Essential function for the calcium sensor STIM1 in mast cell activation and anaphylactic responses.

Mast cells have key functions as effectors of immunoglobulin E-mediated allergic inflammatory diseases. Allergen stimulation induces Ca2+ influx and elicits the secretion of inflammatory mediators from mast cells. Here we show that the Ca2+-binding endoplasmic reticulum protein STIM1 is critical to mast cell function. STIM1-deficient fetal liver-derived mast cells had impaired Ca2+ influx mediated by the high-affinity immunoglobulin E receptor FcepsilonRI and activation of the transcription factors NF-kappaB and NFAT. Mast cells lacking STIM1 also had much less degranulation and cytokine production after FcepsilonRI stimulation. In addition, alterations in STIM1 expression affected the sensitivity of immunoglobulin E-mediated immediate-phase anaphylactic responses in vivo. Thus, STIM1 is key in promoting the Ca2+ influx that is essential for FcepsilonRI-mediated mast cell activation and anaphylaxis.

The calcium sensors STIM1 and STIM2 control B cell regulatory function through interleukin-10 production.

A chief Ca(2+) entry pathway in immune cells is store-operated Ca(2+) (SOC) influx, which is triggered by depletion of Ca(2+) from the endoplasmic reticulum (ER). However, its physiological role in B cells remains elusive. Here, we show that ER calcium sensors STIM1- and STIM2-induced SOC influx is critical for B cell regulatory function. B cell-specific deletion of STIM1 and STIM2 in mice caused a profound defect in B cell receptor (BCR)-induced SOC influx and proliferation. However, B cell development and antibody responses were unaffected. Remarkably, B cells lacking both STIM proteins failed to produce the anti-inflammatory cytokine IL-10 because of defective activation of nuclear factor of activated T cells (NFAT) after BCR stimulation. This resulted in exacerbation of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our data establish STIM-dependent SOC influx as a key signal for B cell regulatory function required to limit autoimmunity.

Mitral annular disjunction in patients with primary severe mitral regurgitation and mitral valve prolapse.

BACKGROUND: Mitral annular disjunction is a structural abnormality of the mitral annulus fibrosus which is often associated with mitral leaflet prolapse. However, few reports have described mitral annular disjunction in mitral valve prolapse (MVP). This study aimed to investigate the characteristics of mitral annular disjunction in patients with severe mitral regurgitation (MR) caused by MVP. METHODS: We reviewed 185 consecutive patients with severe MR caused by fibroelastic deficiency (FED) and Barlow's syndrome from March 2009 to December 2010. The upper limit of the disjunction was defined at the level of the posterior scallop's insertion into the left atrial wall, whereas the lower limit was defined at the level of the left atrium's connection to the ventricular myocardium. The distance between the two levels was called mitral annular disjunction. Prolapse sites in FED patients were categorized into anterior leaflet, posterior leaflet, and commissure groups. Patients with a disjunction distance of ≥2 mm were diagnosed with mitral annular disjunction. RESULTS: Annular disjunction was found in 45 patients (24%). Among them, the most common site of prolapse was the posterior leaflet (n = 35, 77.8%). During a median follow-up of 20.3 years, arrhythmic events and sudden death occurred in seven patients (3.8%). CONCLUSIONS: Mitral annular disjunction was detected in 24% of patients with severe MR and in 90% of the patients with Barlow's syndrome. There were significant differences at its sites of prolapse in FED patients. The presence and site of prolapse with mitral annular disjunction should be actively determined in FED patients.

Significance of isolated papillary muscle hypertrophy: A comparison of left ventricular hypertrophy diagnosed using electrocardiography vs echocardiography.

AIMS: The clinical significance of papillary muscle hypertrophy and its electrocardiography (ECG) findings has not been fully elucidated. This study aimed to investigate the relationship between ECG findings and papillary muscle hypertrophy and to confirm the importance of papillary muscle measurements on transthoracic echocardiography (TTE). METHODS AND RESULTS: Of the 237 consecutive patients who showed left ventricular hypertrophy (LVH) pattern on a 12-lead ECG, TTE data were available for 101 patients. The patients were divided into the two groups according to the presence (ECG-LVH [strain pos] group, n = 60) or absence (ECG-LVH [strain neg] group, n = 41) of LV strain pattern (study 1). The prevalence of papillary muscle hypertrophy using TTE was significantly higher in the ECG-LVH (strain neg) group than in the ECG-LVH (strain pos) group (P = .0002). Of the 42 cases with papillary muscle hypertrophy, 5 cases (12%) showed isolated papillary muscle hypertrophy with normal geometry. ECG data were prospectively analyzed for 36 patients who were diagnosed with papillary muscle hypertrophy by TTE (study 2). The prevalence of LV strain pattern was significantly higher in patients with LV wall hypertrophy than in those without LV wall hypertrophy (P = .04). Of the 25 cases with papillary muscle hypertrophy, 6 cases (24%) showed normal geometry and 4 cases (16%) showed ECG abnormality. CONCLUSIONS: Isolated papillary muscle hypertrophy can cause ECG abnormalities such as LV high voltage and LV strain pattern. Particular attention must be paid to the papillary muscle during echocardiographic examinations.

Association between preoperative characteristics and risk of anaesthesia-related death in dogs in small-animal referral hospitals in Japan.

OBJECTIVE: To explore the major risk factors linking preoperative characteristics and anaesthesia-related death in dogs in referral hospitals in Japan. STUDY DESIGN: Observational cohort study. ANIMALS: From April 1, 2010 to March 31, 2011, 4323 dogs anaesthetized in 18 referral hospitals in Japan. METHODS: Questionnaire forms were collated anonymously. Death occurring within 48 hours after extubation was considered as an anaesthesia-related death. Patient outcome (alive or dead) was set as the outcome variable. Preoperative general physical characteristics, complete blood cell counts, serum biochemical examinations and intraoperative complications were set as explanatory variables. The risk factors for anaesthesia-related death were evaluated using chi-square test or Fisher's exact test, followed by multivariable logistic regression analysis of the data. Significance was set at p < 0.05. RESULTS: Thirteen dogs that died from surgical error or euthanasia were excluded from statistical analysis. The total mortality rate in this study was 0.65% [28/4310 dogs; 95% confidence interval (CI), 0.41-0.89]. Furthermore, 75% (95% CI, 55.1-89.3) of anaesthesia-related deaths occurred in dogs with pre-existing diseases. Most of the deaths occurred postoperatively (23/28; 82.1%; 95% CI, 63.1-93.9). Preoperative serum glucose concentration <77 mg dL-1 (6/46; 13.0%; 95% CI, 4.9-26.3), disturbance of consciousness (6/50; 12.0%; 95% CI, 4.5-24.3), white cell count >15,200 µL-1 (16/499; 3.4%; 95% CI, 1.9-5.5) and American Society of Anesthesiologists grade III-V (19/1092; 1.7%; 95% CI, 1.1-2.7) were identified as risk factors for anaesthesia-related death. Intraoperative hypoxaemia (8/34; 23.5%; 95% CI, 10.7-41.2) and tachycardia (4/148; 2.7%; 95% CI, 0.7-6.8) were also risk factors for anaesthesia-related death. CONCLUSIONS AND CLINICAL RELEVANCE: The results revealed that certain preoperative characteristics were associated with increased odds of anaesthesia-related death, specifically low serum glucose concentration and disturbances of consciousness. Greater attention to correcting preanaesthetic patient abnormalities may reduce the risk of anaesthesia-related death.

Simvastatin and atorvastatin facilitates amyloid ß-protein degradation in extracellular spaces by increasing neprilysin secretion from astrocytes through activation of MAPK/Erk1/2 pathways.

One of the major neuropathological hallmarks of Alzheimer's disease (AD) is the deposition of amyloid ß-protein (Aß) in the brain. Aß accumulation seems to arise from an imbalance between Aß production and clearance. Neprilysin (NEP) and insulin-degrading enzyme (IDE) are the important Aß-degrading enzymes in the brain, and deficits in their expression may promote Aß deposition in patients with sporadic late-onset AD. Statins, which are used clinically for reducing cholesterol levels, can exert beneficial effects on AD. Therefore, we examined whether various statins are associated with Aß degradation by inducing NEP and IDE expression, and then evaluating the relation between activation of intracellular signaling transduction, inhibition of cholesterol production, and morphological changes to astrocytes. Treating cultured rat astrocytes with simvastatin and atorvastatin significantly decreased the expression of NEP but not IDE in a concentration- and time-dependent manner. The decrease in NEP expression was a result of activation of extracellular signal-regulated kinase (ERK) but not the reduction of cholesterol synthesis pathway. This NEP reduction was achieved by the release to the extracellular space of cultured astrocytes. Furthermore, the cultured medium prepared from simvastatin- and atorvastatin-treated astrocytes significantly induced the degradation of exogenous Aß. These results suggest that simvastatin and atorvastatin induce the increase of Aß degradation of NEP on the extracellular of astrocytes by inducing ERK-mediated pathway activity and that these reagents regulate the differential mechanisms between the secretion of NEP, the induction of cholesterol reduction, and the morphological changes in the cultured astrocytes.

Diode laser coagulation for the treatment of epistaxis in a Scottish fold cat.

We report the case of a 4-year-old, castrated 4.2-kg Scottish fold cat with recurrent epistaxis that was unresponsive to medical therapy. Diathermocoagulation of the nasal mucosa with a diode laser controlled the epistaxis and there was no significant recurrence of epistaxis during 1 year of follow-up.

Coagulation à la diode laser pour le traitement de l'épistaxis chez un chat Scottish Fold. Nous signalons le cas d'un chat Scottish Fold castré âgé de 4 ans d'un poids de 4,2 kg atteint d'épistaxis récurrente qui n'a pas répondu au traitement médical. La diathermocoagulation de la muqueuse nasale à l'aide d'une diode laser a contrôlé l'épistaxis et il n'y pas eu de récurrence de l'épistaxis durant le suivi d'un an.(Traduit par Isabelle Vallières).

Fabrication and Characterization of Oleofoams Composed of Tribehenoyl-glycerol: Toward a Stable and Higher Air-content Colloidal System.

Oleofoams have garnered significant attention in many personal care applications because of their favorable physicochemical properties, including texture and detergency. To explore the potential use of mixtures of high-melting-point fat crystals (tribehenoyl-glycerol [BBB]) and edible oils as low-cost and stable aeration systems, we created oleofoams composed of olive oil and BBB. By whipping the BBB/olive oil oleogels after rapid cooling and subsequent heating, we successfully prepared oleofoams without emulsifier additives. Mixtures of the BBB/olive oil formed oleofoams at BBB concentrations of 4.0-20.0 wt.%. The resultant oleofoams maintained their overrun rates and did not coalesce, even with additional whipping after the overrun rate was maximized. More closely packed bubbles, concentrated bubble size distributions, and stronger interfacial elasticity were attributed to the increasing BBB concentrations, and the thermal results revealed that further heating was required to damage the foam structure. The characteristics of these new oleofoams are closely related to their BBB concentrations, and the observed effects are attributed to the network structure of the thickened crystal layer and enhanced gelling in the oil phase.

Cor triatriatum sinister with dextrocardia in association with ostium secundum atrial septal defect, subpulmonary ventricular septal defect and bicuspid pulmonary valve in a pig.

Necropsy of a 52-day-old Camborough pig revealed numerous cardiac malformations. The positional relationship of the atria, ventricles and great vessels was a mirror image type (I, L and L): inverted arrangement of the atria, with a left-sided right atrium and right-sided left atrium (situs inversus); inverted arrangement of the ventricles, with a left-sided morphological right ventricle and right-sided morphological left ventricle (L-loop); and aortic valve to the front left relative to the pulmonary valve (L-malposed). The major malformations included an ostium secundum atrial septal defect, cor triatriatum sinister (CTS), a subpulmonary ventricular septal defect and a bicuspid pulmonary valve. Histological examination revealed myocyte hypertrophy, focal myocardial necrosis and calcification in the left morphological right ventricle of the heart. To the best of our knowledge, this is the first report of CTS in pigs. Although the individual malformations found in the present case are not unique, an unusual combination of these cardiac malformations has not been described in animals.

Refusal of Subsequent Treatment in Patients With EGFR-mutant Non-small-cell Lung Cancer After Response to EGFR-TKIs.

BACKGROUND/AIM: During the course of effective and long-term treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), some elderly patients might decline further treatment after EGFR-TKI. We conducted a study to try and understand the reasons for this treatment decision. PATIENTS AND METHODS: We analyzed the medical records of all patients diagnosed with non-small-cell lung cancer with EGFR mutations between 2016 and 2021. RESULTS: There were 108 patients who received EGFR-TKIs. Of these, 67 patients responded to TKI. These responding patients were divided into two groups according to whether they received subsequent TKI treatment. At their request, 24 patients (group A) did not receive further anticancer treatment following TKI. The other 43 patients (group B) received anticancer therapy following TKI. Progression-free survival in group A patients was significantly longer (median=18 months, range=1-67 months) than in group B patients. The reasons for not wanting subsequent treatment after TKI were older age, reduced general condition, deterioration of physical comorbid disease and dementia. Dementia was the most common reason for patients over 75 years of age. CONCLUSION: Some elderly patients with well-controlled disease might express their refusal of all subsequent anticancer therapy after TKIs. Medical staff should respond seriously to these requests.

Surf4 modulates STIM1-dependent calcium entry.

Store-operated Ca(2+) entry (SOCE) is crucial for various physiological responses in immune cells. Although it is known that STIM1 relocates into discrete puncta juxtaposed to the plasma membrane to initiate SOCE, the machinery modulating the function of STIM1 remains unclear. We explored to find its modulators using affinity purification for STIM1-binding proteins and identified surfeit locus protein 4 (Surf4). Surf4 associated with STIM1 in the endoplasmic reticulum. Deletion of Surf4 in DT40 B cells resulted in marked increase of SOCE and facilitation of STIM1 clustering upon store-depletion. These findings suggest the modulatory function of Surf4 for STIM1-mediated SOCE.

Repeated-Dose Pharmacodynamics of Pimobendan in Healthy Cats.

The aims of this study were to investigate the effects of repeated and multiple-dose pimobendan on cardiac systolic function and the correlations between changes in cardiac systolic function and plasma concentrations of pimobendan and O-desmethylpimobendan (ODMP). Five clinically healthy cats were subjected to four different medication protocols for 14 days, with a washout period of at least 1 month between each protocol. The protocols were pimobendan 0.5 mg/kg q12h (high dosage [HD] group); pimobendan 0.25 mg/kg q12h (standard dosage [SD] group); pimobendan 0.125 mg/kg q12h (low dosage group); and Biofermin R, one tablet q12h (placebo group). Echocardiography and measurement of plasma concentrations of pimobendan and ODMP were performed prior to medication administration (baseline) and 20, 40, 60, 120, 240, 360, and 480 min after administration, and the correlation between the changes in cardiac systolic function and plasma concentration of pimobendan, ODMP, or the sum of both were examined. The cardiac systolic function increased in the HD and SD groups, and there were significant correlations between the lateral peak systolic myocardial velocity (S') changes and plasma pimobendan, plasma ODMP, and the sum of both. Repeated doses of pimobendan in healthy cats increased cardiac systolic function, and there were significant correlations between cardiac function and plasma concentrations of pimobendan and ODMP. The results of this study highlight the effectiveness of a higher dose of pimobendan.

Reference intervals for echocardiographic measurements in healthy Chihuahua dogs.

Chihuahuas are one of the most common small breed dogs in Japan, and this breed is known to be predisposed to myxomatous mitral valve disease (MMVD). Echocardiographic assessment is essential for definitive diagnosis of MMVD in dogs as well as determining the stage. Because the Chihuahua's body size is the smallest among the dog breeds and the widely used echocardiographic reference range is established on the basis of larger dogs, it is unclear whether the existing reference range can be applied to the Chihuahua breed as well. Therefore, this study aimed to determine an echocardiographic reference range for Chihuahua dogs. The left atrial short-axis diameter (LA), aortic valve short-axis diameter, interventricular septum thickness at end-diastole, left ventricular internal dimension at end-diastole (LVIDd), and left ventricular posterior wall thickness at end-diastole from 47 healthy Chihuahuas were analyzed. These parameters increased logarithmically as body weight increased. Furthermore, LA and LVIDd were within the previously established reference range generated primarily from multiple breeds of moderate to large breed dogs.

Effects of combined one-lung ventilation and intrathoracic carbon dioxide insufflation on intrathoracic working space when performing thoracoscopy in dogs.

OBJECTIVE: To evaluate the effects of combining one-lung ventilation and carbon dioxide insufflation (OLV-CDI) on intrathoracic working space (determined by means of CT) during thoracoscopy in dogs and investigate conditions that could safely improve working space compared with OLV alone. ANIMALS: 6 healthy Beagles. PROCEDURES: Dogs were anesthetized, and right- or left-sided (n = 3/side) OLV was instituted. On the blocked side, a laparoscopic trocar sleeve was placed in the ninth intercostal space for CDI. CT was performed under 3 conditions: with OLV alone, with OLV-CDI at an intrapleural pressure (IPP) of 3 mm Hg, and with OLV-CDI at an IPP of 5 mm Hg. Working space volume (WSV), ventilation space volume (VSV), and thoracic cavity volume (TCV) were determined from CT images. RESULTS: With OLV-CDI at an IPP of 3 or 5 mm Hg, WSV and TCV were significantly increased, compared with values obtained during OLV alone. With OLV-CDI at an IPP of 5 mm Hg, VSV and Spo2 were significantly decreased, compared with values obtained during OLV alone. Additionally, contralateral pneumothorax was observed in 4 dogs at an IPP of 5 mm Hg. CLINICAL RELEVANCE: Combining OLV and CDI could provide a larger working space than OLV alone, even with an IPP of 3 mm Hg, in dogs of limited size. However, an evaluation of the effects on oxygenation and cardiovascular variables is needed before clinical use.

Assessment of left ventricular regional function in affected and carrier dogs with Duchenne muscular dystrophy using speckle tracking echocardiography.

BACKGROUND: Two-dimensional speckle tracking echocardiography (STE) is a relatively new method to detect regional myocardial dysfunction. To assess left ventricular (LV) regional myocardial dysfunction using STE in Duchenne muscular dystrophy model dogs (CXMD(J)) without overt clinical signs of heart failure. METHODS: Six affected dogs, 8 carrier dogs with CXMD(J), and 8 control dogs were used. Conventional echocardiography, systolic and diastolic function by Doppler echocardiography, tissue Doppler imaging (TDI), and strain indices using STE, were assessed and compared among the 3 groups. RESULTS: Significant differences were seen in body weight, transmitral E wave and E' wave derived from TDI among the 3 groups. Although no significant difference was observed in any global strain indices, in segmental analysis, the peak radial strain rate during early diastole in posterior segment at chordae the tendineae level showed significant differences among the 3 groups. CONCLUSIONS: The myocardial strain rate by STE served to detect the impaired cardiac diastolic function in CXMD(J) without any obvious LV dilation or clinical signs. The radial strain rate may be a useful parameter to detect early myocardial impairment in CXMD(J).

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy.

AIMS: To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM). METHODS: We enrolled a total of 141 HCM patients with sinus rhythm and normal pump function, and 102 patients (73 men; mean age, 61±13 years) who met inclusion criteria were followed for 30.8±10.0 months. The patients were divided into two groups with or without major adverse cardiac and cerebrovascular events (MACCE), a composite of stroke, sudden death, and congestive heart failure. Detailed clinical and echocardiographic data were obtained. RESULTS: MACCE occurred in 24 patients (18 strokes, 4 congestive heart failure and 2 sudden deaths). Maximum LAV, minimum LAV, and LAV index (LAVI) corrected for body surface area (BSA) were significantly greater in patients with MACCE than those without MACCE (maximum LAV: 64.3±25.0 vs. 51.9±16.0 ml, p=0.005; minimum LAV: 33.9±15.1 vs. 26.2±10.9 ml, p=0.008; LAVI: 40.1±15.4 vs. 31.5±8.7 ml/mm2, p=0.0009), while there were no differences in the other echocardiographic parameters.LAV/BSA of ≥40.4 ml/m2 to identify patients with cardiovascular complications with a sensitivity of 73% and a specificity of 88%. CONCLUSION: LAVI may be an effective marker for detecting the risk of MACCE in patients with HCM and normal pump function.

Fatal aortic endocarditis associated with community-acquired Serratia marcescens infection in a dog.

A 12 yr old Dalmatian was referred for evaluation of acute lethargy, fever, neurologic signs, and a recently ausculted heart murmur. Echocardiography in combination with blood cultures resulted in a diagnosis of nonhospital-acquired Serratia marcescens bacteremia and aortic valve endocarditis. Despite early diagnosis and aggressive therapy, the dog failed to respond to antimicrobials and died within 6 hr after admission. Necropsy findings included aortic valve endocarditis, septicemia, and diffuse thromboembolic disease. There was no history of pre-existing underlying disease or immunosuppressive therapy, and the dog had not been hospitalized before referral.

Longitudinal evaluation of cardiovascular function in six healthy cats aged 1-8 years.

OBJECTIVES: The purpose of this study was to determine the impact of ageing on the cardiovascular system of healthy adult cats. METHODS: Six experimental cats were used. Echocardiography and measurements of systolic blood pressure (SBP) were performed every year for 8 years (from 1 year of age to 8 years of age) in all cats. Age-related changes to left ventricular (LV) structures, LV systolic and diastolic function, and SBP were assessed. RESULTS: There were no significant changes in LV structures and SBP. Peak longitudinal strain rate during systole was decreased at 8 years of age, and peak longitudinal strain rate during diastole was decreased from 6 years of age. CONCLUSIONS AND RELEVANCE: This study revealed that some measures of cardiac function recorded in six healthy cats from 1 to 8 years of age were affected as the cats got older; however, there were no structural changes or changes in measurements that are routinely assessed in clinical practice.

Normal values of combinational elastography in adult liver: the influence of age.

PURPOSE: We aimed to clarify the normal values obtained by simultaneous use of shear wave imaging and strain imaging (combinational elastography) in liver and reveal how aging influences them. METHODS: In our checkup center, 257 examinees were diagnosed with normal liver based on questionnaires about liver disease and their drinking history, liver function test results, and ultrasound B-mode study findings. We estimated the values of combinational elastography and considered the correlation between the values and age. A multivariate analysis was performed concerning several features and the liver fibrosis (LF) index. We divided examinees into a younger group (< 65 years old) and an older group (≥ 65 years old), and assessed the effect of age on the LF index. RESULTS: The mean shear wave velocity (Vs) of shear wave measurement (SWM) was 1.10 ± 0.17 m/s (range 0.84-1.93), and the mean LF index of real-time tissue elastography (RTE) was 1.371 ± 0.458 (range 0.258-3.173). There was no significant correlation between Vs and age. However, the LF index increased significantly with age. The multivariate analysis showed that age (P < 0.001) and BMI (P < 0.05) significantly affected the LF index. Indeed, the LF index in the older group was significantly higher than that in the younger group (P < 0.001). CONCLUSION: In adult liver, the normal Vs of SWM was 1.10 ± 0.17 m/s, and the normal LF index of RTE was 1.371 ± 0.458. The LF index increased significantly with age in contrast to Vs; therefore, the influence of age should be considered when using combinational elastography.

Comparison of left ventricular contraction profiles among small, medium, and large dogs by use of two-dimensional speckle-tracking echocardiography.

OBJECTIVE: To assess differences in left ventricular contractile indices among dogs of 3 body sizes via 2-D speckle-tracking echocardiography (STE) and to determine body weight-independent systolic variables. ANIMALS: 37 clinically normal adult dogs. PROCEDURES: Dogs were allocated into 3 groups on the basis of body weight: small (<7kg), medium (7 to 20kg), and large (>20kg). Right parasternal short-axis echocardiographic views were acquired to measure conventional M-mode variables (left ventricular internal diameter at end diastole, left ventricular internal diameter at end systole, and fractional shortening [FS]) and STE indices (peak systolic strain, peak systolic strain rate, synchrony time index [STI], peak systolic apical rotation, peak systolic basal rotation, peak apical twisting rate, and peak systolic torsion). Values were compared among the 3 groups. RESULTS: STE indices, except for peak systolic radial strain (SRad), peak systolic basal rotation, and STI, were significantly decreased in large dogs, compared with values for small and medium dogs. No significant difference was detected in stroke index, peak systolic SRad, and peak systolic basal rotation among the 3 groups. The STI in large dogs was significantly increased, compared with that of medium dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results revealed that decreased systolic indices in large dogs should not be interpreted as signs of decreased systolic function. Increased STI in large dogs may contribute to decreased FS. Because peak systolic SRad was not affected by body weight, peak systolic SRad might be a better variable than FS for assessing systolic function.