COVID-19-Endothelial Axis and Coronary Artery Bypass Graft Patency: a Target for Therapeutic Intervention?

It has been reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces endothelial inflammation, therefore facilitating the progression of endothelial and vascular dysfunction in coronavirus disease 2019 (COVID-19) patients. Coronary artery bypass grafting (CABG) involves mainly the use of the saphenous vein (SV) and internal mammary artery as graft material in the stenosed coronary arteries. Unfortunately, graft patency of the SV is low due to endothelial dysfunction and inflammation. We propose that SARS-CoV-2 might cause vascular inflammation, endothelial dysfunction, and thrombosis in coronary artery bypass graft vessels by binding angiotensin-converting enzyme 2 receptor. Therefore, in this Special Article, we consider the potential influence of COVID-19 on the patency rates of coronary artery bypass graft vessels, mainly with reference to the SV. Moreover, we discuss the technique of SV graft harvesting and the therapeutic potential of focusing on endothelial dysfunction, vascular inflammation, and thrombosis for protecting coronary artery bypass grafts in COVID-19 infected CABG patients

Aircraft wing design at low speeds using Taguchi method

Purpose - The purpose of this paper is to determine the impact level of parameters affecting wing design at low speeds using Taguchi method

The role of perivascular adipose tissue on human saphenous vein vascular tone

Perivascular adipose tissue (PVAT) is situated outside of almost every blood vessel. Recent studies showed that PVAT provides mechanical support for blood vessels and secretes vasoactive adipokines that could regulate vascular tone. However, most of the studies evaluating PVAT effects on vascular tone have been performed with vessels derived from animals. Therefore, we aimed to investigate the role of PVAT surrounding human coronary bypass graft vessels such as saphenous vein (SV). Human SV preparations were set up in an organ bath in the presence or absence of their PVAT. The presence of PVAT significantly attenuated the contractile response to prostaglandin F-2 alpha (PGF(2 alpha)). However, potassium chloride (KCI)-induced concentration-response curve wasn't modified in PVAT-intact SV preparations. On the other hand, endothelium-dependent relaxation induced by acetylcholine (ACh) or endothelium-independent relaxation induced by sodium nitroprusside (SNP) were similar between SV with PVAT versus SV without PVAT preparations. Sensitivity of the SV to contractile agonists (KCI, PGF(2 alpha)) or relaxant agonists (SNP, ACh) were not modified in the presence of PVAT. These results suggest that PVAT could decrease PGF(2 alpha)-induced contractile tone via endothelium-independent mechanisms in SV. Retaining PVAT in SV preparations during bypass graft surgery could prevent graft vasospasm possibly via PVAT derived relaxant factor(s)

Mitochondrial arginase II modulates nitric-oxide synthesis through nonfreely exchangeable L-arginine pools in human endothelial cells

Reduced synthesis of nitric oxide ( NO) contributes to the endothelial dysfunction and may be related to limited availability of L-arginine, the common substrate of constitutive nitric-oxide synthase ( NOS) and cytosolic arginase I and mitochondrial arginase II. To determine whether arginases modulate the endothelial NO synthesis, we investigated the effects of the competitive arginase inhibitor N omega-hydroxy-nor-L-arginine (NorNOHA) on the activity of NOS, arginases, and L-arginine transporter and on NO release at surface of human umbilical vein endothelial cells (HUVECs). In unstimulated cells, Nor-NOHA dose-dependently reduced the arginase activity with maximal inhibition at 20 mu M. When HUVECs were stimulated by thrombin without extracellular L-arginine, Nor-NOHA dose-dependently increased the NOS activity and the NO release with maximal effects at 20 mu M. Extracellular L-arginine also dose-dependently increased NO release and arginase activity. When HUVECs were stimulated by thrombin in the presence of 100 mu M L- arginine, NOS activity and NO release were similar in untreated and Nor-NOHA-treated cells. However, despite activation of L- arginine uptake, the inhibition of arginase activity by Nor-NOHA was still significant. The depletion of freely exchangeable L- arginine pools with extracellular L- lysine did not prevent Nor-NOHA from increasing the NO release. This indicates the presence of pools, which are accessible to NOS and arginase, but not exchangeable. Interestingly, the mitochondrial arginase II was constitutively expressed, whereas the cytosolic arginase I was barely detectable in HUVECs. These data suggest that endothelial NO synthesis depends on the activity of arginase II in mitochondria and L-arginine carriers in cell membrane

Prostaglandin E-2 induced contraction of human intercostal arteries is mediated by the EP3 receptor

Arterial vascularization of the spinal cord may be mechanically or functionally altered during thoracoabdominal surgery/ intravascular procedures. Increased arterial pressure has been shown to restore spinal perfusion and function probably by increasing the blood flow through the intercostal arteries. The regulation of human intercostal artery (HICA) vascular tone is not well documented. Prostaglandin (PG) E-2 concentration is increased during inflammatory conditions and has been shown to regulate vascular tone in many preparations. In this context, the pharmacological response of HICA to PGE2 and the characterization of the PGE(2) receptor subtypes (EP1, EP2, EP3 or EP4) involved are of importance and that is the aim of this study. Rings of HICA were prepared from 29 patients and suspended in organ baths for isometric recording of tension. Cumulative concentration-response curves were performed in these preparations with various EP receptor agonists in the absence or presence of different receptor antagonists or inhibitors. PGE(2) induced the contraction of HICA (E-max=7.28 +/- 0.16 g; pEC(50) value=0.79 +/- 0.18; n=17); contractions were also observed with the EP3 receptor agonists, sulprostone, 17-phenyl-PGE(2), misoprostol or ONO-AE-248. In conclusion, PGE(2) induced vasoconstriction of HICA via EP3 receptor subtypes and this result was confirmed by the use of selective EP receptor antagonists (L-826266, ONO-8713, SC-51322) and by a strong detection of EP3 mRNA. These observations suggest that in the context of perioperative inflammation, increased PGE2 concentrations could trigger vasoconstriction of HICA and possibly alter spinal vascularization. (C) 2012 Elsevier B.V. All rights reserved

Homocysteine induces oxidative stress by uncoupling of no synthase activity through reduction of tetrahydrobiopterin

International audienc