Effects of a thromboxane receptor antagonist (NT-126) and a thromboxane synthase inhibitor (OKY-O46) on protamine-induced circulatory changes in dogs.
OBJECTIVE
To examine whether a thromboxane receptor antagonist, NT-126, or a thromboxane synthase inhibitor, OKY-046, prevents circulatory changes caused by protamine reversal of heparin and to evaluate the significance of thromboxane generation in the phenomena.


METHODS
Prospective, randomized, controlled, animal study.


METHODS
A university research laboratory.


METHODS
Twenty-four adult mongrel dogs.


METHODS
According to the pretreatments, the animals were divided into 3 groups (n = 8 in each): (1) control (normal saline); (2) NT-126, 0.01 mg/kg; and (3) OKY-046, 1 mg/kg. Under general anesthesia, all animals were anticoagulated with intravenous heparin, 200 IU/kg, 5 minutes before the pretreatment. Five minutes after the pretreatment, protamine sulfate, 2 mg/kg, was administered intravenously over 10 seconds. Hemodynamic variables were recorded repeatedly until 60 minutes after the protamine. Plasma thromboxane B2 level was determined at baseline and 10 minutes after protamine injection.


RESULTS
The average values of mean arterial blood pressure and mean pulmonary artery pressure among the 3 groups in each period and values in each group over the study period were not significantly different. There was weak correlation between maximum percent increases in systolic pulmonary artery pressure or maximum percent decreases in systolic arterial blood pressure for 5 minutes after the protamine versus percent increases in plasma thromboxane B2 level.


CONCLUSIONS
Neither NT-126 nor OKY-046 appears to be effective in preventing protamine-induced circulatory changes in this dog model, suggesting that thromboxane generation alone is not responsible for the phenomena.
Mizutani
T
T
Department of Critical Care Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Takahashi
S
S
Kihara
S
S
Toyooka
H
H
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006494:Heparin Antagonists / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology; D008689:Methacrylates / Q000494:pharmacology*; D011479:Protamines / Q000494:pharmacology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
D000925:Anticoagulants; D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D006494:Heparin Antagonists; D008689:Methacrylates; D011479:Protamines; D017482:Receptors, Thromboxane; C067520:ONO-NT 126; D013929:Thromboxane B2; D006493:Heparin; D013930:Thromboxane-A Synthase; C034364:ozagrel