Pulmonary vasodilation in acute pulmonary embolism - a systematic review

Abstract

Acute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular failure, circulatory collapse and death. Most treatments focus on removal of the mechanical obstruction caused by the embolism, but pulmonary vasoconstriction is a significant contributor to the increased right ventricular afterload and is often left untreated. Pulmonary thromboembolism causes mechanical obstruction of the pulmonary vasculature coupled with a complex interaction between humoral factors from the activated platelets, endothelial effects, reflexes and hypoxia to cause pulmonary vasoconstriction that worsens right ventricular afterload. Vasoconstrictors include serotonin, thromboxane, prostaglandins and endothelins, counterbalanced by vasodilators such as nitric oxide and prostacyclins. Exogenous administration of pulmonary vasodilators in acute pulmonary embolism seems attractive but all come with a risk of systemic vasodilation or worsening of pulmonary ventilation-perfusion mismatch. In animal models of acute pulmonary embolism, modulators of the nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway, endothelin pathway and prostaglandin pathway have been investigated. But only a small number of clinical case reports and prospective clinical trials exist. The aim of this review is to give an overview of the causes of pulmonary embolism-induced pulmonary vasoconstriction and of experimental and human investigations of pulmonary vasodilation in acute pulmonary embolism.

Keywords: animal models; pulmonary circulation; right heart failure; right ventricular afterload.

Fig. 1.

On the left, a schematic pathway showing acute pulmonary embolism (PE) to cause both mechanical obstruction of pulmonary arteries and pulmonary vasoconstriction. Both increases right ventricular (RV) afterload causing acute RV dilatation and interventricular septal shift which have been associated specifically with severe, acute PE. The RV may enter a vicious circle of right ventricular failure, circulatory collapse and death. On the right, focus on pulmonary vasoconstriction induced by a pulmonary embolism. Several mechanisms are potential underlying causes: vasoactive substances from the thrombus, hemolysis, activated platelets, endothelial damage, reflexes, and hypoxia. Please see the text for further details. ET: endothelins; NO: nitric oxide; PEC: pulmonary endothelial cell; RBC: red blood cell; SMC: smooth muscle cell; TXA2: thromboxane A2.

Fig. 2.

Flow diagram of the review selection process. CTEPH: chronic thromboembolic pulmonary hypertension; PE: pulmonary embolism.