Matthews Chacko

SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction

Stem cell transplantation at the time of acute myocardial infarction (AMI) improves cardiac function. Whether the improved cardiac function results from regeneration of cardiac myocytes, modulation of remodeling, or preservation of injured tissue through paracrine mechanisms is actively debated. Because no specific stem cell population has been shown to be optimal, we investigated whether the benefit of stem cell transplantation could be attributed to a trophic effect on injured myocardium. Mesenchymal stem cells secrete SDF‐1 and the interaction of SDF‐1 with its receptor, CXCR4, increases survival of progenitor cells. Therefore, we compared the effects of MSC and MSC engineered to overexpress SDF‐1 on cardiac function after AMI. Tail vein infusion of syngeneic MSC and MSC:SDF‐1 1 day after AMI in the Lewis rat led to improved cardiac function by echocardiography by 70.7% and 238.8%, respectively, compared with saline controls 5 wk later. The beneficial effects of MSC and MSC:SDF‐1 transplantation were mediated primarily through preservation, not regeneration of cardiac myocytes within the infarct zone. The direct effect of SDF‐1 on cardiac myocytes was due to the observation that’ between 24 and 48 h after AMI, SDF‐1‐expressing MSC increased cardiac myocyte surviva, vascular density (18.2±4.0 vs. 7.6±2.3 vessels/mm2, P<0.01; SDF‐1:MSC vs. MSC), and cardiac myosin‐positive area (MSC: 49.5%;mSC:SDF‐1: 162.1%) within the infarct zone. There was no evidence of cardiac regeneration by the infused MSC or endogenous cardiac stem cells based on lack of evidence for cardiac myocytes being derived from replicating cells. These results indicate that stem cell transplantation may have significant beneficial effects on injured organ function independent of tissue regeneration and identify SDF‐1:CXCR4 binding as a novel target for myocardial preservation.—Zhang, M., Mal, N., Kiedrowski, M., Chacko, M., Askari, A. T., Popovic, Z. B., Koc, O. N., Penn, M. S. SDF‐1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J. 21, 3197–3207 (2007)

Effect of Intravenous Fentanyl on Ticagrelor Absorption and Platelet Inhibition Among Patients Undergoing Percutaneous Coronary Intervention: The PACIFY Randomized Clinical Trial.

Fentanyl is a potent opiate commonly administered during cardiac catheterization procedures in North America.1 The question of whether fentanyl could have adverse consequences in patients undergoing percutaneous coronary intervention (PCI) is raised by recent research demonstrating that intravenous morphine significantly delays the absorption of oral P2Y12 platelet inhibitors.2 The presumed mechanism is slowed gastric emptying. The single-center PACIFY trial (Platelet Aggregation With Ticagrelor Inhibition and Fentanyl; ClinicalTrials.gov. Unique identifier: NCT02683707) randomized adults undergoing clinically indicated elective coronary angiography to receive the procedure with or without intravenous fentanyl.3 The study was approved by the Johns Hopkins Medicine Institutional Review Board, and all participants provided written informed consent. Eligible adults had not received P2Y12 inhibitors for 14 days before enrollment. Other exclusion criteria included preprocedural treatment with oral anticoagulants or opiates, platelet count <100 000/mm3, and impaired renal or hepatic function. All participants received subcutaneous lidocaine and intravenous midazolam at the start of the catheterization procedure and as needed thereafter. Doses of all drugs were at the discretion of treating providers. Patients and outcomes assessors were blinded; treating providers were not. Participants who required PCI received an oral dose of 180 mg ticagrelor at the conclusion of diagnostic angiography. Blood samples were collected at baseline and 0.5, 1, 2, 4, and 24 hours after the …

Images in cardiovascular medicine. A "mickey mouse" coronary anomaly: aorto-left atrial fistula with aneurysm.

A 58-year-old asymptomatic man with a heart murmur underwent routine Doppler stress echocardiography that detected abnormal high-intensity flow from the aorta to the left atrium. Coronary angiography with a 6-French Amplatz left catheter (Scimed/Boston Scientific) and MEDRAD (MEDRAD Inc) power injections of radiographic contrast revealed a large aorto-left atrial fistula originating anteriorly from the aorta above the sinotubular junction. The fistula …A 58-year-old asymptomatic man with a heart murmur underwent routine Doppler stress echocardiography that detected abnormal high-intensity flow from the aorta to the left atrium. Coronary angiography with a 6-French Amplatz left catheter (Scimed/Boston Scientific) and MEDRAD (MEDRAD Inc) power injections of radiographic contrast revealed a large aorto-left atrial fistula originating anteriorly from the aorta above the sinotubular junction. The fistula …

A “Mickey Mouse” Coronary Anomaly: Aorto-Left Atrial Fistula With Aneurysm

A 58-year-old asymptomatic man with a heart murmur underwent routine Doppler stress echocardiography that detected abnormal high-intensity flow from the aorta to the left atrium. Coronary angiography with a 6-French Amplatz left catheter (Scimed/Boston Scientific) and MEDRAD (MEDRAD Inc) power injections of radiographic contrast revealed a large aorto-left atrial fistula originating anteriorly from the aorta above the sinotubular junction. The fistula …A 58-year-old asymptomatic man with a heart murmur underwent routine Doppler stress echocardiography that detected abnormal high-intensity flow from the aorta to the left atrium. Coronary angiography with a 6-French Amplatz left catheter (Scimed/Boston Scientific) and MEDRAD (MEDRAD Inc) power injections of radiographic contrast revealed a large aorto-left atrial fistula originating anteriorly from the aorta above the sinotubular junction. The fistula …

A “Mickey Mouse” Coronary Anomaly

A 58-year-old asymptomatic man with a heart murmur underwent routine Doppler stress echocardiography that detected abnormal high-intensity flow from the aorta to the left atrium. Coronary angiography with a 6-French Amplatz left catheter (Scimed/Boston Scientific) and MEDRAD (MEDRAD Inc) power injections of radiographic contrast revealed a large aorto-left atrial fistula originating anteriorly from the aorta above the sinotubular junction. The fistula …A 58-year-old asymptomatic man with a heart murmur underwent routine Doppler stress echocardiography that detected abnormal high-intensity flow from the aorta to the left atrium. Coronary angiography with a 6-French Amplatz left catheter (Scimed/Boston Scientific) and MEDRAD (MEDRAD Inc) power injections of radiographic contrast revealed a large aorto-left atrial fistula originating anteriorly from the aorta above the sinotubular junction. The fistula …