CORONARY VASOREACTIVITY AND THE ACUTE CORONARY SYNDROME
Most patients with acute coronary syndrome (ACS) (myocardial infarction and unstable angina [UA]) have coronary artery disease and,
in these patients, occlusive coronary thrombosis is an established pathogenic mechanism. A sizeable number of patients with ACS,
however, have normal or near normal coronary arteriograms 1 and studies indicate that in such patients vasoconstriction plays a
Recently, studies reported that in patients with UA the culprit lesion is vasoconstrictors and/or vascular muscle hyperactivity is needed. Zeiher at
“hyperactive” (i.e., prone to developing marked vasoconstriction in al3 reported increased endothelin-1 expression in unstable coronary
response to vasoactive stimuli), compared to non-culprit lesions3 and also atherosclerotic lesions compared to stable coronary plaques. Endothelin-1
to coronary stenoses in stable angina patients.4 The mechanisms was localized predominantly with plaque components indicative of chronic
responsible for the increased vasoreactivity of unstable plaques are still inflammation. Tomai et al7 recently showed that in patients with UA
poorly understood, but it is likely that multiple factors play a role. elevated levels ofC-reactive protein are associated with both a greater
Endothelial dysfunction is one of these factors and may lead to impaired dilatation of the culprit lesion after the intracoronary administration of
release of endogenous vasodilators such as nitric oxide (NO) and nitroglycerin and a greater constrictor response of these lesions to the cold
prostaglandins, and the release of constricting factors such as endothelin-1. pressor test. Thus, inflammatory mechanisms and endothelial dysfunction
Endothelial activation also stimulates platelet and leukocyte adhesion and may play a modulatory role of vasomotor tone.
aggregation and thrombus formation. Fukai et al 5 showed that in Endothelial dysfunction, however, is only a wedge in the vasoconstrictor
experimental animals the denuded and irradiated segments of the left status associated with unstable plaques. Other mechanisms are also likely
coronary artery, with regenerated endothelium, were associated with to participate in the increased vasoreactive response, i.e. increased
defective endothelium-dependent vasodilatation. Reduced NO availability sympathetic activity, autonomic nervous system imbalance, and
and increased vascular smooth muscle response to the administration of microvascular spasm. The underlying molecular mechanisms, however,
serotonin were their principal findings. are largely unknown.
Endothelial damage is associated with complex changes in vascular Conclusion
function and haemostatic responses. In the setting of ACS both platelet
Occlusive coronary thrombosis is the most common cause of ACS.
activation and aggregation set off a chain of unfavorable vascular reactions However, subgroups of ACS patients exist in whom coronary
involving t e release of constrictor substances such as serotonin and
vasoconstriction, mediated by a number of mechanisms, is the
thromboxane A 2. Interestingly, in vitro studies by Rubanyi et al6
demonstrated that plasma obtained from the coronary sinus of patients main pathogenic cause. Therapeutic efforts in ACS in recent years
with UA possesses vasoconstrictor activity. Platelet aggregation and have been logically directed mainly at antagonizing platelet
thrombus formation results in ischaemia, which, in turn, triggers the aggregation and thrombus formation. However, the need exists to
release of factors that may exacerbate vasospastic mechanisms. develop more effective strategies to deal with the deleterious
For increased vasoreactivity to occur and cause myocardial ischaemia,
effects of increased vasoconstriction in patients with ACS.
however, increased production of potent endogenous J.C. KASKI and C. PIZZI - London, UK
References: 1. Raymond R et al. J Am Coll Cardiol. 1988;11:471-477. 2. Marzilli M et al. J Am Coll Cardiol. 2000;35:327-334. 3. Zeiher AM et al. Circulation.
1995;91:9 41-947. 4. Bogaty P et al. Circulation. 1994;90:5-11. 5. Fukai T et al. Circulation. 1993;88:1922-1930. 6. Rubanyi GM et al. J Am Coll Cardiol. 1987;9:1243-
1249. 7. Tomai F et al. Circulation. 2001;104:1471-1476.