Endothelial Cell Injury in Cardiovascular Surgery

doi:10.1016/S0003-4975(96)00528-0

The Annals of Thoracic Surgery

Volume 62, Issue 3, August 1996, Pages 915-922

https://doi.org/10.1016/S0003-4975(96)00528-0 Get rights and content

In the last decade the endothelium has been shown to play a major role in regulating membrane permeability, lipid transport, vasomotor tone, coagulation, inflammation, and vascular wall structure. These critical endothelial cell functions are extremely sensitive to injury in the form of hypoxia, exposure to cytokines, endotoxin, cholesterol, nicotine, surgical manipulation, or hemodynamic shear stress. In response to injury endothelial cells become activated, tipping the balance of endothelial-derived factors to disrupt barrier function, and enhance vasoconstriction, coagulation, leukocyte adhesion, and smooth muscle cell proliferation. Although these responses likely exist as protective mechanisms, if the stimuli are severe the responses may become excessive, resulting in damaged tissue, impaired organ function, and an abnormal fibroproliferative response. Recent discoveries in the field of vascular biology have led to an expanded understanding of many of the complications of cardiovascular operations. Because of the wide impact endothelial cell dysfunction has on patients with cardiovascular disease, issues pertaining to endothelial biology are in the forefront of research that will affect the current and future practice of cardiothoracic surgery.

Section snippets

Normal Vascular Form and Function

Normal vascular function is a dynamic process resulting from the interaction of the layers of the vessel wall and the passing elements in the blood. The vessel wall is made up of three distinct layers: the adventitia, the media, and the intima. The adventitia and media compose the structural backbone of the vessel wall and are important in vascular wall remodeling. The intima is lined with the endothelium, which is situated on a basement membrane and subendothelial matrix. Although it consists

Vasomotor Dysfunction

The endothelium produces substances that act locally and remotely to influence the degree of vascular tone. These include constitutively expressed relaxant factors such as nitric oxide (NO), prostacyclin, and adenosine, all of which work together to promote vascular patency by dilating vessels and preventing thrombosis. Additionally, the endothelium produces factors that promote increased vascular tone, such as endothelin, leukotrienes, and angiotensin II. Most patients with end-stage coronary

Coagulation

Given its location between the circulating blood and the interstitial tissues, the vascular endothelium must be an anticoagulant surface under basal conditions [4]. To keep blood in the fluid state the endothelium possesses multiple mechanisms to prevent coagulation. First, the endothelial cell is one of the only cells that does not constitutively express tissue factor, the surface protein responsible for activation of the extrinsic pathway of coagulation. Most other cells, especially in the

Neutrophil–Endothelial Cell Interaction

Recruitment of neutrophils from the blood stream to extravascular sites of injury is a critical event in host defense against bacterial infection and in the repair of damaged tissue [31]. This process probably evolved teleologically to be a localized process, beneficial in fighting an inoculation of bacteria. When the signals are diffuse, as they are after shock, sepsis, or CPB, there may be multiorgan endothelial activation resulting in widespread surface expression of neutrophil adherence

Chronic Endothelial Cell Injury

Atherosclerosis is the principal cause of death in the western world and the main indication for patient referral to cardiothoracic surgeons. In 1973 Ross and Glomset [65] proposed that atherosclerosis resulted from an endothelial cell response to chronic injury that leads to neutrophil, lymphocyte, platelet, and macrophage adhesion and migration into the subendothelium. Subsequently these cells orchestrate the molecular and cellular events that lead to progressive reductions in arterial

Conclusion

Various forms of endothelial cell injury occur commonly and can alter the course of the cardiovascular surgery patient both acutely and chronically, locally and systemically. Because of the wide impact of endothelial cell dysfunction in patients with cardiovascular disease, issues pertaining to endothelial biology are in the forefront of research that will have an effect on the current and future practice of cardiothoracic surgery. Recent discoveries in the field of vascular biology have

References (69)

E.D. Verrier
The vascular endothelium: friend or foe?
Ann Thorac Surg
(1993)
J. Harlan
Leukocyte-endothelial interactions
Blood
(1985)
P.J. Pearson et al.
Bioassay of EDRF from internal mammary arteries: implications for early and late bypass graft patency
Ann Thorac Surg
(1992)
R.C. Woodman et al.
Bleeding complications associated with cardiopulmonary bypass
Blood
(1990)
D.C. Crossman et al.
The regulation of tissue factor mRNA in human endothelial cells in response to endotoxin or phorbol ester
J Biol Chem
(1990)
M.J. Ray et al.
Relationship of platelet aggregation to bleeding after cardiopulmonary bypass
Ann Thorac Surg
(1994)
B.D. Spiess
The contribution of fibrinolysis to postbypass bleeding
J Cardiothorac Vasc Anesth
(1991)
F.A. Bevelaqua et al.
Management of spontaneous pneumothorax with small lumen catheter manual aspiration
Chest
(1982)
S.A. Burns et al.
P-selectin expression in myocardium of children undergoing cardiopulmonary bypass
J Thorac Cardiovasc Surg
(1995)
L.C. Casey
Role of cytokines in the pathogenesis of cardio-pulmonary-induced multisystem organ failure
Ann Thorac Surg
(1993)

D.C. Crossman et al.

(1996)

M.P. Bevilacqua et al.

Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion

Am J Pathol

(1985)

Cited by (149)

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts
2022, American Heart Journal
Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery.
The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization.
The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.
Commentary: Yin and Yang: Antiplatelet and lipid-lowering therapies to prevent vein graft thrombosis and atherosclerosis after coronary artery bypass graft surgery
2022, Journal of Thoracic and Cardiovascular Surgery
Pediatric peripheral vascular injuries and associated orthopedic considerations
2021, Seminars in Pediatric Surgery
Fucoidan for cardiovascular application and the factors mediating its activities
2021, Carbohydrate Polymers
Citation Excerpt :
Endothelial dysfunction is a significant contributor of cardiovascular diseases, such as atherosclerosis, hypertension, and diabetes (Haybar, Shahrabi, Rezaeeyan, Shirzad, & Saki, 2019). Endothelial denudation is the primary factor that causes restenosis after surgical interventions to treat cardiovascular diseases (Verrier & Boyle, 1996). Several studies have shown that fucoidan may have a protective function for ECs.
Fucoidan is a sulfated polysaccharide with various bioactivities. The application of fucoidan in cancer treatment, wound healing, and food industry has been extensively studied. However, the therapeutic value of fucoidan in cardiovascular diseases has been less explored. Increasing number of investigations in the past years have demonstrated the effects of fucoidan on cardiovascular system. In this review, we will focus on the bioactivities related to cardiovascular applications, for example, the modulation functions of fucoidan on coagulation system, inflammation, and vascular cells. Factors mediating those activities will be discussed in detail. Current therapeutic strategies and future opportunities and challenges will be provided to inspire and guide further research.
Chronic Kidney Disease and the Pathophysiology of Valvular Heart Disease
2019, Canadian Journal of Cardiology
Valvular heart calcification is common in patients with chronic kidney disease (CKD), especially in those receiving hemodialysis therapy, and it is associated with poor prognosis. Furthermore, progression of valvular heart disease (VHD) and structural valve deterioration of bioprosthetic valves are faster in these patients. Mechanisms involved in the pathophysiology of VHD are similar between patients with and without impaired kidney function, but CKD is associated with a bone metabolism dysregulation, which might lead to a procalcifying phenotype within vessels and heart valves. CKD is also associated with left ventricular remodelling and dysfunction, which might contribute to increase the risk of heart failure and death in patients with VHD. Even if promising pharmacotherapeutic avenues are in development, no medical treatment can prevent or reduce the valvular calcific process. Patients with advanced CKD should undergo transthoracic echocardiography for detection of VHD, and if present, follow-up should be more frequent than what is recommended in the guidelines. Transcatheter valve replacement might be preferred over surgical replacement in patients with CKD and severe aortic valve stenosis.
Les calcifications valvulaires sont fréquentes chez les atteints d’ isufisance rénale chronique, surtout en cas d’hémodialyse, et leur présence est associée à un mauvais pronostic. De plus, la progression des valvulopathies et la détérioration des bioprothèses sont accélérées dans cette population. Les mécanismes physiopathologiques impliqués dans le développement des valvulopathies sont similaires entre les patients avec et sans insuffisance rénale, cependant la dérégulation du métabolisme osseux est plus prononcée en cas de néphropathie, d’où un phénotype pro-calcifiant. L’insuffisance rénale entraine également un remodelage et une altération de la fonction du ventricule gauche, ce qui contribue à augmenter le risque d’insuffisance cardiaque et de décès en cas de valvulopathie. Même si des pistes thérapeutiques sont en développement, il n’existe aucun traitement médical permettant de prévenir ou de faire régresser les calcifications valvulaires. Chez les patients atteints d’ insuffisance rénale avancée, il est important d’effectuer une échocardiographie pour le dépistage des maladies valvulaires et d’effectuer un suivi plus rapproché que ce qui est recommandé dans les lignes directrices. Le remplacement valvulaire par cathéter semble être préférable au remplacement chirurgical chez les patients atteints d’ insuffisance rénale et de sténose aortique grave.
Regulation of macrophage polarization and promotion of endothelialization by NO generating and PEG-YIGSR modified vascular graft
2018, Materials Science and Engineering C
As an effective clinic treatment for cardiovascular disease, vascular transplantation gains much acceptance recently. However, due to the acute thrombosis and intimal hyperplasia, long-term failure of synthetic grafts after implanted in small diameter blood vessel decelerates its commercial use. The continued acute inflammation and delayed endothelialization have been considered as fundamental reasons. To enhance the adhesion and organization of endothelial cells (ECs) and improve the vascular remodeling process, we have constructed a vascular graft based on electrospun polycaprolactone (PCL) matrix, on which organoselenium-immobilized polyethyleneimine (SePEI) for in situ nitric oxide (NO) generation and hyaluronic acid (HA) grafted with poly (ethylene glycol) (PEG) modified Tyr-Ile-Gly-Ser-Arg (YIGSR) for antifouling and EC adhesion were deposited through electrostatic layer-by-layer assembly. The in vitro results showed that SePEI deposited on the grafts could catalyze stable generation of NO. After in situ implantation in rats for 4 and 8 weeks, the graft promoted the transformation of macrophages into an anti-inflammatory phenotype (M2), which helped endothelium remodeling. YIGSR on the outmost layer facilitated more rapid and organized EC adhesion compared to PCL and non-modified grafts. PEG polymer chain on the outmost layer mitigated nonspecific adsorption of undesirable blood components. In our study, we first demonstrated the regulation of macrophage polarization by an NO-generating vascular graft. The results indicated that the approach of anti-inflammatory macrophage polarization and enhanced endothelialization through NO generation and PEG-modified YIGSR in our study may provide a new perspective for the clinic application of cell-free small-diameter vascular grafts.

View all citing articles on Scopus

View full text

Endothelial Cell Injury in Cardiovascular Surgery

Section snippets

Normal Vascular Form and Function

Vasomotor Dysfunction

Coagulation

Neutrophil–Endothelial Cell Interaction

Chronic Endothelial Cell Injury

Conclusion

Ann Thorac Surg

Blood

Ann Thorac Surg

Blood

J Biol Chem

Ann Thorac Surg

J Cardiothorac Vasc Anesth

Chest

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Surg Res

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Vasc Surg

Endothelial dysfunction in coronary artery disease

Annu Rev Med

Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock

Annu Rev Pharmacol Toxicol

Procoagulant functions of the endothelium

The intima: soil for atherosclerosis and restenosis

Circ Res

Cell biology of atherosclerosis

Annu Rev Physiol

Cytokines and endothelial cell biology

Physiol Rev

The vascular endothelium: a new horizon

Ann Surg

The pathogenesis of atherosclerosis: a perspective for the 1990’s

Nature

Regulatory functions of the vascular endothelium

N Engl J Med

Vascular biology of coronary artery bypass grafts

Coronary Artery Dis

Hypoxia induces endothelin gene expression and secretion in cultured human endothelium

J Clin Invest

Detection of intraluminal release of endothlium-derived relaxing factor from human saphenous veins

Circulation

Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock

Annu Rev Pharmacol Toxicol

The molecular biology of initiation of coagulation by tissue factor

Curr Stud Hematol Blood Transfus

The effects of cardioipulmonary bypass on fibrin formation and lysis: is a normal fibrinolytic response essential?

J Cardiovasc Pharmacol

Interleukin-1 activation of vascular endothelium. Effects on procoagulant activity and leukocyte adhesion

Am J Pathol