Effect of low-molecular-weight heparin on recombinant tissue plasminogen activator-induced thrombolysis in canine pulmonary embolism.
We employed a canine model of pulmonary embolism induced by radioactive blood clots to determine if low-molecular-weight heparin augments recombinant tissue plasminogen activator (rtPA)-induced thrombolysis. Following embolization, dogs were randomized: group 1 dogs received heparin; group 2 dogs received low-molecular-weight heparin; group 3 dogs received 1.5 mg/kg of rtPA over 45 minutes; group 4 dogs received rtPA 3 mg/kg over 45 minutes; and group 5 dogs received 1.5 mg/kg of rtPA plus low-molecular-weight heparin. Over three hours, little thrombolysis occurred in groups 1 and 2. In contrast, significant thrombolysis occurred in groups 3 to 5, 46 percent, 49 percent, and 46 percent, respectively (all p less than 0.01 compared with groups 1 and 2). We conclude that there is an upper limit to the dose-thrombolytic rate relationship with rtPA, and that low-molecular-weight heparin does not augment rtPA-induced thrombolysis.
Werier
J
J
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Ducas
J
J
Gu
S
S
Chan
S M
SM
Prewitt
R M
RM
D000818:Animals; D016280:Atrial Function, Right; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D011651:Pulmonary Artery / Q000503:physiopathology; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins; D012044:Regression Analysis; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D006495:Heparin, Low-Molecular-Weight; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator