Yunya Wang

Induction of Angiogenesis by Controlled Delivery of Vascular Endothelial Growth Factor Using Nanoparticles

AIMS The study reports the feasibility and efficiency of vascular endothelial growth factor (VEGF) delivery using nanoparticles synthesized from glycidyl methacrylated dextran (Dex-GMA) and gelatin for therapeutic angiogenesis. METHODS The nanoparticles were prepared using phase separation method, and the drug release profile was determined by ELISA study. The bioactivity of VEGF-incorporated nanoparticles (VEGF-NPs) were determined using tube formation assay. A rabbit hind limb ischemia model was employed to evaluate the in vivo therapeutic effect. Blood perfusion was measured by single-photon emission computed tomography (SPECT). Vessel formation was evaluated by contrast angiography and immunohistochemistry. RESULTS The nanoparticles synthesized were spherical in shape with evenly distributed size of about 130 ± 3.5 nm. The VEGF encapsulated was released in a biphase manner, with the majority of 69% released over 1-12 days. Tube formation assays showed increased tubular structures by VEGF-NP compared with empty nanoparticles and no treatment. Both free VEGF and VEGF-NP significantly increased blood perfusion compared with empty nanoparticles (both P < 0.001), but it was much higher in VEGF-NP-treated limbs (P < 0.001). Contrast angiography and immunohistological analysis also revealed more significant collateral artery formation and higher capillary density in VEGF-NP-treated limbs. CONCLUSIONS Dex-GMA and gelatin-based nanoparticles could provide sustained release of VEGF and may serve as a new way for angiogenesis.

Effects of insulin therapy on inflammatory mediators in infants undergoing cardiac surgery with cardiopulmonary bypass

To determine whether insulin administration modulates the systemic inflammatory response in infants undergoing cardiac surgery with cardiopulmonary bypass, 60 infants undergoing cardiopulmonary bypass were randomly assigned into a routine therapy group or to an intensive insulin therapy group with 30 infants in each group. Plasma IL-1beta, IL-6, IL-10, and TNF-alpha levels were determined before anesthesia, at the initiation of cardiopulmonary bypass, and at 0, 6, 12, 24, and 48 h after cardiopulmonary bypass. Nuclear factor-kappaBp65 expression and IkappaB expression in peripheral blood mononuclear cells were also measured by Western blot analysis. TNF-alpha, IL-1beta, IL-6, and IL-10 levels were all elevated after the initiation of cardiopulmonary bypass. However, TNF-alpha, IL-1beta, and IL-6 levels were significantly attenuated in the intensive insulin therapy group compared to those in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Meanwhile, plasma IL-10 levels were significantly higher in the intensive insulin therapy group than in the routine therapy group after initiation of cardiopulmonary bypass (p<0.05 or <0.01). Accordingly, Nuclear factor-kappaBp65 expression and IkappaB expression were significantly increased after initiation of cardiopulmonary bypass in both groups (p<0.05 or <0.01). The expression of Nuclear factor-kappaBp65, which induces the transcription of pro-inflammatory cytokines was significantly attenuated in the intensive insulin therapy group (p<0.05 or <0.01). Meanwhile, the expression of IkappaB, an inhibitor of NF-kappaB, was significantly higher in the intensive insulin therapy group (p<0.05 or <0.01). These results suggested that intensive insulin therapy may attenuate the systemic inflammatory response in infants undergoing cardiopulmonary bypass.

No infection with porcine endogenous retrovirus in recipients of acellular porcine aortic valves: a two-year study

Abstract:  Background:  Engineered tissue heart valves may become a promising therapeutics for heart valve disease. Compared with synthetic materials, acellular porcine scaffolds are considered as suitable matrices for tissue‐engineered heart valves for the mechanical and structural properties of native tissue. Whether acellular porcine scaffolds can cause infection in recipients with porcine endogenous retrovirus (PERV) is critical for evaluating the safety of transplantation of tissue‐engineered heart valves based on acellular porcine scaffolds. This study was completed to evaluate the risk of PERV transmission for application of acellular porcine aortic valves (PAVs).

Impacts of intensive insulin therapy in patients undergoing heart valve replacement.

BACKGROUND AND AIMS Cardiac surgery with cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) is associated with severe stress response, systemic inflammatory response, and injury. This study was designed to investigate the effects of intensive insulin therapy on patients undergoing valve replacement with CPB. METHODS One hundred nondiabetic inpatients undergoing valve replacement were randomly assigned to a control group or an intensive insulin therapy (IT) group. Plasma cytokine and cardiac troponin I (cTnI) levels were monitored perioperatively. RESULTS Compared with the control group, the IT group had smaller increases in plasma concentrations of tumor necrosis factor α, interleukin 1β (IL-1β), IL-6, and cTnI, and had a more pronounced increase in IL-10 levels after the initiation of CPB. After surgery, the required inotropes were reduced in the IT group. In the IT group, the time of artificial ventilation and the postoperative length of stay in the hospital were markedly shortened; however, there were no significant differences between the IT and control groups in mortality and the rate of nosocomial infections of deep sternal wounds. CONCLUSIONS IT can significantly attenuate the systemic inflammatory response and improve a damaged cardiac function, but it does not reduce the in-hospital mortality rate.

Surgical Treatment of Giant Coronary Artery Aneurysm Secondary to Kawasaki Disease

AIM To investigate the clinical features and surgical management of giant coronary artery aneurysm during end-stage Kawasaki disease. METHODS From May 2006 to October 2007, 5 patients, 2 to 57 years old, presented with giant coronary artery aneurysm and underwent surgical correction. The coronary aneurysm diameters were 1.5 to 2.5 cm. The coronary aneurysm lesion sites included the right main coronary artery in 1 case, the left main coronary artery in 2 cases, and both the left and right coronary arteries in 2 cases. Preoperative electrocardiogram revealed altered S-T segments in 5 cases and reduced ejection fraction values in 3 cases, resulting in 1 emergency admission for congestive heart failure. Surgical treatments included thromboendarterectomy, thrombectomy, and aneurysmal reconstruction under the orthophoria of extracorporeal circulation. RESULTS There were no operative deaths. All patients recovered and received dopamine 2 to 4 microg/min per kg and nitroglycerine 0.3 to 0.5 microg/min per kg. Time spent by patients in intensive care was uneventful. Following surgery, 4 patients showed ischemic improvement of the S-T segment on electrocardiograms, and 4 patients presented with increased ejection fraction, according to cardiac ultrasound inspection. The improvement of ejection fraction value was not significant in only 1 case. CONCLUSION Surgery is necessary for stage-3 Kawasaki disease patients that have giant coronary artery aneurysm complications. Surgical treatment includes thromboendarterectomy, thrombus clearing, aneurysmal reconstruction, and coronary artery bypass grafting, followed by postoperative anticoagulation and immunotherapy. Myocardial ischemia and cardiac function can be greatly improved through surgery.

Age-dependent mobilization of circulating endothelial progenitor cells in infants and young children undergoing cardiac surgery with cardiopulmonary bypass

This study was designed to find the effects of age on circulating endothelial progenitor cells (EPCs) and their mobilization in infants and young children following surgical correction of congenital heart defects. In 60 consecutive infants and young children (1month to 3years old) undergoing repair of atrial/ventricular septal defect, the numbers of EPCs and plasma levels of IL-6, -8, -10, TNF-alpha, VEGF and G-CSF were determined preoperatively, at the end of cardiopulmonary bypass (CPB), as well as 6, 12, 24, 48, 72 and 96h following surgery. Preoperative EPCs were reduced with increased age, similar to changes in plasma VEGF and G-CSF levels. Rapid mobilizations of EPCs and plasma VEGF, G-CSF were induced by cardiac surgery with CPB in all infants and young children, and the increased volumes of EPCs, VEGF and G-CSF decreased with age decreasing. The increased volumes of IL-6, -8, -10 and TNF-alpha were similar in different age groups. However, mobilization of EPCs, plasma VEGF and G-CSF were limited in infants <6months old, which did not correlate with change in inflammatory IL activation. Preoperative EPCs and plasma levels of VEGF and G-CSF were reduced with increasing age in infants and young children. Although a significant increase in EPCs and release of cytochemokines were observed in infants undergoing CPB, the mobilization of EPCs of the infants <6months old are limited.