Impairment of hypoxic pulmonary vasoconstriction in acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a serious complication of severe systemic or local pulmonary inflammation, such as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ARDS is characterised by diffuse alveolar damage that leads to protein-rich pulmonary oedema, local alveolar hypoventilation and atelectasis. Inadequate perfusion of these areas is the main cause of hypoxaemia in ARDS. High perfusion in relation to ventilation (V/Q<1) and shunting (V/Q=0) is not only caused by impaired hypoxic pulmonary vasoconstriction but also redistribution of perfusion from obstructed lung vessels. Rebalancing the pulmonary vascular tone is a therapeutic challenge. Previous clinical trials on inhaled vasodilators (nitric oxide and prostacyclin) to enhance perfusion to high V/Q areas showed beneficial effects on hypoxaemia but not on mortality. However, specific patient populations with pulmonary hypertension may profit from treatment with inhaled vasodilators. Novel treatment targets to decrease perfusion in low V/Q areas include epoxyeicosatrienoic acids and specific leukotriene receptors. Still, lung protective ventilation and prone positioning are the best available standard of care. This review focuses on disturbed perfusion in ARDS and aims to provide basic scientists and clinicians with an overview of the vascular alterations and mechanisms of V/Q mismatch, current therapeutic strategies, and experimental approaches.

Pathophysiology of Hypoxemia in COVID-19 Lung Disease

“… 15 At this time, there is no clear evidence supporting a direct impact of SARS-CoV-2 infection on local mechanisms of HPV. 44 However, even in the absence of direct modulation by viral infection, local and systemic inflammatory responses to infection can significantly attenuate HPV responses in animal models. 45 Lastly, opening of pre-existing intrapulmonary bronchopulmonary anastomoses could provide a unifying explanation for abnormal ventilation-perfusion matching, without invoking a direct effect on HPV.…”

Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support–Free Days in Patients Hospitalized With COVID-19

“…The domain was terminated due to safety concerns, and findings are inconclusive for non-critically ill patients and those in the combined ARB and DMX-200 treatment group. RAS activation may contribute to poor clinical outcomes in patients with acute hypoxemic respiratory failure, [30][31][32][33][34] including COVID-19. 3,8,[35][36][37] Angiotensin II is upregulated in COVID-19 and other severe respiratory infections, proportional to severity.…”

“…RAS activation may contribute to poor clinical outcomes in patients with acute hypoxemic respiratory failure, including COVID-19 . Angiotensin II is upregulated in COVID-19 and other severe respiratory infections, proportional to severity .…”

Chest dual-energy CT to assess the effects of steroids on lung function in severe COVID-19 patients

“…Although HPV is the primary active mechanism influencing regional lung perfusion, other concomitant factors can have a role. Among others, superinfections by Gram-negative bacteria, potentially less hindered in patients treated with steroids, could possibly attenuate HPV [ 45 ]. At the same time, direct mechanical effects as well as undefined intracellular signaling can be listed among non-hypoxia-related mechanisms affecting regional lung perfusion [ 46 , 47 ].…”