fMLP provokes coronary vasoconstriction and myocardial ischemia in rabbits.
Recent pathological studies of coronary arteries from humans with suspected coronary spasm have revealed an augmented intramural burden of inflammatory cells. To test the hypothesis that inappropriate activation of inflammatory cells participates in the evolution of coronary vasospasm, the present experiments employed a newly developed coronary arteriographic technique for use in pentobarbital-anesthetized rabbits to evaluate the coronary vasomotor actions of the nonselective inflammatory cell stimulant, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). In 10 of 10 animals, selective left intracoronary injection of 200 ng fMLP evoked profound left coronary narrowing accompanied in all cases by ST segment deviation and dysrhythmias. Thallium-201 scintigraphy demonstrated hypoperfusion of the left ventricular free wall and septum supplied by the spastic coronary artery. The fMLP-induced epicardial vaso-constriction, ischemic electrocardiogram (ECG) changes, and thallium perfusion defects were reversed by intravenous nitroglycerin. Neither the right coronary artery nor its distribution were influenced by left coronary injection of fMLP. Additional experiments in isolated, salt solution-perfused rabbit hearts demonstrated that fMLP failed to exert direct coronary vasoconstrictor effects. These observations indicate that the non-selective inflammatory cell stimulant, fMLP, provokes arteriographically demonstrable coronary spasm with attendant myocardial hypoperfusion and ischemic ECG changes in anesthetized rabbits. Such a model may be useful in exploring the dynamic role of inflammatory cells in development of coronary spasm.
Gillespie
M N
MN
Division of Pharmacology and Toxicology, College of Pharmacy, Albert B. Chandler Medical Center, University of Kentucky, Lexington 40536.
Booth
D C
DC
Friedman
B J
BJ
Cunningham
M R
MR
Jay
M
M
DeMaria
A N
AN
D000792:Angiography; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000139:chemically induced* / Q000000981:diagnostic imaging; D003329:Coronary Vasospasm / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D004562:Electrocardiography; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011817:Rabbits; D011877:Radionuclide Imaging; D013793:Thallium; D014661:Vasoconstriction
D009240:N-Formylmethionine Leucyl-Phenylalanine; D013793:Thallium