A novel infrasound and audible machine-learning approach to the diagnosis of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) outbreak has rapidly spread around the world, causing a global public health and economic crisis. A critical limitation in detecting COVID-19-related pneumonia is that it is often manifested as a "silent pneumonia", i.e. pulmonary auscultation that sounds "normal" using a standard stethoscope. Chest computed tomography is the gold standard for detecting COVID-19 pneumonia; however, radiation exposure, availability and cost preclude its utilisation as a screening tool for COVID-19 pneumonia. In this study we hypothesised that COVID-19 pneumonia, "silent" to the human ear using a standard stethoscope, is detectable using a full-spectrum auscultation device that contains a machine-learning analysis. Methods: Lung sound signals were acquired, using a novel full-spectrum (3-2000 Hz) stethoscope, from 164 COVID-19 pneumonia patients, 61 non-COVID-19 pneumonia patients and 141 healthy subjects. A machine-learning classifier was constructed and the data were classified into three groups: 1) normal lung sounds, 2) COVID-19 pneumonia and 3) non-COVID-19 pneumonia. Results: Standard auscultation found that 72% of the non-COVID-19 pneumonia patients had abnormal lung sounds compared with only 25% of the COVID-19 pneumonia patients. The classifier's sensitivity and specificity for the detection of COVID-19 pneumonia were 97% and 93%, respectively, when analysing the sound and infrasound data, and they were reduced to 93% and 80%, respectively, without the infrasound data (p<0.01 difference in receiver operating characteristic curves with and without infrasound). Conclusions: This study reveals that useful clinical information exists in the infrasound spectrum of COVID-19-related pneumonia and machine-learning analysis applied to the full spectrum of lung sounds is useful in its detection.

Speckled Tracking of Pleura-A Novel Tool for Lung Ultrasound; Distinguishing COVID-19 from Acute Heart Failure.

For the acutely dyspneic patient, discerning bedside between acute decompensated heart failure (ADHF) and COVID-19 is crucial. A lung ultrasound (LUS) is sensitive for detecting these conditions, but not in distinguishing between them; both have bilateral B-lines. The Blue protocol uses pleural sliding to differentiate decreased pneumonia; however, this is not the case in ADHF. Nonetheless, this pleural sliding has never been quantified. Speckled tracking is a technology utilized in the echocardiography field that quantifies the motion of tissues by examining the movement of ultrasound speckles. We conducted a retrospective study of LUS performed in emergency room patients during the COVID-19 pandemic. Speckled tracking of the pleura by applying software to the B-mode of pleura was compared between COVID-19 patients, ADHF patients, and patients with no respiratory complaints. A significant difference was found between the patient groups on speckled tracking both in respect of displacement and velocity. ADHF had the highest displacement, followed by COVID-19, and then non-respiratory patients: 1.63 ± 1.89, 0.59 ± 0.71, and 0.24 ± 0.45, respectively (p < 0.01). A similar trend was seen in velocity with ADHF having the highest velocity 0.34 ± 0.37, followed by COVID-19 0.14 ± 0.71, and non-respiratory patients 0.02 ± 0.09 (p <0.01). Speckled tracking of the pleura is a potential tool for discerning between different causes of dyspnea.

A comparison of the power of breathing sounds signals acquired with a smart stethoscope from a cohort of COVID-19 patients at peak disease, and pre-discharge from the hospital.

Objectives: To characterize the frequencies of breathing sounds signals (BS) in COVID-19 patients at peak disease and pre-discharge from hospitalization using a Smart stethoscope. Methods: Prospective cohort study conducted during the first COVID-19 wave (April-August 2020) in Israel. COVID-19 patients (n = 19) were validated by SARS-Cov-2 PCR test. The healthy control group was composed of 153 volunteers who stated that they were healthy. Power of BS was calculated in the frequency ranges of 0-20, 0-200, and 0-2000 Hz. Results: The power calculated over frequency ranges 0-20, 20-200, and 200-2000 Hz contributed approximately 45%, 45%, and 10% to the total power calculated over the range 0-2000 Hz, respectively. Total power calculated from the right side of the back showed an increase of 45-80% during peak disease compared with the healthy controls (p < 0.05). The power calculated over the back, in the infrasound range, 0-20 Hz, and not in the 20-2000 Hz range, was greater for the healthy controls than for patients. Using all 3 ranges of frequencies for distinguishing peak disease from healthy controls resulted in sensitivity and specificity of 84% and 91%, respectively. Omitting the 0-20 Hz range resulted in sensitivity and specificity of 74% and 67%, respectively. Discussion: The BS power acquired from COVID-19 patients at peak disease was significantly greater than that at pre-discharge from the hospital. The infrasound range had a significant contribution to the total power. Although the source of the infrasound is not presently clear, it may serve as an automated diagnostic tool when more clinical experience is gained with this method.

Artificial Intelligence-Based Stethoscope for the Diagnosis of Aortic Stenosis.

BACKGROUND: The diagnostic accuracy of the stethoscope is limited and highly dependent on clinical expertise. Our purpose was to develop an electronic stethoscope, based on artificial intelligence (AI) and infrasound, for the diagnosis of aortic stenosis (AS). METHODS: We used an electronic stethoscope (VoqX; Sanolla, Nesher, Israel) with subsonic capabilities and acoustic range of 3-2000 Hz. The study had 2 stages. In the first stage, using the VoqX, we recorded heart sounds from 100 patients referred for echocardiography (derivation group), 50 with moderate or severe AS and 50 without valvular disease. An AI-based supervised learning model was applied to the auscultation data from the first 100 patients used for training, to construct a diagnostic algorithm that was then tested on a validation group (50 other patients, 25 with AS and 25 without AS). In the second stage, conducted at a different medical center, we tested the device on 106 additional patients referred for echocardiography, which included patients with other valvular diseases. RESULTS: Using data collected at the aortic and pulmonic auscultation points from the derivation group, the AI-based algorithm identified moderate or severe AS with 86% sensitivity and 100% specificity. When applied to the validation group, the sensitivity was 84% and specificity 92%; and in the additional testing group, 90% and 84%, respectively. The sensitivity was 55% for mild, 76% for moderate, and 93% for severe AS. CONCLUSION: Our initial findings show that an AI-based stethoscope with infrasound capabilities can accurately diagnose AS. AI-based electronic auscultation is a promising new tool for automatic screening and diagnosis of valvular heart disease.

Localized Antileptin Therapy Prevents Aortic Root Dilatation and Preserves Left Ventricular Systolic Function in a Murine Model of Marfan Syndrome.

Background Marfan syndrome (MFS) is a genetically transmitted connective tissue disorder characterized by aortic root dilatation, dissection, and rupture. Molecularly, MFS pathological features have been shown to be driven by increased angiotensin II in the aortic wall. Using an angiotensin II-driven aneurysm mouse model, we have recently demonstrated that local inhibition of leptin activity restricts aneurysm formation in the ascending and abdominal aorta. As we observed de novo leptin synthesis in the ascending aortic aneurysm wall of patients with MFS, we hypothesized that local counteracting of leptin activity in MFS may also prevent aortic cardiovascular complications in this context. Methods and Results Fbn1C1039G/+ mice underwent periaortic application of low-dose leptin antagonist at the aortic root. Treatment abolished medial degeneration and prevented increase in aortic root diameter (P<0.001). High levels of leptin, transforming growth factor ß1, Phosphorylated Small mothers against decapentaplegic 2, and angiotensin-converting enzyme 1 observed in saline-treated MFS mice were downregulated in leptin antagonist-treated animals (P<0.01, P<0.05, P<0.001, and P<0.001, respectively). Leptin and angiotensin-converting enzyme 1 expression levels in left ventricular cardiomyocytes were also decreased (P<0.001) and coincided with prevention of left ventricular hypertrophy and aortic and mitral valve leaflet thickening (P<0.01 and P<0.05, respectively) and systolic function preservation. Conclusions Local, periaortic application of leptin antagonist prevented aortic root dilatation and left ventricular valve remodeling, preserving left ventricular systolic function in an MFS mouse model. Our results suggest that local inhibition of leptin may constitute a novel, stand-alone approach to prevent MFS aortic root aneurysms and potentially other similar angiotensin II-driven aortic pathological features.

Newcastle disease virus: is an updated attenuated vaccine needed?

Newcastle disease virus (NDV) is a major cause of infectious mortality and morbidity in poultry worldwide. It is an enveloped virus with two outer-membrane proteins-haemagglutinin-neuraminidase (HN) and fusion protein (F)-that induce neutralizing antibodies. All NDV strains belong to one serotype. Yet, NDV vaccines, derived from genotype II, do not fully prevent infection or shedding of viruses from other genotypes. The aim of this study was to test if an updated vaccine is required. For this purpose, NDVs isolated from infected, albeit heavily vaccinated, flocks were genetically and immunologically characterized. Amino acid differences in F and HN protein sequences were identified between the vaccine strain and each of the isolates, some specifically at the neutralization sites. Whereas all tested isolates showed similar haemagglutination-inhibition (HI) titres, 100-100,000 times higher antibody-to-virus ratios were needed to neutralize viral propagation in embryos by the field isolates versus the vaccine strain. As a result, a model and an equation were developed to explain the phenomenon of escape in one-serotype viruses and to calculate the HI values needed for protection, depending on variation rate at key positions. In conclusion, to confer full protection against NDVs that differ from the vaccine strain at the neutralizing epitopes, very high levels of antibodies should be raised and maintained to compensate for the reduction in the number of effective epitopes; alternatively, an adjusted attenuated vaccine should be developed-a task made possible in the current era of reverse vaccinology.

High-Intensity Training Improves Global and Segmental Strains in Severe Congestive Heart Failure.

BACKGROUND: High-intensity training (HIT) is superior to moderate aerobic training (MAT) for improving quality of life in congestive heart failure (CHF) patients. Speckle-tracking echocardiography (STE) has recently been suggested for estimation of left ventricle global and regional function. We evaluated the utility of STE for characterizing differences in cardiac function following MAT or HIT in a CHF rat model. METHODS AND RESULTS: After baseline physiologic assessment, CHF was induced by means of coronary artery ligation in Sprague-Dawley rats. Repeated measurements confirmed the presence of CHF (ejection fraction 52 ± 10%, global circumferential strain (GCS) 10.5 ± 4, and maximal oxygen uptake (V˙O2max) 71 ± 11 mL⋅min-1⋅kg-1; P < .001 vs baseline for all). Subsequently, rats were divided into training protocols: sedentary (SED), MAT, or HIT. After the training period, rats underwent the same measurements and were killed. Training intensity improved V˙O2max (73 ± 13 mL⋅min-1⋅kg-1 in MAT [P < .01 vs baseline] and 82 ± 6 mL⋅min-1⋅kg-1 in HIT [P < .05 vs baseline or SED] and ejection fraction (50 ± 21% in MAT [P < .001 vs baseline] and 66 ± 7% in HIT [P > .05 vs baseline]). In addition, strains of specific segments adjacent to the infarct zone regained basal values (P > .05 vs baseline), whereas global cardiac functional parameters as assessed with the use of 2-dimensional echocardiography did not improve. CONCLUSIONS: High-intensity exercise training improved function in myocardial segments remote from the scar, which resulted in compensatory cardiac remodeling. This effect is prominent, yet it could be detected only with the use of STE.

Detection of small subendocardial infarction using speckle tracking echocardiography in a rat model.

BACKGROUND: It is challenging to detect small nontransmural infarcts visually or automatically. As it is important to detect myocardial infarction (MI) at early stages, we tested the hypothesis that small nontransmural MI can be detected using speckle tracking echocardiography (STE) at the acute stage. METHODS: Minimal nontransmural infarcts were induced in 18 rats by causing recurrent ischemia-reperfusion of the left anterior descending (LAD) coronary artery, followed by a 30-min ligation and by reperfusion. A week later, the scar size was measured by histological analysis. Each rat underwent three echocardiography measurements: at baseline, 1 day post-MI, and 1 week post-MI. To measure the peak circumferential strain (CS), peak systolic CS, radial strain (RS), and time-to-peak (TTP) of the CS, short-axis view of the apex was analyzed by a STE program. The TTP was normalized by the duration of the heart cycle to create percent change of heart cycle. RESULTS: Histological analysis after 1 week showed scar size of 4±6% at the anterior wall. At 24 h post-MI, the peak CS, peak systolic CS, and RS were reduced compared to baseline at the anterior wall due to the MI, and at the adjacent segments-the anterior septum and lateral wall, due to stunning (P<.05). However, only the anterior wall, the genuine damaged segment, showed prolonged TTP vs baseline (baseline 36%, 24 h 48%, P<.05). CONCLUSION: The TTP of the CS can distinguish between regions adjacent to MI (stunned or tethered) and MI, even in small nontransmural infarcts.

Local Application of Leptin Antagonist Attenuates Angiotensin II-Induced Ascending Aortic Aneurysm and Cardiac Remodeling.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is driven by angiotensin II (AngII) and contributes to the development of left ventricular (LV) remodeling through aortoventricular coupling. We previously showed that locally available leptin augments AngII-induced abdominal aortic aneurysms in apolipoprotein E-deficient mice. We hypothesized that locally synthesized leptin mediates AngII-induced ATAA. METHODS AND RESULTS: Following demonstration of leptin synthesis in samples of human ATAA associated with different etiologies, we modeled in situ leptin expression in apolipoprotein E-deficient mice by applying exogenous leptin on the surface of the ascending aorta. This treatment resulted in local aortic stiffening and dilation, LV hypertrophy, and thickening of aortic/mitral valve leaflets. Similar results were obtained in an AngII-infusion ATAA mouse model. To test the dependence of AngII-induced aortic and LV remodeling on leptin activity, a leptin antagonist was applied to the ascending aorta in AngII-infused mice. Locally applied single low-dose leptin antagonist moderated AngII-induced ascending aortic dilation and protected mice from ATAA rupture. Furthermore, LV hypertrophy was attenuated and thickening of aortic valve leaflets was moderated. Last, analysis of human aortic valve stenosis leaflets revealed de novo leptin synthesis, whereas exogenous leptin stimulated proliferation and promoted mineralization of human valve interstitial cells in culture. CONCLUSIONS: AngII-induced ATAA is mediated by locally synthesized leptin. Aortoventricular hemodynamic coupling drives LV hypertrophy and promotes early aortic valve lesions, possibly mediated by valvular in situ leptin synthesis. Clinical implementation of local leptin antagonist therapy may attenuate AngII-induced ATAA and moderate related LV hypertrophy and pre-aortic valve stenosis lesions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00449306.

The cardioprotective efficacy of TVP1022 against ischemia/reperfusion injury and cardiac remodeling in rats.

Following acute myocardial infarction (MI), early and successful reperfusion is the most effective strategy for reducing infarct size and improving the clinical outcome. However, immediate restoration of blood flow to the ischemic zone results in myocardial damage, defined as "reperfusion-injury". Whereas we previously reported that TVP1022 (the S-isomer of rasagiline, FDA-approved anti-Parkinson drug) decreased infarct size 24 h post ischemia reperfusion (I/R) in rats, in this study we investigated the chronic cardioprotective efficacy of TVP1022 14 days post-I/R. To simulate the clinical settings of acute MI followed by reperfusion therapy, we employed a rat model of left anterior descending artery occlusion for 30 min followed by reperfusion and a follow-up for 14 days. TVP1022 was initially administered postocclusion-prereperfusion, followed by chronic daily administrations. Cardiac performance and remodeling were evaluated using customary and advanced echocardiographic methods, hemodynamic measurements by Millar Mikro-Tip® catheter, and histopathological techniques. TVP1022 administration markedly decreased the remodeling process as illustrated by attenuation of left ventricular enlargement and cardiac hypertrophy (both at the whole heart and the cellular level). Furthermore, TVP1022 inhibited cardiac fibrosis and reduced ventricular BNP levels. Functionally, TVP1022 treatment preserved cardiac wall motion. Specifically, the echocardiographic and most of the direct hemodynamic measures were pronouncedly improved by TVP1022. Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R model.

Left Ventricular Mechanical Property Changes During Acute AV Synchronous Right Ventricular Pacing in Children.

Prolonged RV pacing is recognized as a cause of LV dysfunction due to dyssynchronous activation. There are no specific longitudinal parameters known to help predict RV pacing-induced LV dysfunction. The aim of the study was to assess the acute effects of AV synchronous RV pacing on LV mechanics using echocardiographic speckle tracking. Nineteen children, aged 6-23 years, underwent echocardiographic evaluation prior to and following elective electrophysiology and ablation studies. The subjects were evaluated in sinus rhythm and later with AV synchronous RV pacing at a cycle length of 550 ms with a short AV delay of 80 ms. The echocardiographic clips were analyzed using speckle tracking methods to calculate LV circumferential and longitudinal strain, rotation and twist in all conditions. Acute RV apical pacing decreased LV longitudinal strain from 16.1 ± 3.7% in sinus rhythm to 14.4 ± 3.3% (p = 0.03) and LV base rotation from -8.4° ± 3.6° to -6.4° ± 4.0° (p = 0.04). The circumferential strain, apical rotation and LV twist were not affected. Separate analysis of subjects with no prior preexcitation showed that acute RV pacing caused significant twist reduction, from 15.9° ± 7.6° to 12.1° ± 7.0° (p = 0.02), and decreased longitudinal strain and base rotation. Patients with preexcitation had abnormalities that persisted acutely after ablation. Acute RV apical pacing causes reductions in LV base rotation, longitudinal strain and twist. The recognition of abnormal LV activation patterns may provide longitudinal clues to LV dysfunction in chronically paced patients and potential novel indices of effective CRT interventions to reverse these abnormalities.

Strain Analysis in the Detection of Myocardial Infarction at the Acute and Chronic Stages.

BACKGROUND: Myocardial ischemia causes contractile dysfunction in ischemic, stunned, and tethered regions with larger infarcted zones having a negative prognostic impact on patients' outcomes. To distinguish the infarcted myocardium from the other regions, we investigated the diagnostic potential of circumferential strain (CS) and radial strain (RS) during the acute and chronic stages of myocardial infarction. METHODS: Ten pigs underwent 90-minute occlusion of the left anterior descending artery, followed by reperfusion. Echocardiography was performed at baseline, after 90-minute occlusion, and at 2 hours, 30, and 60 days postreperfusion. CS and RS were measured using speckle tracking echocardiography. Subsequently, the pigs were sacrificed, and histological analysis for infarct size was performed. RESULTS: After 90-minute occlusion, reduced strains were detected for all segments (infarcted anterior wall - baseline: CS: -17.6 ± 5.7%, RS: 54.4 ± 16.9%; 90 min: CS: -10.3 ± 3.0%, RS: 23.3 ± 7.0%; tethered posterior wall - baseline: CS: -18.4 ± 3.5%, RS: 68.7 ± 21.1%; 90 min: CS: -10.7 ± 6.4%, RS: 34.5 ± 14.7%, P < 0.001). However, postsystolic shortening was detected only in the infarcted segments, and the time-to-peak CS was 25% longer (P < 0.05). At 30 and 60 days postreperfusion, time-to-peak CS could only detect large scars in the anterior and anterior-septum walls (P < 0.05), while peak CS also detected smaller scars in the lateral wall (P < 0.05). RS failed to distinguish between normal, stunned/tethered, and infarcted myocardium. CONCLUSIONS: During occlusion and 2 hours postreperfusion, time-to-peak CS could distinguish between infarcted and stunned/tethered myocardial segments, while at 30 and 60 days postreperfusion, peak CS was the best detector of infarction.

TVP1022: A Novel Cardioprotective Drug Attenuates Left Ventricular Remodeling After Ischemia/Reperfusion in Pigs.

BACKGROUND: The current cornerstone treatment of myocardial infarction (MI) is restoration of coronary blood flow by means of thrombolytic therapy or primary percutaneous coronary intervention. However, reperfusion of ischemic myocardium can actually provoke tissue damage, defined as "ischemia-reperfusion (I/R) injury." TVP1022 [the S-isomer of rasagiline (Azilect), FDA-approved anti-Parkinson's drug] was found to exert cardioprotective activities against various cardiac insults, such as chronic heart failure and I/R, in rat models. Therefore, we tested the hypothesis that TVP1022 will provide cardioprotection against I/R injury and post-MI remodeling in a pig model. METHODS: For inducing MI, we used an I/R model of midleft anterior descending artery occlusion for 90 minutes followed by follow-up for 8 weeks in 18 farm pigs (9 pigs in each group, MI + TVP1022 or MI + Vehicle). Echocardiographic measurements were performed and cardiac scar size was calculated using histopathological methods. For fibrosis evaluation, we measured the interstitial collagen volume fraction in the remote noninfarcted tissue. RESULTS: TVP1022 administration significantly decreased cardiac scar size, attenuated left ventricular dilation, and improved cardiac function assessed by segmental circumferential strain analysis. Furthermore, TVP1022 significantly reduced myocardial fibrosis 8 weeks post-MI. CONCLUSIONS: Collectively, these findings indicate that TVP1022 provides prominent cardioprotection against I/R injury and post-MI remodeling in this I/R pig model.

Layer-specific strain analysis: investigation of regional deformations in a rat model of acute versus chronic myocardial infarction.

Myocardial infarction (MI) injury extends from the endocardium toward the epicardium. This phenomenon should be taken into consideration in the detection of MI. To study the extent of damage at different stages of MI, we hypothesized that measurement of layer-specific strain will allow better delineation of the MI extent than total wall thickness strain at acute stages but not at chronic stages, when fibrosis and remodeling have already occurred. After baseline echocardiography scans had been obtained, 24 rats underwent occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion. Thirteen rats were rescanned at 24 h post-MI and eleven rats at 2 wk post-MI. Next, rats were euthanized, and histological analysis for MI size was performed. Echocardiographic scans were postprocessed by a layer-specific speckle tracking program to measure the peak circumferential strain (S(C)(peak)) at the endocardium, midlayer, and epicardium as well as total wall thickness S(C)(peak). Linear regression for MI size versus S(C)(peak) showed that the slope was steeper for the endocardium compared with the other layers (P < 0.001), meaning that the endocardium was more sensitive to MI size than the other layers. Moreover, receiver operating characteristics analysis yielded better sensitivity and specificity in the detection of MI using endocardial S(C)(peak) instead of total wall thickness S(C)(peak) at 24 h post-MI (P < 0.05) but not 2 wk later. In conclusion, at acute stages of MI, before collagen deposition, scar tissue formation, and remodeling have occurred, damage may be nontransmural, and thus the use of endocardial S(C)(peak) is advantageous over total wall thickness S(C)(peak).

Speckle tracking imaging in acute inflammatory pericardial diseases.

BACKGROUND: Left ventricular (LV) function in acute perimyocarditis is variable. We evaluated LV function in patients with acute perimyocarditis with speckle tracking. METHODS: Thirty-eight patients with acute perimyocarditis and 20 normal subjects underwent echocardiographic examination. Three-layers strain and twist angle were assessed with a speckle tracking. Follow-up echo was available in 21 patients. RESULTS: Strain was higher in normal subjects than in patients with perimyocarditis. Twist angle was reduced in perimyocarditis--10.9° ± 5.4 versus 17.6° ± 5.8, P < 0.001. Longitudinal strain and twist angle were higher in normal subjects than in patients with perimyocarditis and apparently normal LV function. Follow-up echo in 21 patients revealed improvement in longitudinal strain. CONCLUSIONS: Patients with acute perimyocarditis have lower twist angle, longitudinal and circumferential strain. Patients with perimyocarditis and normal function have lower longitudinal strain and twist angle. Short-term follow-up demonstrated improvement in clinical parameters and longitudinal strain despite of residual regional LV dysfunction.

The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion.

BACKGROUND AND PURPOSE: Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischaemia and reperfusion (I/R) damage is the focus of intense research. Based on our in vitro findings showing that TVP1022 (the S-enantiomer of rasagiline, an anti-Parkinsonian drug) possesses cardioprotective effects, in the present study we investigated the hypothesis that TVP1022 can attenuate myocardial damage in an I/R model in rats. EXPERIMENTAL APPROACH: The model consisted of 30-min occlusion of the left anterior descending artery followed by 4 or 24 h reperfusion. In addition, we investigated the possible mechanisms of cardioprotection in H9c2 cells and neonatal rat ventricular myocytes (NRVM) exposed to oxidative stress induced by H(2) O(2) . KEY RESULTS: TVP1022 (20 and 40 mg·kg(-1) ) administered 5 min before reperfusion followed by an additional dose 4 h after reperfusion reduced the infarct size and attenuated the decline in ventricular function. TVP1022 also attenuated I/R-induced deterioration in cardiac mitochondrial integrity evaluated by mitochondrial swelling capacity. In vitro, using H9c2 cells and NRVM, TVP1022 attenuated both serum free- and H(2) O(2) -induced damage, preserved mitochondrial membrane potential and Bcl-2 levels, inhibited mitochondrial cytochrome c release and the increase in cleaved caspase 9 and 3 levels, and enhanced the phosphorylation of protein kinase C and glycogen synthase kinase-3ß. CONCLUSIONS AND IMPLICATIONS: TVP1022 provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage resulting from I/R injuries.

Layer-specific assessment of left ventricular function by utilizing wavelet de-noising: a validation study.

Regional myocardial function assessment is essential for diagnosis and evaluation of heart disease. The purpose of this study was to enhance the spatial resolution of a speckle tracking echocardiography approach and enable layer-specific analysis of the myocardium. Following validation with software-implemented and mechanical phantoms versus imposed values, short-axis cines were obtained from 50 rats. The cines were post-processed by a speckle tracking commercial program, and the myocardial velocities were processed by a three-dimensional wavelet de-noising program, instead of the built-in smoothing process of the commercial program. Software-implemented phantom measurements yielded rotation errors of 7.5%, 2.9%, and 3.4%, for inner, middle, and outer layers, respectively. Analysis of a shrinking/expanding mechanical phantom yielded strain errors of 3%, 5%, and 7% for the three layers. Bland-Altman analysis showed agreement between the commercial and enhanced programs. Thus, layer-specific analysis is feasible while using echocardiography even on small animals such as rats.

Layer-specific strain analysis by speckle tracking echocardiography reveals differences in left ventricular function between rats and humans.

The rat heart is commonly used as an experimental model of the human heart in both health and disease states, assuming that heart function of rats and humans is alike. When studying a rat model, echocardiography is usually performed on sedated rats, whereas standard echocardiography on adult humans does not require any sedation. Since echocardiography results of sedated rats are usually inferred to alert humans, in the present study, we tested the hypothesis that differences in left ventricular (LV) function may be present between rats sedated by a low dose of ketamine-xylazine and alert humans. Echocardiography was applied to 110 healthy sedated rats and 120 healthy alert humans. Strain parameters were calculated from the scans using a layer-specific speckle tracking echocardiography program. The results showed that layer longitudinal strain is equal in rats and humans, whereas segmental strain is heterogeneous (P < 0.05) in a different way in rats and humans (P < 0.05). Furthermore, layer circumferential strain is larger in humans (P < 0.001), and the segmental results showed different segmental heterogeneity in rats and humans (P < 0.05). Radial strain was found to be homogeneous at the apex and papillary muscle levels in humans and heterogeneous in rats (P < 0.001). Additionally, whereas LV twist was equal in rats and humans, in rats the rotation was larger at the apex (P < 0.01) and smaller at the base (P < 0.001). The torsion-to-shortening ratio parameter, which indicates the transmural distribution of contractile myofibers, was found to be equal in rats and humans. Thus, when evaluating LV function of sedated rats under ketamine-xylazine, it is recommended to measure the global longitudinal strain, LV twist, and torsion-to-shortening ratio, since no scaling is required when converting these parameters and inferring them to humans.