Why Pulmonary Vasodilation May Be Part of a Key Strategy to Improve Survival in COVID-19.

Oxygenation is a function of both ventilation and perfusion. While approaches to the treatment of COVID-19 have focused largely on ventilation strategies and antiviral therapies, attention towards the improvement of vascular perfusion defects has been neglected. This article examines clinical findings that indicate perfusion defects are a critical component of COVID-19 pathophysiology. They also support the notion that medications that promote perfusion with pulmonary vasodilatation can yield significantly improved outcomes that include overall survival. Calcium channel blocker usage has been associated with improved survival and outcomes in several retrospective reviews of patient populations with COVID-19 from across the world. This includes studies conducted in Paris, France; Wuhan, China; Daegu, South Korea; Brooklyn, New York; Brussels, Belgium; and a national sample from across the United States. These medications are generally prescribed to treat hypertension. Yet, they are also utilized in various pulmonary conditions to effectuate pulmonary vasodilatation. Thus, a concomitant benefit appears to have been revealed as patients that were taking these medications had significantly improved overall survival. Sildenafil is another medication that induces pulmonary vasodilatation. It was found to decrease the need for mechanical ventilation and reduce hospital length of stay in COVID-19 in a triple-blinded randomized control trial. The importance of pulmonary vasodilation in COVID-19 has been evaluated further. In a study of over 100 high-resolution CT scans, patients with COVID-19 showed a significant reduction in pulmonary blood volume contained in small blood vessels of <5 mm2 compared to healthy volunteers. Moreover, this was found to clinically correlate with a need for more oxygen supplementation. In radiologic perfusion studies, hypoperfusion was observed to occur in the healthy lung while hyperperfusion was present in non-healthy COVID-inflicted lung. It appears that perfusion of oxygen-carrying capacity, in the form of hemoglobin-carrying red blood cells, is being misappropriated towards unhealthy lung tissue. This was observed concurrently while the healthy lung had a paucity of perfusion. This can be a key aspect of hypoxic development in COVID-19. Mathematical modeling of perfusion abnormalities in COVID-19 has also implicated extensive perfusion defects, with ventilation-perfusion mismatching in the non-injured lung and hyperperfusion of up to threefold increases to afflicted regions. Vasodilation in the form of systemic intravascular medications may help improve outcomes by resetting this imbalance and by promoting perfusion of the alveolar-capillary unit where gas exchange and oxygenation occurs particularly in the non-injured lung. Furthermore, endothelialitis and microthrombosis have been observed on pathology specimens as many patients develop micro-thrombi following prolonged perfusion deficits. Vasodilatory agents can curb vasoconstriction and drive more perfusion towards healthy tissue. The temporal matching of consistent systemic intravascular vasodilation therapy throughout the gradual and progressive course of the illness may be integral to achieving improved outcomes. Improving perfusion to healthy tissue can help improve oxygenation and overall outcomes in COVID-19. These findings support further utilization and investigation of vasodilatory agents in the treatment of COVID-19.

Cardiac index is associated with oxygenation in COVID-19 acute respiratory distress syndrome.

Eleven participants with COVID-19 acute respiratory distress syndrome requiring mechanical ventilation underwent pulmonary artery catheterization for clinical indications. Clinical interventions or events concurrent with hemodynamic were recorded. Increased cardiac index was associated with worse hypoxemia. Modulation of cardiac index may improve hypoxemia in patients with COVID-19 acute respiratory distress syndrome.

Heterogeneous Perfusion in COVID-19 and High Altitude Pulmonary Edema: A Review of Two Cases Followed by Implications for Hypoxic Pulmonary Vasoconstriction, Thrombosis Development, Ventilation Perfusion Mismatch and Emergence of Treatment Approaches.

Coronavirus disease 2019 (COVID-19) has been compared to high altitude pulmonary edema (HAPE). Multiple similarities between the two conditions were drawn in the past. This article seeks to further clarify potential underlying mechanisms related to hypoxia and pulmonary vascular responses. It does so by looking at perfusion imaging of patients with COVID-19 and comparing them with patterns observed in HAPE and hypoxic exposure. Two separate clinical cases are reviewed. The salient aspect of each case that is emphasized is the perfusion scintigraphy results that revealed heterogeneous perfusion patterns in both patients. Heterogeneous or non-homogeneous perfusion is also observed in HAPE. A detailed clinical course of each patient is described. Medications utilized to treat the conditions are outlined as well as laboratory parameters and clinical findings. Interestingly, both of these patients were treated with calcium channel blockers and this class of medications is utilized to prevent HAPE as well. Discussion following the case presentations attempts to contextualize possible implications of this and other studies on the broader pathophysiology of COVID-19 disease. Findings related to pathophysiologic patterns and treatment strategies are also described. Micro-thrombi formation has been reported in both COVID-19 and HAPE as well and may be an accessory complication of perfusion compromise. In a separate study, vasodilatation with calcium channel blocker (CCB) therapy has been associated with improved mortality in COVID-19 and potential pathophysiologic mechanisms were previously presented. This case report provides further clinical findings that support the notion that perfusion deficits are an integral component of hypoxia in COVID-19. It also advances the basis for use of vasodilator therapy as part of treatment regimens in COVID-19. Vasodilators may improve micro-perfusion. In this way, oxygenation may be promoted by decreasing impedance and improving flow via the alveolar-capillary unit.