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.

Abstract

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.

AIMS:

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.

CONCLUSION:

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.

• Authors: John Christopher Sill, Brian Bertha, Ines Berger, Victoria Southorn, John Folts
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 53 Issue 3 Pg. 246-52 (Mar 2009) ISSN: 1533-4023 [Electronic] United States
• PMID: 19247190 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Platelet Glycoprotein GPIIb-IIIa Complex
• Adenosine Diphosphate
• Thrombin
• Calcium
• Dopamine

Topics

• Acute Disease
• Adenosine Diphosphate (pharmacology)
• Animals
• Blood Platelets (drug effects, metabolism)
• Calcium (metabolism)
• Cardiotonic Agents (administration & dosage, adverse effects)
• Cells, Cultured
• Coronary Thrombosis (chemically induced)
• Disease Models, Animal
• Dogs
• Dopamine (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Platelet Glycoprotein GPIIb-IIIa Complex (agonists)
• Thrombin (pharmacology)