Fetal cardiac muscle contractility decreases with gestational age: a color-coded tissue velocity imaging study

Abstract Background Present data regarding how the fetal heart works and develops throughout gestation is limited. However, the possibility to analyze the myocardial velocity profile provides new possibilities to gain further knowledge in this area. Thus, the objective of this study was to evaluate human fetal myocardial characteristics and deformation properties using color-coded tissue velocity imaging (TVI). Methods TVI recordings from 55 healthy fetuses, at 18 to 42 weeks of gestation, were acquired at a frame rate of 201–273 frames/s for offline analysis using software enabling retrieval of the myocardial velocity curve and 2D anatomical information. The measurements were taken from an apical four-chamber view, and the acquired data was correlated using regression analysis. Results Left ventricular length and width increased uniformly with gestational age. Atrioventricular plane displacement and the E’/A’ ratio also increased with gestational age, while a longitudinal shortening was demonstrated. Conclusions Fetal cardiac muscle contractility decreases with gestational age. As numerous fetal- and pregnancy-associated conditions directly influence the pumping function of the fetal heart, we believe that this new insight into the physiology of the human fetal cardiovascular system could contribute to make diagnosis and risk assessment easier and more accurate.</p

The Cardiac State Diagram As A Novel Approach For The Evaluation Of Pre- And Post-Ejection Phases Of The Cardiac Cycle In Asphyxiated Fetal Lambs

The aim of this study was to investigate myocardial wall motion using echocardiography and color-coded tissue velocity imaging and to generate a cardiac state diagram for evaluation of the duration of the pre- and post-ejection phases in asphyxiated fetal lambs. Six near-term lambs were partly exteriorized and brought to cardiac arrest through asphyxia. Echocardiography measurements were recorded simultaneously with arterial blood sampling for lactate and blood gases. All fetal lambs exhibited prolongation of the pre- and post-ejection phases at the time when the most pronounced changes in lactate concentration and pH occurred. The mean change in duration of the pre- and post-ejection phases for all fetal lambs was 36 +/- 7 ms (p < 0.002) and 77 +/- 17 ms (p < 0.019), respectively, and the percentage change was 50% (p < 0.001) and 38% (p < 0.049), respectively. As asphyxia progressed in fetal lambs, the duration of the pre- and post-ejection phases increased. The cardiac state diagram has the potential to be a comprehensible tool for detecting fetal asphyxia. (E-mail: [email protected]) (C) 2013 World Federation for Ultrasound in Medicine & Biology

A Systematic Screen for CDK4/6 Substrates Links FOXM1 Phosphorylation to Senescence Suppression in Cancer Cells

SummaryCyclin D-dependent kinases (CDK4 and CDK6) are positive regulators of cell cycle entry and they are overactive in the majority of human cancers. However, it is currently not completely understood by which cellular mechanisms CDK4/6 promote tumorigenesis, largely due to the limited number of identified substrates. Here we performed a systematic screen for substrates of cyclin D1-CDK4 and cyclin D3-CDK6. We identified the Forkhead Box M1 (FOXM1) transcription factor as a common critical phosphorylation target. CDK4/6 stabilize and activate FOXM1, thereby maintain expression of G1/S phase genes, suppress the levels of reactive oxygen species (ROS), and protect cancer cells from senescence. Melanoma cells, unlike melanocytes, are highly reliant on CDK4/6-mediated senescence suppression, which makes them particularly susceptible to CDK4/6 inhibition