The Coronary Circulation as a Target of Cardioprotection

Abstract

Abstract:The atherosclerotic coronary vasculature is not only the culprit but also a victim of myocardial ischemia/ reperfusion injury. Manifestations of such injury are increased vascular permeability and edema, endothelial dysfunction and impaired vasomotion, microembolization of atherothrombotic debris, stasis with intravascular cell aggregates, and finally, in its most severe form, capillary destruction with hemorrhage. In animal experiments, local and remote ischemic pre-and postconditioning not only reduce infarct size but also these manifestations of coronary vascular injury, as do drugs which recruit signal transduction steps of conditioning. Clinically, no-reflow is frequently seen after interventional reperfusion, and it carries an adverse prognosis. The translation of cardioprotective interventions to clinical practice has been difficult to date. Only 4 drugs (brain natriuretic peptide, exenatide, metoprolol, and esmolol) stand unchallenged to date in reducing infarct size in patients with reperfused acute myocardial infarction; unfortunately, for these drugs, no information on their impact on the ischemic/reperfused coronary circulation is available. (Circ Res.

Time to Give Up on Cardioprotection?

“…The endothelium, however, is important in mediating the cardioprotective effect of remote ischemic conditioning. 190 The diseased coronary circulation with atherosclerotic plaques in the epicardial arteries and microvascular dysfunction is more susceptible to myocardial ischemia/reperfusion and possibly contributes to such injury, 27 but may also have triggered the development of a collateral circulation which may protect from myocardial ischemia/reperfusion injury. 169,191 Most of the above studies have not taken age or the confounding risk factors and comorbidities into consideration, although some of them excluded patients with diabetes mellitus 144,148 or with an angiographically visible collateral circulation.…”

“…14 The conditioning phenomena protect not only the myocardium but also the coronary microcirculation from ischemia/reperfusion injury. 27 The pathomechanisms of myocardial ischemia/reperfusion injury have been reviewed in detail elsewhere. 18,20 Briefly, cell death arises from necrosis, apoptosis, necroptosis, and autophagy; ischemic injury is exacerbated by reperfusion.…”

Improvement in Microvascular Ischemia After Enzyme Replacement Therapy in Anderson-Fabry Disease — Computed Tomography Myocardial Perfusion Imaging —

“…Deposition of glycosphingolipid within smooth muscle and endothelial cells causes narrowing of the small intramural coronary arteries. 2, 3 ERT is standard therapy for Anderson-Fabry disease, and clears microvascular endothelial glycosphingolipid deposits. 4 Integrated CTP and CCTA were reportedly associated with improved diagnostic accuracy for the detection of significant ischemia.…”

Protection of coronary circulation: Evaluation by PET perfusion imaging

“…4 The coronary vasculature has been considered as a target of RIC in addition to direct effect on the myocardium. 5 Mechanisms of RIC can be briefly summarized as activation of nociceptive fibers during brief, local injury that releases an unidentified molecule into the circulation and/or signal through the spinal cord to activate both cardiac vagal and sympathetic efferent neurons to release cardioprotective substances. 1 Many endogenously derived preconditioning agents are vasoactive (e.g., adenosine, nitric oxide, and bradykinin).…”

“…Studies have shown that RIC prevents peripheral endothelial dysfunction associated with ischemia, 1,2 but the effects on coronary blood flow have been controversial. 1,5 In an experimental model, repeated transient limb ischaemia lead to reduced coronary resistance and increased basal flow in the left anterior descending coronary artery in healthy pigs. 6 Similarly, basal blood flow velocity in the left anterior descending coronary artery assessed by transthoracic Doppler echocardiography was increased shortly after RIC in healthy human subjects.…”