Kyung Jong Yoo

Small-diameter blood vessels engineered with bone marrow-derived cells

Objective:The objective of this study is to investigate if bone marrow–derived cells (BMCs) regenerate vascular tissues and improve patency in tissue-engineered small-diameter (internal diameter = 3 mm) vascular grafts. Summary Background Data:BMCs have demonstrated the ability to differentiate into endothelial-like cells and vascular smooth muscle–like cells and may offer an alternative cell source for vascular tissue engineering. Thus, we tissue-engineered small-diameter vascular grafts with BMCs and decellularized arteries. Methods:Canine BMCs were differentiated in vitro into smooth muscle α-actin/smooth muscle myosin heavy-chain-positive cells and von Willebrand factor/CD31-positive cells and seeded onto decellularized canine carotid arteries (internal diameter = 3 mm). The seeded grafts were implanted in cell donor dogs. The vascular-tissue regeneration and graft patency were investigated with immunohistochemistry and angiography, respectively. Results:The vascular grafts seeded with BMCs remained patent for up to 8 weeks in the canine carotid artery interposition model, whereas nonseeded grafts occluded within 2 weeks. Within 8 weeks after implantation, the vascular grafts showed regeneration of the 3 elements of artery (endothelium, media, and adventitia). BMCs labeled with a fluorescent dye prior to implantation were detected in the retrieved vascular grafts, indicating that the BMCs participated in the vascular tissue regeneration. Conclusions:Here we show that BMCs have the potential to regenerate vascular tissues and improve patency in tissue-engineered small-diameter vascular grafts. This is the first report of a small-diameter neovessel engineered with BMCs as a cell source.

Evidence for In Vivo Growth Potential and Vascular Remodeling of Tissue-Engineered Artery

Nondegradable synthetic polymer vascular grafts currently used in cardiovascular surgery have no growth potential. Tissue-engineered vascular grafts (TEVGs) may solve this problem. In this study, we developed a TEVG using autologous bone marrow-derived cells (BMCs) and decellularized tissue matrices, and tested whether the TEVGs exhibit growth potential and vascular remodeling in vivo. Vascular smooth muscle-like cells and endothelial-like cells were differentiated from bone marrow mononuclear cells in vitro. TEVGs were fabricated by seeding these cells onto decellularized porcine abdominal aortas and implanted into the abdominal aortas of 4-month-old, bone marrow donor pigs (n = 4). Eighteen weeks after implantation, the dimensions of TEVGs were measured and compared with those of native abdominal aortas. Expression of molecules associated with vascular remodeling was examined with reverse transcription-polymerase chain reaction assay and immunohistochemistry. Eighteen weeks after implantation, all TEVGs were patent with no sign of thrombus formation, dilatation, or stenosis. Histological and immunohistochemical analyses of the retrieved TEVGs revealed regeneration of endothelium and smooth muscle and the presence of collagen and elastin. The outer diameter of three of the four TEVGs increased in proportion to increases in body weight and outer native aorta diameter. Considerable extents of expression of molecules associated with extracellular matrix (ECM) degradation (i.e., matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase) and ECM precursors (i.e., procollagen I, procollagen III, and tropoelastin) occurred in the TEVGs, indicating vascular remodeling associated with degradation of exogenous ECMs (implanted decellularized matrices) and synthesis of autologous ECMs. This study demonstrates that the TEVGs with autologous BMCs and decellularized tissue matrices exhibit growth potential and vascular remodeling in vivo of tissue-engineered artery.

Combined therapy with human cord blood cell transplantation and basic fibroblast growth factor delivery for treatment of myocardial infarction.

Transplanting cord blood‐derived cells has been shown to augment neovascularization in ischaemic tissue.

Therapeutic effects of late outgrowth endothelial progenitor cells or mesenchymal stem cells derived from human umbilical cord blood on infarct repair

BACKGROUNDnThis study sought to systematically investigate the derivation of late outgrowth endothelial progenitor cells (late EPC) and mesenchymal stem cells (MSC) from umbilical cord blood (UCB) and to examine their therapeutic effects on myocardial infarction (MI).nnnMETHODSnThe expression of angiogenic genes was determined by qRT-PCR. Myocardial infarction (MI) was induced in rats, and cells were directly transplanted into the border regions of ischemic heart tissue.nnnRESULTSnCulture of UCB mononuclear cells yielded two distinct types of cells by morphology after 2 weeks in the same culture conditions. These cells were identified as late EPC and MSC, and each was intramyocardially injected into rat hearts after induction of MI. Echocardiography and histologic analyses demonstrated that both EPC and MSC improved cardiac function and enhanced vascularization, although fibrosis was reduced only in the EPC transplanted hearts. Different paracrine factors were enriched in EPC and MSC. However, once injected into the hearts, they induced similar types of paracrine factors in the heart. Transplanted EPC or MSC were mostly localized at the perivascular areas. This study demonstrated that EPC and MSC can be simultaneously derived from UCB under the same initial culture conditions, and that common paracrine factors are involved in the repair of MI.nnnCONCLUSIONnLate EPC and MSC are effective for infarct repair, apparently mediated through common humoral mechanisms.

Impact of intraoperative hyperglycaemia on renal dysfunction after off-pump coronary artery bypass

OBJECTIVESnAcute kidney injury (AKI) is one of the most frequently occurring complications after off-pump coronary artery bypass graft (OPCAB). Hyperglycaemia is a major, potentially modifiable risk factor of adverse outcome after cardiac surgery known to aggravate organ damage. The aim of this study was to address the association between intraoperative glucose concentration and postoperative AKI in patients who underwent OPCAB.nnnMETHODSnThe medical records of 880 consecutive patients were retrospectively reviewed. Patients were divided into three groups according to the time-weighted average of intraoperative glucose concentrations (<110, 110-150 and >150 mg/dl), and the incidence of AKI (increase of serum creatinine to >2.0 mg/dl and 2 × most recent preoperative value or a new requirement for dialysis) was compared. Multivariate logistic regression analysis was performed to identify independent risk factors for postoperative AKI.nnnRESULTSnThe incidence of AKI was higher in patients with a glucose level >150 mg/dl than in patients with a glucose level = 110-150 mg/dl [8% (20 of 251) vs 3% (14 of 453), P = 0.004]. On multivariate analysis, glucose >150 mg/dl (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.12-6.86, P = 0.027), coefficient of variation of glucose (OR, 1.04; 95% CI, 1.01-1.07, P = 0.027) and preoperative serum creatinine >1.4 mg/dl (OR, 8.81; 95% CI, 3.90-19.9, P < 0.001) were identified as independent risk factors for postoperative AKI.nnnCONCLUSIONSnIntraoperative glucose concentration >150 mg/dl and increased variability of glucose were independently associated with AKI after OPCAB. Tight intraoperative glycaemic control (<110 mg/dl) does not seem to provide additional benefit in terms of AKI.

Carbon dioxide embolism induced right coronary artery ischaemia during off-pump obtuse marginalis artery grafting

Although use of carbon dioxide (CO2) blower has been regarded safe during off-pump coronary bypass surgery (OPCAB), we experienced a case of right coronary artery ischaemia induced by retrograde CO2 embolism originating from the opened obtuse marginalis artery during OPCAB. The spray pressure can exceed the diastolic pressure, especially during grafting at the lateral or posterior wall when haemodynamic compromise due to mechanical heart displacement is most severe. In this situation, CO2 blowing at an incompletely slinged coronary arteriotomy site can result in retrograde migration of CO2 into the ascending aorta causing coronary embolism of the right coronary artery. When signs of ischaemia on the right coronary artery are encountered during grafting of other coronary artery, although CO2 blower has been used, gas embolism should also be considered as the cause and identified at the mid-oesophageal aortic valve long-axis view. When confirmed, the use of gas blower should immediately be discontinued and coronary perfusion pressure increased while allowing time for the CO2 to be absorbed. In case of massive embolism, needle aspiration of the gas should also be considered.

The incidence and clinical outcome of constrictive physiology after coronary artery bypass graft surgery.

To the Editor:nnPrevious reports have shown changes in the etiologic spectrum of constrictive pericarditis, characterized mainly by a declining incidence of tuberculous pericarditis and an increase in cases resulting from cardiac surgery ([1][1]). Constrictive physiology (CP) not only is found in

Outcome of veno-venous extracorporeal membrane oxygenation use in acute respiratory distress syndrome after cardiac surgery with cardiopulmonary bypass.

BACKGROUNDnCardiac surgery with cardiopulmonary bypass (CPB) is a known risk factor for acute respiratory distress syndrome (ARDS). We aimed to analyze the treatment outcome in patients who required veno-venous extracorporeal membrane oxygenation (VV-ECMO) for postcardiotomy ARDS despite other rescue modalities.nnnMETHODSnWe retrospectively reviewed the outcomes in 13 patients (mean age, 54.7±5.9 years) who received VV-ECMO support for refractory ARDS after cardiac surgery between March 2013 and February 2016 at Severance Hospital, Yonsei University (Seoul, Korea).nnnRESULTSnAt the start of VV-ECMO, the average lung injury score was 3.0±0.2, and the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score was -4±1.1. Although 7 patients initiated VV-ECMO support within 24 h from operation, the remaining 6 started at a median of 8.5 days (range, 5-16 days). Nine (69.3%) patients were successfully weaned from VV-ECMO. After a median follow-up duration of 14.5 months (range, 1.0-33.0 months) for survivors, the 1-year overall survival was 58.6%±14.4%. The differences in the overall survival from VV-ECMO according to the RESP score risk classes were borderline significant (100% in class III, 50%±25% in class IV, and 20%±17.9% in class V; P=0.088).nnnCONCLUSIONSnVV-ECMO support can be a feasible rescue strategy for adult patients who develop refractory ARDS after a cardiac surgery. Additionally, the RESP score seems a valuable prognostic tool for post-ECMO survival outcome in this patient population as well.