Myocardial dysfunction with coronary microembolization: Signal transduction through a sequence of no, TNFα and sphingosine

Thielmann, Matthias; Belosjorow, Sergej; Martin, Claus; Schwanke, Uwe; Sand, Anita van de; Konietzka, Ina; Schutz, Rainer; Heusch, Gerd

doi:10.1016/s0022-2828(02)90978-8

Cited by 67 publications

(102 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Indeed, this study suggests that the previously reported microembolization-induced contractile dysfunction (23,34) may be related, at least in part, to myocardial edema resulting from increased permeability, as demonstrated by increased diastolic wall thickness and increased volume of myocardium within the LAD perfusion territory (Fig. 4A).…”

Section: Discussionsupporting

confidence: 54%

“…Inflammatory mediators such as TNF-␣, free oxygen radicals, and interleukins have been shown to play a major role in contractile dysfunction in the microembolized myocardium following coronary microembolization (15,17,34), possibly indicating the role of inflammation and/or edema in its pathogenesis. Such mediators can likely more easily diffuse into the perfused myocardium from the interfacial region between perfused and nonperfused myocardium (i.e., proportional to the interface's surface area) rather than from deep within the nonperfused myocardium, which would make the effect more proportional to the volume of nonperfused myocardium.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Malyar

Lerman

Gössl

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Malyar NM, Lerman LO, Gössl M, Beighley PE, Ritman EL. Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization. Am J Physiol Regul Integr Comp Physiol 301: R430-R437, 2011. First published May 4, 2011 doi:10.1152/ajpregu.00428.2010.-Myocardial microvascular permeability and coronary sinus concentration of muscle metabolites have been shown to increase after myocardial ischemia due to epicardial coronary artery occlusion and reperfusion. However, their association with coronary microembolization is not well defined. This study tested the hypothesis that acute coronary microembolization increases microvascular permeability in the porcine heart. The left anterior descending perfusion territories of 34 anesthetized pigs (32 Ϯ 3 kg) were embolized with equal volumes of microspheres of one of three diameters (10, 30, or 100 m) and at three different doses for each size. Electron beam computed tomography (EBCT) was used to assess in vivo, microvascular extraction of a nonionic contrast agent (an index of microvascular permeability) before and after microembolization with microspheres at baseline and during adenosine infusion. A high-resolution three-dimensional microcomputed tomography (micro-CT) scanner was subsequently used to obtain ex vivo, the volume and corresponding surface area of the embolized myocardial islands within the perfusion territories of the microembolized coronary artery. EBCT-derived microvascular extraction of contrast agent increased within minutes after coronary microembolization (P Ͻ 0.001 vs. baseline and vs. control values). The increase in coronary microvascular permeability was highly correlated to the micro-CT-derived total surface area of the nonperfused myocardium (r ϭ 0.83, P Ͻ 0.001). In conclusion, myocardial extravascular accumulation of contrast agent is markedly increased after coronary microembolization and its magnitude is in proportion to the surface area of the interface between the nonperfused and perfused territories. microspheres; EBCT; micro-CT; microvascular permeability A BALANCE BETWEEN DELIVERY of vital nutrients and removal of waste products from the myocardium is pivotal for maintaining the physiological contractile function of the myocytes and for the coordinated electrical conductance along the cells' membranes. However, it has been shown that myocardial microvascular permeability can change under various pathologic and metabolic circumstances such as diabetes mellitus (24, 41), hypercholesterolemia (32), hypertension (31), and acute myocardial ischemia followed by reperfusion (29). Embolization of microscopic plaque debris into the distal coronary bed during coronary interventions is a common and frequent event (9, 10, 35) that might be associated with microinfarctions and with adverse clinical outcome (7, 10).We have previously demonstrated that experimental coronary microembolization leads to a decrease in regional myocardial contractility that is proportional to the surface...

show abstract

Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Malyar

Lerman

Gössl

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…5 In subsequent studies, a causal role of tumor necrosis factor (TNF)-␣ and sphingosine in this progressive contractile dysfunction was demonstrated. 6,7 These experiments were limited to a time frame of 8 hours, and it remained unclear whether the progressive contractile dysfunction eventually recovers. We have therefore now monitored the time course of the progressive contractile dysfunction until full recovery in chronically instrumented conscious dogs.…”

mentioning

confidence: 99%

Glucocorticoid Treatment Prevents Progressive Myocardial Dysfunction Resulting From Experimental Coronary Microembolization

et al. 2004

Self Cite

View full text Add to dashboard Cite

Background-The frequency and importance of microembolization in patients with acute coronary syndromes and during coronary interventions have recently been appreciated. Experimental microembolization induces immediate ischemic dysfunction, which recovers within minutes. Subsequently, progressive contractile dysfunction develops over several hours and is not associated with reduced regional myocardial blood flow (perfusion-contraction mismatch) but rather with a local inflammatory reaction. We have now studied the effect of antiinflammatory glucocorticoid treatment on this progressive contractile dysfunction. Methods and Results-Microembolization was induced by injecting microspheres (42-m diameter) into the left circumflex coronary artery. Anesthetized dogs were followed up for 8 hours and received placebo (nϭ7) or methylprednisolone 30 mg/kg IV either 30 minutes before (nϭ7) or 30 minutes after (nϭ5) microembolization. In addition, chronically instrumented dogs received either placebo (nϭ4) or methylprednisolone (nϭ4) 30 minutes after microembolization and were followed up for 1 week. In acute placebo dogs, posterior systolic wall thickening was decreased from 20.0Ϯ2.1% (meanϮSEM) at baseline to 5.8Ϯ0.6% at 8 hours after microembolization. Methylprednisolone prevented the progressive myocardial dysfunction. Increased leukocyte infiltration in the embolized myocardium was prevented only when methylprednisolone was given before microembolization. In chronic placebo dogs, progressive dysfunction recovered from 5.0Ϯ0.7% at 4 to 6 hours after microembolization back to baseline (19.1Ϯ1.6%) within 5 days. Again, methylprednisolone prevented the progressive myocardial dysfunction. Conclusions-Methylprednisolone, even when given after microembolization, prevents progressive contractile dysfunction.

show abstract

“…The emboli that were collected by distal protection devices during PCI differed widely in size, ranging from 47 to 2504 m. 28 As evidenced by experimental studies, microembolization from a fissuring/rupturing atherosclerotic plaque in an epicardial coronary artery caused not only physical obstruction of the downstream microcirculation but also a marked inflammatory response in the affected myocardium. 5,6,8 Elevated levels of hsCRP as a marker of inflammation strongly predicted early complications (30-day risk of death or MI) after stent deployment in patients with coronary artery disease, and the risk associated with elevated CRP was independent of but additive to the American College of Cardiology/American Heart Association lesion score. 7,29 In the present study, 30 patients did not show a postprocedural cTnI elevation, although 8 of these 30 had Ͼ20 microemboli during PCI.…”

Section: Microembolization and Cardiac Biomarker Elevationsmentioning

confidence: 99%

“…3,4 Experimentally, a progressive contractile dysfunction developed in response to coronary microembolization over a period of hours; it was not associated with reduced regional myocardial blood flow (perfusion-contraction mismatch) but rather with a local inflammatory reaction. 5,6 Reminiscent of these experimental studies, elevated levels of high-sensitivity C-reactive protein (hsCRP) as a marker of systemic inflammation provide prognostic information for patients undergoing PCI. 7 The source of C-reactive protein (CRP) was traditionally assumed to be the atherosclerotic plaque, but it equally well may be derived from the microcirculatory inflammation in response to microembolization and associated microinfarcts.…”

mentioning

confidence: 99%

Detection of Coronary Microembolization by Doppler Ultrasound in Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions

et al. 2007

Self Cite

View full text Add to dashboard Cite

Background-Intracoronary Doppler guidewires can be used for real-time detection and quantification of microembolism during percutaneous coronary interventions (PCIs). We investigated whether the frequency of Doppler-detected microembolism is related to the incidence of myonecrosis during elective PCI. Methods and Results-The study population included 52 consecutive patients (aged 64Ϯ10 years; 36 men, 16 women) with coronary artery disease who underwent elective PCI of a single-vessel stenosis. Using intracoronary Doppler ultrasound, we compared the frequency of microembolism during PCI in 22 patients with periprocedural non-STsegment elevation myocardial infarctions (pNSTEMI) and 30 patients without pNSTEMI. The 2 groups were comparable with regard to their clinical and procedural characteristics. In the group with pNSTEMI, the total number of coronary microemboli after PCI (27Ϯ10 versus 16Ϯ8, PϽ0.001) was higher than in the group without pNSTEMI. Although high-sensitivity C-reactive protein plasma levels were similar before PCI (2.9Ϯ2.2 versus 3.4Ϯ1.7 mg/L, PϭNS), they were higher in the group with pNSTEMI after PCI (12.6Ϯ10.

show abstract

Myocardial dysfunction with coronary microembolization: Signal transduction through a sequence of no, TNFα and sphingosine

Cited by 67 publications

References 0 publications

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Glucocorticoid Treatment Prevents Progressive Myocardial Dysfunction Resulting From Experimental Coronary Microembolization

Detection of Coronary Microembolization by Doppler Ultrasound in Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions

Contact Info

Product

Resources

About