Effects of recombinant tissue-type plasminogen activator on life-threatening acute pulmonary thromboembolism in a canine model: a comparative study of e6010 and alteplase.
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.
Tagami
H
H
First Department of Surgery, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto 860-0811, Japan.
Utoh
J
J
Sun
L B
LB
Okamoto
K
K
Moriyama
S
S
Kunitomo
R
R
Kitamura
N
N
D000208:Acute Disease; D000818:Animals; D004285:Dogs; D004815:Epidermal Growth Factor / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D011655:Pulmonary Embolism / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; C076356:E 6010; D004815:Epidermal Growth Factor; D010959:Tissue Plasminogen Activator