Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion.

Dreyer, William J.; Michael, L H; West, Michael R.; Smith, C. W.; Rothlein, Robert; Rossen, Roger D.; Anderson, D C; Entman, Mark L.

doi:10.1161/01.cir.84.1.400

Cited by 264 publications

(104 citation statements)

References 17 publications

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“…Because leukocyte adhesion and transmigration might induce genes in the endothelium either through paracrine cytokine secretion mechanisms or through direct stimulation associated with adhesion, we chose to examine MCP-1 induction in a model using brief, nonlethal ischemia followed by reperfusion that has been well characterized in the past as inducing ROI formation and secretion from myocytes associated with dysfunction but no cell death. 5,[12][13][14] We have also confirmed that there is no significant leukocyte infiltration associated with this protocol.…”

Section: Discussionsupporting

confidence: 68%

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Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Lakshminarayanan

Lewallen

Frangogiannis

et al. 2001

The American Journal of Pathology

102

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Monocyte chemotactic protein (MCP)-1 is a member of the CC chemokine family and serves as a chemotactic factor for the recruitment of monocytes and subpopulations of T cells during inflammation. 1 It is induced by the proinflammatory cytokines interleukin (IL)-1␤ and tumor necrosis factor (TNF)-␣, as well as phorbol esters, which regulate its induction at the transcriptional level through the cooperative interaction of the transcription factors AP-1 and nuclear factor (NF)-B. 2-4 Specifically, in endothelial cells, IL-1␤, TNF-␣, and phorbol esters mediate human MCP-1 gene expression through the cooperative interaction of the NF-B binding site at Ϫ90 bp (relative to the start site) and the AP-1 binding site at Ϫ68 bp. 2,3 Early reperfusion of the ischemic myocardium is a key clinical intervention after myocardial infarction and is attended by a robust inflammatory reaction involving both neutrophils and mononuclear cells. 5,6 It has been shown that late reperfusion, when myocardial salvage is no longer possible, improves myocardial repair and obviates infarct expansion.

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Section: Discussionsupporting

confidence: 68%

“…2,3 Early reperfusion of the ischemic myocardium is a key clinical intervention after myocardial infarction and is attended by a robust inflammatory reaction involving both neutrophils and mononuclear cells. 5,6 It has been shown that late reperfusion, when myocardial salvage is no longer possible, improves myocardial repair and obviates infarct expansion. …”

mentioning

confidence: 99%

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Lakshminarayanan

Lewallen

Frangogiannis

et al. 2001

The American Journal of Pathology

102

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“…However, when administered 30 minutes after established coronary microembolization, methylprednisolone no longer prevented leukocyte infiltration, possibly because initial steps of leukocyte activation and leukocyte/endothelium interaction had already occurred. 31,35,36 Glucocorticoids have previously been shown to inhibit the expression of TNF-␣ mRNA in immunologically activated rat peritoneal mast cells, 16 to suppress the production of TNF-␣ in serum and myocardium of lipopolysaccharidestimulated rats, 17 and to abolish the release of TNF-␣ into serum of humans during cardiac surgery. 15 Glucocorticoids also attenuate the infiltration of TNF-␣-producing macrophages/monocytes after coronary microembolization in pigs.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid Treatment Prevents Progressive Myocardial Dysfunction Resulting From Experimental Coronary Microembolization

et al. 2004

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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.

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“…Our findings corroborate postmortem histological studies that have demonstrated a time-dependent shift in the location of leukocytes in postischemic myocardium from intravascular (which peaks about 1 hour after reflow) to interstitial (which peaks Ͼ5 hours after reflow). 9,10 Using MCE perfusion imaging with nontargeted microbubbles to assess collateral perfusion within the risk area, we were able to uniquely determine that leukocyte recruitment was attenuated but not completely prevented by collateral flow. These results support previous demonstration of an inverse relation between myocardial blood flow and postischemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…These results support previous demonstration of an inverse relation between myocardial blood flow and postischemic inflammation. 10 We anticipated that targeted microbubble imaging in the setting of ischemia/reperfusion would be problematic because microbubble entry into portions of the infarct zone would be prevented by low-or no-reflow. In the first several hours after reflow, however, there is marked heterogeneity of microvascular perfusion within risk area and hyperemia within the infarct region, 11 which should facilitate microbubble entry even within necrotic tissue.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Imaging of Myocardial Reperfusion Injury Using Leukocyte-Targeted Contrast Echocardiography

et al. 2002

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Background-We hypothesized that myocardial contrast echocardiography (MCE) with leukocyte-targeted microbubbles could temporally and spatially characterize the severity of postischemic myocardial inflammation. Methods and Results-In 9 open-chest dogs, either the left anterior descending or left circumflex coronary artery was occluded for 90 minutes (nϭ6), while the remaining dogs served as non-ischemic controls. During occlusion, MCE was performed to determine the risk area (RA) and regions supplied by collateral flow. Myocardial inflammation was assessed 5, 60, and 120 minutes after reflow by MCE imaging of leukocyte-targeted (phosphatidylserine-containing) lipid microbubbles. The spatial extent and severity of inflammation were also assessed by radionuclide imaging of the neutrophil-avid tracer 99m TcRP517 and tissue myeloperoxidase activity. Early after reflow, MCE detected inflammation throughout the entire risk area, the extent of which decreased over time due to reduced signal in collateral-supplied regions. The spatial extent of inflammation late after reflow was similar for MCE and radionuclide imaging. The severity of inflammation in the infarct zone, the noninfarcted risk area, and collateral-supplied territories determined by quantitative MCE correlated well with myeloperoxidase activity (rϭ0.81). Conclusions-MCE with leukocyte-targeted microbubbles can temporally assess the severity and extent of postischemic myocardial inflammation and could be used to evaluate new treatment strategies designed to limit inflammation in acute coronary syndromes. Key Words: echocardiography Ⅲ inflammation Ⅲ ischemia L eukocyte infiltration into the myocardium can play a detrimental role after myocardial ischemia/reperfusion by contributing to myocellular injury and necrosis 1,2 and to microvascular no-reflow. 3 An accurate, noninvasive method for routinely assessing inflammation is not currently available but would be valuable for further characterizing the contribution of inflammation to reperfusion injury in patients and for evaluating new treatment strategies that attenuate postischemic leukocyte recruitment.We have recently demonstrated that inflammation can be assessed using contrast-enhanced ultrasound with microbubbles that bind to activated leukocytes adherent to the venular endothelium. 4 -6 Leukocyte avidity for lipid microbubbles has been greatly enhanced by incorporating phosphatidylserine (PS) into the shell, which increases microbubble retention in inflamed tissue. 6 In this study, we hypothesized that the severity of myocardial inflammation after ischemia/ reperfusion injury could be assessed both spatially and temporally using myocardial contrast echocardiography (MCE) with leukocyte-targeted microbubbles. Methods Animal PreparationThe study was approved by the Animal Research Committee at the University of Virginia. Nine anesthetized open-chest dogs (30 to 35 kg) were studied (Haycock Kennels). Ultrasound flow probes were placed around proximal portions of the left anterior descending (LAD) and left ...

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Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion.

Cited by 264 publications

References 17 publications

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Reactive Oxygen Intermediates Induce Monocyte Chemotactic Protein-1 in Vascular Endothelium after Brief Ischemia

Glucocorticoid Treatment Prevents Progressive Myocardial Dysfunction Resulting From Experimental Coronary Microembolization

Noninvasive Imaging of Myocardial Reperfusion Injury Using Leukocyte-Targeted Contrast Echocardiography

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