Influence of Local Myocardial Infarction on Endothelial Function, Neointimal Progression, and Inflammation in Target and Non-Target Vascular Territories in a Porcine Model of Acute Myocardial Infarction

BACKGROUND: Patients with acute myocardial infarction (AMI) have worse clinical outcomes than those with stable coronary artery disease despite revascularization. Non-culprit lesions of AMI also involve more adverse cardiovascular events. This study aimed to investigate the influence of AMI on endothelial function, neointimal progression, and inflammation in target and non-target vessels. METHODS: In castrated male pigs, AMI was induced by balloon occlusion and reperfusion into the left anterior descending artery (LAD). Everolimus-eluting stents (EES) were implanted in the LAD and left circumflex (LCX) artery 2 days after AMI induction. In the control group, EES were implanted in the LAD and LCX in a similar fashion without AMI induction. Endothelial function was assessed using acetylcholine infusion before enrollment, after the AMI or sham operation, and at 1 month follow-up. A histological examination was conducted 1 month after stenting. RESULTS: A total of 10 pigs implanted with 20 EES in the LAD and LCX were included. Significant paradoxical vasoconstriction was assessed after acetylcholine challenge in the AMI group compared with the control group. In the histologic analysis, the AMI group showed a larger neointimal area and larger area of stenosis than the control group after EES implantation. Peri-strut inflammation and fibrin formation were significant in the AMI group without differences in injury score. The non-target vessel of the AMI also showed similar findings to the target vessel compared with the control group. CONCLUSION: In the pig model, AMI events induced endothelial dysfunction, inflammation, and neointimal progression in the target and non-target vessels.

A Slight Variation in the Age of Rats Commonly used as a Carotid Artery Injury Model Results in a Large Difference in Neointima Formation

BACKGROUND AND OBJECTIVES: The degree of neointima formation after infliction of a carotid artery balloon injury in rats varies greatly depending on the sex, age, species and operational method. Strong variation is common, even within only a single control. This study attempted to find if there was any significant difference in neointima formation following a carotid artery balloon injury in 6 to 12 week old rats; the age commonly used in these types of experiments. MATERIALS AND METHODS: A balloon injury was inflicted on the carotid arteries of male SpragueDawley rats at 6 (n=9, 250-270 g), 8 (n=8, 280-300 g) and 11 weeks (n=10, 320-340 g) of age. Two weeks postoperation, a histomorphometric analysis was carried out. The vascular smooth muscle cell proliferation was measured in situ via BrdU incorporation 2 days after injury infliction. RESULTS: The neointima areas of the 6 week (0.22+/-0.04 mm2) and 8 week old groups (0.17+/-0.08 mm2) were 3.1 and 2.4 times larger than that of the 11 week old group (0.07+/-0.03 mm2). The mitotic index was significantly reduced in 11 week old group (n=4, 9.22+/-1.51%) compared to those of the 6 (n=4, 25.03+/-3.92%) and 8 week old (n=4, 21.66+/-3.66%) groups. CONCLUSION: Special care should be taken when interpreting neointima formation, as even a slight variation in the age and weight in 6 to 12 week old (250-340 g) rats; the age commonly used in these types of experiments, results in an unexpectedly large difference.

Effect of Radix Paeoniae Bubra on NADPH oxidase p22phox,MCP-1 mRNA expression and neointimal hyperplasia after balloon injury in cholesterol-fed rabbits / 中华中医药杂志

Objective:To observe the effect of Radix Paeoniae Bubra(RPB)on NADPH oxidase p22phox,monocyte chemotactic protein-1(MCP-1)mRNA expression and neointimal hyperplasia after carotid artery balloon injury in cholesterol-fed rabbits.Methods:The rabbit model of carotid balloon injury was established adopting Clowes method,and treated with extract of RPB.Component of neointima and expression of proliferating cell nuclear antigen(PCNA)and macrophage was determined by immunochemical stain.The collagen of typeⅠwas detected by special staining for blood vessels and the area of neointima was measured by image assay system.Expression of NADPH oxidase p22phox mRNA,MCP-1 mRNA was detected by in situ hybridization and transcription-polymerase chain reaction.Results:RPB can attenuate the neointima area and proliferation of collagen typeⅠinduced by balloon-injury,remarkable prevent the formation of restenosi,and down-regulate expression of NADPH oxidase p22 and MCP-1mRNA significantly and decrease the degree of macrophages infiltration especially in vessel wall of injuring carotid artery.Conclusions:RPB inhibited NADPH oxidase P22Phox and MCP-1 mRNA expression,and modestly reduced neointimal hyperplasia,which might be partly attributed to its antioxidant and inflammatory effects.

The Effect of External Beam Radiation on Neointimal Formation in the Rat Carotid Injury Model

BACKGROUND: Restenosis after successful percutaneous transluminal coronary angioplasty remains a major obstacle to the long-term success of the procedure. Uncontrolled proliferation and extracelluar matrix synthesis in response to mechanical injury are important contributors to this proces. External beam radiation or gamma radiation affects self-renewing tissues by arresting cell division, and therefore limits proliferation by reducing the number of clonal progenitors. The purpose of this study was to determine whether external beam radiation (EBR) could reduce the extent of neointimal formation after balloon injury in the rat carotid injury model and, if it could, to define the minimum effective dose. METHODS: 32 Sprague-Dawley rats (mean weight : 370+/-78g) underwent carotid injury by using 2F Fogarty balloon and EBR with doses ranging from 5 to 20 Gy. Rats were sacrificed after 2 weeks. The arteries were perfusin-fixed in paraformaldehyde. The dose was specified to a depth of 15mm. Histomorphometry was performed to compare external elastic lamina (EEL) area (mm2), lumen area (mm2)and neointimal area (mm2 of the injured segments. RESULTS: EEL area showed no significant difference in each different radiation group. Low dose EBR (5 Gy and 10Gy) had no significant impact on neointimal hyperplasia in rat carotid injury model. However, in high dose group (15Gy and 20Gy) neointimal area was significantly reduced (p<0.01) indicating high dose EBR markedly prevented neointimal hyperplasia. CONCLUSION: Radiation therapy may be an effective adjunctive method for reducing the restenosis rate after successful angioplasty in the rat carotid injury model.

IRRADIATION WITH ~(32)P LIQUID FILLED BALLOON TO PREVENT CELL PROLIFERATION AND NEOINTIMAL FORMATION AFTER CORONARY ANGIOPLAST IN SWINES / 解放军医学杂志

miniature swines were randomly divided into irradiation group ( n =7) and control group ( n =8). Immediately after balloon overstretch injury to LAD, radioactive liquid perfused balloon irradiation was performed at the target segment; radioactive dose was 24Gy. 35 days after the operation, the target segments were harvested to perform histologic and morphologic study (HE, MS, VVG) and immunohistochemical study (PCNA, ? smooth muscle actin). Results showed that the lumen area was significantly larger, the neointima area and vascular stenosis level were smaller, and less PCNA positive cells were present in the vascular wall in the irradiation group than in the control group ( P all