Dataset Information

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

ABSTRACT:

Background

Intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMMNC), after acute myocardial infarction (AMI), has been shown to improve myocardial function. However, therapeutic efficacy is limited, possibly because cell retention rates are low, suggesting that optimization of cell retention might increase therapeutic efficacy. Since retention of injected BMMNC is observed only within infarcted, but not remote, myocardium, we hypothesized that adhesion molecules on activated endothelium following reperfusion are essential. Consequently, we investigated the role of vascular cell adhesion molecule 1 (VCAM-1) in BMMNC retention in swine undergoing reperfused AMI produced by 120 min of percutaneous left circumflex coronary occlusion.

Methods and results

VCAM-1 expression in the infarct and remote region was quantified at 1, 3, 7, 14, and 35 days, post-reperfusion (n?6 swine per group). Since expression levels were significantly higher at 3 days (2.41±0.62%) than at 7 days (0.98±0.28%; p<0.05), we compared the degree of cell retention at those time points in a follow-up study, in which an average of 43·106 autologous BMMNCs were infused intracoronary at 3, or 7 days, post-reperfusion (n = 6 swine per group) and retention was histologically quantified one hour after intracoronary infusion of autologous BMMNCs. Although VCAM-1 expression correlated with retention of BMMNC within each time point, overall BMMNC retention was similar at day 3 and day 7 (2.3±1.3% vs. 3.1±1.4%, p = 0.72). This was not due to the composition of infused bone marrow cell fractions (analyzed with flow cytometry; n = 5 per group), as cell composition of the infused BMMNC fractions was similar.

Conclusion

These findings suggest that VCAM-1 expression influences to a small degree, but is not the principal determinant of, BMMNC retention.

SUBMITTER: Uitterdijk A

PROVIDER: S-EPMC5476248 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

Uitterdijk André A Groenendijk Bianca C W BCW Gorsse-Bakker Charlotte C Panasewicz Anna A Sneep Stefan S Tempel Dennie D van de Kamp Esther H EH Merkus Daphne D van der Giessen Willem J WJ Duncker Dirk J DJ

PloS one 20170619 6

<h4>Background</h4>Intracoronary infusion of autologous bone marrow-derived mononuclear cells (BMMNC), after acute myocardial infarction (AMI), has been shown to improve myocardial function. However, therapeutic efficacy is limited, possibly because cell retention rates are low, suggesting that optimization of cell retention might increase therapeutic efficacy. Since retention of injected BMMNC is observed only within infarcted, but not remote, myocardium, we hypothesized that adhesion molecules ...[more]

PMID: 28628621

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Project description:Most studies on intracoronary bone marrow mononuclear cell transplantation for acute myocardial infarction involve treatment 3-7 days after primary percutaneous coronary intervention (PCI); however, the optimal timing is unknown. The present study assessed the therapeutic effect at different times after ST-elevation myocardial infarction.The present trial was not blinded. A total of 104 patients with a first ST-elevation myocardial infarction and a left ventricular ejection fraction below 50 %, who had PCI of the infarct-related artery, were randomly assigned to receive intracoronary infusion of bone marrow mononuclear cells within 24 hours (group A, n = 27), 3 to 7 days after PCI (group B, n = 26), or 7 to 30 days after PCI (group C, n = 26), or to the control group (n = 25), which received saline infusion performed immediately after emergency PCI. All patients in groups A, B and C received an injection of 15 ml cell suspension containing approximately 4.9 × 10(8) bone marrow mononuclear cells into the infarct-related artery after successful PCI.Compared to control and group C patients, group A and B patients had a significantly higher absolute increase in left ventricular ejection fraction from baseline to 12 months (change: 3.4 ± 5.7 % in control, 7.9 ± 4.9 % in group A, 6.9 ± 3.9 % in group B, 4.7 ± 3.7 % in group C), a greater decrease in left ventricular end-systolic volumes (change: -6.4 ± 15.9 ml in control, -20.5 ± 13.3 ml in group A, -19.6 ± 11.1 ml in group B, -9.4 ± 16.3 ml in group C), and significantly greater myocardial perfusion (change from baseline: -4.7 ± 5.7 % in control, -7.8 ± 4.5 % in group A, -7.5 ± 2.9 % in group B, -5.0 ± 4.0 % in group C). Group A and B patients had similar beneficial effects on cardiac function (p = 0.163) and left ventricular geometry (left ventricular end-distolic volume: p = 0.685; left ventricular end-systolic volume: p = 0.622) assessed by echocardiography, whereas group C showed similar results to those of the control group. Group B showed more expensive care (p < 0.001) and longer hospital stays during the first month after emergency PCI (p < 0.001) than group A, with a similar improvement after repeat cardiac catheterization following emergency PCI.Cell therapy in acute myocardial infarction patients that is given within 24 hours is similar to 3-7 days after the primary PCI.NCT02425358 , registered 30 April 2015.

Project description:RationaleMetformin has been demonstrated to decrease infarct size (IS) and prevent postinfarction left ventricular (LV) remodeling in rodents when given intravenously at the time of reperfusion. It remains unclear whether similar cardioprotection can be achieved in a large animal model.ObjectiveThe objective of this study was to determine whether intravascular infusion of metformin at the time of reperfusion reduces myocardial IS in a porcine model of acute myocardial infarction.Methods and resultsIn a blinded and randomized preclinical study, closed-chest swine (n=20) were subjected to a 60-minute left anterior descending coronary artery occlusion to produce myocardial infarction. Contrast-enhanced computed tomography was performed during left anterior descending coronary artery occlusion to assess the ischemic area-at-risk. Animals were randomized to receive either metformin or vehicle as an initial intravenous bolus (5 mg/kg) 8 minutes before reperfusion, followed by a 15-minute left coronary artery infusion (1 mg/kg per minute) commencing with the onset of reperfusion. Echocardiography and computed tomographic imaging of LV function were performed 1 week later, at which time the heart was removed for postmortem pathological analysis of area-at-risk and IS (triphenyltetrazolium chloride). Baseline variables including hemodynamics and LV function were similar between groups. Peak circulating metformin concentrations of 374±35 µmol/L were achieved 15 minutes after reperfusion. There was no difference between the area-at-risk as a percent of LV mass by computed tomography (vehicle: 20.7%±1.1% versus metformin: 19.7%±1.3%; P=0.59) or postmortem pathology (22.4%±1.2% versus 20.2%±1.2%; P=0.21). IS relative to area-at-risk averaged 44.5%±5.0% in vehicle-treated versus 38.2%±6.8% in metformin-treated animals ( P=0.46). There was no difference in global function 7 days after myocardial infarction as assessed by echocardiography or computed tomographic ejection fraction (56.2%±2.6% versus 56.3%±2.4%; P=0.98).ConclusionsIn contrast to rodent hearts, postconditioning with high-dose metformin administered immediately before reperfusion does not reduce IS or improve LV function 7 days after myocardial infarction in swine. These results reinforce the importance of rigorously testing therapies in large animal models to facilitate clinical translation of novel cardioprotective therapies.

Dataset Information

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

Background

Methods and results

Conclusion

Publications

Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells.

Similar Datasets

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