{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T20:01:56Z","timestamp":1769457716903,"version":"3.49.0"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,6,22]],"date-time":"2019-06-22T00:00:00Z","timestamp":1561161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Obstructive disease of the epicardial coronary arteries is the main cause of angina. However, a number of patients with anginal symptoms have normal coronaries or non-obstructive coronary artery disease (CAD) despite electrocardiographic evidence of ischaemia during stress testing. In addition to limited microvascular vasodilator capacity, the coronary microcirculation of these patients is particularly sensitive to vasoconstrictor stimuli, in a condition known as microvascular angina. This review briefly summarizes the determinants and control of coronary blood flow (CBF) and myocardial perfusion. It subsequently analyses the mechanisms responsible for transient myocardial ischaemia: obstructive CAD, coronary spasm and coronary microvascular dysfunction in the absence of epicardial coronary lesions, and variable combinations of structural anomalies, impaired endothelium-dependent and\/or -independent vasodilation, and enhanced perception of pain. Lastly, we exemplify mechanism of angina during tachycardia. Distal to a coronary stenosis, coronary dilator reserve is already recruited and can be nearly exhausted at rest distal to a severe stenosis. Increased heart rate reduces the duration of diastole and thus CBF when metabolic vasodilation is no longer able to increase CBF. The increase in myocardial oxygen consumption and resulting metabolic vasodilation in adjacent myocardium without stenotic coronary arteries further acts to divert blood flow away from the post-stenotic coronary vascular bed through collaterals.<\/jats:p>","DOI":"10.1093\/cvr\/cvz160","type":"journal-article","created":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T15:11:16Z","timestamp":1560784276000},"page":"1460-1470","source":"Crossref","is-referenced-by-count":41,"title":["The many faces of myocardial ischaemia and angina"],"prefix":"10.1093","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-5347","authenticated-orcid":false,"given":"Bernard I","family":"Levy","sequence":"first","affiliation":[{"name":"Inserm U970 and Vessels and Blood Institute, 8 Rue Guy Patin, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Heusch","sequence":"additional","affiliation":[{"name":"Institute for Pathophysiology, West German Heart and Vascular Center, Universit\u00e4tsklinikum Essen, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo G","family":"Camici","sequence":"additional","affiliation":[{"name":"Vita Salute University and San Raffaele Hospital, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,22]]},"reference":[{"key":"2019072309503168100_cvz160-B1","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1056\/NEJMra061889","article-title":"Coronary microvascular dysfunction","volume":"356","author":"Camici","year":"2007","journal-title":"N Engl J Med"},{"key":"2019072309503168100_cvz160-B2","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1056\/NEJMoa0907272","article-title":"Low diagnostic yield of elective coronary angiography","volume":"362","author":"Patel","year":"2010","journal-title":"N Engl J 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I. 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