Effect of low-molecular-weight heparin and urokinase on pulmonary arteries involved in pulmonary embolism

Background Pulmonary embolism (PE) is a common and often fatal disease. Early after pulmonary thromboembolism, inflammation and associated intimal hyperplasia occur within the pulmonary arteries, similar to what is observed with chronic thromboembolic pulmonary hypertension. This study tested the hypothesis that thrombolytic and anticoagulant agents would have anti-inflammatory effects or inhibit intimal hyperplasia of involved pulmonary arteries. Methods Seventy-two male New Zealand white rabbits were randomly divided into two groups (54 rabbits in the PE group and 18 in the sham group). Experimental PE was induced in 54 rabbits by femoral vein injection of autologous blood clots and confirmed with pulmonary angiography, and other 18 rabbits underwent sham operations. Fifty-four rabbits in the PE group were randomly divided into three groups: a control group (treated with normal saline), a low-molecular-weight heparin (LMWH) group (treated with LMWH), and a urokinase (UK) group (treated with UK). Arterial blood gas was analyzed at 2, 7, and 28 days ( n =6 per time point by random group division), then lung tissues were removed and were analyzed for pro-inflammatory cytokines and chemokines, and were stained for intimal hyperplasia. Results The overall survival of rabbits undergoing PE was 100%. PE distribution detected on digital signal angiography (DSA) and histopathology was shown in 67% of rabbits (36/54) in the bilateral low lobar pulmonary arteries (PAs). The results showed that alveolar-arterial partial pressure of oxygen (PO 2 ) difference (P A-a O 2 ) significantly increased and PO 2 decreased in the control group compared with the sham group. Compared with controls, the UK group had a decreased level of P A-a O 2 on day 2 ( P <0.05), however, there was no significant difference in the LMWH group. Compared with controls, the LMWH group had a decreased level of monocyte chemoattractant protein-1 (MCP-1) in affected tissue and serum samples on days 7 and 28 ( P <0.05), and the UK group had decreased levels on days 2 and 7 ( P <0.05). Compared with sham group, all PE groups had an increased level of interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) in unaffected lung tissue samples at days 2 and 7. IL-13 in affected lung tissue in the LMWH group was decreased at all time points compared with controls ( P <0.05). However, TGF-β in affected lung tissue of the LMWH and UK groups increased at day 28. There was less intimal hyperplasia in involved pulmonary arteries at days 7 and 28 in the LMWH group compared with controls; there was no statistical difference in the UK group compared with controls. Conclusions UK treatment can rapidly improve the V/Q mismatch in PE and appears a short-term anti-inflammatory benefit. However, LMWH maybe inhibit the later local inflammatory reaction and reduce intimal hyperplasia.