Saverio La Francesca

All Publications

• A multilayer scaffold design with spatial arrangement of cells to modulate esophageal tissue growth JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS Soliman, S., Laurent, J., Kalenjian, L., Burnette, K., Hedberg, B., La Francesca, S. 2019; 107 (2): 324–31

  Abstract

  Esophageal diseases may require resectioning of the damaged portion. The current standard of care requires the replacement of the esophagus with the stomach or the intestine. Such procedures have high rates of mortality and morbidity; therefore, the use of alternative conduits is needed. A tissue engineering approach that allows for the regeneration of esophageal tissues would have significant clinical application. A cell-seeded synthetic scaffold could replace the resected part of the esophagus and elicit tissue regrowth. In order to ideally recreate a functioning esophagus, its two crucial tissue layers should be induced: an epithelium on the luminal surface and a muscle layer on the exterior surface. To create a bioengineered esophagus with both tissue layers, a multilayer (ML) tubular scaffold design was considered. Luminal and exterior layers were electrospun with broad pore size to promote penetration and proliferation of mesenchymal stem cells on the lumen and smooth muscle cells on the external. These two layers would be separated by a thin layer with substantially narrower pore size intended to act as a barrier for the two cell types. This ML scaffold design was achieved via electrospinning by tuning the solution and the process parameters. Analysis of the scaffold demonstrated that this tuning enabled the production of three integrated layers with distinguishable microstructures and good mechanical integrity. In vitro validation was conducted on the separated unilayer components of the ML scaffold. The resultant proof-of-concept ML scaffold design could possibly support the spatial arrangement of cells needed to promote esophageal tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 324-331, 2019.

  View details for DOI 10.1002/jbm.b.34124

  View details for Web of Science ID 000455252200012

  View details for PubMedID 29717817

• Production and transplantation of bioengineered lung into a large-animal model SCIENCE TRANSLATIONAL MEDICINE Nichols, J. E., La Francesca, S., Niles, J. A., Vega, S. P., Argueta, L. B., Frank, L., Christiani, D. C., Pyles, R. B., Himes, B. E., Zhang, R., Li, S., Sakamoto, J., Rhudy, J., Hendricks, G., Begarani, F., Liu, X., Patrikeev, I., Pal, R., Usheva, E., Vargas, G., Miller, A., Woodson, L., Wacher, A., Grimaldo, M., Weaver, D., Mlcak, R., Cortiella, J. 2018; 10 (452)

  Abstract

  The inability to produce perfusable microvasculature networks capable of supporting tissue survival and of withstanding physiological pressures without leakage is a fundamental problem facing the field of tissue engineering. Microvasculature is critically important for production of bioengineered lung (BEL), which requires systemic circulation to support tissue survival and coordination of circulatory and respiratory systems to ensure proper gas exchange. To advance our understanding of vascularization after bioengineered organ transplantation, we produced and transplanted BEL without creation of a pulmonary artery anastomosis in a porcine model. A single pneumonectomy, performed 1 month before BEL implantation, provided the source of autologous cells used to bioengineer the organ on an acellular lung scaffold. During 30 days of bioreactor culture, we facilitated systemic vessel development using growth factor-loaded microparticles. We evaluated recipient survival, autograft (BEL) vascular and parenchymal tissue development, graft rejection, and microbiome reestablishment in autografted animals 10 hours, 2 weeks, 1 month, and 2 months after transplant. BEL became well vascularized as early as 2 weeks after transplant, and formation of alveolar tissue was observed in all animals (n = 4). There was no indication of transplant rejection. BEL continued to develop after transplant and did not require addition of exogenous growth factors to drive cell proliferation or lung and vascular tissue development. The sterile BEL was seeded and colonized by the bacterial community of the native lung.

  View details for DOI 10.1126/scitranslmed.aao3926

  View details for Web of Science ID 000440494900002

  View details for PubMedID 30068570

• Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells SCIENTIFIC REPORTS La Francesca, S., Aho, J. M., Barron, M. R., Blanco, E. W., Soliman, S., Kalenjian, L., Hanson, A. D., Todorova, E., Marsh, M., Burnette, K., DerSimonian, H., Odze, R. D., Wigle, D. A. 2018; 8: 4123

  Abstract

  Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.

  View details for DOI 10.1038/s41598-018-22401-x

  View details for Web of Science ID 000426814000021

  View details for PubMedID 29515136

  View details for PubMedCentralID PMC5841275

• Giving new life to old lungs: methods to produce and assess whole human paediatric bioengineered lungs. Journal of tissue engineering and regenerative medicine Nichols, J. E., La Francesca, S., Vega, S. P., Niles, J. A., Argueta, L. B., Riddle, M., Sakamoto, J., Vargas, G., Pal, R., Woodson, L., Rhudy, J., Lee, D., Seanor, D., Campbell, G., Schnadig, V., Cortiella, J. 2017; 11 (7): 2136–52

  Abstract

  We report, for the first time, the development of an organ culture system and protocols to support recellularization of whole acellular (AC) human paediatric lung scaffolds. The protocol for paediatric lung recellularization was developed using human transformed or immortalized cell lines and single human AC lung scaffolds. Using these surrogate cell populations, we identified cell number requirements, cell type and order of cell installations, flow rates and bioreactor management methods necessary for bioengineering whole lungs. Following the development of appropriate cell installation protocols, paediatric AC scaffolds were recellularized using primary lung alveolar epithelial cells (AECs), vascular cells and tracheal/bronchial cells isolated from discarded human adult lungs. Bioengineered paediatric lungs were shown to contain well-developed vascular, respiratory epithelial and lung tissue, with evidence of alveolar-capillary junction formation. Types I and II AECs were found thoughout the paediatric lungs. Furthermore, surfactant protein-C and -D and collagen I were produced in the bioengineered lungs, which resulted in normal lung compliance measurements. Although this is a first step in the process of developing tissues for transplantation, this study demonstrates the feasibility of producing bioengineered lungs for clinical use. Copyright © 2016 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/term.2113

  View details for PubMedID 26756722

• Nanotechnology toward Advancing Personalized Medicine HANDBOOK OF CLINICAL NANOMEDICINE: LAW, BUSINESS, REGULATION, SAFETY, AND RISK Sakamoto, J. H., Godin, B., Hu, Y., Blanco, E., van de Ven, A. L., Vellaichamy, A., Murphy, M. B., La Francesca, S., Schuenemeyer, T., Given, B., Meyn, A., Ferrari, M., Bawa, R., Audette, G. F., Reese, B. E. 2016; 2: 1347–1411

  View details for Web of Science ID 000468294400060

• Silencing of Tumor Necrosis Factor Receptor-1 in Human Lung Microvascular Endothelial Cells Using Particle Platforms for siRNA Delivery. Current drug targets Bai, L., Andersson, H. A., McConnell, K. I., Chan, D. L., Hernandez, M., Gonzalez, J., Liu, X., La Francesca, S., Sakamoto, J. H., Serda, R. E. 2015; 16 (13): 1531–39

  Abstract

  Acute lung injury (ALI) and its most severe manifestation, acute respiratory distress syndrome (ARDS), is a clinical syndrome defined by acute hypoxemic respiratory failure and bilateral pulmonary infiltrates consistent with edema. In-hospital mortality is 38.5% for AL, and 41.1% for ARDS. Activation of alveolar macrophages in the donor lung causes the release of pro-inflammatory chemokines and cytokines, such as TNF-α. To determine the relevance of TNF-α in disrupting bronchial endothelial cell function, we stimulated human THP-1 macrophages with lipopolysaccharide (LPS) and used the resulting cytokine-supplemented media to disrupt normal endothelial cell functions. Endothelial tube formation was disrupted in the presence of LPS-activated THP- 1 conditioned media, with reversal of the effect occurring in the presence of 0.1µg/ml Enbrel, indicating that TNF-α was the major serum component inhibiting endothelial tube formation. To facilitate lung conditioning, we tested liposomal and porous silicon (pSi) delivery systems for their ability to selectively silence TNFR1 using siRNA technology. Of the three types of liposomes tested, only cationic liposomes had substantial endothelial uptake, with human cells taking up 10-fold more liposomes than their pig counterparts; however, non-specific cellular activation prohibited their use as immunosuppressive agents. On the other hand, pSi microparticles enabled the accumulation of large amounts of siRNA in endothelial cells compared to standard transfection with Lipofectamine(®) LTX, in the absence of non-specific activation of endothelia. Silencing of TNFR1 decreased TNF-α mediated inhibition of endothelial tube formation, as well as TNF-α-induced upregulation of ICAM-1, VCAM, and E-selection in human lung microvascular endothelial cells.

  View details for DOI 10.2174/1389450115666140828105507

  View details for PubMedID 26201489

• Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles. Journal of controlled release : official journal of the Controlled Release Society McConnell, K. I., Rhudy, J., Yokoi, K., Gu, J., Mack, A., Suh, J., La Francesca, S., Sakamoto, J., Serda, R. E. 2014; 194: 113–21

  Abstract

  There is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticle-nanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells.

  View details for DOI 10.1016/j.jconrel.2014.08.020

  View details for PubMedID 25180449

  View details for PubMedCentralID PMC4254029

• Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study. Transplantation research La Francesca, S., Ting, A. E., Sakamoto, J., Rhudy, J., Bonenfant, N. R., Borg, Z. D., Cruz, F. F., Goodwin, M., Lehman, N. A., Taggart, J. M., Deans, R., Weiss, D. J. 2014; 3 (1): 19

  Abstract

  Primary graft dysfunction (PGD) is a significant cause of early morbidity and mortality following lung transplantation. Improved organ preservation techniques will decrease ischemia-reperfusion injury (IRI) contributing to PGD. Adult bone marrow-derived adherent stem cells, including mesenchymal stromal (stem) cells (MSCs) and multipotent adult progenitor cells (MAPCs), have potent anti-inflammatory actions, and we thus postulated that intratracheal MAPC administration during donor lung processing would decrease IRI. The goal of the study was therefore to determine if intratracheal MAPC instillation would decrease lung injury and inflammation in an ex vivo human lung explant model of prolonged cold storage and subsequent reperfusion.Four donor lungs not utilized for transplant underwent 8 h of cold storage (4°C). Following rewarming for approximately 30 min, non-HLA-matched allogeneic MAPCs (1 × 10(7) MAPCs/lung) were bronchoscopically instilled into the left lower lobe (LLL) and vehicle comparably instilled into the right lower lobe (RLL). The lungs were then perfused and mechanically ventilated for 4 h and subsequently assessed for histologic injury and for inflammatory markers in bronchoalveolar lavage fluid (BALF) and lung tissue.All LLLs consistently demonstrated a significant decrease in histologic and BALF inflammation compared to vehicle-treated RLLs.These initial pilot studies suggest that use of non-HLA-matched allogeneic MAPCs during donor lung processing can decrease markers of cold ischemia-induced lung injury.

  View details for DOI 10.1186/2047-1440-3-19

  View details for PubMedID 25671090

  View details for PubMedCentralID PMC4323223

• Production and assessment of decellularized pig and human lung scaffolds. Tissue engineering. Part A Nichols, J. E., Niles, J., Riddle, M., Vargas, G., Schilagard, T., Ma, L., Edward, K., La Francesca, S., Sakamoto, J., Vega, S., Ogadegbe, M., Mlcak, R., Deyo, D., Woodson, L., McQuitty, C., Lick, S., Beckles, D., Melo, E., Cortiella, J. 2013; 19 (17-18): 2045–62

  Abstract

  The authors have previously shown that acellular (AC) trachea-lung scaffolds can (1) be produced from natural rat lungs, (2) retain critical components of the extracellular matrix (ECM) such as collagen-1 and elastin, and (3) be used to produce lung tissue after recellularization with murine embryonic stem cells. The aim of this study was to produce large (porcine or human) AC lung scaffolds to determine the feasibility of producing scaffolds with potential clinical applicability. We report here the first attempt to produce AC pig or human trachea-lung scaffold. Using a combination of freezing and sodium dodecyl sulfate washes, pig trachea-lungs and human trachea-lungs were decellularized. Once decellularization was complete we evaluated the structural integrity of the AC lung scaffolds using bronchoscopy, multiphoton microscopy (MPM), assessment of the ECM utilizing immunocytochemistry and evaluation of mechanics through the use of pulmonary function tests (PFTs). Immunocytochemistry indicated that there was loss of collagen type IV and laminin in the AC lung scaffold, but retention of collagen-1, elastin, and fibronectin in some regions. MPM scoring was also used to examine the AC lung scaffold ECM structure and to evaluate the amount of collagen I in normal and AC lung. MPM was used to examine the physical arrangement of collagen-1 and elastin in the pleura, distal lung, lung borders, and trachea or bronchi. MPM and bronchoscopy of trachea and lung tissues showed that no cells or cell debris remained in the AC scaffolds. PFT measurements of the trachea-lungs showed no relevant differences in peak pressure, dynamic or static compliance, and a nonrestricted flow pattern in AC compared to normal lungs. Although there were changes in content of collagen I and elastin this did not affect the mechanics of lung function as evidenced by normal PFT values. When repopulated with a variety of stem or adult cells including human adult primary alveolar epithelial type II cells both pig and human AC scaffolds supported cell attachment and cell viability. Examination of scaffolds produced using a variety of detergents indicated that detergent choice influenced human immune response in terms of T cell activation and chemokine production.

  View details for DOI 10.1089/ten.TEA.2012.0250

  View details for PubMedID 23638920

  View details for PubMedCentralID PMC3725800

• Nanotechnology and stem cell therapy for cardiovascular diseases: potential applications. Methodist DeBakey cardiovascular journal La Francesca, S. 2012; 8 (1): 28–35

  Abstract

  The use of stem cell therapy for the treatment of cardiovascular diseases has generated significant interest in recent years. Limitations to the clinical application of this therapy center on issues of stem cell delivery, engraftment, and fate. Nanotechnology-based cell labeling and imaging techniques facilitate stem cell tracking and engraftment studies. Nanotechnology also brings exciting new opportunities to translational stem cell research as it enables the controlled engineering of nanoparticles and nanomaterials that can properly relate to the physical scale of cell-cell and cell-niche interactions. This review summarizes the most relevant potential applications of nanoscale technologies to the field of stem cell therapy for the treatment of cardiovascular diseases.

  View details for DOI 10.14797/mdcj-8-1-28

  View details for PubMedID 22891108

  View details for PubMedCentralID PMC3405790

• Selective and self-guided micro-ablation of tissue with plasmonic nanobubbles. The Journal of surgical research Lukianova-Hleb, E. Y., Koneva, I. I., Oginsky, A. O., La Francesca, S., Lapotko, D. O. 2011; 166 (1): e3–13

  Abstract

  The accuracy, selectivity, and safety of surgical and laser methods for tissue elimination are often limited at microscale.We developed a novel agent, the plasmonic nanobubble (PNB), for optically guided selective elimination of the target tissue with micrometer precision. PNBs were tested in vitro in the two different models of superficial tumors and vascular plaques.PNBs were selectively generated around gold nanoparticles (delivered to the target tissues) with short laser pulses. Monolayers of cancerous cells and atherosclerotic plaque tissue were eliminated with PNBs with micrometer accuracy and without thermal and mechanical damage to collateral normal tissues. The effect of the PNB was dynamically controlled through the fluence of laser pulses (532 nm, duration 0.5 and 10 ns) and was guided through the optical scattering by PNB.Plasmonic nanobubbles were shown to provide precise, tunable, selective, and guided ablation of tissue at a microscopic level and could be employed as a new generation of surgical tools.

  View details for DOI 10.1016/j.jss.2010.10.039

  View details for PubMedID 21176913

  View details for PubMedCentralID PMC3042052

• Experience of sternal secondary closure by means of a titanium fixation system after transverse thoracosternotomy. Artificial organs Motomura, T., Bruckner, B., La Francesca, S., Mittelhaus, S., Chike-Obi, C., Leon-Becerril, J., Ngo, U., Loebe, M. 2011; 35 (8): E168–73

  Abstract

  Sternal dehiscence is a common complication after transverse thoracosternotomy in patients undergoing bilateral sequential lung transplantation (BSLT). These patients can be treated with conservative therapy, but severe dehiscence requires surgical reapproximation and secondary closure of the sternum. Seventy-one cases of patients who underwent BSLT between January 2007 and May 2009 were reviewed retrospectively. Out of 71 patients, the sternum was intact in two cases due to the use of bilateral anterolateral thoracotomy, and a clamshell incision had been utilized in 69 patients. Four patients (6.8%) presented with persistent chest pain with severe sternal dehiscence diagnosed by chest X-ray and/or chest computed tomography, and underwent sternal reapproximation using the Synthes Titanium Sternal Fixation System for longitudinal sternal plating. All four patients had successful sternal realignment and resolution of their preoperative clinical symptoms. No perioperative or postoperative complications were observed. The Synthes Titanium Sternal Fixation System is an appropriate and effective method for internal fixation of the sternum when used for symptomatic severe sternal dehiscence after sequential BSLT via transverse thoracosternotomy.

  View details for DOI 10.1111/j.1525-1594.2011.01295.x

  View details for PubMedID 21790677

• Techniques and Complications of TandemHeart Ventricular Assist Device Insertion During Cardiac Procedures ASAIO JOURNAL Gregoric, I. D., Bruckner, B. A., Jacob, L., Loyalka, P., Kar, B., La Francesca, S., Myers, T., Frazier, O. H. 2009; 55 (3): 251–54

  Abstract

  Patients with heart failure and profound cardiogenic shock, who are unresponsive to vasopressors and intra-aortic balloon pump insertion, have few options except for mechanical cardiac support with a ventricular assist device. The TandemHeart is a new assist device that may be percutaneously or surgically inserted. We review techniques for percutaneous and intraoperative placement of the TandemHeart, including detailed descriptions of its insertion. Additionally, we present the most common complications associated with the percutaneous or operative approaches and suggest ways to avoid these complications. Whether placed percutaneously or surgically, the TandemHeart can provide adequate hemodynamic support for heart failure patients. If the device is placed by surgeons in the operating room, there must be strict adherence to protocols and de-airing techniques. Complications may occur with either insertion technique, so knowledge of the most common types of complications and their prevention is necessary.

  View details for DOI 10.1097/MAT.0b013e31819644b3

  View details for Web of Science ID 000265895100014

  View details for PubMedID 19357499

• Clinical Experience with the TandemHeart Percutaneous Ventricular Assist Device as a Bridge to Cardiac Transplantation TEXAS HEART INSTITUTE JOURNAL Bruckner, B. A., Jacob, L. P., Gregoric, I. D., Loyalka, P., Kar, B., Cohn, W. E., La Francesca, S., Radovancevic, B., Frazier, O. H. 2008; 35 (4): 447–50

  Abstract

  Cardiac support with a ventricular assist device is among the few treatments for heart-failure patients who have profound cardiogenic shock unresponsive to vasopressors and intra-aortic balloon pumps. The TandemHeart percutaneous ventricular assist device can provide temporary support until another device can be placed or a donor heart becomes available. We examined the TandemHeart's effect on cardiac index, central venous pressure, mixed venous oxygen saturation, creatinine, mean arterial pressure, urine output, and 30-day mortality rate in 5 heart-failure patients (2 with nonischemic and 3 with ischemic cardiomyopathy; mean preoperative left ventricular ejection fraction, 0.17 +/- 0.056). Two patients were undergoing cardiopulmonary resuscitation when the device was inserted. The average duration of TandemHeart support was 7.6 +/- 3.2 days; all patients were successfully bridged to transplantation. The TandemHeart improved the cardiac index (1.9 +/- 0.3 vs 3.5 +/- 0.8 L/[min.m2], P= 0.01), mean arterial pressure (69 +/- 12.5 vs 91 +/- 4.3 mmHg, P=0.009), mixed venous oxygen saturation (45.4 +/- 14.3 vs 71.4 +/- 7.5, P=0.009), and urine output (1,861 +/- 988 vs 4,314 +/- 1,346 mL/hr, P=0.01). The device decreased central venous pressure (21.2 +/- 7.4 vs 12.8 +/- 5.9 mmHg, P=0.02) and pressor requirements (2.4 +/- 1.1 vs 1.0 +/- 0.7 agents, P=0.02). Average long-term follow-up after heart transplantation was 8.4 +/- 9.9 months, with no deaths. We conclude that the TandemHeart can provide hemodynamic support for patients with profound, refractory cardiogenic shock. Furthermore, the device can bridge patients to cardiac transplantation and can be placed percutaneously, without invasive surgery.

  View details for Web of Science ID 000262188900014

  View details for PubMedID 19156239

  View details for PubMedCentralID PMC2607106

• Clinical experience with sternotomy versus subcostal approach for exchange of the HeartMate XVE to the HeartMate II ventricular assist device ANNALS OF THORACIC SURGERY Gregoric, I. D., Bruckner, B. A., Jacob, L., Kar, B., Cohn, W. E., La Francesca, S., Frazier, O. H. 2008; 85 (5): 1646–50

  Abstract

  Most patients undergoing destination therapy with a HeartMate XVE left ventricular assist device will eventually require pump exchange to continue long-term cardiac support.To determine whether left ventricular assist device exchange can be accomplished with low morbidity and mortality, we retrospectively reviewed the records of 14 patients who experienced pump malfunction and subsequently required replacement of their HeartMate XVE left ventricular assist devices with HeartMate II axial-flow pumps. We collected data regarding duration of support and reasons for pump failure, perioperative characteristics, and operative approach.On average, patients were supported 473 +/- 233 days with HeartMate XVE pumps. Seven early patients required both subcostal and sternotomy incisions; 7 later patients had subcostal incisions only. Thirteen patients underwent successful exchange to the HeartMate II; 1 patient died in the operating room. Another patient died in the perioperative period (30-day mortality, 14% [2 of 14]). There were significant differences between the two groups. The patients who required only subcostal incisions had shorter operative times (187 versus 220 minutes; p = 0.04) and required fewer transfused blood products (packed red blood cells, 8.6 versus 28.7 units; p = 0.03; and fresh-frozen plasma, 12.4 versus 30.9 units; p = 0.04). Additionally, the patients with subcostal incisions had shorter postoperative intensive care unit stays (5.3 +/- 1.1 versus 8.4 +/- 3.1 days for redo sternotomy patients; p = 0.03). Of the survivors, average hospital stay was 22 +/- 14 days. Average long-term follow-up was 11.2 +/- 7.8 months; 71% (10 of 14) of patients are currently alive.Exchange of a HeartMate XVE to a HeartMate II can be accomplished with relatively low morbidity and mortality through a subcostal approach.

  View details for DOI 10.1016/j.athoracsur.2008.01.020

  View details for Web of Science ID 000255319900021

  View details for PubMedID 18442556

• A less invasive approach to axial flow pump insertion JOURNAL OF HEART AND LUNG TRANSPLANTATION Gregoric, I. D., La Francesca, S., Myers, T., Cohn, W., Loyalka, P., Kar, B., Gemmato, C., Frazier, O. H. 2008; 27 (4): 423–26

  Abstract

  Implantation of a HeartMate II or a Jarvik 2000 FlowMaker left ventricular assist system (LVAS) usually involves a mid-line sternotomy and the use of cardiopulmonary bypass (CPB). In patients with numerous co-morbid conditions, however, surgical trauma may be minimized by implanting the LVAS via a minimally invasive approach, preferably without CPB.In 6 patients with end-stage heart failure and other serious co-morbidities, we implanted a HeartMate II (n = 3) or a Jarvik 2000 FlowMaker (n = 3) LVAS via a right mini-thoracotomy and a left sub-costal incision. Patients included 3 men and 3 women with a mean age of 41 years. In 3 cases, the LVAS was implanted without CPB.After a mean follow-up period of 6 months, 5 patients are alive and well and on the transplant waiting list. Seven months after LVAS implantation, the remaining patient developed a hemorrhagic stroke necessitating Jarvik 2000 replacement with a new pump of the same type.In this small series, the combined sub-costal and mini-thoracotomy incision proved safe and technically feasible. It may be useful for other LVAS candidates who have serious co-morbidities that preclude traditional implant operations.

  View details for DOI 10.1016/j.healun.2008.01.002

  View details for Web of Science ID 000254799800010

  View details for PubMedID 18374879

• CentriMag left ventricular assist system - Cannulation through a bight minithoracotomy TEXAS HEART INSTITUTE JOURNAL Gregoric, I. D., Cohn, W. E., Akay, M. H., La Francesca, S., Myers, T., Frazier, O. H. 2008; 35 (2): 184–85

  Abstract

  The CentriMag left ventricular assist system can be used for perioperative or postcardiotomy circulatory support of the failing heart. The device resides at the patient's bedside, and the cannulae are usually inserted through a midline sternotomy, with the inflow cannula in the left ventricle or right superior pulmonary vein and the outflow cannula in the aorta. In a patient whose chest has been closed and who has a delayed need for temporary mechanical support, a less invasive method of left ventricular assist device cannula insertion is preferred. In these cases, the CentriMag cannulae can be inserted through a right minithoracotomy with the inflow cannula in the right superior pulmonary vein and the outflow cannula in the aorta, with no heparinization. Herein, we describe this approach in a patient who experienced postcardiotomy cardiogenic shock after aortocoronary bypass surgery. This technique may facilitate ambulation and recovery in selected patients.

  View details for Web of Science ID 000257097700016

  View details for PubMedID 18612493

  View details for PubMedCentralID PMC2435439

• The TandemHeart as a bridge to a long-term axial-flow loft ventriculair assist device (Bridge to Bridge) TEXAS HEART INSTITUTE JOURNAL Gregoric, I. D., Jacob, L. P., La Francesca, S., Bruckner, B. A., Cohn, W. E., Loyalka, P., Kar, B., Frazier, O. H. 2008; 35 (2): 125–29

  Abstract

  End-stage heart-failure patients in acute refractory cardiogenic shock with multi-organ dysfunction require aggressive medical therapy that includes inotropic support. Historically, the intra-aortic balloon pump was the last option for patients who were dying of acute cardiogenic shock. Short-term extracorporeal pulsatile or nonpulsatile cardiac assist devices or extracorporeal membrane oxygenation offered further treatment options; however, these therapies required invasive surgical procedures. Patients in this high-risk group had increased mortality rates from major procedures that required cardiopulmonary bypass. We used the TandemHeart, a percutaneously implanted device for short-term cardiac assistance, to lower the risk of death and improve hemodynamic performance and end-organ perfusion before implanting long-term assist devices in selected patients with signs of profound cardiogenic shock. Nine end-stage heart-failure patients (mean age, 37.7 yr) in acute refractory hemodynamic decompensation received a percutaneously implanted TandemHeart pump as a bridge to an implantable axial-flow pump. To determine the relative risk for these patients, prognostic scores were calculated before and after insertion of the TandemHeart. Percutaneous support times ranged from 1 to 22 days (mean, 5.9 d). The mean cardiac index before support, 1.02 L/(min.m2) (range, 0.0-1.8 L/[min.m2]) (0.0 L/[min.m2] implies active cardiopulmonary resuscitation), improved to 2.97 L/(min.m2) (range, 2.2-4.0 L/[min.m2]) during support. Three patients underwent successful cardiac transplantation; 5 are currently supported by axial-flow pumps; and 1 died of complications unrelated to the axial-flow pump, after 587 days. End-organ function and overall condition improved uniformly in our patients, thus decreasing the preoperative risk factors for implantation of the long-term device.

  View details for Web of Science ID 000257097700006

  View details for PubMedID 18612448

  View details for PubMedCentralID PMC2435454

• High cardiac output due to fistula after cardiac transplantation. Congestive heart failure (Greenwich, Conn.) Palanichamy, N., Letsou, G. V., Cohn, W., La Francesca, S., Kar, B., Gregoric, I. D. 2007; 13 (4): 237–39

  View details for DOI 10.1111/j.1527-5299.2007.06571.x

  View details for PubMedID 17673877

• Successful resection of a primary left ventricular schwannoma ANNALS OF THORACIC SURGERY La Francesca, S., Gregoric, I. D., Cohn, W. E., Frazier, O. H. 2007; 83 (5): 1881–82

  Abstract

  Nerve sheath neoplasm of the heart is rare. We report the case of a patient with a giant schwannoma of unique ventricular origin. Resection of the schwannoma and subsequent coronary reconstruction were required.

  View details for DOI 10.1016/j.athoracsur.2006.12.012

  View details for Web of Science ID 000245975700051

  View details for PubMedID 17462424

• Bedside right ventricular assist device removal in the conscious patient ANNALS OF THORACIC SURGERY Cohn, W. E., Gregoric, I. D., La Francesca, S., Frazier, O. H. 2007; 83 (4): 1556–57

  Abstract

  A technique is described for simple bedside removal of a right ventricular assist device system from a conscious patient. This technique allows weaning from the support of the right ventricular assist device without the confounding hemodynamic challenges of positive pressure ventilation and sternal closure.

  View details for DOI 10.1016/j.athoracsur.2005.06.044

  View details for Web of Science ID 000245178900063

  View details for PubMedID 17383390

• Simultaneous insertion of a left ventricular assist system and repair of an ascending aortic dissection TEXAS HEART INSTITUTE JOURNAL Gregoric, I. D., Palanichamy, N., La Francesca, S., Smith, R. D., Myers, T. J. 2007; 34 (4): 463–65

  Abstract

  Operative methods for repairing ascending aortic dissections and for implanting left ventricular assist systems have been thoroughly presented in the medical literature. Only a few reports, however, describe the concomitant performance of these procedures in 1 patient. We report the repair of an acute ascending aortic dissection with simultaneous placement of a long-term left ventricular assist system. One week earlier, the patient had undergone emergent coronary artery bypass grafting and short-term postcardiotomy ventricular assistance when he could not be weaned from cardiopulmonary bypass. By creating a graft-to-graft anastomosis on the bench during cooling of the patient on cardiopulmonary bypass, we were able to shorten to 21 minutes the period of hypothermic circulatory arrest required during ascending aortic dissection repair. The procedures were completed successfully. However, the patient developed pneumonia and sepsis during his extended hospital stay and died of multiorgan failure 5 weeks postoperatively.

  View details for Web of Science ID 000251694400018

  View details for PubMedID 18172532

  View details for PubMedCentralID PMC2170509

• Management of multiple left ventricular assist device failures in a patient JOURNAL OF HEART AND LUNG TRANSPLANTATION Myers, T. J., Palanichamy, N., La Francesca, S., Odegaard, P. A., Gregoric, I. D., Frazier, O. H. 2007; 26 (1): 98–100

  Abstract

  Device failure is a rare but life-threatening complication in patients receiving mechanical circulatory support. Because patients are supported by these devices for longer periods, the incidence of device failure has increased. We report 3 instances of device failure and successful surgical management in a single patient.

  View details for DOI 10.1016/j.healun.2006.10.009

  View details for Web of Science ID 000243950900016

  View details for PubMedID 17234525

• Management of air embolism during HeartMate (R) XVE exchange TEXAS HEART INSTITUTE JOURNAL Gregoric, I. D., Myers, T. J., Kar, B., Loyalka, P., Reverdin, S., La Francesca, S., Odegaard, P., Gemmato, C. J., Frazier, O. H. 2007; 34 (1): 19–22

  Abstract

  Air embolism is a rare and usually fatal complication of major cardiac surgery. We present a case in which a 45-year-old man supported by a HeartMate(R) XVE left ventricular assist device required a pump exchange due to failure of the device motor. During pump dissection, a massive amount of air entered the systemic circulation. Urgent cannulation for cardiopulmonary bypass was performed, and cardiopulmonary bypass was initiated, followed by profound hypothermia, circulatory arrest, retrograde cerebral perfusion, retrograde coronary sinus perfusion, and then barbiturate coma and steroid therapy. The HeartMate XVE left ventricular assist device was removed, and a HeartMate II was implanted. After 5 days, the patient awoke with left hemiparesis, which nearly resolved with aggressive physical therapy. Forty-four days after the pump exchange operation, the patient was discharged from the hospital with only mild left hemiparesis. Exposure of the left ventricular assist device or its external components requires careful monitoring, because air can enter the pump-particularly in a hypovolemic patient. Rapid response after massive air entry into the left ventricular assist device system, as in our patient, can result in a successful outcome.

  View details for Web of Science ID 000245344000006

  View details for PubMedID 17420788

  View details for PubMedCentralID PMC1847928

• Replacement of a malfunctioning HeartMate II left ventricular assist device in a 14-year-old after a sudden fall JOURNAL OF HEART AND LUNG TRANSPLANTATION La Francesca, S., Smith, R., Gregoric, I. D., Kar, B., Myers, T. J., Price, J., Kennedy, D., Frazier, O. H. 2006; 25 (7): 862–64

  Abstract

  An increasing number of patients are returning to normal activity after implantation of intracorporeal left ventricular assist devices. We describe the emergency replacement of the impeller portion of a HeartMate II left ventricular assist system that had stopped functioning after the 14-year-old recipient experienced a sudden fall from a skateboard.

  View details for DOI 10.1016/j.healun.2006.03.012

  View details for Web of Science ID 000239019700017

  View details for PubMedID 16818132

• Mycotic pseudo-aneurysm of the ascending thoracic aorta after cardiac transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Palanichamy, N., Gregoric, I. D., La Francesca, S., Smart, F. W. 2006; 25 (6): 730–33

  Abstract

  A large mycotic pseudo-aneurysm of the ascending thoracic aorta was found in a patient with empyema and infectious mediastinitis after an orthotopic heart transplant procedure. The patient underwent surgical resection of the pseudo-aneurysm with patch aortoplasty and was treated with appropriate long-term antibiotic therapy. The patient continues to do well 3 months after surgery. Early surgical intervention combined with pre-operative and prolonged post-operative antibiotic therapy and close follow-up is essential in these patients.

  View details for DOI 10.1016/j.healun.2006.02.009

  View details for Web of Science ID 000238195800016

  View details for PubMedID 16730580

• First use of the TandemHeart (R) percutaneous left vientricular assist device as a short-term bridge to cardiac transplantation TEXAS HEART INSTITUTE JOURNAL La Francesca, S., Palanichamy, N., Kar, B., Gregoric, I. D. 2006; 33 (4): 490–91

  Abstract

  Advanced heart failure may be refractory despite aggressive support with inotropic agents and intra-aortic balloon pumping. Implantable left ventricular assist devices are increasingly being used as bridges to cardiac transplantation or as destination therapy because of the limited availability of donor organs. We report the 1st use of the TandemHeart percutaneous ventricular assist device as a short-term bridge to cardiac transplantation.

  View details for Web of Science ID 000243097800017

  View details for PubMedID 17215977

  View details for PubMedCentralID PMC1764955

• Percutaneous tracheostomy after mechanical ventricular assist device implantation JOURNAL OF HEART AND LUNG TRANSPLANTATION Gregoric, I. D., Harting, M. T., Kosir, R., Patel, V. S., Ksela, J., Messner, G. N., La Francesca, S., Frazier, O. H. 2005; 24 (10): 1513–16

  Abstract

  Several studies have shown that percutaneous dilational tracheostomy (PDT) is safe and cost-effective for patients recovering from surgery that requires a median sternotomy. We report our experience with PDT in patients receiving mechanical cardiac assistance.We reviewed the medical records of all patients who underwent ventricular assist device implantation at our institution between July 2000 and July 2003, and who subsequently required long-term ventilatory support during the same hospital admission. Data obtained from the records included demographic and biometric information, primary diagnosis, early (< or =30days) and late (>30days) complications, date and cause of death, type of anti-coagulation used at the time of tracheostomy, and various coagulation measures.Thirty-one consecutive patients (29 men, 2 women; mean age, 56 years) had PDT after ventricular assist device implantation. Four minor complications occurred among 3 of the patients (10%), including 3 early complications (2 peristomal oozing and 1 peristomal cellulitis) and 1 late complication (recurrent peristomal cellulitis), none of which affected long-term outcome. No major adverse events, long-term complications, or deaths resulted from the PDT procedure.PDT is feasible for patients with mechanical support devices who require long-term ventilatory support. Although some of these patients are coagulopathic, our results indicate that PDT is safe and effective in this challenging patient population.

  View details for DOI 10.1016/j.healun.2004.12.109

  View details for Web of Science ID 000232506500009

  View details for PubMedID 16210123

• Left ventricular assist device implantation - in a patient with congenitally corrected transposition of the great arteries TEXAS HEART INSTITUTE JOURNAL Gregoric, I. D., Kosir, R., Smart, F. W., Messner, G. N., Patel, V. S., La Francesca, S., Cervera, R. D., Frazier, O. H. 2005; 32 (4): 567–69

  Abstract

  Congenitally corrected transposition of the great arteries (ccTGA) is a rare anomaly characterized by atrioventricular and ventriculo-arterial discordance and several other malformations that eventually lead to heart failure. We describe the case of a 53-year-old woman with ccTGA and aortic insufficiency who was a candidate for heart transplantation due to end-stage congestive heart failure. Her condition deteriorated before a suitable donor heart could be found; therefore, we placed a left ventricular assist device in the right (systemic) ventricle. Concomitantly, we removed the aortic (systemic) valve, closed the aortic annulus with a bovine pericardial patch, and repaired the mitral valve. The patient recovered uneventfully and was discharged from the hospital 2 months postoperatively. She underwent cardiac transplantation approximately 6 months later and continued to do well after 18 months.

  View details for Web of Science ID 000234318700020

  View details for PubMedID 16429905

  View details for PubMedCentralID PMC1351832

• Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Monti, F., Iwashiro, K., Picard, S., Criniti, A., La Francesca, S., Ruvolo, G., Papalia, U., Campa, P. P., Marino, B., Puddu, P. E. 2000; 119 (4): 842–48

  Abstract

  Although adenosine triphosphate-dependent potassium channel openers have been shown to enhance cardioplegic protection in animal myocardium, there is a lack of data on human cardiac tissues. We aimed at determining, on human atrial muscle, whether adenosine triphosphate- dependent potassium channels are involved in protection caused by high-potassium cardioplegia and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial stunning.Human atrial trabeculae were obtained from adult patients undergoing cardiac operations. In an organ bath at 37 degrees C, the preparations were subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control, n = 17) or in St Thomas' Hospital solution without additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 micromol/L glibenclamide (n = 7), followed by 60 minutes of reoxygenation and 15 minutes of positive inotropic stimulation with 1 micromol/L dobutamine.Atrial developed tension was reduced by hypoxia to 27% +/- 5% of baseline and incompletely recovered after reoxygenation to 38% +/- 7%, whereas dobutamine restored contractility to 74% +/- 7% of basal values. St Thomas' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P <.0001 vs control), whereas glibenclamide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle length) but recovered during dobutamine superfusion.Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial trabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to cardioplegia enhanced protection.

  View details for DOI 10.1016/S0022-5223(00)70022-5

  View details for Web of Science ID 000086530600033

  View details for PubMedID 10733778

• Effects of bimakalim on human cardiac action potentials: Comparison with guinea pig and nicorandil and use-dependent study JOURNAL OF CARDIOVASCULAR PHARMACOLOGY Rouet, R., Picard, S., Criniti, A., Monti, F., Dawodu, A. A., Ruvolo, G., La Francesca, S., Macrina, F., Tonelli, E., Ducouret, P., Puddu, P. E. 1999; 33 (2): 255–63

  Abstract

  Electrophysiologic effects of K(ATP) channel openers (KCOs) are rarely studied for tissue and species specificity, and use-dependent investigations in human tissues are lacking. We therefore investigated in vitro the concentration-dependent effects of the KCO bimakalim [from 10 nM to 10 microM, at 1,000 ms of cycle length (CL) and 37 degrees C] on human (atrium, n = 4, and ventricle, n = 6) and guinea pig (atrium, n = 7, and ventricle, n = 6) transmembrane action potential (AP). The frequency relation (from CL 1,600 to 300 ms, 31 degrees C) of human atrial AP duration 90% (APD90) shortening (10 microM vs. baseline, n = 7) also was determined. A parallel study was performed with the KCO nicorandil (from 10 nM to 1 mM, n = 3) in human atrial APs, at 31 degrees C. Resting membrane potential and maximal upstroke velocity of AP were not modified by bimakalim at maximal concentration, whereas AP amplitude was decreased in both guinea pig preparations (p < 0.05); APD90 was shortened in all tissues (p < 0.01). Median effective concentration (EC50) for APD90 shortening at 37 degrees C was 0.54 and 2.74 microM in atrial and ventricular human tissue, respectively, and 8.55 and 0.89 microM in atrial and ventricular guinea pig tissue, respectively. In human atrial tissue at 31 degrees C, EC50 with bimakalim was 0.39 microM; a much higher value was seen with nicorandil (210 microM). Bimakalim (10 microM)-induced APD90 shortening as a function of stimulation rate was greatest at longest CL. Evidence is provided for (a) species (human vs. guinea pig) and tissue (atrium vs. ventricle) differential AP sensitivity to bimakalim; (b) an approximately 500-fold higher efficacy of bimakalim versus nicorandil to shorten human atrial APD90; and (c) normal use-dependence of human atrial APD90 shortening with bimakalim at 10 microM.

  View details for DOI 10.1097/00005344-199902000-00012

  View details for Web of Science ID 000078466300012

  View details for PubMedID 10028934

• CONCOMITANT CARDIAC AND PULMONARY OPERATIONS FOR LUNG-CANCER TEXAS HEART INSTITUTE JOURNAL LAFRANCESCA, S., FRAZIER, O. H., RADOVANCEVIC, B., DECARO, L. F., REUL, G. J., COOLEY, D. A. 1995; 22 (4): 296–300

  Abstract

  From 1973 through 1990, 21 patients (17 men and 4 women) underwent concomitant cardiac operation and pulmonary resection for lung cancer. The mean age was 65.3 years (range, 50 to 80 years). Eighteen patients underwent coronary artery bypass; 1 underwent coronary bypass and mitral valve replacement; 1, aortic valve replacement; and 1, left ventricular aneurysmectomy. Pulmonary procedures included 16 lobectomies, 3 segmentectomies, and 2 wedge resections. Nine resections were performed during cardiopulmonary bypass, and 12 were performed either before or after bypass. On final pathologic diagnosis, 11 patients had adenocarcinoma, 7 had squamous cell carcinoma, and 3 had undifferentiated lesions. Twelve patients were in cancer stage 1 and 9 were in stage II. Placement of an intraaortic balloon pump was required in 3 patients. No patient sustained excessive blood loss requiring reoperation. Only 2 incidents (9.5%) of disseminated infection were reported. The overall 1-year survival rate was 90.5% and the 5-year survival rate was 52.4%. We found concomitant cardiac operation and pulmonary resection for lung cancer to be a safe and effective alternative to staged treatment in patients not requiring a pneumonectomy. Combined cardiac and pulmonary surgery spares the patient the risk and cost of a 2nd major surgical procedure without compromising long-term survival.

  View details for Web of Science ID A1995TH90200003

  View details for PubMedID 8605428

  View details for PubMedCentralID PMC325276