Transmyocardial Revascularization Research Articles

Synergistic Effect of Transmyocardial Revascularization and Platelet-Rich Plasma on Improving Cardiac Function After Coronary Artery Bypass Grafting.

Background Coronary artery disease (CAD) is a global health burden, contributing to mortality and morbidity. A proportion of patients with CAD suffer from diffuse CAD, where conventional revascularization techniques such as percutaneous coronary intervention and coronary artery bypass grafting (CABG) may be insufficient to adequately restore myocardial perfusion. Transmyocardial revascularization (TMR) uses a laser to create microscopic channels in the myocardium, inducing inflammation, angiogenesis, and neovascularization to improve perfusion to ischemic regions. Platelet-rich plasma (PRP) is an autologous concentrate of platelets that contains a myriad of growth factors and bioactive proteins, which have been shown to promote tissue regeneration and wound healing. The combination of TMR and PRP therapies has been proposed to synergistically enhance myocardial revascularization and functional recovery in patients with advanced CAD undergoing surgical revascularization. Methods This study evaluated the efficacy of combining TMR and PRP with CABG in improving cardiac function in diffuse CAD patients. Fifty-two patients were randomized to CABG alone (n = 16), CABG+TMR (n = 17), CABG+PRP (n = 10), and CABG+TMR+PRP (n = 9). TMR was performed using a holmium:YAG laser to create 10 channels in the inferolateral left ventricular wall. PRP was prepared from autologous whole blood and injected into the myocardium adjacent to the TMR channels. Cardiac function was assessed using speckle-tracking echocardiography preoperatively, postoperatively, and at one-year follow-up. Adverse events, including post-operative atrial fibrillation, acute kidney injury, and readmissions, were also recorded. Statistical analyses were performed to compare outcomes between the treatment groups. Results The CABG+TMR+PRP group showed significantly improved global longitudinal strain (GLS) at one year compared to CABG alone (mean GLS -15.96 vs -12.09, p = 0.02). Post-operative left ventricular ejection fraction trended higher in the TMR+PRP group (57.78%) vs other groups, but not significantly. Post-operative atrial fibrillation was higher in the TMR+PRP group (67% vs 25%, p = 0.04), potentially reflecting increased inflammation. No significant differences were observed in other adverse events. Conclusions The results of this study suggest a synergistic benefit of combining TMR and PRP therapies as an adjunct to CABG in patients with diffuse CAD. The significant improvement in GLS at one year in the TMR+PRP group compared to CABG alone indicates enhanced myocardial remodeling and functional recovery, which may translate to improved long-term outcomes. The higher incidence of postoperative atrial fibrillation in the TMR+PRP group warrants further investigation but may reflect the heightened inflammatory response necessary for angiogenesis and tissue regeneration. Prospective, randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings and optimize treatment protocols. Nonetheless, concomitant TMR+PRP therapy represents a promising approach to augmenting myocardial revascularization and recovery in patients with advanced CAD undergoing surgical revascularization.

Abstract 13346: Long Term, Synergistic Benefit of Transmyocardial Laser Revascularization and Platelet Rich Plasma - Significant Improvement of Global Longitudinal Strain in Coronary Artery Bypass Graft Patients

Introduction: Transmyocardial revascularization (TMR) is a procedure designed to treat patients with end-stage coronary artery disease (CAD). TMR creates myocardial micropores which undergo endothelialization and redistribute ischemic stress, thereby improving regional wall motion. Autologous platelet rich plasma (PRP) growth factors contribute to endothelialization and neovascularization. In this study, we evaluate the effectiveness of TMR combined with PRP to improve cardiac function in patients undergoing CABG using echocardiograms. Methods: A single-center, single surgeon retrospective analysis of CABG patients was performed (2019-2021). Patients in the TMR group had ten channels (7 Watts/channel) created in the infero-lateral wall of the left ventricle (LV) and those in the PRP group had autologous PRP extract injected(1ml, without calcium) in the same area. In patients treated with both TMR and PRP, ten channels were made in the inferolateral LV with PRP extract injected in the peri-TMR zone, 5mm adjacent to the channels. Post-operative ejection fraction (EF) and global longitudinal strain (GLS) were measured using speckle tracking up to one year. Results: Fifty-two patients (71% men, mean age 66y ±9.04y) were enrolled in the study and randomized to four experimental groups: CABG only (n=16); CABG/TMR (n=17); CABG/PRP (n=10); and CABG/TMR/PRP (n=9). At one-year follow-up, patients treated with both TMR and PRP had a significant improvement in average GLS (-15.96, p= 0.02) compared to TMR alone (-13.78, p= 0.26) and PRP alone (-15.79, p= 0.08). Patients treated with TMR and PRP also had a significant rise in post-operative EF (57.78%, SD +/- 6.18) compared to TMR alone (55.0%, SD +/- 6.85) and PRP alone (49.5%, SD +/- 11.65). Conclusions: TMR with PRP extract treatment at the time of CABG confers a significant one year improvement in cardiac function as measured by LVEF and GLS. These outcome metrics highlight cardiac remodeling and can mitigate the incidence of heart failure readmissions. With further prospective trials and longer follow-up periods, concomitant adjunctive TMR with PRP extract therapy at time of CABG may have durable and significant cardiac scar remodeling benefits leading to heart recovery in CABG patients.

NON-CONVENTIONAL APPROACHES FOR THE MANAGEMENT OF ANGINA

Angina is usually classified as a symptom of an underlying cardiovasculardisease which is one of the most common disorder that is affecting the human lifenow a days. It is presented as a throbbing chest pain that can radiate to left armand back due to ischemia of major vessel supplying blood to heart. Several drugclasses and their combination has long been used to treat angina for e.g. Nitrates,Nitrites, Calcium channel blockers, Beta blockers and sodium channel blockersto improve the demand vs supply ratio of oxygen so that the heart muscles canperform its function effectively. The increasing prevalence of disease andresulting resistance to conventional therapy has urged scientists to find otherways that can help in the management of this disease. Cardiovascular andconsequently angina is thus the focus of many studies. In this review a number ofstrategies and their associated mechanisms has been discussed which includeLife style modification, Yoga, Acupuncture therapy, Herbal treatment , L-arginine,L-carnitine, Omega 3 fatty acids, Gene therapy, Cell therapy, Chinese Medicine,and Interventions like Spinal cord Stimulation, Percutaneous coronaryintervention, Enhance external counter pulsation, Extracorporeal shockwavemyocardial revascularization, Transmyocardial laser revascularization,transcutaneous electrical nerve stimulation, percutaneous retrograde coronarysinus perfusion. Coronary sinus perfusion, Coronary sinus reducer, Videothoracoscopic sympathectomy (VTSY) may help in short term and long-termmanagement of angina

Intramyocardial Bone Marrow Stem Cells in Patients Undergoing Cardiac Surgical Revascularization

Bone marrow stromal or stem cells (BMSCs) remain a promising potential therapy for ischemic cardiomyopathy. The primary objective of this study was to evaluate the safety and feasibility of direct intramyocardial injection of autologous BMSCs in patients undergoing transmyocardial revascularization (TMR) or coronary artery bypass graft surgery (CABG). A phase I trial was conducted on adult patients who had ischemic heart disease with depressed left ventricular ejection fraction and who were scheduled to undergo TMR or CABG. Autologous BMSCs were expanded for 3 weeks before the scheduled surgery. After completion of surgical revascularization, BMSCs were directly injected into ischemic myocardium. Safety and feasibility of therapy were assessed. Cardiac functional status and changes in quality of life were evaluated at 1 year. A total of 14 patients underwent simultaneous BMSC and surgical revascularization therapy (TMR+BMSCs= 10; CABG+BMSCs= 4). BMSCs were successfully expanded, and no significant complications occurred as a result of the procedure. Regional contractility in the cell-treated areas demonstrated improvement at 12 months compared with baseline (TMR+BMSCs Δ strain:-4.6% ± 2.1%; P=.02; CABG+MSCs Δ strain:-4.2% ± 6.0%; P= .30). Quality of life was enhanced, with substantial reduction in angina scores at 1 year after treatment (TMR+BMSCs: 1.3 ± 1.2; CABG+MSCs: 1.0 ± 1.4). In this phase I trial, direct intramyocardial injection of autologous BMSCs in conjunction with TMR or CABG was technically feasible and could be performed safely. Preliminary results demonstrate improved cardiac function and quality of life in patients at 1 year after treatment.

EP13 EVOLUTIONARY AND CYCLICAL CHANGES IN CARDIAC SURGERY

Abstract Background and aim: The analysis of modern models and criteria discloses that current cardiac surgery often recalls the past. The aim of this study is to investigate whether historical knowledge is an important tool for research in aortic valve surgery and myocardial revascularization. Methods: PubMed, Scopus and Sciencedirect analysis of past and current literature were adopted to compare previous and current ideas. Results: In 1922, Graham and Allen introduced a cardioscope and a knife through the subclavian artery, or the left ventricular apex, to divide calcified aortic valve leaflets. This technique is a precursor of TAVI. The concept of sutureless prosthesis existed in the fifties and sixties. Hufnagel routinely implanted sutureless prostheses in the descending thoracic aorta to treat aortic insufficiency. The sutureless Magovern-Cromie valve has been implanted in orthotropic position from 1964 onward. The Sen's technique of trans-ventricular tunnels is a precursor of laser trans-myocardial revascularization. The Italian technique of internal mammary arteries ligature to treat angina pectoris, dating back to 1939 (Fieschi), and to the 50’ (Battezzati) was rediscovered, following 50 years of silence, in 2010. Endovascular occlusion of the mammary arteries by embolization has been suggested to treat patients suffering from angina not amenable to conventional revascularization techniques. Conclusions: Knowledge of old ideas and experiments, released from the technological constraints of their time, can be useful in current research. Ingenious theories that have fallen by the wayside can be brought back and explored again. History is a cycle. Heart valve surgery and myocardial revascularization are no exception.

Transmyocardial revascularization (TMR): current status and future directions.

Cardiac surgeons are increasingly faced with a more complex patient who has developed a pattern of diffuse coronary artery disease (CAD), which is refractory to medical, percutaneous, and surgical interventions. This paper will review the clinical science surrounding transmyocardial revascularization (TMR) with an emphasis on the results from randomized controlled trials. Randomized controlled trials which evaluated TMR used as sole therapy and when combined with coronary artery bypass grafting were reviewed. Pertinent basic science papers exploring TMR's possible mechanism of action along with future directions, including the synergism between TMR and cell-based therapies were reviewed. Two laser-based systems have been approved by the United States Food and Drug Administration (FDA) to deliver laser therapy to targeted areas of the left ventricle (LV) that cannot be revascularized using conventional methods: the holmium:yttrium-aluminum-garnet (Ho:YAG) laser system (CryoLife, Inc., Kennesaw, GA) and the carbon dioxide (CO2) Heart Laser System (Novadaq Technologies Inc., (Mississauga, Canada). TMR can be performed either as a stand-alone procedure (sole therapy) or in conjunction with coronary artery bypass graft (CABG) surgery in patients who would be incompletely revascularized by CABG alone. Societal practice guidelines have been established and are supportive of using TMR in the difficult population of patients with diffuse CAD. Patients with diffuse CAD have increased operative and long-term cardiac risks predicted by incomplete revascularization. The documented operative and long-term benefits associated with sole therapy and adjunctive TMR in randomized trials supports TMR's increased use in this difficult patient population.

Cirugía coronaria híbrida y tratamiento con láser y células madre. Anomalías coronarias. Cirugía del remodelado ventricular

In this article we review different aspects beyond the CABG First, we will define the concept of hybrid revascularization and the use of transmyocardial revascularization and stem cell therapy in coronary patients. Secondly, we will define coronary anomalies and when and how they must be managed. Finally, we will focus on left ventricle aneurysm management, Dor surgery and other techniques in left ventricle remodeling.

Angina and Its Management.

Angina pectoris is defined as substernal chest pain, pressure, or discomfort that is typically exacerbated by exertion and/or emotional stress, lasts greater than 30 to 60 seconds, and is relieved by rest and nitroglycerin. There are approximately 10 million people in the United States who have angina, and there are over 500 000 cases diagnosed per year. Several studies now show that angina itself is a predictor of major adverse cardiac events. In addition, angina is a serious morbidity that impedes quality of life and should be treated. In the United States, pharmacologic therapy for angina includes β-blockers, nitrates, calcium channel blockers, and the late sodium current blocker ranolazine. In other countries, additional pharmacologic agents include trimetazidine, ivabradine, nicorandil, fasudil, and others. Revascularization is indicated in certain high-risk individuals and also has been shown to improve angina. However, even after revascularization, a substantial percentage of patients return with recurrent or continued angina, requiring newer and better therapies. Treatment for refractory angina not amenable to usual pharmacologic therapies or revascularization procedures, includes enhanced external counterpulsation, transmyocardial revascularization, and stem cell therapy. Angina continues to be a significant cause of morbidity. Therapy should be geared not only to treating the risk factors for atherosclerotic disease and improving survival but should also be aimed at eliminating or reducing the occurrence of angina and improving the ability of patients to be active.

Remodeling an infarcted heart: novel hybrid treatment with transmyocardial revascularization and stem cell therapy.

Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. Recent studies indicate that the volume of surgical cases being performed with TMR have been steadily rising, utilizing TMR as an adjunctive therapy. Therefore the purpose of this review is to provide an up-to-date appreciation of the current state of TMR and its future developmental directions on CAD treatment. The current potential of this therapy focuses on the implementation of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing these cells with a favorable microenvironment that will enhance stem cell engraftment.

Impact of Transmyocardial laser revascularization on Pathomorphological and Physiological Patterns of Myocardial Microcirculation in patients with advanced CAD

The mechanism by which transmyocardial revascularization (TMR) offers clinical benefit is controversial. We hypothesized that TMR ameliorates vasoconstriction in patients with ENDCAD

Transmyocardial Revascularization Enhances Bone Marrow Stem Cell Engraftment in Infarcted Hearts Through SCF-C-kit and SDF-1-CXCR4 Signaling Axes.

We investigated the roles of stem cell factor (SCF)-c-kit and stromal derived factor-1 (SDF-1)-CXCR4 signaling axes in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted bone marrow stem cells (BMSCs) in infarcted hearts. 3weeks after LAD ligation, female Lewis rats underwent 10-channel needle-TMR, followed by daily IV injections of 1 million male donor BMSC for 5days, either wild type (WT) or with knockdown (K/D) of c-kit or CXCR4, accomplished via a shRNA + plasmid in a lentiviral vector (N = 6/group). In our rat infarct model, 3days after last BMSC injection, the number of BMSCs that homed into infarct was affected by both TMR and donor cell type, with greater BMSC engraftment with TMR and with WT BMSC (TMR, cell type, and interaction, P < 0.05). At 1week, these differences persisted (TMR and cell type, P < 0.05). At 3days, TMR significantly upregulated transcription of c-kit (TMR, p < 0.05), SCF (TMR and cell type, P < 0.05), CXCR4 (TMR and cell type, p < 0.05), and SDF-1 (TMR and cell type, P < 0.05). At 1week, we saw similar declines in expression of c-kit (cell type, P < 0.05), SCF (TMR, P < 0.05), CXCR4 (TMR and cell type, P < 0.05), and SDF-1 (TMR, P < 0.05). At 1week, TMR improved LV ejection fraction (LVEF) (N = 5) when WT BMSCs were infused, but knockdown of either c-kit or CXCR4 completely abrogated this TMR-mediated augmentation of BMSC reparative effect (TMR and cell type, P < 0.05). Downregulation of either c-kit or CXCR4 in BMSC decreased engraftment of circulating BMSC and inhibited reparative effects of TMR.

Robotically assisted, completely endoscopic transmyocardial revascularization is feasible.

The purpose of this study was to assess the feasibility of an endoscopic, optical-fiber-based, laser delivery system (LDS) developed to perform sole-therapy transmyocardial revascularization (TMR) in a totally endoscopic, robotically assisted operation. Forty-two patients were enrolled in a multicenter, prospective, single-arm clinical trial conducted at four US centers between 2005 and 2007. Transmyocardial revascularization was performed completely endoscopically with robotic assistance, introducing the Holmium:Yttrium aluminum garnet (YAG) LDS via a 5-mm port. Completion of the operation endoscopically defined procedural success. Clinical data were recorded before, during, and at least 30 days after the procedure. All patients had Canadian Cardiovascular Score angina class IV at baseline. The mean ejection fraction was 49% (range [R], 28-71), the mean age was 59.1 years (R, 36-80), 71% (30/42) were men, 86% (36/42) underwent previous coronary artery bypass grafting surgery, and 76% (32/42) underwent prior coronary stenting. Procedural success was accomplished in 93% (39/42). For the procedural successes, the mean number of TMR channels was 32 (R, 16-50), the median operative time was 88 minutes (R, 48-250 minutes), and the median length of stay postoperatively was 2.5 days (R, 1-10). There was no operative or 30-day mortality, and no patient received any transfusion. At 30 days, freedom from major adverse cardiac events was 95% (two patients had transient congestive heart failure). At the median 6-month follow-up (single-center data, n = 12), the mean (SD) Canadian Cardiovascular Score angina score was 1.3 (0.05) (P < 0.001 vs baseline). Robotically assisted TMR can be performed using an endoscopic, optical-fiber-based LDS, with high procedural success, avoidance of early adverse clinical events, and potential for successful angina relief.

Robotically Assisted, Completely Endoscopic Transmyocardial Revascularization is Feasible

Robotically Assisted, Completely Endoscopic Transmyocardial Revascularization is Feasible

Transmyocardial Revascularization Enhances Mesenchymal Stem Cell Engraftment in Infarcted Hearts through SCF–c-Kit and SDF-1–CXCR4 Signaling Axes

Purpose We investigated the roles of stem cell factor(SCF)–c-kit and stromal derived factor-1(SDF-1)–chemokine receptor type 4(CXCR4) stem cell signaling axes in transmyocardial revascularization (TMR)-enhanced engraftment of transplanted mesenchymal stem cells (MSC) in infarcted hearts. Methods and Materials 3 weeks after LAD ligation, female Lewis rats underwent 10-channel needle TMR, followed by daily IV injections of 1 million male donor MSC for 5 days, either wild type (WT) or with knockdown (K/D) of c-kit or CXCR4, accomplished via a shRNA+plasmid in a lentiviral vector. Experimental groups included: WT MSC with or without TMR, c-kit K/D MSC with or without TMR, and CXCR4 K/D MSC with or without TMR (N=6/group). Results In vitro cell surface expression of c-kit (N=3) was reduced from 14±0.7% of WT MSC to 1.6±0.4% c-kit K/D MSC, and CXCR4 (N=3) was reduced from 39±10% WT MSCs to 3.7±0.7% CXCR4 K/D MSC after 1 week (p Conclusions Downregulation of either c-kit or CXCR4 in MSC decreased engraftment of circulating MSC and inhibited the reparative effects of TMR. Hence, both SCF–c-kit and SDF-1–CXCR4 signaling axes are required for TMR-augmented repair of the infarcted heart.

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease

A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2012.07.013

Effects of transmyocardial jet revascularization with chitosan hydrogel on channel patency and angiogenesis in canine infarcted hearts

The purpose of this study was to investigate whether transmyocardial jet revascularization (TMJR) with chitosan scaffolds retains channel patency and enhances angiogenesis after acute myocardial infarction (AMI) in a canine model. A total of 32 canines were randomly divided into four groups: myocardial infarction (MI), normal saline (NS), chitosan hydrogel (CH), and chitosan plus growth factor (CH + GF) groups. TMJR was performed surgically using a needle-free injector from the epicardium of canines in the NS, CH, and CH + GF groups; channels were filled with NS, CH, and CH + GF, respectively. After 6 weeks, the patency of the channels and angiogenesis around the channels were assessed by hematoxylin-eosin staining, immunohistochemistry, and Masson's trichrome staining. Results suggest that the channels in the CH and CH + GF groups may retain patency with luminal endothelization. Moreover, the vessel densities of the NS, CH, and CH + GF groups were significantly higher than that of the MI group, and that of the CH + GF group was the highest (p < 0.05). This study suggests that TMJR with chitosan scaffolds may help retain transmyocardial channel patency and enhance angiogenesis after AMI in canines.

Long-Term Outcomes After Transmyocardial Revascularization

Two independent reports documented substantially higher operative mortality associated with transmyocardial revascularization (TMR) when used in isolation than that reported in the premarket clinical trials. To clarify the state of the art, this article assesses temporal trends in the use of TMR, short-term and long-term outcomes, and outcomes stratified by procedure type (TMR only and TMR + coronary artery bypass graft [CABG]) and by the 2 specific TMR devices. The study population included all patients undergoing TMR in isolation or in combination with CABG at 435 cardiothoracic hospitals in the United States participating in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) from January 2000 through November 2006 (n = 15,386). Analysis of long-term outcomes was accomplished through linkage to Medicare claims data. Short-term and long-term (7 years) adverse outcomes were assessed and compared between the 2 TMR device types. The use of TMR in conjunction with CABG surgery is increasing. This study showed modest differences in short-term morbidity and mortality between the 2 devices. In combination with CABG, after risk adjustment, patients treated with the holmium:YAG laser (experienced a higher rate of operative mortality (3.5% vs 2.5%; adjusted hazard ratio 1.39, 95% confidence level 1.03 to 1.87) but no difference in the composite short-term rate of major morbidity or mortality, compared with the Heart Laser CO2 transmyocardial revascularization system (PLC Medical Systems, Inc, Milford, MA). However, there were no clinically meaningful differences in long-term results. Modest differences in short-term morbidity and mortality between the 2 devices suggest the usefulness of further research.

Invited Commentary

Invited Commentary

Évolution de la fonction respiratoire après dix ans de plongée professionnelle

To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction (AMI).A model of AMI was generated by ligating the mid-third of left anterior descending artery (LAD) of miniswine. After 6 h, the animals were divided into none-treatment (control) group (n = 6) and TMDRSI group (n = 6). For TMDRSI group, two channels with 3.5 mm in diameter were established by a self-made drill in the AMI region, into which a stent was implanted. Expression of stromal cell-derived factor-1α (SDF-1α) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell (CSC)-mediated myocardial regeneration, myocardial apoptosis, myocardial viability, and cardiac function were assessed at various time-points.Six weeks after the operation, CSCs were found to have differentiated into cardiomyocytes to repair the infarcted myocardium, and all above indices showed much improvement in the TMDRSI group compared with the control group (P < 0.001).The new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI.

Transmyocardial Revascularization Induces Mesenchymal Stem Cell Engraftment in Infarcted Hearts

Transmyocardial revascularization (TMR) prior to mesenchymal stem cell (MSC) transplantation augments repair of infarcted hearts. We evaluated the effects of TMR on homing and engraftment of circulating MSCs and mediators of this effect. Three weeks after left anterior descending coronary artery ligation in female rats, 10-channel needle TMR was performed in the infarct, followed by daily intravenous injections of 1 million male MSCs for 5 days. Control rats had MSC infusions without TMR (n=16/group). Donor MSC survival was evaluated at 3 days and at 1 week by quantitative polymerase chain reaction, as well as expression of stem cell factor (SCF), stromal derived factor-1 (SDF-1), c-kit, and chemokine receptor type 4 (CXCR4). The MSCs engrafted into the infarct, clustering around TMR channels. The MSC engraftment was greater in TMR hearts at 3 days and at 1 week. Both SCF (p=0.03) and c-kit (p=0.01) were upregulated by TMR at 3 days, but their levels fell at 1 week (p=0.3, p=0.5, respectively). The SDF-1 levels were higher in TMR hearts at both 3 days (p=0.04) and at 1 week (p=0.04). The CXCR4 was upregulated early by TMR (p=0.0002) but levels dropped dramatically at 1 week (p=0.045). Transmyocardial revascularization induces transmigration and engraftment of circulating MSCs. Post TMR, the transcription of SCF and c-kit is rapid and corresponds temporally to MSC engraftment, while SDF-1 levels rise slowly. The CXCR4 is also transiently upregulated. The TMR-augmented repair of infarcted hearts by stem cell transplantation may be mediated by a novel mechanism: transmigration and engraftment of circulating progenitor cells.