Clinically relevant concentrations of dopamine do not amplify agonist-induced human platelet Ca2+ mobilization or GP IIb IIIa activation and do not accelerate acute coronary thrombosis in dogs.
BACKGROUND
Dopamine is an inotrope effective in the short term treatment of acute heart failure - including that caused by coronary artery disease. Catecholamines however can potentiate platelet activation and pre-dispose to coronary thrombosis.


OBJECTIVE
Dopamine was studied for effect on agonist induced human platelet Ca mobilization, human platelet GP iib iiia receptor activation and acute coronary thrombosis in dogs. Calcium sensitive indo-1, fluorescent immunostaining and flow cytometry were used for platelet studies while coronary thrombosis was induced in anesthetized dogs via endothelial damage, arterial wall injury and critical stenosis.


RESULTS
Dopamine 10 and 10 M had no effect on the amplitude of the platelet Ca signal evoked by thrombin 0.1 U/mL. Likewise, dopamine 10 M had no effect on GP IIb IIIa activation evoked by ADP 10 M and by thrombin 0.1 U/mL. In dogs, intravenous dopamine 8 ug/Kg/min had no effect on repetitive cycles of acute coronary thrombus formation. In positive control studies, epinephrine increased platelet responsiveness and accelerated canine coronary thrombosis.


CONCLUSIONS
Clinically relevant concentrations of dopamine did not amplify agonist induced human platelet Ca activation, GPiib iiia expression or experimental canine coronary thrombosis--providing a degree of reassurance concerning this versatile inotrope.
Sill
John Christopher
JC
Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA. sill.john@mayo.edu
Bertha
Brian
B
Berger
Ines
I
Southorn
Victoria
V
Folts
John
J
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002478:Cells, Cultured; D003328:Coronary Thrombosis / Q000139:chemically induced*; D004195:Disease Models, Animal; D004285:Dogs; D004298:Dopamine / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000819:agonists*; D013917:Thrombin / Q000494:pharmacology
D002316:Cardiotonic Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D013917:Thrombin; D002118:Calcium; D004298:Dopamine