Author
Jonathan Leor
Other affiliations: Soroka Medical Center, Bikur Cholim Hospital, University of Erlangen-Nuremberg ...read more
Bio: Jonathan Leor is an academic researcher from Sheba Medical Center. The author has contributed to research in topics: Myocardial infarction & Heart failure. The author has an hindex of 55, co-authored 222 publications receiving 14215 citations. Previous affiliations of Jonathan Leor include Soroka Medical Center & Bikur Cholim Hospital.
Papers published on a yearly basis
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TL;DR: Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs, which enhances migration and colonization of the cells preferentially to the ischemic myocardium.
Abstract: Background— Systemic delivery of bone marrow–derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI). Methods and Results— BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-labeled cells (4×106) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the 99mTc-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in...
1,231 citations
TL;DR: There was a sharp increase in the number of sudden deaths from cardiac causes that were related to atherosclerotic cardiovascular disease, from a daily average of 4.6±2.1 in the preceding week to 24 on the day of the earthquake.
Abstract: Background The earthquake that struck the Los Angeles area at 4:31 a.m. on January 17, 1994, was one of the strongest earthquakes ever recorded in a major city in North America. Once the life-threatening situation was over, the Northridge earthquake, so called because its epicenter was near Northridge, California, just north of Los Angeles, provided investigators an unusual opportunity to examine the relation between emotional stress and sudden cardiac death. Methods We reviewed the records of the Department of Coroner of Los Angeles County for the week before the earthquake, the day of the earthquake, the six days after the earthquake, and corresponding control periods in 1991, 1992, and 1993. Results On the day of the earthquake, there was a sharp increase in the number of sudden deaths from cardiac causes that were related to atherosclerotic cardiovascular disease, from a daily average (±SD) of 4.6±2.1 in the preceding week to 24 on the day of the earthquake (z = 4.41, P<0.001). Sixteen victims of sudd...
726 citations
TL;DR: PCI did not reduce the occurrence of death, reinFarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction.
Abstract: BACKGROUND: It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events. METHODS: We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure. RESULTS: The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P=0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P=0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P=0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization). CONCLUSIONS: PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction.
681 citations
TL;DR: After implantation into the infarcted myocardium, the biografts stimulated intense neovascularization and attenuated LV dilatation and failure in experimental rats compared with controls, suggesting alginate scaffolds provide a conducive environment to facilitate the 3D culturing of cardiac cells.
Abstract: Background—The myocardium is unable to regenerate because cardiomyocytes cannot replicate after injury. The heart is therefore an attractive target for tissue engineering to replace infarcted myocardium and enhance cardiac function. We tested the feasibility of bioengineering cardiac tissue within novel 3-dimensional (3D) scaffolds. Methods and Results—We isolated and grew fetal cardiac cells within 3D porous alginate scaffolds. The cell constructs were cultured for 4 days to evaluate viability and morphology before implantation. Light microscopy revealed that within 2 to 3 days in culture, the dissociated cardiac cells form distinctive, multicellular contracting aggregates within the scaffold pores. Seven days after myocardial infarction, rats were randomized to biograft implantation (n=6) or sham-operation (n=6) into the myocardial scar. Echocardiography study was performed before and 65±5 days after implantation to assess left ventricular (LV) remodeling and function. Hearts were harvested 9 weeks afte...
580 citations
TL;DR: The role of the NRG1 co-receptor ERBB2 in cardiac regeneration is explored using loss- and gain-of-function genetic tools, and it is shown that ER BB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
Abstract: The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 (NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (caERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3β/β-catenin signalling pathways. Transient induction of caERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.
512 citations
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Journal Article•
28,685 citations
TL;DR: The once-in-a-lifetime treatment with Abciximab Intracoronary for acute coronary syndrome and a second dose intravenously for atrial fibrillation is recommended for adults with high blood pressure.
Abstract: ACE
: angiotensin-converting enzyme
ACS
: acute coronary syndrome
ADP
: adenosine diphosphate
AF
: atrial fibrillation
AMI
: acute myocardial infarction
AV
: atrioventricular
AIDA-4
: Abciximab Intracoronary vs. intravenously Drug Application
APACHE II
: Acute Physiology Aand Chronic
7,519 citations
TL;DR: The current guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation are based on the findings of the ESC Task Force on 12 March 2015.
Abstract: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation : The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
6,866 citations
TL;DR: 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation are published.
Abstract: 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)
6,599 citations