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Increasing evidence indicates that inflammation plays an important role in intimal hyperplasia (IH) induced by autologous vein grafts. The proteasome inhibitor bortezomib shows anti-inflammatory effects, so we used an autologous vein transplantation model to test whether bortezomib inhibits neointimal formation in transplant-induced vasculopathy.We subjected 88 rats to autologous external jugular vein grafting surgery randomly assigned to be treated with bortezomib or vehicle. After 24 or 72 hours, rats were humanely killed and vein grafts processed for real-time RT-PCR (24 and 72 hours), ELISA (24 hours), or neutrophil chemotaxis assay (24 hours). Subsequently, rats were humanely killed at 1 and 2 weeks after grafting with samples processed for morphometric analysis.Bortezomib significantly inhibited IH at 2 weeks compared with untreated controls (P.05). Expression of mRNA for vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant 2beta, monocyte chemoattractant-1, interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha markedly increased in injured vessels during the first day after surgery declining over the following 3 days. Bortezomib significantly attenuated gene expression and protein levels of most inflammatory mediators (P.05), simultaneously inhibiting neutrophil chemotactic activity of vessel homogenates.Bortezomib inhibited neointimal formation at least partially by attenuating the inflammatory response in transplant-induced vasculopathy. It may become a novel vasoprotective agent in the clinical field.

Olmesartan, as a new angiotensin II receptor blocker, has shown beneficial effects on cardiovascular diseases. Nevertheless, the effect of olmesartan on ischemia/reperfusion (I/R) injury in the hypertensive heart has not been investigated. Therefore, the present study aimed to investigate the effect of olmesartan on I/R injury in spontaneously hypertensive rats (SHRs). Experimental groups were designed with a 2×2 factorial design for olmesartan and I/R effects. In the I/R group, the left anterior descending coronary artery (LAD) was ligated for 40 min followed by a 180-min reperfusion. In the sham group, SHRs underwent the same surgical procedure as the I/R group, with the exception that the suture passed under the LAD without being tightened. In the Olm-I/R group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the I/R group. In the Olm-sham group, the SHRs received olmesartan (5 mg/kg) for 4 weeks prior to surgery and other procedures were the same as for the sham group. Infarct size was measured for the I/R and Olm-I/R groups. Blood pressure (BP), serum creatine kinase (CK), left ventricular mass index (LVMI), high mobility group box 1 (HMGB1) protein expression levels and hypoxia-inducible factor-1α (HIF-1α) mRNA expression levels were measured for all four groups. Olmesartan significantly reduced BP and LVMI in the olmesartan-treated SHRs compared with those in the SHRs that were not treated with olmesartan. HMGB1 and HIF-1α expression levels were significantly decreased in the Olm-sham and Olm-I/R groups compared with those in the sham and I/R groups, respectively. The proportional increase in HIF-1α expression due to I/R was greater in the olmesartan-treated rats than in the untreated rats. Serum CK levels were significantly reduced in the Olm-I/R group compared with those in the I/R group. In conclusion, olmesartan ameliorates left ventricular hypotrophy and protects the heart against I/R injury in addition to lowing BP in SHRs. The protective effect of olmesartan may be partly due to its antioxidative and anti-inflammatory properties.

OBJECTIVES: Internal mammary arteries graft failure in coronary artery bypass grafting (CABG) is mostly considered to be a result of competitive flow (CF) from the native coronary artery, which significantly limits future revascularization options. METHODS: With the left internal mammary artery (LIMA) anastomosed to the left anterior descending (LAD) coronary artery using an off-pump technique, CABG was performed on 15 Chinese swine. Then we produced varying degrees of stenosis in the proximal LAD coronary artery with an adjustable flow occluder, measured the mean flow of the LIMA and LAD coronary artery and detected the plasma concentrations of nitric oxide (NO) and endothelin (ET) in the LIMA graft. RESULTS: When stenosis of the proximal LAD artery was decreased, the CF of the native LAD coronary artery showed an increasing trend, while the mean flow of the LIMA revealed a decreasing trend. Distal LAD coronary artery flow remained nearly constant, despite the varying proximal LAD artery or LIMA flow rates. An oscillating flow pattern (retrograde/antegrade) was noted in the LIMA graft when the proximal LAD coronary artery was not fully occluded. The plasma concentration of ET in the LIMA graft was significantly higher than that before grafting (P< 0.05), and the plasma concentration of NO was significantly lower (P< 0.05). The concentration of NO was positively related to the mean flow in the LIMA (r= 0.872, P< 0.05). CONCLUSIONS: CF from the native LAD coronary artery can decrease the blood flow in the LIMA graft and even change the direction of the flow. These changes may impair the function of the LIMA graft and affect ET or NO production, which in turn may lead to early LIMA graft failure.

To study the roles of serum inflammatory factors IL-6 and TNF-alpha and allograft adventitial inflammation in the pathogenesis of allograft arteriosclerosis in rats.Thirty-six allogeneic allograft rats and 16 syngeneic allograft rats were randomly divided into 4 groups (9 rats in each experimental group and 4 in each control group): A, harvested at Week 1 post-operation; B, harvested at Week 2 post-operation; C, harvested at Week 3 post-operation; D, harvested at Week 4 post-operation. Blood samples were collected before transplantation and after harvest. The method of ELISA was used for testing serum inflammatory factors including interleukin-6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), HE staining for pathologic changes of aortic allograft and immunohistochemical method for expression of alpha-actin, cyclin dependent kinase-1 (CDK(1)) and proliferating cell nuclear antigen (PCNA). Compare the inflammatory factors and other observations between groups and preoperative.At Week 1 post-operation, a large amount of inflammatory cell infiltration in adventitia was observed; at Week 2 post-operation, slight collagen fibers hyperplasia with inflammatory infiltration; at Week 4 post-operation, obvious adventitia thickening with a large number of smooth muscle cells, collagen fibers and inflammatory cells, smooth muscle cells migration from adventitia to intima. Expressions of alpha-actin, CDK(1) and PCNA kept increasing with time in adventitia (P0.05). There was a significant increase in serum TNF-alpha level in Groups A, B, C and D, as compared with pre-operative basal level (P0.01). There was no difference between controls and pre-operative basal level. IL-6 level slightly declined in the middle stage, but finally increased in experimental group B (P0.05) while it significantly increased in Groups A, C, D (P0.01). In the control groups A, B, C, it was higher than pre-operative level (P0.05). In experimental groups A, C, D, it had a significant increase as compared with controls (P0.01).In abdominal aortic allograft models, obvious angiosclerosis was found in adventitia and intima in accordance with the severity of adventitial inflammation. Thus the inflammatory factors and inflammatory cell infiltration in adventitia are both involved in the pathogenesis of early allograft arteriosclerosis.

Autologous vein grafts is still commonly used for arterial reconstructive procedures. Their success is limited by the development of neointimal hyperplasia. Clinical and experimental evidence suggest that the bone marrow derived mesenchymal stem cells (MSCs) participate in the neovascularization. The current study used a direct approach to test the hypothesis that, after vein grafting in a rat model, MSCs have potential effects on reendothelialization and neointimal formation. MSCs were isolated by bone marrow cell adherence. Autologously interpositioning left external jugular vein (LEJV) to left common carotid artery-induced vein grafting model of r at w as utilized. Vascular lesion formation after transplantation of MSCs labeled with 4',6-diamidino-2-phenylindole (DAPI) was investigated. Two weeks after implantation, immunofluorescence studies revealed that engrafted cells acquired an endothelial phenotype, and some expressed endothelial nitric oxide synthase (eNOS). Furthermore, proliferation of cells and neointimal formation decreased significantly after MSC implantation. Real-time reverse transcription-PCR and western blotting analysis showed a rise of eNOS expression in the MSC group compared with the vein grafting group. Therefore, engrafted MSCs appeared to differentiate into endothelial cells, diminish the neointima formation and contribute to the improvement on endothelial function, which indicates that MSCs may exert an important function as repair mechanism in vascular injury after vein grafting.

To explore the effect of one-way valved patch used in congenital heart disease with severe pulmonary hypertension.One-way valved patch was used in 30 patients of congenital heart disease with severe pulmonary hypertension (PP/PS0.75) in operation. Follow-up of 6 approximately 86 months was conducted to observe its effect.The pulmonary artery pressure was significantly decreased without trans-patch shunt in 11 cases postoperatively. Trans-patch shunt was determined in 27 cases within postperative 72 hours. There were 2 postoperative deaths out of these 27 patients: one died of low cardiac output syndrome 72 hours after operation, and the other died of right heart failure 4 weeks after operation. Thirty-six patients were restored to health and discharged. Three-month follow-up showed trans-patch shunt in 7 cases, including right-to left shunt in 4 cases and two-side shunt in other 3 cases. Color Doppler ultrasonography conducted 6 months after operation proved trans-patch shunt in 4 cases, right-to-left shunt in 1 case, two-side shunt in 2 cases, and left-to-right shunt in 1 case (PP/PS = 0.45).One-way valved patch is useful in selected patients in which postoperative right heart failure can be anticipated so as to shunt the blood in the right heart to the left heart and increase the blood volume in the left heart system to ensure the left heart output and minimize the risk of postoperative right heart failure, at the expense of systemic low oxygen saturation that is, however, well tolerated.

[Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 45-year-old man with significant ST-segment changes in anterolateral derivations underwent cardiac catheterization. A coronary angiogram revealed severe stenosis and ectasia of