The thromboxane receptor antagonist, daltroban, protects the myocardium from ischaemic injury resulting in suppression of leukocytosis.
The cardioprotective action of the new selective inhibitor of thromboxane receptors, daltroban (BM 13.505), was studied in cats subjected to 3 h of coronary artery ligation followed by 2 h of reperfusion. In comparison with vehicle (physiological saline)-treated cats, daltroban (20 mg/kg per h i.v.) reduced the ischaemia-induced rise in the ST segment and prevented the development of a Q-wave in the ECG during reperfusion. This was paralleled by a significantly improved preservation of creatine-phosphokinase activity in the ischaemic myocardium. Daltroban significantly attenuated platelet ATP secretion, the U-46.619-induced contraction of the cat thoracic aorta ex vivo and the myeloperoxidase-associated generation of reactive oxygen species ex vivo. These effects could be largely attributed to the inhibition of ischaemia-induced leukocytosis. It is concluded that daltroban protects the myocardium from ischaemic injury and that this effect involves prevention of ischaemia-induced leukocytosis.
Thiemermann
C
C
Institut für Pharmakologie, Universität Düsseldorf, F.R.G.
Ney
P
P
Schrör
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D003402:Creatine Kinase / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007964:Leukocytosis / Q000209:etiology* / Q000517:prevention & control; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010648:Phenylacetates / Q000494:pharmacology*; D010976:Platelet Count; D011982:Receptors, Prostaglandin / Q000378:metabolism; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D010648:Phenylacetates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; C051762:daltroban; D010100:Oxygen