Coronary microembolization does not induce acute preconditioning against infarction in pigs?the role of adenosine

Skyschally, Andreas; Schulz, Rainer; Gres, Petra; Konietzka, Ina; Martin, Claus; Haude, Michael; Erbel, Raimund; Heusch, Gerd

doi:10.1016/j.cardiores.2004.04.003

Cited by 29 publications

(21 citation statements)

References 28 publications

(49 reference statements)

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“…144 Coronary microembolization with release of adenosine into the coronary vasculature does not induce acute preconditioning and reduce infarct size or, conversely, interfere with protection by ischemic preconditioning. 103,145 Somewhat paradoxically, the increase in tumor necrosis factor α expression secondary to coronary microembolization can induce delayed protection and reduce infarct size from subsequent coronary occlusion/reperfusion, 146 such that the actual impact of coronary microembolization on infarct size depends critically on timing and is difficult to predict. Preinfarction angina is considered a clinical correlate of ischemic preconditioning.…”

Section: Coronary Vascular Protection By Ischemic Preconditioningmentioning

confidence: 99%

The Coronary Circulation as a Target of Cardioprotection

Heusch

2016

Circulation Research

206

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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Section: Coronary Vascular Protection By Ischemic Preconditioningmentioning

confidence: 99%

The Coronary Circulation as a Target of Cardioprotection

Heusch

2016

Circulation Research

206

160

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“…Although the aggregate amount of infarction is small (Ͻ5% of the microembolized myocardium in our experimental studies in dogs and pigs 8,9,11 ), these microinfarcts initiate a typical inflammatory response, characterized by increased myocardial TNF-␣ expression and leukocyte infiltration. 8,11,21 The increased TNF-␣ expression is an autocrine/paracrine response of viable cardiomyocytes surrounding the microinfarcts, possibly mediated by local shear stress between contracting and noncontracting, infarcted myocardium. 8 The increasing tissue concentration of TNF-␣ is causal for the resulting progressive myocardial dysfunction.…”

Section: Skyschally Et Al Bidirectional Role Of Tnf-␣ 143mentioning

confidence: 99%

“…In TNF-␣ knockout mice, acute 14 and delayed ischemic preconditioning 16 are abrogated and TNF-␣ antibodies inhibit delayed ischemic preconditioning in rats. 17 Therefore, for the present report, we used our established model of coronary microembolization in pigs 11,12 to investi-gate whether 6 hours after coronary microembolization-at a time when TNF-␣ tissue levels are increased and contractile dysfunction has developed 11 -the myocardium is protected against infarction. This experimental protocol attempts to replicate the clinical scenario of a patient experiencing coronary microembolization caused by fissure of an unstable coronary plaque and subsequent massive plaque rupture and thrombotic occlusion of a large epicardial coronary artery with impending myocardial infarction some hours later.…”

mentioning

confidence: 99%

“…The major sources of TNF-␣ in microembolized myocardium are the viable cardiomyocytes surrounding the microinfarcts, 8 and it is this increase in myocardial TNF-␣ that is causal for the progressive contractile dysfunction. 8 -10 Although coronary microembolization causes the release of coronary venous adenosine, 5,11 it neither induces acute preconditioning against acute infarction 11 nor interferes with a classic ischemic preconditioning protocol. 12 We now wondered whether the increased TNF-␣ expression may not only mediate progressive contractile dysfunction but also induce delayed protection against infarction.…”

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confidence: 99%

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Bidirectional Role of Tumor Necrosis Factor-α in Coronary Microembolization

Skyschally¹,

Gres²,

Hoffmann³

et al. 2007

Circulation Research

143

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Abstract-In patients with unstable angina, plaque rupture and coronary microembolization (ME) can precede complete coronary artery occlusion and impending infarction. ME-induced microinfarcts initiate an inflammatory reaction with increased tumor necrosis factor-␣ (TNF-␣) expression, resulting in progressive contractile dysfunction. However, TNF-␣ is not only a negative inotrope but can also protect the myocardium against infarction. In anesthetized pigs, we studied whether ME protects against infarction when TNF-␣ expression is increased. ME (group1; nϭ7) was induced by intracoronary infusion of microspheres (42 m; 3000 per mL/min inflow). Controls (group 2; nϭ8) received saline. Groups 3 and 4 (nϭ4 each) were pretreated with ovine TNF-␣ antibodies (25 mg/kg body weight) 30 minutes before ME or placebo, respectively. Ischemia (90 minutes) was induced 6 hours after ME when TNF-␣ was increased (66Ϯ21 pg/g wet weight; meanϮSEM) or after placebo (TNF-␣, 21Ϯ10 pg/g; PϽ0.05). Infarct size (percentage area at risk) was determined after 2 hours of reperfusion (triphenyl tetrazolium chloride staining). ME decreased systolic wall thickening progressively over 6 hours (group 1 versus group 2, 65Ϯ4% versus 90Ϯ1%; percentage of baseline; PϽ0.05). TNF-␣ antibodies attenuated the progressive decrease in systolic wall thickening following ME (group 3, 77Ϯ5% of baseline; PϽ0.05 versus group 1) with no effect in controls (group 4; 90Ϯ8% of baseline). With ME, infarct size was decreased to 18Ϯ4% versus 33Ϯ4% in group 2 (PϽ0.05). The infarct size reduction was abolished by TNF-␣ antibodies (group 3 versus group 4, 29Ϯ3% versus 35Ϯ5%). In ME, TNF-␣ is responsible for both progressive contractile dysfunction and delayed protection against infarction. (Circ Res. 2007;100:140-146.)

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“…40 In anesthetized open-chest pigs, coronary microembolization failed to raise the interstitial adenosine concentration sufficiently to precondition and protect the myocardium short term, but it increased the infarct size by the additional amount that resulted from prior microembolization. 41 However, protection became apparent several hours after coronary microembolization when TNF-␣ expression was increased, and conversely, protection was abolished by TNF-␣-neutralizing antibodies 42 ; therefore, coronary microembolization can elicit a "third window" of preconditioning protection that is triggered by inflammation. 43 …”

Section: Interaction With Preconditioningmentioning

confidence: 99%

Coronary Microembolization

et al. 2009

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Abstract-Coronary microembolization from the erosion or rupture of a vulnerable atherosclerotic plaque occurs spontaneously in acute coronary syndromes and iatrogenically during percutaneous coronary interventions. Typical consequences of coronary microembolization are microinfarcts with an inflammatory response, contractile dysfunction, and reduced coronary reserve. Apart from transient elevations of creatine kinase and troponin, microemboli can be visualized by intracoronary Doppler and the resulting microinfarcts by late-enhancement nuclear magnetic resonance. Statins, antiplatelet agents, and coronary vasodilators protect against microembolization and microinfarction when started before percutaneous coronary interventions. Distal protection devices can retrieve atherothrombotic debris and prevent its embolization into the microcirculation, but their effect on clinical outcome has been disappointing so far, except for saphenous vein bypass grafts. Devices for aspiration of thrombi and thrombus-derived vasoconstrictor, thrombogenic, and inflammatory substances, however, reduce thrombus burden, improve perfusion, and provide protection in patients with acute myocardial infarction. Key Words:he rupture of an atherosclerotic plaque in an epicardial coronary artery does not always result in complete thrombotic coronary occlusion and impending myocardial infarction; milder forms of plaque rupture may leave some residual blood flow and result in the washout of atherothrombotic debris into the coronary microcirculation and its subsequent embolization. Coronary microembolization became a focus of attention about a decade ago with the awareness that coronary microembolization and its sequelae are a frequent iatrogenic complication of percutaneous coronary interventions (PCIs). 1,2 However, coronary microembolization was recognized much earlier as being the underlying pathophysiological event in sudden death of patients with unstable angina. [3][4][5][6] The present review summarizes and updates the pathophysiology of coronary microembolization and the clinical evidence for its diagnosis and its prevention.The incidence of coronary microembolization is difficult to judge. Spontaneous coronary microembolization occurs, but most likely, only the tip of the iceberg is recognized. Periprocedural coronary microembolization occurs on average in 25% of all PCIs, but its incidence ranges from 0% to 70%, in part depending on the method of its assessment. 7 The incidence of periprocedural coronary microembolization depends on factors related to the clinical condition of the patient, notably preexisting kidney disease or underlying unstable angina; factors related to the length 8 or complexity of the lesion; and finally, factors related to the procedure, notably the use of a stent rather than percutaneous transluminal coronary angioplasty, the number and duration of inflations, and particularly the use of atherectomy and rotablation. 7 In patients with an acute myocardial infarction, an angiographic distal filling defect occurred ...

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Coronary microembolization does not induce acute preconditioning against infarction in pigs?the role of adenosine

Abstract: ME released adenosine into the vasculature and increased coronary blood flow. The failure of iADO to increase with ME possibly explains the lack of protection against infarction after ME.

Cited by 29 publications

References 28 publications

The Coronary Circulation as a Target of Cardioprotection

The Coronary Circulation as a Target of Cardioprotection

Bidirectional Role of Tumor Necrosis Factor-α in Coronary Microembolization

Coronary Microembolization

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