Placental oxidative stress and monoamine oxidase expression are increased in severe preeclampsia: a pilot study.

Preeclampsia (PE) is the most severe complication of pregnancy with substantial burden of morbidity and mortality for mother and neonate. The increased placental oxidative stress (OS) has been involved as central pathomechanism, yet the sources of reactive oxygen species (ROS) are partially elucidated. Monoamine oxidase (MAO) with 2 isoforms, A and B, at the outer mitochondrial membrane has emerged as a constant source of ROS in cardiometabolic pathologies. The present pilot study was purported to assess as follows: (i) the magnitude of placental OS in relation to the site of sampling and (ii) the expression of placental MAO in the setting of PE. To this aim, central and placental samples were harvested during cesarean section from mild and severe PE versus healthy pregnancies. ROS generation (dihydroethidium staining) and MAO expression were assessed (confocal microscopy). MAO gene transcript was evaluated by RT-PCR. The main findings are as follows: (i) a significant increase in placental OS was found in severe (but not in mild) PE with no regional differences between central and peripheral areas and (ii) placental MAO-A and B (gene and protein) were significantly increased in severe preeclampsia. The signal transduction of the latter finding, particularly in relation with mitochondrial dysfunction, is worth further studying.

Impairment of mitochondrial respiration in platelets and placentas: a pilot study in preeclamptic pregnancies.

Preeclampsia (PE) is a major complication of pregnancy with partially elucidated pathophysiology. Placental mitochondrial dysfunction has been increasingly studied as major pathomechanism in both early- and late-onset PE. Impairment of mitochondrial respiration in platelets has recently emerged as a peripheral biomarker that may mirror organ mitochondrial dysfunction in several acute and chronic pathologies. The present study was purported to assess mitochondrial respiratory dys/function in both platelets and placental mitochondria in PE pregnancies. To this aim, a high-resolution respirometry SUIT (Substrate-Uncoupler-Inhibitor-Titration) protocol was adapted to assess complex I (glutamate + malate)- and complex II (succinate)-supported respiration. A decrease in all respiratory parameters (basal, coupled, and maximal uncoupled respiration) in peripheral platelets was found in preeclamptic as compared to healthy pregnancies. At variance, placental mitochondria showed a dichotomous behavior in preeclampsia in relation to the fetal birth weight. PE pregnancies with fetal growth restriction were associated with decreased in coupled respiration (oxidative phosphorylation/OXPHOS capacity) and maximal uncoupled respiration (electron transfer/ET capacity). At variance, these respiratory parameters were increased for both complex I- and II-supported respiration in PE pregnancies with normal weight fetuses. Large randomized controlled clinical studies are needed in order to advance our understanding of mitochondrial adaptive vs. pathological changes in preeclampsia.

Helical type coronary bypass graft performance: Experimental investigations.

Optimal graft design has been an objective of many researchers to find correlations between hemodynamics and graft failure. Compared to planar grafts, the helical graft configurations improve hemodynamic performance including the promotion of flow mixing and reduction of flow stagnation regions. In order to evaluate the advantages and disadvantages of the suggested helical type bypass graft model in comparison to a conventional bypass graft configuration, three experimental models were designed and evaluated. The character of complex vortex structures created in the area between the heel and the occluded section depends on the flow parameters (in the case of the straight graft). We have identified two vortices in the symmetrical plane (proximal and distal to the anastomosis). In the new design of the two-turn helical graft, the stagnation point is eliminated from the anastomoses at different time intervals compared to the conventional straight bypass model The present study indicated that the magnitude of the pressure drop along a helical graft was considerably increased compared to a traditional graft which, while still physiologically advantageous, can be surpassed by an optimal geometry model.

Hemodynamic parameters measurements to assess severity of serial lesions in patient specific right coronary artery.

In this study, effects of serial stenosis on coronary hemodynamics were investigated in the human right coronary artery (RCA) using blood flow analysis. A 3-D model of a serial stenosed RCA was reconstructed based on multislice computerized tomography images. Numerical analysis examined the effect of multiple serial stenoses on the hemodynamic characteristics such as flow separation, pressure drop and FFR. Pressure loss associated with flow expansion after each constriction was large. Overall pressure drop increased from 1700 Pa (12.75 mmHg) at the end diastole to 11000 Pa (82.5 mmHg) at the peak systole. In two stenoses the corresponding pressure gradients werearound 30 mmHg and corresponded to the stenosis with FFR < 0.7 (associated to the sever stenosis). Severe stenosies caused large pressure drops across the throat. Blood flow distal to the stenosis was associated with fluctuations of the wall shear stress and vorticity.

Comparison between experimentally measured flow patterns for straight and helical type graft.

The long-term success of arterial bypass surgery is often limited by the progression of intimal hyperplasia at the anastomosis between the graft and the native artery. The experimental models were manufactured from glass tubing with constant internal diameter of 8 mm, fashioned into a straight configuration and helical configuration. The aim of this study was to determine the three-dimensional flow structures that occur at the proximal anastomosis under pulsatile flow conditions, to investigate the changes that resulted from variations in the anastomosis angle and flow division, and to establishing the major differences between the straight and helical graft. In the anastomosis domain, a strong region of recirculation is observed near the occluded end of the artery, which forces the flow to move into the perfused host coronary artery. The proximal portion of the host tube shows weak counter-rotating vortices on the symmetry plane. The exact locations and strengths of the vortices in this region are only weakly dependent on Re. A detailed comparison of experimentally measured axial velocity patterns for straight and helical grafts confirm the very strong nature of the secondary flows in the helical geometry. The helical configuration promotes the mixing effect of vortex motion such that the flow particles are mixed into the blood stream disal to the anastomotic junction.