Research Spotlight

Posted May 21st 2021

Cartiotonic steroids affect monolayer permeability in lymphatic endothelial cells.

AHM Zuberi Ashraf, M(ASCP)

AHM Zuberi Ashraf, M(ASCP)

Horvat, D., Afroze, S.H., Cromer, W.E., Pantho, A.F., Ashraf, Z.A.H.M., Kuehl, T.J., Zawieja, D.C. and Uddin, M.N. (2021). “Cartiotonic steroids affect monolayer permeability in lymphatic endothelial cells.” Mol Cell Biochem.

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Edema is common in preeclampsia (preE), a hypertensive disorder of pregnancy. Cardiotonic steroids (CTSs) such as marinobufagenin (MBG) are involved in the pathogenesis of preE. To assess whether CTSs are involved in the leakage of lymphatic endothelial cell (LEC), we evaluated their effect on monolayer permeability of LECs (MPLEC) in culture. A rat mesenteric LECs were treated with DMSO (vehicle), and CTSs (MBG, CINO, OUB) at concentrations of 1, 10, and 100 nM. Some LECs were pretreated with 1 μM L-NAME (N-Nitro-L-Arginine Methyl Ester) before adding 100 nM MBG or cinobufotalin (CINO). Expression of β-catenin and vascular endothelial (VE)-cadherin in CTS-treated LECs was measured by immunofluorescence and MPLEC was quantified using a fluorescence plate reader. Western blot was performed to measure β-catenin and VE-cadherin protein levels and myosin light chain 20 (MLC20) phosphorylation. MBG (≥ 1 nM) and CINO (≥ 10 nM) caused an increase (p < 0.05) in the MPLEC compared to DMSO while ouabain (OUB) had no effect. Pretreatment of LECs with 1 μM L-NAME attenuated (p < 0.05) the MPLEC. The β-catenin expression in LECs was downregulated (p < 0.05) by MBG and CINO. However, there was no effect on the LECs tight junctions for the CINO group. VE-cadherin expression was downregulated (p < 0.05) by CINO, and MLC20 phosphorylation was upregulated (p < 0.05) by MBG. We demonstrated that MBG and CINO caused an increase in the MPLEC, which were attenuated by L-NAME pretreatment. The data suggest that CTSs exert their effect via nitric-oxide-dependent signaling pathway and may be involved in vascular leak syndrome of LEC lining in preE.


Posted May 21st 2021

Distal versus proximal radial artery access for cardiac catheterization and intervention: Design and rationale of the DIPRA trial.

Karim Al-Azizi, M.D.

Karim Al-Azizi, M.D.

Al-Azizi, K.M., Idris, A., Christensen, J., Hamandi, M., Hale, S., Martits-Chalangari, K., Van Zyl, J.S., Ravindranathan, P., Banwait, J.K., McKracken, J., Smith, A., Apakama, G., Swim, J., Dolton, P., Chionh, K., Dimaio, M., Thomas, S., Szerlip, M., Sayfo, S., Dib, C., Mack, M. and Potluri, S. (2021). “Distal versus proximal radial artery access for cardiac catheterization and intervention: Design and rationale of the DIPRA trial.” Cardiovasc Revasc Med.

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BACKGROUND: Radial artery (RA) catheterization is the access of choice over femoral artery access for most interventional vascular procedures given its safety and faster patient recovery. There has been growing interest in distal radial artery (dRA) access as an alternative to the conventional proximal radial artery (pRA) access. Preserving the RA is important which serves as a potential conduit for future coronary artery bypass surgery, dialysis conduit or preserve the artery for future cardiovascular procedures. The dRA runs in close proximity to the radial nerve, which raises the concern of potential detrimental effects on hand function. STUDY DESIGN: The Distal versus Proximal Radial Artery Access for cardiac catheterization and intervention (DIPRA) trial is a prospective, randomized, parallel-controlled, open-label, single center study evaluating the outcomes of hand function and effectiveness of dRA compared to pRA access in patients undergoing cardiac catheterization. The eligible subjects will be randomized to dRA and pRA access in a (1:1) fashion. The primary end point is an evaluation of hand function at one and twelve months follow-up. Secondary end points include rates of access site hematoma, access site bleeding, other vascular access complications, arterial access success rate, and RA occlusion at one and twelve months follow up. CONCLUSION: Effects of dRA on hand function remains unknown and it’s use questionable in the presence of a widely accepted pRA. DIPRA trial is designed to determine the safety and effectiveness of dRA for diagnostic and interventional cardiovascular procedures compared to the standard of care pRA.


Posted May 21st 2021

Per pass analysis of thrombus composition retrieved by mechanical thrombectomy.

Kennith F. Layton, M.D.

Kennith F. Layton, M.D.

Abbasi, M., Kvamme, P., Layton, K.F., Hanel, R.A., Almekhlafi, M.A., Delgado, J.E., Pereira, V.M., Patel, B.M., Jahromi, B.S., Yoo, A.J., Nogueira, R.G., Gounis, M.J., Fitzgerald, S., Mereuta, O.M., Dai, D., Kadirvel, R., Kallmes, D.F., Doyle, K.M., Savastano, L.E., Cloft, H.J., Liu, Y., Thacker, I.C., Aghaebrahim, A., Sauvageau, E., Demchuk, A.M., Kayan, Y., Copelan, A.Z., Entwistle, J., Nazari, P., Cantrell, D.R., Bhuva, P., Soomro, J., Haussen, D.C., Al-Bayati, A., Mohammaden, M., Pisani, L., Rodrigues, G., Puri, A.S. and Brinjikji, W. (2021). “Per pass analysis of thrombus composition retrieved by mechanical thrombectomy.” Interv Neuroradiol: 15910199211009119.

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BACKGROUND AND AIM: Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. METHODS: Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. RESULTS: 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). CONCLUSION: Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.


Posted May 21st 2021

Underutilized Fuel: Angiotensin II for Vasoplegia in the Heart Failure Patient Population.

Amit Alam M.D.

Amit Alam M.D.

Alam, A., Burkhoff, D., Enter, D.H. and Jermyn, R. (2021). “Underutilized Fuel: Angiotensin II for Vasoplegia in the Heart Failure Patient Population.” J Cardiothorac Vasc Anesth.

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In this trial, patients who received ANG-II were more likely to achieve a mean arterial pressure of 75 mmHg or an increase in mean arterial pressure by 10 mmHg above that seen in patients who received placebo in as little as three hours. Furthermore, the median pressor dose decreased from baseline by 76.5% in the ANG-II group compared with an increase of 7.8% in the placebo group (p ≤ 0.05). [No abstract; excerpt from Letter].


Posted May 21st 2021

Violence in the first millennium BCE Eurasian steppe: Cranial trauma in three Turpan Basin populations from Xinjiang, China.

Qian Wang, Ph.D.

Qian Wang, Ph.D.

Zhang, W., Zhang, Q., McSweeney, K., Han, T., Man, X., Yang, S., Wang, L., Zhu, H., Zhang, Q. and Wang, Q. (2021). “Violence in the first millennium BCE Eurasian steppe: Cranial trauma in three Turpan Basin populations from Xinjiang, China.” Am J Phys Anthropol 175(1): 81-94.

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OBJECTIVES: Violence affected daily life in prehistoric societies, especially at conflict zones where different peoples fought over resources and for other reasons. In this study, cranial trauma was analyzed to discuss the pattern of violence experienced by three Bronze to early Iron Age populations (1,000-100 BCE) that belonged to the Subeixi culture. These populations lived in the Turpan Basin, a conflict zone in the middle of the Eurasian Steppe. METHODS: The injuries on 129 complete crania unearthed from the Subeixi cemeteries were examined for crude prevalence rate (CPR), trauma type, time of occurrence, possible weapon, and direction of the blow. Thirty-three injuries identified from poorly preserved crania were also included in the analyses except for the CPR. Data was also compared between the samples and with four other populations that had violence-related backgrounds. RESULTS: Overall, 16.3% (21/129) of the individuals showed violence-induced traumatic lesions. Results also indicated that most of the injuries were perimortem (81.6%), and that women and children were more involved in conflict than the other comparative populations. Wounds from weapons accounted for 42.1% of the identified cranial injuries. Distribution analysis suggested no dominant handedness of the attackers, and that blows came from all directions including the top (17.1%). Wounds caused by arrowheads and a special type of battle-ax popular in middle and eastern Eurasian Steppe were also recognized. DISCUSSION: A comprehensive analysis of the skeletal evidence, historical records, and archeological background would suggest that the raiding to be the most possible conflict pattern reflected by the samples. The attackers were likely to have been nomadic invaders from the steppe (such as the Xiongnu from historical records), who attacked the residents in the basin more likely for their resources rather than territory or labor force.