Improved Ca2+ release synchrony following selective modification of Itof and phase 1 repolarization in normal and failing ventricular myocytes.

Loss of ventricular action potential (AP) early phase 1 repolarization may contribute to the impaired Ca2+ release and increased risk of sudden cardiac death in heart failure. Therefore, restoring AP phase 1 by augmenting the fast transient outward K+ current (Itof) might be beneficial, but direct experimental evidence to support this proposition in failing cardiomyocytes is limited. Dynamic clamp was used to selectively modulate the contribution of Itof to the AP and Ca2+ transient in both normal (guinea pig and rabbit) and in failing rabbit cardiac myocytes. Opposing native Itof in non-failing rabbit myocytes increased Ca2+ release heterogeneity, late Ca2+ sparks (LCS) frequency and AP duration. (APD). In contrast, increasing Itof in failing myocytes and guinea pig myocytes (the latter normally lacking Itof) increased Ca2+ transient amplitude, Ca2+ release synchrony, and shortened APD. Computer simulations also showed faster Ca2+ transient decay (mainly due to fewer LCS), decreased inward Na+/Ca2+ exchange current and APD. When the Itof conductance was increased to ~0.2 nS/pF in failing cells (a value slightly greater than seen in typical human epicardial myocytes), Ca2+ release synchrony improved and AP duration decreased slightly. Further increases in Itof can cause Ca2+ release to decrease as the peak of the bell-shaped ICa-voltage relationship is passed and premature AP repolarization develops. These results suggest that there is an optimal range for Itof enhancement that may support Ca2+ release synchrony and improve electrical stability in heart failure with the caveat that uncontrolled Itof enhancement should be avoided.

The equine diaphragm: A novel technique for repeatable ultrasound measurement.

The diaphragm is an important respiratory muscle, playing a key role during exercise. In humans, diaphragm thickness increases in response to training and is correlated with inspiratory strength. In order to assess respiratory strength in the horse, new evaluation techniques are required and measurement of diaphragm thickness, in a non-invasive and repeatable manner, is a possible approach. The purposes of this four-part, prospective, pilot study were to develop and describe a repeatable method to measure the diaphragm thickness, using ultrasonography, in Thoroughbred racehorses. A standardized technique was developed whereby the ultrasound transducer was positioned 1 cm below a line between the cranioventral aspect of the tuber coxae and olecranon. The diaphragm thickness was measured on three occasions 1 week apart, by a single observer to determine the intraobserver repeatability, and by a second observer on one occasion to assess interobserver reproducibility. The diaphragm was observed in all intercostal spaces (ICS) from 7 to 17 on the left side, and 6 to 17 on the right side in a single horse. The thickest measurement (1.42 cm), obtained from 11 horses, was at ICS 11 on the left-side during inspiration. The narrowest measurement (0.56 cm) was obtained at ICS 16 on the right-side during expiration. There was no significant difference between the measurements obtained by a single observer on three occasions (P < .05). This is the first study to provide a detailed description of ultrasonographic imaging and measurement of the equine diaphragm. The novel technique developed to position the ultrasound transducer in a standardized location allowed examination and measurement of the diaphragm with good repeatability.

Training the equine respiratory muscles: Ultrasonographic measurement of muscle size.

BACKGROUND: Limited information exists regarding changes in the size of respiratory and locomotor muscles in response to exercise training in the Thoroughbred racehorse. OBJECTIVES: To describe and compare the responses of the respiratory and locomotor muscles to conventional exercise training and inspiratory muscle training (IMT). STUDY DESIGN: Prospective randomised controlled trial. METHODS: Thoroughbred racehorses, in training for competition in National Hunt races, were recruited from two training establishments. Ultrasonographic images were obtained for selected muscles of the upper airway, diaphragm, accessory respiratory, and locomotor systems and their sizes measured. Examinations were performed at three timepoints: (A) when unfit, (B) following 12 weeks of conventional exercise training and (C) following 10-12 weeks continued training at race fitness. In addition, horses at yard 1 performed IMT, between timepoint B and C, and were randomly assigned into high-load (treatment) or low-load (control) group. Repeated measures models were constructed to compare the change in muscle measurements over time, and to investigate the effects of yard, previous airway surgery and IMT on the change in ultrasonographic size measurements obtained. RESULTS: Upper airway muscle size increased in response to conventional race training between timepoints A-C, and B-C. Diaphragm size increased in response to conventional exercise training between timepoints A and B. The diaphragm size of horses that undertook high-load IMT was either maintained or increased, whereas diaphragm size decreased in horses that undertook low-load IMT or no IMT between timepoints B and C. A significant interaction between gluteal muscle size and airway surgery status was observed, with greater gluteal muscle thicknesses measured in horses that had not previously undergone airway surgery (left gluteal 3.9%, p < 0.001; right 4.5%, p = 0.04). MAIN LIMITATIONS: Low number of horses underwent IMT. CONCLUSIONS: Respiratory and locomotor muscles increase in size in response to conventional exercise training, with a further change in diaphragm size in response to inspiratory muscle training.

Training the equine respiratory muscles: Inspiratory muscle strength.

BACKGROUND: Little is known about the response of the equine respiratory muscles to training. OBJECTIVES: To measure an index of inspiratory muscle strength (IMSi) before and after a period of conventional exercise training (phase 1) and inspiratory muscle training (IMT), comparing high-load (treatment) and low-load (control) groups (phase 2). STUDY DESIGN: Prospective randomised controlled trial. METHODS: Phase 1: Twenty National Hunt Thoroughbred racehorses performed an inspiratory muscle strength test (IMST) twice on two occasions; when unfit at timepoint A (July), and when race fit at timepoint B (October). Phase 2: Thirty-five Thoroughbred racehorses at race fitness were randomly assigned into a high-load (treatment, n = 20) or low-load (control, n = 15) IMT group. The high-load group followed an IMT protocol that gradually increased the inspiratory pressure applied every 4 days. The low-load group underwent sham IMT with a low training load. The IMT was performed 5 days/week for 10 weeks. The IMST was performed twice on two occasions, timepoint B (October) and timepoint C (January). Conventional exercise training and racing continued during the study period. The peak IMSi values obtained from the different groups at timepoints A, B and C were compared using a Wilcoxon Signed Rank Test. RESULTS: Phase 1: There was a significant increase in IMSi from timepoint A: 22.5 cmH2 O (21-25) to timepoint B: 26 cmH2 O (24-30) (p = 0.015). Phase 2: From timepoint B to C there was a significant increase in IMSi for the high-load group 34 cmH2 O (28-36) (p = 0.001) but not the low-load group 26 cmH2 O (24-30) (p = 0.929). The peak IMSi at timepoint C was significantly higher for the high-load than low-load group (p = 0.019). MAIN LIMITATIONS: Single centre study with only National Hunt horses undergoing race-training included. CONCLUSIONS: In horses undergoing race training there is a significant increase in IMSi in response to conventional exercise training and high-load IMT.

Prevalence of ultrasonographic gastrointestinal wall changes in dogs with acute pancreatitis: A retrospective study (2012-2020).

BACKGROUND: Ultrasonographic gastrointestinal wall changes in dogs with acute pancreatitis (AP) are not well characterized in the literature. No detailed studies have described their prevalence, characteristics, distribution, or clinical relevance. HYPOTHESIS/OBJECTIVES: Describe the prevalence of ultrasonographic gastrointestinal wall changes in a population of dogs with AP and evaluate for associations between the presence of gastrointestinal wall changes and clinical or clinicopathological variables. ANIMALS: Referral population of 66 client-owned dogs with AP. METHODS: Retrospective search of clinical records to identify dogs with AP. Clinical variables, clinicopathological variables and ultrasonographic findings were reported using descriptive statistics. A binary logistic regression model was used to evaluate for associations between the presence of gastrointestinal wall changes and clinical or clinicopathological variables. RESULTS: Sixty-six dogs were included. Forty-seven percent of dogs (95% confidence interval [CI], 35.0%-59.0%; n = 31) with AP had ultrasonographic gastrointestinal wall changes. Gastrointestinal wall changes were most common in the duodenum and identified in 71% (n = 22) of affected dogs. Of dogs with gastrointestinal wall changes, 74.2% (n = 23) had wall thickening, 61.3% (n = 19) had abnormal wall layering, and 35.5% (n = 11) had wall corrugation. In the multivariable model, only heart rate remained an independent predictor of ultrasonographic gastrointestinal wall changes (P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Ultrasonographic gastrointestinal wall changes in this population of dogs with AP were common. Increased heart rate was the only independent predictor of gastrointestinal wall changes, which might imply more severe disease. Additional studies are required to elucidate whether ultrasonographic gastrointestinal wall changes reflect disease severity in AP.

Effect of preoperative administration of atenolol to dogs with pulmonic stenosis undergoing interventional procedures.

BACKGROUND: Beta-blockade is sometimes used in dogs with pulmonic stenosis with the intent of reducing frequency of ventricular arrhythmias during right heart catheterization. OBJECTIVES: To evaluate if pretreatment with atenolol reduces frequency of ventricular arrhythmias, anesthetist interventions, or shortens procedure time. ANIMALS: Thirty dogs with pulmonic stenosis scheduled for interventional procedures. METHODS: Single center, prospective, randomized, open-label study. Dogs were randomized to treatment with atenolol or no treatment preoperatively for a minimum of 10 days. Variables recorded included heart rate, arrhythmias and complexity, total procedure time and administration of antiarrhythmic treatment, vasopressors, positive chronotropes, or fluid boluses. RESULTS: Fifteen dogs were enrolled in each group. Dogs receiving atenolol had lower mean heart rates during the procedure (atenolol 100 ± 11 bpm vs untreated 115 ± 19 bpm, P = .01). There were no significant differences between the atenolol and untreated groups in the frequency of ventricular ectopic complexes (535 [6-5296] vs 553 [79-2863], P = .9), ventricular couplets (46 [0-481] vs 29 [3-121], P = .59), ventricular triplets (20 [0-265] vs 16 [1-82], P = .67), ventricular tachycardia (8 [0-224] vs 8 [1-118], P = .99), proportion exhibiting R-on-T phenomenon (11/15 vs 14/15, P = .33), proportion receiving intraoperative lidocaine (1/15 vs 3/15, P = .6), vasopressors/positive chronotropes (11/15 vs 5/15, P = .06), or fluid boluses (12/15 vs 7/15, P = .13). The procedure time was similar (atenolol 41 [23-68] min vs untreated 35 [18-98] min, P = .91). CONCLUSIONS AND CLINICAL IMPORTANCE: No benefit of preoperative atenolol treatment was identified in this small group of dogs.

Validation of a focused echocardiographic training program in first opinion practice.

BACKGROUND: The EPIC study defines criteria, including echocardiographic assessments of left atrial to aortic ratio (LA: Ao) and left ventricular internal diameter in diastole normalized for body weight (LVIDdN), for dogs with preclinical myxomatous mitral valve disease (MMVD) likely to benefit from pimobendan therapy. Access to echocardiography by a cardiologist is not universally available. HYPOTHESIS/OBJECTIVES: Completion of a focused echocardiographic training program would result in accurate identification of dogs fulfilling the EPIC criteria by primary care veterinarians (PC). PARTICIPANTS: Six PCs with no previous echocardiographic experience. METHODS: Prospective diagnostic test accuracy study. After training, each PC evaluated ≤10 dogs that they believed to have preclinical MMVD. The evaluation was repeated by 1 of 3 cardiology diplomates, blinded to the PC's findings. Agreement between clinical assessments and echocardiographic measurements was assessed. RESULTS: Fifty-seven dogs were evaluated by PCs; 1 dog was withdrawn because of congestive heart failure. The median time between PC and cardiologist evaluation was 0 days (range, 0-8). One incorrect diagnosis of MMVD was made by a PC (this dog had dilated cardiomyopathy [DCM]); preclinical MMVD was confirmed by the cardiologist in 55 dogs. No difference in LA: Ao (P = .96; CV = 6.9%) was detected between PCs and cardiologists. LVIDdN (1.69 cm/kg0.294 (1.26-2.21) vs 1.73 cm/kg0.294 (1.32-2.73); P = .001; CV = 6.5%), was significantly lower when measured by PCs vs cardiologists. PCs and cardiologists agreed regarding assessment of EPIC criteria in 49/56 dogs (Alpha = .761, 95% confidence interval 0.697-0.922). CONCLUSIONS AND CLINICAL IMPORTANCE: The program effectively trained PCs to accurately assess EPIC criteria in dogs with preclinical MMVD.

The microvascular endothelial glycocalyx: An additional piece of the puzzle in veterinary medicine.

The endothelial glycocalyx (eGlx) is a critically important structure lining the luminal surface of endothelial cells. There is increasing evidence, in human patients and animal models, for its crucial role in the maintenance of health. Moreover, its damage is associated with the pathogenesis of multiple disease states. This review provides readers with an overview of the eGlx; summarising its structure, essential functions, and evidence for its role in disease. We highlight the lack of studies regarding the eGlx in cats and dogs, particularly in naturally occurring diseases. Importantly, we discuss techniques to aid its study, which can be applied to veterinary species. Finally, we present targeted therapies aimed at preserving, and in some cases, restoring damaged eGlx.

Circulating hyaluronan as a marker of endothelial glycocalyx damage in dogs with myxomatous mitral valve disease and dogs in a hypercoagulable state.

The endothelial glycocalyx (eGlx) lines the luminal surface of endothelial cells, maintaining vascular health. Glycocalyx damage is pathophysiologically important in many diseases across species however few studies have investigated its breakdown in naturally occurring disease in dogs. The aims of the study were to investigate eGlx damage in dogs with myxomatous mitral valve disease (MMVD) diagnosed on echocardiography, and dogs in a hypercoagulable state diagnosed using thromboelastography (TEG), by measuring serum hyaluronan concentrations. Serum hyaluronan was quantified in dogs with MMVD (n = 27), hypercoagulability (n = 21), and in healthy controls dogs (n = 18). Serum hyaluronan concentrations were measured using a commercially-available ELISA validated for use in dogs. Hyaluronan concentrations were compared among groups using Kruskal-Wallis tests, and post-hoc with Dunn's tests. Serum hyaluronan concentrations (median [range]) were significantly increased in dogs with MMVD (62.4 [22.8-201] ng/mL; P = 0.031) and hypercoagulability (92.40 [16.9-247.6] ng/mL; P < 0.001) compared to controls (45.7 [8.7-80.2] ng/mL). Measurement of serum hyaluronan concentration offers a clinically applicable marker of eGlx health and suggests the presence of eGlx damage in dogs with MMVD and dogs in a hypercoagulable state.

Evaluation of serum cardiac troponin-I concentrations for diagnosis of infective endocarditis in dogs.

BACKGROUND: Infective endocarditis (IE) in dogs is associated with severe disease and a high case fatality rate but often presents with nonspecific clinical signs. HYPOTHESIS/OBJECTIVES: Serum concentration of cardiac troponin-I (cTnI) is elevated in dogs with IE and can differentiate dogs with IE from dogs with other diseases with similar clinical features. Concentration of serum cTnI is negatively correlated with survival time in dogs with IE. ANIMALS: Seventy-two client-owned dogs; 29 with IE, 27 with stage-B myxomatous mitral valve disease (MMVD), and 16 with immune-mediated disease (IMD). METHODS: Retrospective clinical cohort study. Concentration of serum cTnI was measured in all dogs at time of diagnosis. Clinical findings and echocardiographic interpretation were also recorded. Statistical analyses included Kruskal-Wallis test, pairwise Mann-Whitney U tests, receiver operator characteristic, and Cox proportional hazards. RESULTS: Serum concentration of cTnI was significantly higher in the IE group (0.69 ng/mL [0.03-80.8]) than in the MMVD (0.05 ng/mL [0.02-0.11], P < .001) and IMD groups (0.05 ng/mL [0.03-0.57], P < .001). Increased cTnI was a moderately accurate predictor of IE (area under the curve 0.857 (95% confidence interval [CI] 0.745-0.968, P < .001). A cTnI cutoff of 0.625 ng/mL had 100% specificity (95% CI 90%-100%) and 52% sensitivity (95% CI 33%-70%) in this study sample. There was no association between cTnI concentration and survival time in dogs with IE (hazard ratio 1.013, 95% CI 0.993-1.034, P = .2). CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac troponin-I concentrations are higher in dogs with IE compared to dogs with preclinical MMVD or IMD. In dogs with a compatible clinical presentation, serum cTnI concentrations >0.625 ng/mL are supportive of IE.