Hemodynamic determinants of left atrial strain in patients with hypertrophic cardiomyopathy:A combined echocardiography and CMR study

BackgroundLeft atrial (LA) strain is associated with symptomatic status and atrial fibrillation in patients with hypertrophic cardiomyopathy (HCM). However, hemodynamic determinants of LA reservoir (LARS), conduit, and pump strains have not been examined and data are needed on the relation of LA strain with exercise tolerance in HCM.MethodsFifty HCM patients with echocardiographic and CMR imaging within 30 days were included. Left ventricular (LV) volumes, mass, EF, scar extent, extracellular volume fraction (ECV), and LA maximum volume were measured by CMR. Echo studies were analyzed for mitral inflow, pulmonary vein flow, mitral annulus tissue Doppler velocities, LV global longitudinal strain, and LA strain. Twenty six patients able and willing to exercise underwent cardiopulmonary stress testing for peak oxygen consumption (MVO2), and VE/VCO2 slope. Patients were followed for clinical events.FindingsLARS was significantly associated with indices of LA systolic function, LV GLS, and LV filling pressures (PConclusionsLV structure, systolic and diastolic function, and LA systolic function determine the 3 components of LA strain. LA strain is associated with exercise tolerance and clinical events in patients with HCM

The evaluation of the antiproliferative activity of selected compounds with high histamine H3 receptor affinity.

Doskonałym wstępem ogólnie pojmowanych badań toksykologicznych niezbędnych do określenia bezpieczeństwa nowych związków – kandydatów na leki są badania cytotoksyczności na hodowlach komórkowych in vitro. Termin cytotoksyczności ma często szerokie i źle definiowane znaczenie w odkrywaniu leków i rozwoju medycyny.W hodowlach komórkowych in vitro, związek lub substancję leczniczą uznaje się za cytotoksyczną jeśli zakłóca fizjologię komórki, znacząco zmieniając morfologię, co negatywnie wpływa na szybkość wzrostu albo powoduje jej śmierć. W zależności od przeznaczenia leczniczego danego związku, aktywność cytotoksyczna jest parametrem dyskwalifikującym lub aktywnością pożądaną, jak ma to miejsce w przypadku cytostatyków stosowanych w terapii chorób nowotworowych. Substancje chemiczne mogą w różny sposób wpływać na komórkę zaburzając jej procesy fizjologiczne, a zaistniałe zmiany można zaobserwować używając różnych technik pomiarowych jak np.: fluorymetrię, kolorymetrię, bioluminescencję.W niniejszej pracy starano się ocenić właściwości antyproliferacyjne wybranych ligandów receptora histaminowego H3. W przeprowadzonych badaniach in vitro na dwóch liniach komórkowych HEK-293 i IMR-32 jako związek odniesienia wykorzystano doksorubicynę o znanych wartościach IC50 dla tych obu linii komórkowych. Do oceny właściwości hamowania podziałów komórkowych zastosowano test EZ4U, którego metoda polega na zdolności żywych komórek do redukcji (o mało intensywnym zabarwieniu lub bezbarwnych) soli tetrazolu do zabarwionych pochodnych formazonu. W doświadczeniu użyto następujących stężeń badanych związków: 0,01-250 µM. W wyniku przeprowadzonego doświadczenia stwierdzono, iż badane związki wykazały słabe lub nieznaczące właściwości antyproliferacyjne.The perfect introduction to generally conceived toxicology studies, which are essential to establish the safety of drugs candidates, is the cytotoxicity analysis using cell cultures in vitro. The term cytotoxicity possess broad and often ill-defined role in drug discovery and development of medicine. In cell cultures in vitro, the compound or drug substance is considered to be cytotoxic if it interferes physiology of cells, significantly changing the morphology, which negatively affects the growth rate or cause her death. Depending on the intended use of the medicinal compound, the cytotoxic activity is a parameter disqualifying or is desired in the case of cytostatics used in cancer therapy. Chemicals may differently affect the cell interfering with the physiological processes, and these changes can be observed with different measuring techniques such as .: fluorimetry, colorimetry, bioluminescence. The aim of this thesis is the evaluation of the antiproliferative activity of selected compounds with high histamine H3 receptor affinity.The studies were conducted in vitro on two cell lines HEK-293 and IMR-32 using doxorubicin as a reference compound (the IC50 of doxorubicin against used cell lines were calculated previously). To evaluate the inhibition of cell proliferation the colorimetric EZ4U test was used. This method relies on the ability of viable cells to reduce (by low intensity color or colorless) tetrazolium salt to colored derivative - formazan. During the experiments the following concentrations of the histamine receptor ligands were used: 0,01-250 µM. As a result of the experiments it was found that the examined compounds possess weak or insignificant antiproliferative activity

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction–confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present