epidermal-growth-factor and Pulmonary-Embolism

We compared the effects a novel recombinant tissue-type plasminogen activator (rt-PA) E6010 with the more conventional therapeutic agent alteplase in a new canine model of life-threatening acute pulmonary thromboembolism (APTE). Fifty milliliters of autologous blood was obtained from anesthetized, adult mongrel dogs and mixed with 10,000 units of thrombin. The left pulmonary artery, pulmonary vein, and bronchus were ligated, and previously prepared blood clots were injected via the femoral vein until the mean pulmonary artery pressure (mPA) increased to 2.5-3.0 times over baseline mPA (control). E6010 (0.4 mg/kg) or alteplase (1.33 mg/kg) was administered to other animals following inducement of APTE. In control animals, 60 min after embolization, mPA increased from 13+/-3 mm Hg to 31+/-3 mm Hg (p < 0.0001), cardiac output (CO) decreased from 1.47+/-0.35 l/min to 1.15+/-0.39 l/min (p < 0.0001), and PaO2 decreased from 101+/-31 mm Hg to 65+/-20 mm Hg (p < 0.001). E6010 significantly reduced mPA from 31+/-3 mm Hg to 25+/-4 mm Hg (p < 0.0001) 30 min after administration. In the alteplase group, however, mPA did not significantly change. At 180 min following drug administration, further reduction of mPA was significantly observed in both treatments. CO and PaO2 did not improve after either treatment. The present study indicated that E6010 more rapidly reduced pulmonary hypertension in our APTE model. Because of its rapid action, E6010 might be a promising thrombolytic agent for treatment of APTE.

Topics: Acute Disease; Animals; Dogs; Epidermal Growth Factor; Fibrinolytic Agents; Hemodynamics; Hypertension, Pulmonary; Pulmonary Embolism; Time Factors; Tissue Plasminogen Activator

A 22-year-old man was admitted to our hospital because of sudden dyspnea and dizziness. Hypoxemia was found. Lung perfusion scintigraphy and pulmonary angiography showed massive pulmonary thromboembolism. The patient received E6010, a derivative of tissue plasminogen activator by intravenous injection for about 2 minutes. One hour after this treatment, pulmonary angiography showed lysis of the ciot, the pulmonary arterial pressure had decreased, and the cardiac index and PaO2 had increased. Despite anticoagulant therapy, pulmonary embolism recurred so we implanted a Greenfield filter in the inferior vena cava. This was the first case of pulmonary thromboembolism in which E6010 had a beneficial effect. We were also able to document hemodynamic and radiologic changes after intravenous infusion of this drug. Recurrent pulmonary embolism is an indication for filter placement, and this patient will need a long period of follow-up.

Topics: Acute Disease; Adult; Epidermal Growth Factor; Fibrinolytic Agents; Humans; Infusions, Intravenous; Male; Pulmonary Embolism; Vena Cava Filters