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Minimally invasive mitral valve repair utilizing an efficient, effective leaflet remodeling technique
CARDIOTHORACIC SURGERY I transplanted engineered MSCs are capable of improving cardiac function and angiogenesis in a rat MI model.
Minimally invasive mitral valve repair utilizing an efficient, effective leaflet remodeling technique John W MacArthur, MD, Jeffrey E Cohen, MD, Andrew B Goldstone, MD, Alexander S Fairman, BA, Alen Trubelja, BS, Bryan B Edwards, BS, Jay Patel, BS, Pavan Atluri, MD, Y Joseph Woo, MD, FACS University of Pennsylvania, Philadelphia, PA
METHODS: Rats were randomized into control sham (CS), control-MI (CMI), MSC-LacZ-MI (MLZMI) & MSC-Trx-1-MI (MTRXMI) (n¼20/group). MI was induced by permanent LAD ligation, immediately after which MSCs preconditioned with either AdLacz or AdTrx1 were administered at 4 sites in the border zone around the infarction.
INTRODUCTION: Both leaflet resection and neochordal construction are highly effective mitral repair techniques but may become incrementally time consuming when employing minimally invasive approaches. We have utilized a single-suture leaflet-remodeling technique which is straightforward, expeditious and facilitates a minimally invasive approach.
RESULTS: We observed increased capillary density (2450107.2 vs 1541177.8 & 2026202; counts/mm2)(60d after MI) in the MTRXMI compared to both CMI and MLZMI. Western blot analysis 4d after MI showed increased expression of HSPA12B (HSP70 family member) and VEGF in MTRXMI compared to CMI. Echocardiography (60d after MI) showed increased ejection fraction (50 vs 31%) and fractional shortening (27 vs 16%) in the MTRXMI compared to CMI group. Myocardial fibrosis was less extensive in the MTRXMI group (4.8%) compared to CMI group (16.6%). Immunohistochemistry confirmed increased intercellular connection by measuring connexin-43 in the treatment group.
METHODS: 103 patients with degenerative mitral regurgitation (MR) underwent single-suture repair of the mitral valve through a 3-cm right chest incision from May 2007 through December 2012. The prolapsed segment of the mitral valve was imbricated with a double running CV 5 Gore-Tex suture, resulting in a smooth plane of coaptation. Preoperative and perioperative echocardiograms as well as patient outcomes were analyzed and compared to patients undergoing minimally invasive isolated mitral valve repair using quadrangular resection at the same institution during the same time period.
CONCLUSIONS: Our approach of Trx1 engineered MSC therapy may prove to be a strategic therapeutic modality in the treatment of cardiac failure by inducing HSPA12B and VEGF expression, neovessel formation, reducing fibrosis and by increasing functional recovery in the rat MI model.
RESULTS: All 103 patients had a successful mitral repair. 95/103 patients had zero MR on postop echo, while 8/103 had trace to 1+MR. Patients in the nonresectional group had significantly shorter cardiopulmonary bypass and cross clamp times compared to the quadrangular resection group (115.841.7 min vs 144.938.2 min, p<0.05; 76.228.1 min vs 112.633.5 min, p<0.05). The mean length of stay was 7.53days. On subsequent average follow-up of one year, all patients are alive and well, there have been no reoperations for MR, and no patients have significant recurrent MR.
The novel chemokine engineered stromal cell derived factor-1alpha recruits endothelial progenitor cells to the infarct borderzone; results from an egfp+ bone marrow chimera model John W MacArthur, MD, Jeffrey E Cohen, MD, Yasuhiro Shudo, MD, Alen Trubelja, BS, Alexander S Fairman, BA, Jay Patel, BS, Bryan B Edwards, BS, William Hiesinger, MD, Pavan Atluri, MD, Y Joseph Woo, MD, FACS University of Pennsylvania, Philadelphia, PA
CONCLUSIONS: An effective, highly efficient, and thus far durable single-suture mitral leaflet remodeling technique has been utilized to facilitate minimally invasive repair of degenerative MR in 103 patients.
INTRODUCTION: Significant alterations in microvascular perfusion occur after a myocardial infarction. In this study, we hypothesized that treatment of infarcted hearts with the chemokine engineered stromal cell derived factor-1alpha (ESA) would cause migration of bone marrow progenitor cells to the infarct, resulting in improved angiogenesis and ventricular function.
Thioredoxin-1 (Trx-1) engineered mesenchymal stem cell therapy increased proangiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium Mahesh Thirunavukkarasu, PhD*, Sumanth Channapatna Suresh, MD, Vaithinathan Selvaraju, PhD, Juan A Sanchez, MD, FACS, J Alexander Palesty, MD, FACS, David W McFadden, MD, FACS, Nilanjana Maulik, PhD University of Connecticut Health Center, Farmington, CT
METHODS: Bone marrow was harvested from transgenic male Wistar rats ubiquitously expressing the enhanced green fluorescence protein (eGFP). Wild type male Wistar rats were lethally irradiated (9 Gray) and rescued with injection of 30 x 106 eGFP+ bone marrow cells. Eight weeks after engraftment, animals underwent myocardial infarction by suture ligation of the left anterior descending coronary artery, and were randomized to receive either saline (n¼6, 0.1mL) or ESA (n¼6, 6mg/kg). Echocardiograms were performed on all animals to assess ventricular function. Four weeks after MI, animals were euthanized, bone marrow
INTRODUCTION: Engraftment of mesenchymal stem cells (MSCs) has emerged as a powerful candidate in mediating myocardial repair. In this study, we genetically modified MSCs with adenovector encoding thioredoxin-1 (Ad.Trx1), apart from its antioxidative role Trx-1 is described as a growth regulator, transcription factor regulator, and a cofactor. We explored whether these
ª 2013 by the American College of Surgeons Published by Elsevier Inc.
S34
ISSN 1072-7515/13/$36.00 http://dx.doi.org/10.1016/j.jamcollsurg.2013.07.064
Minimally invasive mitral valve repair utilizing an efficient, effective leaflet remodeling technique John W MacArthur, MD, Jeffrey E Cohen, MD, Andrew B Goldstone, MD, Alexander S Fairman, BA, Alen Trubelja, BS, Bryan B Edwards, BS, Jay Patel, BS, Pavan Atluri, MD, Y Joseph Woo, MD, FACS University of Pennsylvania, Philadelphia, PA
METHODS: Rats were randomized into control sham (CS), control-MI (CMI), MSC-LacZ-MI (MLZMI) & MSC-Trx-1-MI (MTRXMI) (n¼20/group). MI was induced by permanent LAD ligation, immediately after which MSCs preconditioned with either AdLacz or AdTrx1 were administered at 4 sites in the border zone around the infarction.
INTRODUCTION: Both leaflet resection and neochordal construction are highly effective mitral repair techniques but may become incrementally time consuming when employing minimally invasive approaches. We have utilized a single-suture leaflet-remodeling technique which is straightforward, expeditious and facilitates a minimally invasive approach.
RESULTS: We observed increased capillary density (2450107.2 vs 1541177.8 & 2026202; counts/mm2)(60d after MI) in the MTRXMI compared to both CMI and MLZMI. Western blot analysis 4d after MI showed increased expression of HSPA12B (HSP70 family member) and VEGF in MTRXMI compared to CMI. Echocardiography (60d after MI) showed increased ejection fraction (50 vs 31%) and fractional shortening (27 vs 16%) in the MTRXMI compared to CMI group. Myocardial fibrosis was less extensive in the MTRXMI group (4.8%) compared to CMI group (16.6%). Immunohistochemistry confirmed increased intercellular connection by measuring connexin-43 in the treatment group.
METHODS: 103 patients with degenerative mitral regurgitation (MR) underwent single-suture repair of the mitral valve through a 3-cm right chest incision from May 2007 through December 2012. The prolapsed segment of the mitral valve was imbricated with a double running CV 5 Gore-Tex suture, resulting in a smooth plane of coaptation. Preoperative and perioperative echocardiograms as well as patient outcomes were analyzed and compared to patients undergoing minimally invasive isolated mitral valve repair using quadrangular resection at the same institution during the same time period.
CONCLUSIONS: Our approach of Trx1 engineered MSC therapy may prove to be a strategic therapeutic modality in the treatment of cardiac failure by inducing HSPA12B and VEGF expression, neovessel formation, reducing fibrosis and by increasing functional recovery in the rat MI model.
RESULTS: All 103 patients had a successful mitral repair. 95/103 patients had zero MR on postop echo, while 8/103 had trace to 1+MR. Patients in the nonresectional group had significantly shorter cardiopulmonary bypass and cross clamp times compared to the quadrangular resection group (115.841.7 min vs 144.938.2 min, p<0.05; 76.228.1 min vs 112.633.5 min, p<0.05). The mean length of stay was 7.53days. On subsequent average follow-up of one year, all patients are alive and well, there have been no reoperations for MR, and no patients have significant recurrent MR.
The novel chemokine engineered stromal cell derived factor-1alpha recruits endothelial progenitor cells to the infarct borderzone; results from an egfp+ bone marrow chimera model John W MacArthur, MD, Jeffrey E Cohen, MD, Yasuhiro Shudo, MD, Alen Trubelja, BS, Alexander S Fairman, BA, Jay Patel, BS, Bryan B Edwards, BS, William Hiesinger, MD, Pavan Atluri, MD, Y Joseph Woo, MD, FACS University of Pennsylvania, Philadelphia, PA
CONCLUSIONS: An effective, highly efficient, and thus far durable single-suture mitral leaflet remodeling technique has been utilized to facilitate minimally invasive repair of degenerative MR in 103 patients.
INTRODUCTION: Significant alterations in microvascular perfusion occur after a myocardial infarction. In this study, we hypothesized that treatment of infarcted hearts with the chemokine engineered stromal cell derived factor-1alpha (ESA) would cause migration of bone marrow progenitor cells to the infarct, resulting in improved angiogenesis and ventricular function.
Thioredoxin-1 (Trx-1) engineered mesenchymal stem cell therapy increased proangiogenic factors, reduced fibrosis and improved heart function in the infarcted rat myocardium Mahesh Thirunavukkarasu, PhD*, Sumanth Channapatna Suresh, MD, Vaithinathan Selvaraju, PhD, Juan A Sanchez, MD, FACS, J Alexander Palesty, MD, FACS, David W McFadden, MD, FACS, Nilanjana Maulik, PhD University of Connecticut Health Center, Farmington, CT
METHODS: Bone marrow was harvested from transgenic male Wistar rats ubiquitously expressing the enhanced green fluorescence protein (eGFP). Wild type male Wistar rats were lethally irradiated (9 Gray) and rescued with injection of 30 x 106 eGFP+ bone marrow cells. Eight weeks after engraftment, animals underwent myocardial infarction by suture ligation of the left anterior descending coronary artery, and were randomized to receive either saline (n¼6, 0.1mL) or ESA (n¼6, 6mg/kg). Echocardiograms were performed on all animals to assess ventricular function. Four weeks after MI, animals were euthanized, bone marrow
INTRODUCTION: Engraftment of mesenchymal stem cells (MSCs) has emerged as a powerful candidate in mediating myocardial repair. In this study, we genetically modified MSCs with adenovector encoding thioredoxin-1 (Ad.Trx1), apart from its antioxidative role Trx-1 is described as a growth regulator, transcription factor regulator, and a cofactor. We explored whether these
ª 2013 by the American College of Surgeons Published by Elsevier Inc.
S34
ISSN 1072-7515/13/$36.00 http://dx.doi.org/10.1016/j.jamcollsurg.2013.07.064