated by combined water deprivation and furosemide administration until a 4-7% reduction in bodyweight was achieved. Statistical analyses were performed by paired t-tests. RESULTS: Hypohydration decreased left ventricular internal diameter in systole (0.8 ± 0.6 cm) and diastole (1.7 ± 0.9 cm), left atrial diameter (1.5 ± 0.4 cm) and left ventricular volume (490 ± 251 mL) (P-values < .01), and increased septal wall thickness in diastole (0.6 ± 0.3 cm), free wall thickness in diastole (0.5 ± 0.3 cm), mean wall thickness (0.5 ± 0.2 cm) and relative wall thickness (0.2 ± 0.1 cm) (P-values < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Hypohydration produces changes in left ventricular and atrial size that could mask or promote the severity of cardiac disease. The thickened, "pseudohypertrophied" appearance of the left ventricle in hypohydrated horses could affect interpretation of echocardiographic variables that are applied to the prediction of athletic performance. Echocardiography may prove a noninvasive method of monitoring volume status and response to fluid therapy in hypovolemic horses.

The effects of hypohydration on central venous pressure and splenic volume in adult horses.

BACKGROUND: Central venous pressure (CVP) is used in many species to monitor right-sided intravascular volume status, especially in critical care medicine. HYPOTHESIS: That hypohydration in adult horses is associated with a proportional reduction in CVP. ANIMALS: Ten healthy adult horses from the university teaching herd. METHODS: In this experimental study, horses underwent central venous catheter placement and CVP readings were obtained by water manometry. The horses were then deprived of water and administered furosemide (1 mg/kg IV q6h) for up to 36 hours. Weight, CVP, vital signs, PCV, total protein (TP), and serum lactate were monitored at baseline and every 6 hours until a target of 5% decrease in body weight loss was achieved. The spleen volume was estimated sonographically at baseline and peak volume depletion. Linear regression analysis was used to assess the association of CVP and other clinical parameters with degree of body weight loss over time. RESULTS: There was a significant association between CVP and decline in body weight (P < .001), with a decrease in CVP of 2.2 cmH(2)O for every percentage point decrease in body weight. Other significant associations between volume depletion and parameters measured included increased TP (P = .007), increased serum lactate concentration (P = .048), and decreased splenic volume (P = .046). There was no significant association between CVP and vital signs or PCV. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest that CVP monitoring might be a useful addition to the clinical evaluation of hydration status in adult horses.

Inhibition of Hes1 activity in gall bladder epithelial cells promotes insulin expression and glucose responsiveness.

The biliary system has a close developmental relationship with the pancreas, evidenced by the natural occurrence of small numbers of biliary-derived beta-cells in the biliary system and by the replacement of biliary epithelium with pancreatic tissue in mice lacking the transcription factor Hes1. In normal pancreatic development, Hes1 is known to repress endocrine cell formation. Here we show that glucose-responsive insulin secretion can be induced in biliary epithelial cells when activity of the transcription factor Hes1 is antagonised. We describe a new culture system for adult murine gall bladder epithelial cells (GBECs), free from fibroblast contamination. We show that Hes1 is expressed both in adult murine gall bladder and in cultured GBECs. We have created a new dominant negative Hes1 (DeltaHes1) by removal of the DNA-binding domain, and show that it antagonises Hes1 function in vivo. When DeltaHes1 is introduced into the GBEC it causes expression of insulin RNA and protein. Furthermore, it confers upon the cells the ability to secrete insulin following exposure to increased external glucose. GBEC cultures are induced to express a wider range of mature beta cell markers when co-transduced with DeltaHes1 and the pancreatic transcription factor Pdx1. Introduction of DeltaHes1 and Pdx1 can therefore initiate a partial respecification of phenotype from biliary epithelial cell towards the pancreatic beta cell.

Use of adenovirus for ectopic gene expression in Xenopus.

We show that replication defective adenovirus can be used for localized overexpression of a chosen gene in Xenopus tadpoles. Xenopus contains two homologs of the Coxsackie and Adenovirus Receptor (xCAR1 and 2), both of which can confer sensitivity for adenovirus infection. xCAR1 mRNA is present from the late gastrula stage and xCAR2 throughout development, both being widely expressed in the embryo and tadpole. Consistent with the expression of the receptors, adenovirus will infect a wide range of Xenopus tissues cultured in vitro. It will also infect early embryos when injected into the blastocoel or archenteron cavities. Furthermore, adenovirus can be delivered by localized injection to tadpoles and will infect a patch of cells around the injection site. The expression of green fluorescent protein in infected cells persists for several weeks. This new gene delivery method complements the others that are already available. Developmental Dynamics 238:1412-1421, 2009. (c) 2009 Wiley-Liss, Inc.

Metaplasia and somatic cell reprogramming.

The nature and occurrence of metaplasia is briefly reviewed. A theory of how metaplasia is initiated is presented, depending on the idea that it represents an alteration in the combination of developmental transcription factors that are expressed. Two examples of experimental metaplasia, provoked by over-expression of specific transcription factors, are presented: the transformation of B lymphocytes to macrophages, and of pancreatic exocrine cells to hepatocytes. The formation of induced pluripotential stem cells (iPS cells) is considered an example of the same process, in which the destination state is the embryonic stem cell. It is noted that iPS cell production is a stochastic process, depending on selection to obtain the desired cell type. It is proposed that analogous technology, using the appropriate transcription factors, could be used to bring about transformation to cell types other than embryonic stem cells.

Origin of stem cells in organogenesis.

The development of individual organs in animal embryos involves the formation of tissue-specific stem cells that sustain cell renewal of their own tissue for the lifetime of the organism. Although details of their origin are not always known, tissue-specific stem cells usually share the expression of key transcription factors with cells of the embryonic rudiment from which they arise, and are probably in a similar developmental state. On the other hand, the isolation of pluripotent stem cells from the postnatal organism has encouraged the formulation of models of embryonic and postnatal development that are at variance with the conventional ones. Possible explanations for the existence of such cells, and the issue of whether they also exist in vivo, are discussed.