A.104 Role of pulmonary and bronchial circulation in neutrophil-mediated lung damage induced by cardiopulmonary bypass

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

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Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

Scientific Reports ◽

10.1038/s41598-020-79607-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shinjini Chakraborty ◽

Veronika Eva Winkelmann ◽

Sonja Braumüller ◽

Annette Palmer ◽

Anke Schultze ◽

...

Keyword(s):

Hemorrhagic Shock ◽

Inflammatory Responses ◽

Experimental Models ◽

Lung Damage ◽

C5a Receptor ◽

Cytokine Levels ◽

Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

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Reduced Flow-Mediated Dilatation Is Not Related to COVID-19 Severity Three Months after Hospitalization for SARS-CoV-2 Infection

Journal of Clinical Medicine ◽

10.3390/jcm10061318 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1318

Author(s):

Marianne Riou ◽

Walid Oulehri ◽

Cedric Momas ◽

Olivier Rouyer ◽

Fabienne Lebourg ◽

...

Keyword(s):

Vascular Endothelium ◽

Matched Control ◽

Acute Infection ◽

Critical Role ◽

Lung Damage ◽

Vascular Effect ◽

Flow Mediated Dilatation ◽

Artery Flow

The coronavirus disease 2019 (COVID-19) pandemic has spread rapidly worldwide, with more than two million deaths. Evidence indicates the critical role of the vascular endothelium in its pathophysiology but, like potential changes in functional vasodilation, the vascular effect of SARS-CoV-2 at a given distance from the acute infection is largely unknown. We assessed brachial artery flow-mediated dilatation (FMD) in 27 COVID-19 patients needing conventional or intensive care unit hospitalization, three months after SARS-CoV-2 infection diagnosis and in nine age- and sex- matched control subjects. Interestingly, the FMD was lower in COVID-19 patients as compared to controls (8.2 (7.2–8.9) vs. 10.3 (9.1–11.7)); p = 0.002, and half of the hospitalized COVID-19 survivors presented with a reduced FMD < 8% at three months of COVID-19 onset. Impaired FMD was not associated with severe or critical SARS-CoV-2 infection, reflected by ICU hospitalization, total hospitalization duration, or severity of lung damage. In conclusion, reduced FMD is often observed even three months after hospitalization for SARS-CoV-2 infection, but such alteration predominantly appears to not be related to COVID-19 severity. Longer and larger follow-up studies will help to clarify the potential prognosis value of FMD among COVID-19 patients, as well as to further determine the mechanisms involved.

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Role of nitric oxide and nitrosative protein damage in cigarette smoke-induced emphysematous lung damage: Attenuation by vitamin C

Nitric Oxide ◽

10.1016/j.niox.2012.04.146 ◽

2012 ◽

Vol 27 ◽

pp. S41

Author(s):

Indranil Gupta ◽

Arijit Ghosh ◽

Koustubh Panda

Keyword(s):

Nitric Oxide ◽

Vitamin C ◽

Cigarette Smoke ◽

Lung Damage ◽

Protein Damage ◽

Emphysematous Lung

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Role of Metalloproteinases and Tissue Inhibitors of Metalloproteinases During Cardiopulmonary Bypass in Rats

ASAIO Journal ◽

10.1097/mat.0b013e31824709d5 ◽

2012 ◽

Vol 58 (3) ◽

pp. 204-211 ◽

Cited By ~ 2

Author(s):

Ralf Guenzinger ◽

Harald Lahm ◽

Michael Wottke ◽

Ruediger Lange

Keyword(s):

Cardiopulmonary Bypass ◽

Tissue Inhibitors Of Metalloproteinases ◽

Tissue Inhibitors

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Surgical setup for cardiopulmonary bypass through central cannulation

10.1510/mmcts.2021.041 ◽

2021 ◽

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Surgical Care ◽

Heart Lung Machine ◽

American College Of Surgeons ◽

History Of ◽

Central Cannulation ◽

First John ◽

Clinical Advances

The introduction of cardiopulmonary bypass was one of the most important clinical advances of 1952. In that year, John Gibbon performed the first successful cardiac surgery using cardiopulmonary bypass. The procedure has been described as “One of the most impressive evidences of the role of investigative surgery in the history of medicine in the persevering efforts of Dr. Gibbon for more than 20 years, which finally culminated in a practical heart-lung machine”, at the first John H. Gibbon, Jr. Lecture at the annual meeting of the American College of Surgeons. Due to on-going advancements in cardiopulmonary bypass, many patients with complex heart disease requiring surgical care undergo cardiac surgery while the other organs remain adequately oxygenated and perfused. This tutorial discusses the access, surgical technique, and initiation of cardiopulmonary bypass through central cannulation and describes the safeguards and pitfalls.

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