Michael Ma

All Publications

• Corrected Transposition: Anatomic Repair Using the Hemi-Mustard Atrial Baffle and Bidirectional Superior Cavopulmonary Connection. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual Ma, M., Mainwaring, R. D., Hanley, F. L. 2019; 22: 51–56

  Abstract

  Anatomic repair for congenitally corrected transposition requires thoughtful surgical planning at both initial (neonatal or late) presentation, and during definitive repair. An algorithmic approach to the overall management of this lesion, with its many associated intracardiac anomalies, is presented. Modified atrial switch with bidirectional superior cavopulmonary connection is commonly utilized and demonstrates favorable results through a 20-year experience. Herein, technical considerations learned during the implementation of this strategy are described and emphasize the concept, in selected cases, of native pulmonary root preservation by translocation as an adjunct that is uniquely suited by adopting this approach.

  View details for PubMedID 31027564

• Comprehensive Management of Major Aortopulmonary Collaterals in the Repair of Tetralogy of Fallot. Seminars in thoracic and cardiovascular surgery. Pediatric cardiac surgery annual Ma, M., Mainwaring, R. D., Hanley, F. L. 2018; 21: 75–82

  Abstract

  The heterogenous anatomy of Tetralogy of Fallot with major aortopulmonary collateral arteries has engendered a similar degree of diversity in its management and, ultimately, outcome. We summarize our comprehensive treatment paradigm for this lesion evolved over 15 years of experience through 458 patients and the results obtained. An updated analysis of 307 patients treated primarily at our institution is included. A review of recent literature, comparison of management strategies, and discussion of ongoing controversies are provided.

  View details for PubMedID 29425528

• A novel inflow cannulation strategy for pediatric mechanical circulatory support in small left ventricles. journal of thoracic and cardiovascular surgery Ma, M., Yarlagadda, V. V., Rosenthal, D. N., Maeda, K. 2017

  View details for DOI 10.1016/j.jtcvs.2017.03.034

  View details for PubMedID 28416331

• Mid-Term Outcomes After Unifocalization Guided by Intraoperative Pulmonary Flow Study. World journal for pediatric & congenital heart surgery Goodman, A., Ma, M., Zhang, Y., Ryan, K. R., Jahadi, O., Wise-Faberowski, L., Hanley, F. L., McElhinney, D. B. 2021; 12 (1): 76–83

  Abstract

  BACKGROUND: Repair of tetralogy of Fallot (TOF) with major aortopulmonary collateral arteries (MAPCAs) requires unifocalization of pulmonary circulation, intracardiac repair with the closure of the ventricular septal defect, and placement of a right ventricle (RV) to pulmonary artery (PA) conduit. The decision to perform complete repair is sometimes aided by an intraoperative flow study to estimate the total resistance of the reconstructed pulmonary circulation.METHODS: We reviewed patients who underwent unifocalization and PA reconstruction for TOF/MAPCAs to evaluate acute and mid-term outcomes after repair with and without flow studies and to characterize the relationship between PA pressure during the flow study and postrepair RV pressure.RESULTS: Among 579 patients who underwent unifocalization and PA reconstruction for TOF/MAPCAs, 99 (17%) had an intraoperative flow study during one (n = 91) or more (n = 8) operations to determine the suitability for a complete repair. There was a reasonably good correlation between mean PA pressure at 3 L/min/m2 during the flow study and postrepair RV pressure and RV:aortic pressure ratio. Acute and mid-term outcomes (median: 3.8 years) after complete repair in the flow study patients (n = 78) did not differ significantly from those in whom the flow study was not performed (n = 444). Furthermore, prior failed flow study was not associated with differences in outcome after subsequent intracardiac repair.CONCLUSIONS: The intraoperative flow study remains a useful adjunct for determining the suitability for complete repair in a subset of patients undergoing surgery for TOF/MAPCAs, as it is reasonably accurate for estimating postoperative PA pressure and serves as a reliable guide for the feasibility of single-stage complete repair.

  View details for DOI 10.1177/2150135120964427

  View details for PubMedID 33407027

• Longevity of large aortic allograft conduits in Tetralogy with major aortopulmonary collaterals. The Annals of thoracic surgery Ma, M., Arunamata, A., Peng, L. F., Wise-Faberowski, L., Hanley, F. L., McElhinney, D. B. 2021

  Abstract

  Appropriate conduit selection for right ventricle (RV) to pulmonary artery (PA) connection has been extensively studied, with older implantation age, pulmonary (v. aortic) homografts, and true-sizing associated with increased longevity. Notably, patients with PA arborization abnormalities (ie MAPCAs) are reported to require earlier and more frequent conduit interventions. We aim to understand the behavior of large diameter aortic homografts in patients with MAPCAs, which are programmatically utilized at our institution.This is a single-center retrospective cohort study including all children < 12 years of age who underwent RV-PA connection using an aortic homograft ≥ 16mm diameter between 2002-2019, with a primary outcome of freedom from any RV-PA reintervention and a secondary outcome of freedom from surgical reintervention. Patients were grouped by absolute and indexed conduit sizes for further analysis.A total of 336 conduits were followed for a median of 3.0 years; transcatheter (n = 30) and/or surgical (n = 35) reintervention was performed on 64 conduits. Estimated freedom from reintervention and surgical replacement was 84% and 90% at 5 years. Younger age and smaller absolute conduit size were associated with earlier reintervention, but conduit z-score (median 3.5) was not assocated with outcome.The programmatic use of oversized aortic homograft RV-PA conduits in the surgical repair of MAPCAs provides a focused experience that demonstrates similar longevity to reported best alternatives. Secondarily, conduit oversizing may improve durability and enables an increased likelihood of non-operative reintervention.

  View details for DOI 10.1016/j.athoracsur.2021.01.054

  View details for PubMedID 33600790

• Recent outcomes of the extracardiac Fontan procedure in patients with hypoplastic left heart syndrome ANNALS OF PEDIATRIC CARDIOLOGY Arunamata, A., Tacy, T. A., Kache, S., Mainwaring, R. D., Ma, M., Maeda, K., Punn, R. 2020; 13 (3): 186–93

  View details for DOI 10.4103/apc.APC_5_20

  View details for Web of Science ID 000552113300002

• RAPID AORTIC HOMOGRAFT DEGENERATION AND VAD SUPPORT IN A NEONATE WITH SINGLE VENTRICLE HEART DISEASE Ahmed, H., Chen, S., Yarlagadda, V., Almond, C., Murray, J., Rosenthal, D. N., Ma, M., Dykes, J., Maeda, K. ELSEVIER SCIENCE INC. 2020: 2865

  View details for Web of Science ID 000522979102649

• A novel cross-species model of Barlow's disease to biomechanically analyze repair techniques in an exvivo left heart simulator. The Journal of thoracic and cardiovascular surgery Imbrie-Moore, A. M., Paulsen, M. J., Zhu, Y., Wang, H., Lucian, H. J., Farry, J. M., MacArthur, J. W., Ma, M., Woo, Y. J. 2020

  Abstract

  OBJECTIVE: Barlow's disease remains challenging to repair, given the complex valvular morphology and lack of quantitative data to compare techniques. Although there have been recent strides in exvivo evaluation of cardiac mechanics, to our knowledge, there is no disease model that accurately simulates the morphology and pathophysiology of Barlow's disease. The purpose of this study was to design such a model.METHODS: To simulate Barlow's disease, a cross-species exvivo model was developed. Bovine mitral valves (n=4) were sewn into a porcine annulus mount to create excess leaflet tissue and elongated chordae. A heart simulator generated physiologic conditions while hemodynamic data, high-speed videography, and chordal force measurements were collected. The regurgitant valves were repaired using nonresectional repair techniques such as neochord placement.RESULTS: The model successfully imitated the complexities of Barlow's disease, including redundant, billowing bileaflet tissues with notable regurgitation. After repair, hemodynamic data confirmed reduction of mitral leakage volume (25.9±2.9 vs 2.1±1.8mL, P<.001) and strain gauge analysis revealed lower primary chordae forces (0.51±0.17 vs 0.10±0.05N, P<.001). In addition, the maximum rate of change of force was significantly lower postrepair for both primary (30.80±11.38 vs 8.59±4.83N/s, P<.001) and secondary chordae (33.52±10.59 vs 19.07±7.00N/s, P=.006).CONCLUSIONS: This study provides insight into the biomechanics of Barlow's disease, including sharply fluctuating force profiles experienced by elongated chordae prerepair, as well as restoration of primary chordae forces postrepair. Our disease model facilitates further in-depth analyses to optimize the repair of Barlow's disease.

  View details for DOI 10.1016/j.jtcvs.2020.01.086

  View details for PubMedID 32249088

• Comprehensive Ex Vivo Comparison of 5 Clinically Used Conduit Configurations for Valve-Sparing Aortic Root Replacement Using a 3-Dimensional-Printed Heart Simulator. Circulation Paulsen, M. J., Imbrie-Moore, A. M., Baiocchi, M., Wang, H., Hironaka, C. E., Lucian, H. J., Farry, J. M., Thakore, A. D., Zhu, Y., Ma, M., MacArthur, J. W., Woo, Y. J. 2020; 142 (14): 1361–73

  Abstract

  Many graft configurations are clinically used for valve-sparing aortic root replacement, some specifically focused on recapitulating neosinus geometry. However, the specific impact of such neosinuses on valvular and root biomechanics and the potential influence on long-term durability are unknown.Using a custom 3-dimenstional-printed heart simulator with porcine aortic roots (n=5), the anticommissural plication, Stanford modification, straight graft (SG), Uni-Graft, and Valsalva graft configurations were tested in series using an incomplete counterbalanced measures design, with the native root as a control, to mitigate ordering effects. Hemodynamic and videometric data were analyzed using linear models with conduit as the fixed effect of interest and valve as a fixed nuisance effect with post hoc pairwise testing using Tukey's correction.Hemodynamics were clinically similar between grafts and control aortic roots. Regurgitant fraction varied between grafts, with SG and Uni-Graft groups having the lowest regurgitant fractions and anticommissural plication having the highest. Root distensibility was significantly lower in SG versus both control roots and all other grafts aside from the Stanford modification (P≤0.01 for each). All grafts except SG had significantly higher cusp opening velocities versus native roots (P<0.01 for each). Relative cusp opening forces were similar between SG, Uni-Graft, and control groups, whereas anticommissural plication, Stanford modification, and Valsalva grafts had significantly higher opening forces versus controls (P<0.01). Cusp closing velocities were similar between native roots and the SG group, and were significantly lower than observed in the other conduits (P≤0.01 for each). Only SG and Uni-Graft groups experienced relative cusp closing forces approaching that of the native root, whereas relative forces were >5-fold higher in the anticommissural plication, Stanford modification, and Valsalva graft groups.In this ex vivo modeling system, clinically used valve-sparing aortic root replacement conduit configurations have comparable hemodynamics but differ in biomechanical performance, with the straight graft most closely recapitulating native aortic root biomechanics.

  View details for DOI 10.1161/CIRCULATIONAHA.120.046612

  View details for PubMedID 33017215

• Unifocalization and pulmonary artery reconstruction in patients with tetralogy of Fallot and major aortopulmonary collateral arteries who underwent surgery before referral. The Journal of thoracic and cardiovascular surgery Ma, M., Zhang, Y., Wise-Faberowski, L., Lin, A., Asija, R., Hanley, F. L., McElhinney, D. B. 2020

  Abstract

  The study objective was to characterize and analyze outcomes in patients with tetralogy of Fallot and major aortopulmonary collateral arteries who had undergone surgery elsewhere before referral (prereferral surgery).Patients with tetralogy of Fallot and major aortopulmonary collateral arteries who underwent surgery between 2001 and 2019 at our center were reviewed. Prereferral surgery and unoperated patients were compared, as were subsets of prereferral surgery patients who had undergone different types of prior procedures. Primary outcomes included complete repair with survival to 6 months, death, and perioperative metrics.Of 576 patients studied, 200 (35%) had undergone a wide range and number of prior operations elsewhere, including 92 who had pulmonary blood supply through a shunt and 108 who had a right ventricle pulmonary artery connection. Patients who underwent prereferral surgery with an existing right ventricle pulmonary artery connection had undergone more prereferral surgery procedures than those with a shunt and were more likely to have a right ventricle outflow tract pseudoaneurysm or pulmonary artery stent (all P < .001) at the time of referral. The cumulative incidences of complete repair and death were similar regardless of prereferral surgery status, but the cumulative incidence of complete repair with 6-month survival was higher (P = .002) and of death lower (P = .18) in patients who had prior right ventricle pulmonary artery connection compared with those who had received a prior shunt only.Our comprehensive management strategy for tetralogy of Fallot and major aortopulmonary collateral arteries can be applied with excellent procedural results in both unoperated patients and those who have undergone multiple and varied procedures elsewhere.

  View details for DOI 10.1016/j.jtcvs.2020.03.062

  View details for PubMedID 32444187

• In Vivo Validation of Restored Chordal Biomechanics After Mitral Ring Annuloplasty in a Rare Ovine Case of Natural Chronic Functional Mitral Regurgitation. Journal of cardiovascular development and disease Wang, H., Paulsen, M. J., Imbrie-Moore, A. M., Tada, Y., Bergamasco, H., Baker, S. W., Shudo, Y., Ma, M., Woo, J. Y. 2020; 7 (2)

  Abstract

  Mitral valve chordae tendineae forces are elevated in the setting of mitral regurgitation (MR). Ring annuloplasty is an essential component of surgical repair for MR, but whether chordal forces are reduced after mitral annuloplasty has never been validated in vivo. Here, we present an extremely rare ovine case of natural, severe chronic functional MR, in which we used force-sensing fiber Bragg grating neochordae to directly measure chordal forces in the baseline setting of severe MR, as well as after successful mitral ring annuloplasty repair. Overall, our report is the first to confirm in vivo that mitral ring annuloplasty reduces elevated chordae tendineae forces associated with chronic functional MR.

  View details for DOI 10.3390/jcdd7020017

  View details for PubMedID 32429298

• Recent outcomes of the extracardiac Fontan procedure in patients with hypoplastic left heart syndrome. Annals of pediatric cardiology Arunamata, A., Tacy, T. A., Kache, S., Mainwaring, R. D., Ma, M., Maeda, K., Punn, R. 2020; 13 (3): 186–93

  Abstract

  To investigate patient-related factors, echocardiographic, and anatomic variables associated with immediate and long-term clinical outcomes after extracardiac Fontan procedure at our institution.Retrospective review of preoperative cardiac catheterizations and echocardiograms as well as medical records of all children with hypoplastic left heart syndrome (HLHS) who underwent Fontan between June 2002 and December 2018.Seventy-seven patients with HLHS were included (age 4 years [1.5-11.7]). Seventy patients (91%) received a nonfenestrated Fontan and 57 patients (74%) underwent Fontan without cardiopulmonary bypass (CPB). Presence of a Fontan fenestration (P = 0.69) and use of CPB (P = 0.79) did not differ between those with <2 weeks compared to those with ≥2 weeks of chest tube drainage. There were no differences in either pre- or intra-operative hemodynamics between patients who weighed <15 kg compared to those who weighed ≥15 kg at time of surgery; incidence of death, transplant, and transplant listing were similar between weight groups. Inferior vena cava (IVC) diameter z-score did not differ among patients with and without chylous chest tube drainage (P = 0.78), with and without development of protein losing enteropathy (P = 0.23), or death/heart transplant/transplant listing compared to survivors without transplant (P = 0.26).In HLHS patients undergoing Fontan, preoperative weight and IVC diameter appeared to have no influence on immediate postoperative outcomes. Performing the Fontan off CPB and with a fenestration also conferred no added clinical benefit. These observations should be considered when deciding optimal timing for Fontan completion.

  View details for DOI 10.4103/apc.APC_5_20

  View details for PubMedID 32863652

  View details for PubMedCentralID PMC7437630

• Unilateral branch pulmonary artery origin from a solitary arterial trunk with major aortopulmonary collaterals to the contralateral lung: anatomic and developmental considerations. Seminars in thoracic and cardiovascular surgery Adamson, G. T., Houyel, L., McElhinney, D. B., Maskatia, S. A., Ma, M., Hanley, F. L., Lopez, L. 2020

  Abstract

  In both truncus arteriosus communis (TAC) and tetralogy of Fallot (TOF), there is a rare phenotype that includes a single branch pulmonary artery (PA) arising from a solitary great artery and major aortopulmonary collaterals (MAPCAs) supplying the contralateral lung. We describe the intracardiac and great vessel anatomy of infants with this phenotype, consider rationale for classifying patients as TOF vs. TAC, and describe surgical outcomes. Our institution's surgical database was reviewed for patients with a single branch PA from a solitary arterial trunk and contralateral MAPCAs from 2007 to 2019. Demographic, imaging, and surgical data were collected and described. All 11 patients underwent complete repair with a median right ventricular to aortic pressure ratio of 0.36 (range 0.26-0.50). At 0.1-9.1 years after repair (median 0.8 years) there was approximately balanced left-right lung perfusion (median 52% to the right lung, range 34-74%). The MAPCA lungs exemplified the full spectrum of PA and MAPCA anatomy, from absent intrapericardial PAs with all single supply MAPCAs to a normally arborizing PA with all dual supply MAPCAs and present pulmonary valve leaflet tissue. All patients had a systemic semilunar valve with 3 thin and similarly sized leaflets and fibrous continuity with the tricuspid valve, and all had coronary origins and outflow tract morphology more consistent with TOF. It is appropriate to classify all patients with a single anomalous PA from a solitary arterial trunk and MAPCAs to the contralateral lung as TOF rather than TAC Type A3. All variants were amenable to surgical repair.

  View details for DOI 10.1053/j.semtcvs.2020.11.009

  View details for PubMedID 33181302

• Outcomes in Patients with Alagille Syndrome and Complex Pulmonary Artery Disease. The Journal of pediatrics Luong, R., Feinstein, J. A., Ma, M., Ebel, N. H., Wise-Faberowski, L., Zhang, Y., Peng, L. F., Yarlagadda, V. V., Shek, J., Hanley, F. L., McElhinney, D. B. 2020

  Abstract

  To assess outcomes in a large cohort of patients with Alagille Syndrome (ALGS) who underwent pulmonary artery reconstruction surgery for complex PA disease.Patients with ALGS who underwent PA reconstruction surgery at Lucile Packard Children's Hospital Stanford were reviewed. Patients were examined as an overall cohort and based on the primary cardiovascular diagnosis: severe isolated branch PA stenosis, tetralogy of Fallot (TOF) without major aortopulmonary collateral arteries (MAPCAs), or TOF with MAPCAs RESULTS: Fifty-one patients with ALGS underwent PA surgery at our center: 22 with severe branch PA stenosis, 9 with TOF without MAPCAs, and 20 with TOF and MAPCAs. Forty-one patients (80%) achieved a complete repair. Five of the patients with TOF with MAPCAs (25%) had a complete repair at the first surgery, compared with 8 (89%) and 19 (86%) with TOF without MAPCAs and isolated branch PA stenosis, respectively. At a median follow-up of 1.7 years after the first surgery, 39 patients (76%) were alive, 36 with a complete repair and a median PA:aortic systolic pressure ratio of 0.38. Nine patients (18%), 8 with isolated branch PA stenosis, underwent liver transplantation.Most patients with ALGS and complex PA disease can undergo complete repair with low postoperative right ventricular pressure. Patients with TOF/MAPCAs had the worst outcome, with higher mortality and more frequent PA interventions compared with patients with TOF without MAPCAs or isolated branch PA stenosis. Complex PA disease is not a contraindication to liver transplantation in patients with ALGS.

  View details for DOI 10.1016/j.jpeds.2020.09.053

  View details for PubMedID 32980376

• Angiographic Anatomy of Major Aortopulmonary Collateral Arteries and Association With Early Surgical Outcomes in Tetralogy of Fallot. Journal of the American Heart Association Adamson, G. T., McElhinney, D. B., Zhang, Y., Feinstein, J. A., Peng, L. F., Ma, M., Algaze, C. A., Hanley, F. L., Perry, S. B. 2020: e017981

  Abstract

  Background Due in part to the heterogeneity of the pulmonary circulation in patients with tetralogy of Fallot and major aortopulmonary collateral arteries (MAPCAs), research on this condition has focused on relatively basic anatomic characteristics. We aimed to detail pulmonary artery (PA) and MAPCA anatomy in a large group of infants, assess relationships between anatomy and early surgical outcomes, and consider systems for classifying MAPCAs. Methods and Results All infants ( <1 year of age) undergoing first cardiac surgery for tetralogy of Fallot/MAPCAs from 2001 to 2019 at Stanford University were identified. Preoperative angiograms delineating supply to all 18 pulmonary segments were reviewed for details of each MAPCA and the arborization and size of central PAs. We studied 276 patients with 1068 MAPCAs and the following PA patterns: 152 (55%) incompletely arborizing PAs, 48 (17%) normally arborizing PAs, 45 (16%) absent PAs, and 31 (11%) unilateral MAPCAs. There was extensive anatomic variability, but no difference in early outcomes according to PA arborization or the predominance of PAs or MAPCAs. Patients with low total MAPCA and/or PA cross-sectional area were less likely to undergo complete repair. Conclusions MAPCA anatomy is highly variable and essentially unique for each patient. Though each pulmonary segment can be supplied by a MAPCA, central PA, or both, all anatomic combinations are similarly conducive to a good repair. Total cross-sectional area of central PA and MAPCA material is an important driver of outcome. We elucidate a number of novel associations between anatomic features, but the extreme variability of the pulmonary circulation makes a granular tetralogy of Fallot/MAPCA classification system unrealistic.

  View details for DOI 10.1161/JAHA.120.017981

  View details for PubMedID 33283588

• Postoperative Recovery of Left Ventricular Function following Repair of Large Ventricular Septal Defects in Infants. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Adamson, G. T., Arunamata, A., Tacy, T. A., Silverman, N. H., Ma, M., Maskatia, S. A., Punn, R. 2019

  Abstract

  INTRODUCTION: Early postoperative left ventricular (LV) dysfunction is observed following repair of large ventricular septal defects (VSDs), but the frequency and rate of recovery of LV function are unknown. This study aims to characterize the incidence and rate of recovery of postoperative LV dysfunction following repair of large VSDs and to improve understanding of LV mechanics before and after VSD repair.METHODS: Infants who underwent surgical repair of an isolated large VSD were included. Pre- and postoperative echocardiographic images were reviewed, and LV function was assessed by both conventional echocardiography and speckle-tracking strain analyses. Postoperative LV dysfunction was defined as an LV ejection fraction (LVEF)<50% using the 5/6 area-length method. Echocardiograms were reviewed to assess LVEF and LV volume through 1-year follow-up.RESULTS: Of 104 infants evaluated (median age, 0.31 [0.22, 0.56] years), all had normal preoperative LVEF and 39 (38%) had postoperative LV dysfunction. Follow-up echocardiograms were available in 31 (80%) patients, all of whom had LVEF>50% within 9months of surgery. Lower preoperative apical four-chamber longitudinal strain (A4LS) and greater LV end-diastolic volume indexed to body surface area1.38 were independently associated with postoperative LV dysfunction. An absolute preoperative A4LS < 16.7% (area under the curve=0.87; 95% CI, 0.78-0.95; P<.001) was most strongly associated with postoperative dysfunction.CONCLUSIONS: Infants with LV dysfunction following repair of large VSDs recover function within 9months. Preoperative A4LS can be helpful to detect subclinical LV dysfunction in the setting of a large hemodynamically significant VSD and guide postoperative expectations for providers and families.

  View details for DOI 10.1016/j.echo.2019.10.003

  View details for PubMedID 31866322

• Redo Valve-Sparing Root Replacement for Delayed Cusp Derangement From Ventricular Septal Defect ANNALS OF THORACIC SURGERY Zhu, Y., Cohen, J. E., Ma, M., Woo, Y. 2019; 108 (5): E295–E296

  View details for DOI 10.1016/j.athoracsur.2019.03.040

  View details for Web of Science ID 000492187300005

• Outcomes After Aortopulmonary Window for Hypoplastic Pulmonary Arteries and Dual-Supply Collaterals ANNALS OF THORACIC SURGERY Bauser-Heaton, H., Ma, M., McElhinney, D. B., Goodyer, W. R., Zhang, Y., Chan, F. P., Asija, R., Shek, J., Wise-Faberowski, L., Hanley, F. L. 2019; 108 (3): 820–27

  View details for DOI 10.1016/j.athoracsur.2019.03.022

  View details for Web of Science ID 000482187400054

• Surgical results of unifocalization revision Mainwaring, R. D., Patrick, W. L., Rosenblatt, T. R., Ma, M., Kamra, K., Arunamata, A., Hanley, F. L. MOSBY-ELSEVIER. 2019: 534–44

  View details for DOI 10.1016/j.jtcvs.2018.09.135

  View details for Web of Science ID 000475496900070

• Modeling conduit choice for valve-sparing aortic root replacement on biomechanics with a 3-dimensional-printed heart simulator JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Paulsen, M. J., Kasinpila, P., Imbrie-Moore, A. M., Wang, H., Hironaka, C. E., Koyano, T. K., Fong, R., Chiu, P., Goldstone, A. B., Steele, A. N., Stapleton, L. M., Ma, M., Woo, Y. 2019; 158 (2): 392–403

  View details for DOI 10.1016/j.jtcvs.2018.10.145

  View details for Web of Science ID 000475496900041

• Redo Valve-Sparing Root Replacement for Delayed Cusp Derangement from Ventricular Septal Defect. The Annals of thoracic surgery Zhu, Y., Cohen, J. E., Ma, M., Woo, Y. J. 2019

  Abstract

  A 28-year-old gentleman with ventricular septal defect (VSD), double-chambered right ventricle (DCRV) with associated right ventricular outflow tract obstruction, and anomalous right coronary artery (RCA) underwent resection of the DCRV, trans-aortic VSD repair, and unroofing of anomalous RCA. Two years later, he returned with delayed presentation of VSD flow funnel related aortic cusp prolapse and symptomatic severe aortic regurgitation. He underwent reoperative valve-sparing aortic root replacement and aortic cusp repair with an excellent outcome.

  View details for PubMedID 30986415

• Outcomes After Aortopulmonary Window for Hypoplastic Pulmonary Arteries and Dual-Supply Collaterals. The Annals of thoracic surgery Bauser-Heaton, H., Ma, M., McElhinney, D. B., Goodyer, W. R., Zhang, Y., Chan, F. P., Asija, R., Shek, J., Wise-Faberowski, L., Hanley, F. L. 2019

  Abstract

  BACKGROUND: Our institutional approach to tetralogy of Fallot (TOF) with major aortopulmonary collateral arteries (MAPCAs) emphasizes early unifocalization and complete repair (CR). In the small subset of patients with dual-supply MAPCAs and confluent but hypoplastic central pulmonary arteries (PAs), our surgical approach is early creation of an aortopulmonary window (APW) to promote PA growth. Factors associated with successful progression to CR, and mid-term outcomes have not been assessed.METHODS: Clinical data were reviewed. PA diameters were measured off-line from angiograms prior to APW and on follow-up catheterization >1 month after APW but prior to any additional surgical interventions.RESULTS: From 11/01-3/18, 352 patients with TOF/MAPCAs underwent initial surgery at our center, 40 of whom had a simple APW with or without ligation of MAPCAs as the first procedure (median age 1.4 months). All PA diameters increased significantly on follow-up angiography. Ultimately, 35 patients underwent CR after APW. Nine of these patients (26%) underwent intermediate palliative operation between 5 and 39 months (median 8 months). There were no early deaths. The cumulative incidence of CR was 65% 1 year post-APW and 87% at 3 years. Repaired patients were followed for a median of 4.2 years after repair; the median PA:aortic pressure ratio was 0.39 (0.22-0.74).CONCLUSIONS: Most patients with TOF/MAPCAs and hypoplastic but normally arborizing PAs and dual-supply MAPCAs are able to undergo CR with low right ventricular pressure after APW early in life. Long-term outcomes were good, with acceptable PA pressures in most patients.

  View details for PubMedID 30980823

• Outcomes After Initial Unifocalization to a Shunt in Complex Tetralogy of Fallot with MAPCAs. The Annals of thoracic surgery Bauser-Heaton, H., Ma, M., Wise-Faberowski, L., Asija, R., Shek, J., Zhang, Y., Peng, L. F., Sidell, D. R., Hanley, F. L., McElhinney, D. B. 2019

  Abstract

  Our approach to tetralogy of Fallot (TOF) with pulmonary atresia and major aortopulmonary collateral arteries (MAPCAs) emphasizes early single-stage unifocalization and intracardiac repair. However, a subset of patients with small native pulmonary arteries (PAs) and MAPCAs undergo unifocalization to a shunt rather than simultaneous intracardiac repair.Patients with TOF/MAPCAs who underwent unifocalization to a systemic-to-PA shunt by a single surgeon were reviewed. The decision to perform simultaneous intracardiac repair was based on an intraoperative flow study or empirical assessment of PA and MAPCA size.From 11/01-12/17, 57 patients with TOF/MAPCAs underwent unifocalization to a shunt at a median age of 6.9 months. Genetic abnormalities were documented in 60% of patients, including a chromosome 22q11 deletion in 25 and Alagille syndrome in 8. Twenty patients (35%) had undergone prior surgery elsewhere (n=16) and/or at our center (n=7). During a median follow-up of 5.4 years, 9 patients had additional surgery to revise the PA reconstruction before complete repair, and 38 patients underwent complete repair. Survival was 74±6% 5 years after unifocalization. At follow-up, the median PA:aortic systolic pressure ratio was 0.36 and was >0.50 in 2 patients.In patients with the smallest MAPCAs and PAs, single-stage unifocalization to a shunt followed by intracardiac repair yields an excellent outcome in most cases.

  View details for DOI 10.1016/j.athoracsur.2019.01.030

  View details for PubMedID 30772338

• Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nature biomedical engineering Stapleton, L. M., Steele, A. N., Wang, H., Lopez Hernandez, H., Yu, A. C., Paulsen, M. J., Smith, A. A., Roth, G. A., Thakore, A. D., Lucian, H. J., Totherow, K. P., Baker, S. W., Tada, Y., Farry, J. M., Eskandari, A., Hironaka, C. E., Jaatinen, K. J., Williams, K. M., Bergamasco, H., Marschel, C., Chadwick, B., Grady, F., Ma, M., Appel, E. A., Woo, Y. J. 2019; 3 (8): 611–20

  Abstract

  Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

  View details for DOI 10.1038/s41551-019-0442-z

  View details for PubMedID 31391596

• Surgical Repair of Ebstein's Anomaly Utilizing A Bicuspidization Approach. The Annals of thoracic surgery Mainwaring, R. D., Rosenblatt, T. R., Lui, G. K., Ma, M., Hanley, F. L. 2019

  Abstract

  Ebstein's anomaly of the tricuspid valve is a rare and heterogeneous form of congenital heart defect. The purpose of this study was to review the surgical experience with Ebstein's anomaly at a single institution.This was a retrospective review of 47 patients with Ebstein's anomaly who were previously unrepaired and underwent surgical repair of the tricuspid valve. Our surgical approach repairs the leaflets at the pre-existing level and does not attempt to reposition the hingepoints at the anatomic annulus. The median age at surgery was 17 years (range 2 to 53 years). Pre-operatively, the median degree of tricuspid regurgitation was graded as moderate-to-severe and the median right ventricular function was slightly below normal.Forty-seven patients underwent surgical repair without any mortality. Forty-three of the 47 patients (91%) had a successful repair as evidenced by a decrease in the amount of tricuspid regurgitation to trace/mild. Four patients (9%) had an unsuccessful initial repair. Thirteen of the 47 (29%) underwent a concomitant bi-directional Glenn procedure. There were 8 patients (17%) who have required late re-operation. Seven of these 8 patients initially had undergone a successful repair but returned with recurrent tricuspid regurgitation. Six of the 8 late re-operations entailed a re-repair, while two (4%) required ; tricuspid valve replacement.The bicuspidization surgical technique resulted in 91% percent of patients undergoing a successful initial repair. These results suggest this technique may be a viable alternative to the "cone" procedure.

  View details for DOI 10.1016/j.athoracsur.2019.06.026

  View details for PubMedID 31394091

• Surgical results of unifocalization revision. The Journal of thoracic and cardiovascular surgery Mainwaring, R. D., Patrick, W. L., Rosenblatt, T. R., Ma, M., Kamra, K., Arunamata, A., Hanley, F. L. 2018

  Abstract

  OBJECTIVE: Midline unifocalization has been developed for the surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. All patients will eventually require reoperation due to the presence of a conduit, and some may also require revision of the distal unifocalized bed. The purpose of this study was to evaluate the surgical results of unifocalization revision.METHODS: This was a retrospective review of 254 patients who underwent midline unifocalization for treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Forty-eight of 254 patients (18%) have subsequently undergone unifocalization revision. Thirty-two of these patients had previously undergone a single-stage complete repair, whereas 16 had a unifocalization and placement of a central shunt.RESULTS: For the 32 patients who previously underwent a complete repair, there have been no early or late deaths. The peak systolic pulmonary artery to aortic pressure ratio was 0.44±0.11 after the initial repair and increased to 0.82±0.18 before revision. The pressure ratio decreased to 0.41±0.09 after revision. Three of 32 patients (9%) have subsequently undergone a second unifocalization revision. The 16 patients who previously had a unifocalization/shunt underwent unifocalization revision and complete repair (n=14) and revision and repeat shunt (n=2). There was 1 operative mortality and 3 late deaths (25% total) in this cohort. Three (25%) of 12 survivors have subsequently undergone a second unifocalization revision.CONCLUSIONS: The data demonstrate that unifocalization revision can be performed with a successful outcome in a majority of patients. Patients who underwent an initial unifocalization/shunt had a higher failure rate than patients who were initially repaired.

  View details for PubMedID 30982588

• Modeling conduit choice for valve-sparing aortic root replacement on biomechanics with a 3-dimensional-printed heart simulator. The Journal of thoracic and cardiovascular surgery Paulsen, M. J., Kasinpila, P., Imbrie-Moore, A. M., Wang, H., Hironaka, C. E., Koyano, T. K., Fong, R., Chiu, P., Goldstone, A. B., Steele, A. N., Stapleton, L. M., Ma, M., Woo, Y. J. 2018

  Abstract

  OBJECTIVE: The optimal conduit for valve-sparing aortic root replacement is still debated, with several conduit variations available, ranging from straight tubular grafts to Valsalva grafts. Benefits of neosinus reconstruction include enhanced flow profiles and improved hemodynamics. Curiously, however, some clinical data suggest that straight grafts may have greater long-term durability. In this study, we hypothesized that straight tubular grafts may help maintain the native cylindrical position of the aortic valve commissures radially, resulting in preserved leaflet coaptation, reduced stresses, and potentially improved valve performance.METHODS: Using 3D printing, a left heart simulator with a valve-sparing root replacement model and a physiologic coronary circulation was constructed. Aortic valves were dissected from fresh porcine hearts and reimplanted into either straight tubular grafts (n=6) or Valsalva grafts (n=6). Conduits were mounted into the heart simulator and hemodynamic, echocardiographic, and high-speed videometric data were collected.RESULTS: Hemodynamic parameters and coronary blood flow were similar between straight and Valsalva grafts, although the former were associated with lower regurgitant fractions, less peak intercommissural radial separation, preserved leaflet coaptation, decreased leaflet velocities, and lower relative leaflet forces compared with Valsalva grafts.CONCLUSIONS: Valsalva grafts and straight grafts perform equally well in terms of gross hemodyanics and coronary blood flow. Interestingly, however, the biomechanics of these 2 conduits differ considerably, with straight grafts providing increased radial commissural stability and leaflet coaptation. Further investigation into how these parameters influence clinical outcomes is warranted.

  View details for PubMedID 30745047

• Repair of Ductus or Hemi-Truncus to One Lung and Major Aortopulmonary Collaterals to the Other Lung. The Annals of thoracic surgery Mainwaring, R. D., Rosenblatt, T. R., Patrick, W. L., Ma, M., Peng, L., Hanley, F. L. 2018

  Abstract

  BACKGROUND: There are patients born with pulmonary atresia and a ductus arteriosus or hemi-truncus to one lung and major aortopulmonary collateral arteries (MAPCAs) to the contralateral lung. The purpose of this study was to review our surgical results for this relatively rare subset of patients.METHODS: This was a retrospective review of 35 patients with ductus/hemi-truncus in association with pulmonary atresia with ventricular septal defect and MAPCAs. Our surgical algorithm is bifurcated into two strategies: 1) patients with "favorable" MAPCAs are candidates for single stage complete repair, and 2) patients with "unfavorable" MAPCAs undergo a staged approach. The median age at surgery was 3 months (range 1-7 months), and the mean number of MAPCAs was 3.1 ± 1.3.RESULTS: Twenty patients underwent a single stage complete repair. All 20 of these patients are alive with a right ventricle to aortic pressure ratio of 0.34 ± 0.07. The distribution of pulmonary blood flow by lung perfusion scan was 44% to the right and 56% to the left lung. Fifteen patients underwent a staged approach, including unifocalization of the MAPCAs to a central shunt. There were two interim deaths. Twelve patients have undergone complete repair with a right ventricle to aortic pressure ratio of 0.38 ± 0.07. There was one late death after complete repair. The distribution of pulmonary blood flow was 39% to the right and 61% to the left lung.CONCLUSIONS: The data demonstrate that 32 of 35 patients with ductus/hemi-truncus and MAPCAs ultimately achieved complete repair with relatively low pulmonary artery pressures.

  View details for PubMedID 29684371

• An analysis of patients requiring unifocalization revision following midline unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery Mainwaring, R. D., Patrick, W. L., Ma, M., Hanley, F. L. 2018

  Abstract

  OBJECTIVES: Midline unifocalization has been developed for the surgical treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. All patients will eventually require reoperation because of the presence of a conduit, and some patients may also require revision of the distal unifocalized bed. The purpose of this study was to analyse the need for unifocalization revision following midline unifocalization.METHODS: This was a retrospective review of 241 patients who underwent midline unifocalization for the treatment of pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Two hundred and four (85.4%) patients had a single-stage complete repair, whereas 37 patients had a unifocalization and placement of a central shunt. Seventy-eight patients have subsequently undergone reoperations at our institution, including 44 operations that required unifocalization revision. These 44 patients were compared with the 191 operative survivors who did not require revision.RESULTS: An analysis of risk factors for requiring unifocalization revision included the following: (i) single-stage complete repair versus unifocalization and shunt (14.7% vs 37.8%, P<0.001), (ii) right ventricle to aortic pressure ratio at the initial repair (0.33±0.07 vs 0.44±0.08, P<0.001) and (iii) absence of central pulmonary arteries (32.8% vs 13.4%, P<0.001).CONCLUSIONS: Data demonstrate that 44 of 241 (18%) patients who underwent midline unifocalization have subsequently required revision of their unifocalization. The need for unifocalization revision was associated with 3 factors, all of which were known at the time of discharge from the initial unifocalization. These data suggest that potentially higher risk patients should be monitored more closely than their lower risk counterparts.

  View details for PubMedID 29447337

• Current status of domino heart transplantation. Journal of cardiac surgery Shudo, Y., Ma, M., Boyd, J. H., Woo, Y. J. 2017; 32 (3): 229-232

  Abstract

  Domino heart transplant, wherein the explanted heart from the recipient of an en-bloc heart-lung is utilized for a second recipient, represents a unique surgical strategy for patients with end-stage heart failure. With a better understanding of the potential advantages and disadvantages of this procedure, its selective use in the current era can improve and maximize organ allocation in the United States. In this report, we reviewed the current status of domino heart transplantation.

  View details for DOI 10.1111/jocs.13104

  View details for PubMedID 28219115

• Recovery of a Missile Embolus From the Right Ventricle. Annals of thoracic surgery Marshall, C. D., Ma, M. R., Park, J., Sheckter, C. C., Massoudi, R. A., Ligman, C. M., Jou, R. M., Ogden, W. D. 2017; 103 (1): e69-e71

  Abstract

  Missile embolism is a clinical entity in which a projectile object enters a blood vessel and is carried to a distant part of the body. We present a case of the discovery of an iliac vein to right ventricle missile embolus in a young man, with successful extraction through a right atriotomy. We provide a historical overview of the literature concerning missile embolism, and we argue that whereas acute embolized projectiles should be removed in almost all cases, it may be reasonable to simply observe an asymptomatic chronic missile embolus.

  View details for DOI 10.1016/j.athoracsur.2016.06.107

  View details for PubMedID 28007279

• Pulmonary Valve Repair for Patients With Acquired Pulmonary Valve Insufficiency ANNALS OF THORACIC SURGERY Said, S. M., Mainwaring, R. D., Ma, M., Tacy, T. A., Hanley, F. L. 2016; 101 (6): 2294-2301

  Abstract

  Pulmonary valve (PV) insufficiency is often an acquired condition after treatment for pulmonary stenosis. It is recognized that PV insufficiency has serious deleterious effects. Although surgical replacement of the PV is efficacious, artificial valves inevitably fail and require re-intervention. The purpose of this study was to summarize our experience with PV repair in patients with acquired PV insufficiency.This was a retrospective review of 16 patients with marked PV insufficiency who underwent PV repair. Thirteen of these patients were born with tetralogy of Fallot (TOF) and had undergone a previous transannular patch repair. Three patients were born with critical pulmonary stenosis and had a surgical valvotomy or balloon valvuloplasty.The 13 patients with TOF had resection of their previously placed transannular patch with re-approximation of the anterior commissure. All 13 patients experienced a marked reduction in the degree of pulmonary insufficiency. None of these patients have experienced any increase in insufficiency during follow-up. The 3 patients with critical pulmonary stenosis had a variety of pathologic findings identified at the surgical procedure. One patient had a large gap between a commissure and underwent closure of that commissure. The second and third patients had torn leaflets repaired with pericardial and Gore-Tex patches (Gore, Inc, Flagstaff, AZ). The degree of PV insufficiency was decreased to mild in all 3 patients. However, 2 of these 3 patients have subsequently had an increase in the degree of pulmonary insufficiency.Patients with TOF who underwent a previous transannular patch may be candidates for bicuspidization of their native PV, and the results of this procedure have been quite stable at follow-up. PV repair for torn leaflets was effective in the short term but was less stable over time.

  View details for DOI 10.1016/j.athoracsur.2016.01.035

  View details for Web of Science ID 000376502600043

  View details for PubMedID 27083251

• Anatomic Factors Associated With Truncal Valve Insufficiency and the Need for Truncal Valve Repair. World journal for pediatric & congenital heart surgery Patrick, W. L., Mainwaring, R. D., Carrillo, S. A., Ma, M., Reinhartz, O., Petrossian, E., Selamet Tierney, E. S., Reddy, V. M., Hanley, F. L. 2016; 7 (1): 9-15

  Abstract

  Truncus arteriosus is a complex and heterogeneous form of congenital heart defect. Many of the risk factors from several decades ago, including late repair and interrupted aortic arch, have been mitigated through better understanding of the entity and improved surgical techniques. However, truncal valve dysfunction remains an important cause of morbidity and mortality. The purpose of this study was to evaluate the anatomic factors associated with truncal valve dysfunction and the need for truncal valve surgery.This was a retrospective review of 72 infants who underwent repair of truncus arteriosus at our institution. The median age at surgery was nine days, and the median weight was 3.1 kg. Preoperative assessment of truncal valve insufficiency by echocardiography revealed no or trace insufficiency in 30, mild in 25, moderate in 10, and severe in 7. The need for truncal valve surgery was dictated by the severity of truncal valve insufficiency.Sixteen (22%) of the 72 patients undergoing truncus arteriosus repair had concomitant truncal valve surgery. Anatomic factors associated with the need for truncal valve surgery included an abnormal number of truncal valve cusps (P < .005), presence of valve dysplasia (P < .005), and the presence of an anomalous coronary artery pattern (P < .005). Fifteen (94%) of the sixteen patients who underwent concomitant surgery had two or all three of these anatomic factors (sensitivity = 94%, specificity = 85%).This study demonstrates that the presence of specific anatomic factors was closely associated with the presence of truncal valve insufficiency and the need for concomitant truncal valve surgery. Preoperative evaluation of these anatomic factors may provide a useful tool in determining who should undergo concomitant truncal valve surgery.

  View details for DOI 10.1177/2150135115608093

  View details for PubMedID 26714988

• POST-TRANSPLANT HEMODIALYSIS DRASTICALLY REDUCES ONE-YEAR SURVIVAL IN PATIENTS ENTERING LIVER TRANSPLANTATION WITHOUT RENAL DYSFUNCTION 15th Annual Congress of the International-Liver-Transplantation-Society Ma, M., Brennan, T., Reyes, I., Tamura, M., Feng, S. WILEY-BLACKWELL. 2009: S156–S156

  View details for Web of Science ID 000267792300280

• Post-Transplant Hemodialysis Drastically Reduces One-Year Survival in Patients Entering Liver Transplantation without Renal Dysfunction. 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantation Ma, M., Brennan, T., Reyes, I., Tamura, M., Feng, S. WILEY-BLACKWELL. 2009: 261–261

  View details for Web of Science ID 000265068800245

• Transplantation of hNT neurons into the ischemic cortex: Cell survival and effect on sensorimotor behavior JOURNAL OF NEUROSCIENCE RESEARCH Bliss, T. M., Kelly, S., Shah, A. K., Foo, W. C., Kohli, P., Stokes, C., Sun, G. H., Ma, M., Masel, J., Kleppner, S. R., Schallert, T., Palmer, T., Steinberg, G. K. 2006; 83 (6): 1004-1014

  Abstract

  Cell transplantation offers a potential new treatment for stroke. Animal studies using models that produce ischemic damage in both the striatum and the frontal cortex have shown beneficial effects when hNT cells (postmitotic immature neurons) were transplanted into the ischemic striatum. In this study, we investigated the effect of hNT cells in a model of stroke in which the striatum remains intact and damage is restricted to the cortex. hNT cells were transplanted into the ischemic cortex 1 week after stroke induced by distal middle cerebral artery occlusion (dMCAo). The cells exhibited robust survival at 4 weeks posttransplant even at the lesion border. hNT cells did not migrate, but they did extend long neurites into the surrounding parenchyma mainly through the white matter. Neurite extension was predominantly toward the lesion in ischemic animals but was bidirectional in uninjured animals. Extension of neurites through the cortex toward the lesion was also seen when there was some surviving cortical tissue between the graft and the infarct. Prolonged deficits were obtained in four tests of sensory-motor function. hNT-transplanted animals showed a significant improvement in functional recovery on one motor test, but there was no effect on the other three tests relative to control animals. Thus, despite clear evidence of graft survival and neurite extension, the functional benefit of hNT cells after ischemia is not guaranteed. Functional benefit could depend on other variables, such as infarct location, whether the cells mature, the behavioral tests employed, rehabilitation training, or as yet unidentified factors.

  View details for DOI 10.1002/jnr.20800

  View details for Web of Science ID 000237217100008

  View details for PubMedID 16496370

• Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Kelly, S., Bliss, T. M., Shah, A. K., Sun, G. H., Ma, M., Foo, W. C., Masel, J., Yenari, M. A., Weissman, I. L., Uchida, N., Palmer, T., Steinberg, G. K. 2004; 101 (32): 11839-11844

  Abstract

  We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances ( approximately 1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker beta-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

  View details for DOI 10.1073/pnas.0404474101

  View details for Web of Science ID 000223276700056

  View details for PubMedID 15280535

  View details for PubMedCentralID PMC511061