TY - JOUR
T1 - fMLP provokes coronary vasconstriction and myocardial ischemia in rabbits
AU - Gillespie, M. N.
AU - Booth, D. C.
AU - Friedman, B. J.
AU - Cunningham, M. R.
AU - Jay, M.
AU - DeMaria, A. N.
PY - 1988
Y1 - 1988
N2 - 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 vasoconstriction, 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.
AB - 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 vasoconstriction, 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.
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M3 - Article
C2 - 3348426
AN - SCOPUS:0023895025
SN - 0002-9513
VL - 254
SP - 23/3
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3
ER -