Proinflammatory Cytokines Are Not Released in the Circulation Following Acute Pulmonary Thromboembolism in Pigs

Abstract

Histological examination of acute lung injury associated with sepsis often revealed thromboembolic lesions in the pulmonary microcirculation. Several inflammatory mediators such as platelet activating factor, thromboxane, and endothelins have also been implicated in the pathogenesis of acute pulmonary thromboembolism (APTE). In the present study we examined the roles of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-8, in the early phase of APTE. APTE was induced in 13 anesthetized piglets (22+/-4 kg) by injecting thrombin-induced blood clots directly into the left lower lobar pulmonary artery. Five animals that received only warm sterile saline served as controls. Arterial plasma samples were collected regularly over 8 h so that cytokine levels could be measured later by enzyme-linked immunosorbent assay (ELISA). Administration of clots doubled the mean pulmonary arterial pressure (from 13+/-5 to 26+/-7 mm Hg) and caused significant decrease in arterial oxygen tension (PaO2 from 390+/-85 to 256+/-89 mm Hg while the FiO2 was maintained at 1.0). Mean arterial blood pressure and cardiac output remained comparable throughout the experiments after initial fluid resuscitation. Plasma levels of TNF-alpha, IL-1beta, and IL-8 were not significantly increased in the APTE group when compared with their baseline values or the control group. Our results thus show that APTE is associated with pulmonary hypertension and deterioration of gas exchange but not with the systemic release of TNF-alpha, IL-1beta, or IL-8. We conclude that these cytokines have minimal impact on the systemic circulation during APTE.

Spatial pattern of ventilation-perfusion mismatch following acute pulmonary thromboembolism in pigs

“…Furthermore, Malik and van der Zee (17) also found that there was more fibrin deposition in the nonembolized regions of the lung, presumably because of the increased Q in these areas after acute embolic injury. Investigators over the past few decades proposed that there were some vasoactive or bronchospastic mediators released after APTE, such as histamine (27), serotonin (11,15), platelet-activating factor (5,6), prostaglandins (27,21), endothelin-1 (16), or cytokines (26), etc., which could explain the pulmonary hypertension and possibly the disturbances in regional ventilation-perfusion (V A/ Q ) matching. However, most of these reports were based on pharmacological studies using different antagonists to provide indirect evidence, but their casual relationships have not been well established.…”

Pulmonary embolism and cardiac enzymes

“…[13][14][15][16][17] One of the main pulmonary hemodynamic response to Table III A: No significant association was found between PE (with and without chest pain) and abnormal cardiac enzymes (P Ͼ .10).…”

Pentraxin 3: a new biomarker for determining the probability of acute pulmonary embolism

“…All of these may elevate Ptx3 levels in angina pectoris, acute myocardial infarction heart failure, and sepsis/systemic inflammatory response syndrome [10,[17][18][19][20]. Several inflammatory mediators such as platelet activating factor, thromboxane, and endothelins have also been implicated in the pathogenesis of acute PE [21]. However, whether Ptx3 could be one of the biomarkers in patients with PE is unclear.…”