OBJECTIVE: We tested the hypothesis that a venous thromboembolism to the pulmonary arterial system (pulmonary embolism [PE]) would cause an inflammatory response within the pulmonary arterial (PA) wall marked by elevated cytokines and chemokines and an influx of inflammatory cells. METHODS: Experimental PE was induced in 70 rats and confirmed with angiography and O(2) saturation depression, and an additional 70 rats underwent sham operations. PA and lung tissue were removed at 3 hours and at 1, 2, 4, 6, 8, and 14 days (n = 10 per time point), were analyzed for proinflammatory cytokines and chemokines, and underwent histologic analysis. Data were analyzed with analysis of variance and the unpaired Student t test. RESULTS: Average gross PE resolution was 40% at 2 days, 90% at 4 days, and 100% at 6 days. Only monocyte chemoattractant protein-1 levels were greater in affected PAs compared with sham PAs at 3 hours, 1 day, and 2 days (137 +/- 13 pg/mg protein, 285 +/- 40 pg/mg protein, and 249 +/- 36 pg/mg protein versus 101 +/- 6 pg/mg protein, 150 +/- 36 pg/mg protein, and 92 +/- 3 pg/mg protein; P <.01 for all). Keratinocyte-derived chemokine, tissue necrosis factor, interleukin-10, nitric oxide, P-selectin, and E-selectin levels were not elevated. Neutrophils infiltrated the PA wall beginning at 3 hours, peaked at 2 days (69.4 +/- 21.7 per five high-power fields; P <.01), and returned to baseline by 8 days after PE. Macrophages peaked at 1 day after PE (29.3 +/- 6.9; P <.01) and returned to baseline by 4 days after PE. PE also was associated with a significantly increased intima to media ratio (P <.05), apparent at 4 days after PE and persisting through 14 days. CONCLUSION: PE is associated with an early influx of polymorphonuclears and macrophages and monocyte chemoattractant protein-1 elevation within the PA wall. These are temporally associated with thrombus resolution and intimal hyperplasia. These factors may mediate these two processes after PE. This offers targets for further study with the hopes of minimizing the pathophysiologic response to PE.
OBJECTIVE: We tested the hypothesis that a venous thromboembolism to the pulmonary arterial system (pulmonary embolism [PE]) would cause an inflammatory response within the pulmonary arterial (PA) wall marked by elevated cytokines and chemokines and an influx of inflammatory cells. METHODS: Experimental PE was induced in 70 rats and confirmed with angiography and O(2) saturation depression, and an additional 70 rats underwent sham operations. PA and lung tissue were removed at 3 hours and at 1, 2, 4, 6, 8, and 14 days (n = 10 per time point), were analyzed for proinflammatory cytokines and chemokines, and underwent histologic analysis. Data were analyzed with analysis of variance and the unpaired Student t test. RESULTS: Average gross PE resolution was 40% at 2 days, 90% at 4 days, and 100% at 6 days. Only monocyte chemoattractant protein-1 levels were greater in affected PAs compared with sham PAs at 3 hours, 1 day, and 2 days (137 +/- 13 pg/mg protein, 285 +/- 40 pg/mg protein, and 249 +/- 36 pg/mg protein versus 101 +/- 6 pg/mg protein, 150 +/- 36 pg/mg protein, and 92 +/- 3 pg/mg protein; P <.01 for all). Keratinocyte-derived chemokine, tissue necrosis factor, interleukin-10, nitric oxide, P-selectin, and E-selectin levels were not elevated. Neutrophils infiltrated the PA wall beginning at 3 hours, peaked at 2 days (69.4 +/- 21.7 per five high-power fields; P <.01), and returned to baseline by 8 days after PE. Macrophages peaked at 1 day after PE (29.3 +/- 6.9; P <.01) and returned to baseline by 4 days after PE. PE also was associated with a significantly increased intima to media ratio (P <.05), apparent at 4 days after PE and persisting through 14 days. CONCLUSION: PE is associated with an early influx of polymorphonuclears and macrophages and monocyte chemoattractant protein-1 elevation within the PA wall. These are temporally associated with thrombus resolution and intimal hyperplasia. These factors may mediate these two processes after PE. This offers targets for further study with the hopes of minimizing the pathophysiologic response to PE.