Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Kleinbongard, Petra; Böse, Dirk; Baars, Theodor; Möhlenkamp, Stefan; Konorza, Thomas; Schöner, S; Elter-Schulz, Miriam; Eggebrecht, Holger; Degen, Hubertus; Haude, Michael; Levkau, Bodo; Schulz, Rainer; Erbel, Raimund; Heusch, Gerd

doi:10.1161/circresaha.110.235713

Cited by 104 publications

(93 citation statements)

References 55 publications

(33 reference statements)

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“…We detected a release of the soluble mediators serotonin, TxB 2 , and TNF␣ into the aspirate of nRCA and SVG-RCA, confirming our prior studies in SVG lesions (2,16,21). However, the release of these mediators was comparable between nRCA and SVG-RCA.…”

Section: Discussionsupporting

confidence: 89%

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Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Kleinbongard

Baars

Möhlenkamp

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Kleinbongard P, Baars T, Möhlenkamp S, Kahlert P, Erbel R, Heusch G. Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris. Am J Physiol Heart Circ Physiol 305: H1222-H1229, 2013. First published August 9, 2013; doi:10.1152/ajpheart.00358.2013.-Stent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances that contribute to impaired microvascular perfusion. Here we addressed the potential for microvascular obstruction in patients with stenotic native right coronary arteries (nRCA) compared with saphenous vein grafts on right coronary arteries (SVG-RCA). We enrolled symptomatic, male patients with stable angina pectoris and a flow-limiting stenosis in their nRCA or SVG-RCA (n ϭ 18/18). Plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation under protection with a distal occlusion/aspiration device and divided into particulate debris and plasma. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor-␣ was measured. The response of rat mesenteric arteries with intact (ϩE) and denuded (ϪE) endothelium to aspirate plasma (without and with selective endothelin receptor blockade) was normalized to that by potassium chloride (KClmax ϭ 100%). Plaque volume and composition were not different between nRCA and SVG-RCA. There was less particulate debris (65 Ϯ 8 vs. 146 Ϯ 23 mg; P Ͻ 0.05) and more endothelin release (5.8 Ϯ 0.8 vs. 1.3 Ϯ 0.7 pg/ml; P Ͻ 0.05) in nRCA than in SVG-RCA, whereas the release of the other mediators was not different. Aspirate from nRCA induced stronger vasoconstriction than that from SVG-RCA [nRCA, 78 Ϯ 6% (ϩE)/84 Ϯ 5% (ϪE); SVG-RCA, 59 Ϯ 6% (ϩE)/68 Ϯ 3% (ϪE); P Ͻ 0.05 nRCA vs. SVG-RCA], which was attenuated by a nonspecific endothelin and a specific endothelin receptor A antagonist. Thus coronary aspirate from stented nRCA is characterized by less debris but more endothelin and stronger vasoconstrictor response than that from SVG-RCA. coronary disease; ischemia; native coronary artery; saphenous vein graft; vasoconstriction INTERVENTIONAL PLAQUE RUPTURE induces the release of not only particulate debris but also soluble vasoconstrictor, thrombogenic, and inflammatory substances from the lesion that all contribute to impair microvascular coronary perfusion. Typical consequences of coronary microvascular obstruction are microinfarcts with subsequent inflammation, arrhythmias, contractile dysfunction, and impaired coronary flow reserve (14). Various protection devices have been used to capture and remove the released plaque material. A prognostic benefit from distal protection devices in elective interventions has been established only for saphenous vein grafts (SVGs) (3, 39), whereas a benefit for native coronary arteries still remains to be demonstrated (14).The underlying atherosclerosis in native coronary arteries differs from that in SVGs,...

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Section: Discussionsupporting

confidence: 89%

“…The vasoconstrictor endothelin is released into native coronary arteries during acute coronary syndromes (1). In contrast, endothelin is not released into SVGs during elective stent implantation (16).…”

mentioning

confidence: 99%

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Kleinbongard

Baars

Möhlenkamp

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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“…plugging (9)(10)(11)(12). At coronary angiography in PPCI patients, MVO manifests as sluggish coronary blood flow, impaired myocardial blush grade, and a characteristic coronary flow velocity profile (13).…”

Section: Pathophysiology Of Myocardial Ischemic Injurymentioning

confidence: 99%

Myocardial ischemia-reperfusion injury: a neglected therapeutic target

Hausenloy¹,

Yellon²

2013

J. Clin. Invest.

1,821

1,473

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Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.

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“…89,90 Such α-adrenergic coronary constrictor impact is also seen in humans with chronic stable angina 91 and during PCIs. 92,93 The release of vasoconstrictor substances, such as thromboxane, serotonin, 94,95 and endothelin 96 from the rupturing culprit lesion into the microcirculation, in conjunction with the impairment of endothelial function by ischemia/reperfusion per se 60,87,88,97,98 or by tumor necrosis factor α, 95 can contribute to such enhanced vasoconstrictor responsiveness during myocardial ischemia/reperfusion. With more prolonged ischemia in hibernating myocardium, there is structural remodeling of the microvasculature with hypertrophy of smaller and atrophy of larger vessels, reduced vascular distensibility, and increased vasoconstriction in response to endothelin.…”

Section: Vasomotionmentioning

confidence: 99%

The Coronary Circulation as a Target of Cardioprotection

Heusch

2016

Circulation Research

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160

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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.

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Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Cited by 104 publications

References 55 publications

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Myocardial ischemia-reperfusion injury: a neglected therapeutic target

The Coronary Circulation as a Target of Cardioprotection

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