Effects of hydralazine and increased cardiac output on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.
We employed a canine model of pulmonary embolism, induced by injection of autologous radiolabelled blood clots, to investigate effects of hydralazine and an increase in cardiac output per se on recombinant tissue plasminogen activator-induced thrombolysis. Emboli increased pulmonary artery pressure (PAP) and decreased CO from 2.7 to 1.8 L/min-1. Following embolization, dogs were randomly divided into three groups. Group 1 received .5 mg/kg of rtPA over 30 minutes. Group 2 received the same dose of rtPA and were pretreated with hydralazine to increase CO approximately 50 percent. In the group 3 dogs, CO was increased by opening a systemic A-V fistula. Following embolization, CO remained low in group 1, the mean 2 h time-averaged CO was 1.9 L/min-1. The CO was 2.9 and 3.1 L/min-1 in groups 2 and 3, respectively. Corresponding to the increased flow in groups 2 and 3, rate and extent of pulmonary thrombolysis significantly increased. These results indicate that an increase in CO augments rtPA-induced pulmonary thrombolysis.
Prewitt
R M
RM
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Downes
A M
AM
Gu
S A
SA
Chan
S M
SM
Ducas
J
J
D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001794:Blood Pressure; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D005342:Fibrinolysis; D006830:Hydralazine / Q000008:administration & dosage / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins; D013671:Technetium Tc 99m Sulfur Colloid; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D011994:Recombinant Proteins; D006830:Hydralazine; D013671:Technetium Tc 99m Sulfur Colloid; D010959:Tissue Plasminogen Activator