© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Constriction of native coronary collaterals
Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
* Tel.: +1-410-955-5997; fax: +1-410-955-0852 lbecker{at}welchlink.welch.jhu.edu
Received 16 May 2000; accepted 16 May 2000
See article by Mansaray et al. [5] (pages 359–366) in this issue.
Interconnections between adjacent coronary arteries, known as "collateral vessels," were discovered as early as the 17th century [1]. Anatomically, collaterals provide conduits through which blood can flow from normal to jeopardized myocardial regions, following obstruction of the antegrade blood supply. However, controversy has existed for decades about the true functional significance of the coronary collateral system. Native collateral vessels, consisting of thin walled vascular structures with a rudimentary smooth muscle coat, were thought for many years to be passive tubes through which blood flowed as a result of a mechanical pressure gradient between the normal and occluded vascular beds. The concept that native collaterals were capable of significant vasomotion, either dilatation or constriction, was not widely accepted.
In recent years, however, a number of studies in different animal models have consistently demonstrated that collaterals dilate over the first several minutes following an acute coronary artery occlusion, resulting in a significant increase in blood flow. The mechanism for acute collateral enlargement, however, remains unknown. Collateral dilatation could potentially be mediated by mechanical stretching, endothelium-dependent relaxation of vascular smooth muscle, or possibly other mechanisms. Native collaterals have been shown to respond to various vasodilator stimuli, supporting the concept that receptor-mediated mechanisms are operative in such vessels. For example, nitrates, prostaglandins E1 and I2, and adenosine have all been shown to dilate native collaterals in canine models, despite the fact that these vessels were already "maximally" dilated through mechanical stretch and ischemia-related mechanisms [2–4].
The article by Mansaray et al. in this issue of the Journal [5] extends the paradigm further. They report that native collaterals, partially opened by application of a critical coronary artery stenosis, can acutely constrict during formation of an intracoronary thrombus at the site of the stenosis. Although they attribute this effect to release of vasoconstrictors from aggregating platelets (based on the fact that platelet aggregation is strongly implicated in the Folts model used by the authors), the experiments do not definitively identify platelets as the responsible source, nor do they identify the specific molecules or receptors responsible for the constrictor effect. Interestingly, collateral constriction did not occur during thrombus formation when the antegrade coronary artery was completely occluded rather than merely critically narrowed. The authors hypothesize that the vasoconstrictor stimulus resulting from thrombus formation was not sufficiently potent to overcome "maximal" collateral dilatation caused by a complete coronary artery occlusion. Although it is well accepted that platelet aggregation within the coronary arteries at the site of an ulcerated atherosclerotic plaque can produce local arterial constriction, or downstream microvascular constriction, the finding that coronary collaterals may also be affected is a new observation.
Because the experimental model required a patent rather than an occluded antegrade vessel, the authors could not measure collateral blood flow and collateral resistance using standard approaches. Instead, they employed a clever modification of the microsphere technique in which collateral flow was estimated as the difference between total flow to the jeopardized region (measured with microspheres) and antegrade flow (measured with an electromagnetic flowmeter), with antegrade flow converted to a tissue perfusion equivalent by reference to the baseline measurement. Because of the instrumentation involved, this approach is essentially applicable only to acute, large animal models. Nevertheless, the concept that vasoconstriction may be apparent only in partially dilated (but not fully dilated) collaterals is potentially important and merits confirmation.
This study does not clarify why platelet aggregation in a stenotic vessel should cause vasoconstriction in collaterals arising from normal arteries and anastomosing downstream to the stenosed vessel. These collaterals are presumably carrying blood which has not come into direct contact with the developing thrombus. Perhaps collateral resistance can be significantly increased by exposure of only the distal anastomotic ends of the collaterals to platelet-derived vasoconstrictors. Alternatively, vasoactive substances may be released in large enough amounts from the aggregating platelets that circulating blood levels are increased. Coronary collaterals could be particularly sensitive to these agents, but other vascular beds might also exhibit vasoconstrictive effects. Furthermore, coronary collaterals might constrict in response to a variety of agonists, and not just to platelet-derived products.
The authors have focused on native coronary collaterals, but some of the same issues could apply to remodeled mature collateral vessels resulting from chronic or recurrent ischemia. These vessels carry considerably more blood flow, have a well-developed media, and exhibit much clearer evidence of vasomotion than native collaterals. Nevertheless, the results from the study by Mansaray et al. cannot be automatically applied to well-developed collaterals, because the regulatory mechanisms for vasomotor control may differ substantially. Further studies will be necessary to determine whether these results can be generalized to all types of collaterals.
Finally, what relevance do the results of Mansaray et al. have for human coronary disease? It is now accepted that coronary vasomotion plays a central role in the pathophysiology of myocardial ischemia. Constriction of collateral vessels, as described by Mansaray et al., could contribute to more severe ischemia downstream from a critically stenotic vessel during development of an acute coronary thrombus, and could thereby lead to a worse outcome in patients with acute coronary syndromes. If collaterals are sensitive to a variety of vasoconstrictive stimuli, such as the catecholamine surge occurring with exercise or mental stress, collateral constriction may contribute to exercise- or mental stress-induced ischemia. A fuller consideration of the effects of collateral vasomotion should help provide a more accurate and comprehensive understanding of human coronary pathophysiology.
 |
References |
|---|
 Top References |
|---|
- Lower R. Tractatus de Corde. (1669) Amsterdam: Elsevier.
- Becker L.C. Effect of nitroglycerin and dipyridamole on regional left ventricular blood flow during coronary artery occlusion. J Clin Invest (1976) 58:1287–1296.[Web of Science][Medline]
- Jugdutt B.I., Hutchins G.M., Bulkley B.H., Becker L.C. Dissimilar effects of prostacyclin, prostaglandin E1, and prostaglandin E2 on myocardial infarct size after coronary occlusion in conscious dogs. Circ Res (1981) 49:685–700.
[Free Full Text] - Aversano T.A., Becker L.C. Persistence of coronary vasodilator reserve despite functionally significant flow reduction. Am J Physiol (1985) 248:H403–411.[Web of Science][Medline]
- Mansaray M., Hynd J.W., Vergroesen I., Belcher P.R., Drake-Holland A.J., Noble M.I.M. Measurement of coronary collateral flow and resistance in the presence of an open critical stenosis, and the response to intra-arterial thrombosis. Cardiovasc Res (2000) 47:359–366.
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||