Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including func...Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α<sub>1</sub>-adrenergic receptors (α<sub>1</sub>-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10<sup>−5</sup> M), and in some experiments, 5-Methylurapidil (α<sub>1A</sub>-AR antagonist), AH11110A (α<sub>1B</sub>-AR antagonist), or BMY-7378 (α<sub>1D</sub>-AR antagonist), were used to identify the α<sub>1</sub>-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α<sub>1D</sub>-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α<sub>1</sub>-ARs proteins were evaluated. α<sub>1D</sub>-AR increased at 30 and 60 min post Ang II exposure, the α<sub>1A</sub>-AR diminished from 1 to 4 h, while α<sub>1B</sub>-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α<sub>1D</sub>-AR at short times, and BMY-7378 protected α<sub>1D</sub>-AR from desensitization.展开更多
Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensit...Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.展开更多
BACKGROUND Postoperative aortobronchial fistula(ABF)is a rare complication that can occur in 0.3%-5.0%of patients over an extended period of time after thoracic aortic surgery.Direct visualization of the fistula via i...BACKGROUND Postoperative aortobronchial fistula(ABF)is a rare complication that can occur in 0.3%-5.0%of patients over an extended period of time after thoracic aortic surgery.Direct visualization of the fistula via imaging is rare.AIM To investigate the relationship between computed tomography(CT)findings and the clinical signs/symptoms of ABF after thoracic aortic surgery.METHODS Six patients(mean age 71 years,including 4 men and 2 women)with suspected ABF on CT(air around the graft)at our hospital were included in this retrospective study between January 2004 and September 2022.Chest CT findings included direct confirmation of ABF,peri-graft fluid,ring enhancement,dirty fat sign,atelectasis,pulmonary hemorrhage,and bronchodilation,and the clinical course were retrospectively reviewed.The proportion of each type of CT finding was calculated.RESULTS ABF detection after surgery was found to have a mean and median of 14 and 13 years,respectively.Initial signs and symptoms were asymptomatic in 4 patients,bloody sputum was found in 1 patient,and fever was present in 1 patient.The complications of ABF included graft infection in 2 patients and graft infection with hemoptysis in 2 patients.Of the 6 patients,3 survived,2 died,and 1 was lost to follow-up.The locations of the ABFs were as follows:1 in the ascending aorta;1 in the aortic arch;2 in the aortic arch leading to the descending aorta;and 2 in the descending aorta.ABFs were directly confirmed by CT in 4/6(67%)patients.Peri-graft dirty fat(4/6,67%)and peri-graft ring enhancement(3/6,50%)were associated with graft infection,endoleaks and pseudoaneurysms were associated with hemoptysis(2/6,33%).CONCLUSION Asymptomatic ABF after thoracic aortic surgery can be confirmed on chest CT.CT is useful for the diagnosis of ABF and its complications.展开更多
Objective:To investigate the expression of phosphorylated peroxisome proliferators-activated receptor y(p-PPARY) in the aging thoracic aorta of spontaneously hypertensive rat(SHR) and the inhibitory effect of rosiglit...Objective:To investigate the expression of phosphorylated peroxisome proliferators-activated receptor y(p-PPARY) in the aging thoracic aorta of spontaneously hypertensive rat(SHR) and the inhibitory effect of rosiglitazone on the phosphorylation of PPART.Methods:16,32 and 64 week-old Wistar-Kyoto rats(WKY) and SHR were randomly and respectively divided into WKY,SHR and SHR+rosiglitazone group(9 in each group).The rats in SHR+rosiglitazone group were treated with rosiglitazone(5 mg/kg,intragastrically) for 56 d,whereas normal saline was applied in WKY and SHR groups.Systolic blood pressure(SBP)of rats was measured by tail cuff method.Histopathological damage of thoracic aorta was analyzed using Hematoxylin-Eosin(HE) staining.Immunohistochemical staining and western blot were performed to test the level of p-PPARY protein in the thoracic aorta arising from each group.Results:The SBP in 16,32 and 64 week-old SHR were significantly higher as compared with those in matched WKY rats(P【0.05,respectively).HE staining showed increased content of smooth muscle cell,wrinkled lining endothelium and increased thickness of internal elastic lamina in the thoracic aorta of SHR.Immunohistochemical staining and western blot indicated that the levels of p-PPARY in the thoracic aorta arising from SHR were obviously higher than those in the thoracic aorta arising from WKY rats(P【0.05,respectively).Importantly,the high SBP,histopathological abnormalities of the thoracic aorta and elevated p-PPARY expression were prominently abrogated by rosiglitazone treatment in SHR(P【0.05,respectively).Furthermore,the SBP,histopathological abnormalities of the thoracic aorta and p-PPARY expression were positively correlated with age in SHR(P【0.05,respectively).Conclusions:The PPARY phosphorylation was observed in the thoracic aorta of SHR and its expression was increased by the increase of age.Furthermore,rosiglitazone inhibited the PPARY phosphorylation and suppressed vascular aging in SHR.展开更多
In order to study the effect of and mechanism of lysophosphatidylcholine (LysoPC) on proliferation of the calf thoracic aorta smooth muscle cells (ASMCs), the ASMCs were used to observe the effects of LysoPC induced ...In order to study the effect of and mechanism of lysophosphatidylcholine (LysoPC) on proliferation of the calf thoracic aorta smooth muscle cells (ASMCs), the ASMCs were used to observe the effects of LysoPC induced endothelial cell conditioned medium on the DNA content and proliferating cell nuclear antigen (PCNA) expression in the calf thoracic ASMCs by flow cytometry and Western Blot technique. It was found that LysoPC induced endothelial cell conditioned medium could significantly promote PCNA expression of the calf ASMCs, induce the converting of ASMCs from G 0 /G 1 phase to S phase of DNA synthesis, and increase the tyrosine phosphorylation protein expression. Tyrosine protein kinase inhibitor (TPKi) RG50864 could obviously inhibit proliferation of LysoPC induced ASMCs in a dose dependence manner. The results indicated that the effect of LysoPC promoting the proliferation of ASMCs is partly evoked by endothelial cell derived growth factors such as PDGF and so on.展开更多
Background:Extracellular matrix (ECM) plays a very important role in the development ofrestenosis after PTCA The MMPs,enymes specialized in degradation of ECM,probably partciptesin extracelular matrix remodeling after...Background:Extracellular matrix (ECM) plays a very important role in the development ofrestenosis after PTCA The MMPs,enymes specialized in degradation of ECM,probably partciptesin extracelular matrix remodeling after balloon injury,but the factors that regulates MMPs activity arenot completely understood Basic fibroblast growth factor (bFGF),as a mitogen for a variety of cellstypes,influences metabolism of ECM.However,if effects on MMPs are not known.Methodsand Results:24 male Wistar rats were divided randomly into control group,balloon-injuried group andbFGF-treated group.The rats of control group were not treated.The rats in balloon-injuried group weredamaged by balloon and the thoracic aortas were harvested after two weeks.In the bFGF-treated grorp,balloon injury and the injuried vessels were collected after two weeks.The northern blot was used toinvestigate the MMP1,MMP2 and MMP9 mRNA expression of vesss.At the same time,the effectsof differet dose bFGF (0ng/ml,40ng/ml,80ng/ml and 120ng/ml) on the MMPs expression of culturedVSMCs were examined The results showed the bFGF can selectively increase the expression ofMMP1 and MMP9 mRNA without effect on the MMP2 on the injuried rat thoracic aorta,and dosedependently increase the MMP1 mRNA expression of cultured VSMCs without MMP2 and MMP9expression Conclusion:bFGF selectively increased MMPs mRNA expression on both injuried ratthoracic aorta and cultured VSMCs.This effect may be related to the degradation of ECM,remodelingof vessel after injuty.展开更多
Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contract...Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.展开更多
BACKGROUND:Fatal aortic rupture caused by esophageal foreign body(EFB),is associated with a high mortality,but can be prevented by thoracic endovascular aorta repair(TEVAR)that performed increasingly as technology imp...BACKGROUND:Fatal aortic rupture caused by esophageal foreign body(EFB),is associated with a high mortality,but can be prevented by thoracic endovascular aorta repair(TEVAR)that performed increasingly as technology improves.This study aims to investigate the cause,management and prognosis of suspected penetrating aortoesophageal foreign body injury.METHODS:Twelve cases who met the criteria were enrolled in this study.The demographic and clinical data were reviewed for evaluating the characteristics of EFB.RESULTS:Among 12 cases enrolled,7 were males and 5 were females,with an age 27–86 years.The distance of EFB from aorta(DFA)of 7 cases were less than or equal to 0 mm,5 cases were 0–2 mm.Eleven cases were managed with TEVAR,only one case was with open surgery standby but finally treated by flexible endoscopy(FE)successfully,without TEVAR.In group with TEVAR,EFB of 7 cases were successfully removed by rigid endoscopy(RE),and one of them was failed at the first RE treatment.EFB of 2 cases were successfully removed by open surgery with TEVAR,and other 9 cases were managed by endoscopies with TEVAR.The mean length of stay of hospitalization(LOS)and length of ICU stay of patients treated by open surgery with TEVAR(18.50±2.12 days and 5.50±0.71 days)was significantly longer than those of patients treated by endoscopy with TEVAR(7.00±2.74 days and 1.33±1.12 days,P<0.001 and P=0.001,respectively).Five cases had severe complications.CONCLUSION:Rational application of TEVAR can be a life-saving management for aortoesophageal foreign body injury,and jointed with endoscopy is safe and effective with a shorter length of ICU or total hospital stay.展开更多
AIM: To investigating the relationship between thoracic and cardiac <sup>18</sup>F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors.METHODS: Seventy-e...AIM: To investigating the relationship between thoracic and cardiac <sup>18</sup>F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors.METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F-NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to-background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta.RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 ± 0.76 vs 1.07 ± 0.3, P < 0.001), but also between MR and HR-LR (1.4 ± 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively).CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients’ risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination.展开更多
<strong>Objectives:</strong> To describe our technique for the implantation of the Thoraflex Hybrid prosthesis for replacement of the aortic arch in a safe and reproducible way. <strong>Materials:<...<strong>Objectives:</strong> To describe our technique for the implantation of the Thoraflex Hybrid prosthesis for replacement of the aortic arch in a safe and reproducible way. <strong>Materials:</strong> Thoraflex<span style="font-size:12.0pt;line-height:107%;font-family:;" "="">™</span> Hybrid Plexus Device (Terumo Aortic).<strong> Design:</strong> Drawing on our own experience over the past 4 years in the management of acute type A aortic dissection, we have distilled the essentials of our “Frozen Elephant Trunk” technique which have led us through our own learning curve to the improved management of this taxing condition. <strong>Method/ Results:</strong> Small extension of the median sternotomy incision along the medial border of sternocleidomastoid muscle. End to side graft anastomosis near the origin of the left subclavian artery during cooling on bypass towards 20 degrees. Attention to cardiac protection and maintenance of cerebral perfusion during the shortened corporeal arrest period. Excellent results in 24 consecutive AAAD patients with just one hospital mortality. <strong>Conclusions:</strong> We believe we are entering a new phase in the treatment of AAAD, facilitated by the availability of a hybrid prosthesis which combines expanding stent technology with familiar surgical graft material. Our particular management of the left subclavian artery and of the cerebral circulation during implantation has contributed to an expeditious and reproducible method of treating dissection within the arch of the aorta and beyond.展开更多
Backgroud Thoracic aortic aneurysm (TAA) disease is a serious condition with both high mortality and morbidity rates associated with surgical therapy. Further understanding of the formation and progression of TAAs may...Backgroud Thoracic aortic aneurysm (TAA) disease is a serious condition with both high mortality and morbidity rates associated with surgical therapy. Further understanding of the formation and progression of TAAs may provide novel, less invasive therapeutic strategies in patients with this devastating disease. Aneurysm formation is a complicated, dynamic process involving both cellular and extracellular processes. The mechanisms of TAA formation are poorly understood, mainly due to the lack of a useful and reproducible model. In 2003, Ikonomidis in South Carolina developed a murine model of TAA.The mouse model was less satisfactory because the small size of the murine aorta. The rat model has the advantage of larger aorta and the ability to do more research. Proper animal models are useful to understand the aetiology and evolution and they can be used to evaluate the efficacy of new treatments.Objective The goal of this study was to test the hypothesis that abluminal calcium chloride application could creat TAAs in the SD rats.MethOds Eight-week-old male Sprague-Dawley(SD) rats(n=60) were divided into two groups equally. All rats were anesthetized. An angiocath was then advanced through the mouth into the trachea under direct vision and connected to a rodent ventilator set at a respiratory rate of 180 breaths per minute. And their thoracic aortas were exposed via left thoracotomy. In the experiment group,a sponge soaked in 0.5 mol/L CaCl2 was placed on the distal half of the exposed descending thoracic aorta under direct vision. As control group, 0.5 mol/L CaCl2 was instead of 0.9% NaCl. After 15 min, the sponge was removed. Then the chest was closed. At 4,8,12 weeks, all animals undergoing fixation and aortic harvest were reanesthetized and the thorax was then opened beneath the xiphoid process. Potassium chloride was injected into the left ventricle under direct vision to arrest the heart. Then it was perfusion program and the entire animal was immersed in formalin. Seven days after fixation, the animal was removed from formalin, and the aorta was carefully harvested from its root to the renal arteries. The aorta was then immersed in an individually labeled jar containing a mixture of 80% methanol and 20% dimethyl sulfoxide (Dent’s solution).Diameter measurements were made using Axioplan 2 imaging system. Hematoxylin and eosin staining and Van Gieson and Verhoeff staining showed the elastic architecture and collagen structure. Immunohistochemical staining was performed to evaluate the presence of lymphocytes and macrophages. Results 12 weeks of CaCl2 treatment resulted in visually obvious dilation of the exposed distal descending thoracic aortic segment.The distal descending thoracic aortic diameter at 4,8,12 weeks was (0.82±0.13), (1.12±0.43), (1.65±0.58)μm respectively. The control group at 4,8,12 weeks was (0.81±0.04) , (0.94±0.12), (1.09±0.03)μm respectively. The diameter of the ascending aorta (used as an internal control) were not significantly different between groups. Hematoxylin and eosin stained slides showed disruption of the normal elastic lamellar architecture of the CaCl2-exposed aortic wall compared to the contralateral wall or untreated control. Van Gieson-stained sections showed decreased collagen content in the exposed region of aortic wall. Immunohistochemical study indicated significantly more CD3+cells and CD68+ cells in the aortas of CaCl2 treated groups than in control aortas. CD3+ cells were located in the media and surrounding the vasa vasorum in the adventitia. Conclusion We conclude that abluminal application of CaCl2 to the thoracic aorta reliably produces dilation, wall-thinning, and disruption of mural architecture, the hallmark signs of aneurysm formation. These results suggest that the rat is a useful and technically feasible model for the study of TAAs. To our knowledge, these findings describe for the first time the generation of a reproducible model of isolated TAA formation in SD rat.展开更多
The human body has been the subject of thorough researches—not only from medical perspective but from a technical one as well—are very rich, amongst them we find blood circulation system comprising: the heart, the a...The human body has been the subject of thorough researches—not only from medical perspective but from a technical one as well—are very rich, amongst them we find blood circulation system comprising: the heart, the arteries and the veins. The overriding role of these researches is to explain some cardiovascular pathology and provide an aid tool for the endoprothesis positioning in blood vessels while treating them. In this study we have developed a digital pattern using the common (engineering technique of the) finite element method (FEM) to simulate the mechanical behavior of the thoracic aorta and the abdominal aorta below the kidney under blood pressure effect. This pattern calculates the displacements, the stresses (constraints) and the deformations of the two arteries’ walls enabling us to know their experimentally determined mechanical and geometric properties. This pattern could be applied to detect the aneurysm and dissection phenomena.展开更多
Object To elucidate the physiological significance of the spiral flow in the arterial system from the viewpoint of atherogenic lipid transport,an ex vivo experimental comparative
目的探讨沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog-1,SIRT1)抑制剂EX-527与激动剂SRT1720对老化内皮细胞成血管能力的影响。方法采用体外培养大鼠原代主动脉内皮细胞衰老技术,通过培养细胞的自...目的探讨沉默信息调节因子2相关酶1(silent mating type information regulation 2 homolog-1,SIRT1)抑制剂EX-527与激动剂SRT1720对老化内皮细胞成血管能力的影响。方法采用体外培养大鼠原代主动脉内皮细胞衰老技术,通过培养细胞的自然倍增建立大鼠主动脉内皮细胞(rat aorta endothelial cell,RAEC)衰老的细胞模型。内皮细胞的衰老用SA-β-Gal染色进行鉴定。衰老细胞模型建立后,对衰老的RAEC分别给予SIRT1抑制剂EX527和SIRT1激动剂SRT1720干预。运用Ki-67免疫荧光染色检测内皮细胞增殖,采用基质胶内皮管形成实验检测内皮细胞内皮管形成,应用蛋白印迹技术检测内皮细胞eNOS表达。结果SIRT1激动剂抑制老化RAEC增殖能力、内皮管形成能力和eNOS表达的降低,而SIRT1抑制剂使老化RAEC的增殖能力、内皮管形成能力和eNOS表达降低。结论SIRT1促进RAEC的增殖和内皮管形成,并增强RAEC中eNOS的表达;SIRT1改善衰老内皮细胞受损的成血管能力可能与其抑制衰老RAEC eNOS表达的下调有关。展开更多
文摘Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT<sub>1</sub> and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α<sub>1</sub>-adrenergic receptors (α<sub>1</sub>-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10<sup>−5</sup> M), and in some experiments, 5-Methylurapidil (α<sub>1A</sub>-AR antagonist), AH11110A (α<sub>1B</sub>-AR antagonist), or BMY-7378 (α<sub>1D</sub>-AR antagonist), were used to identify the α<sub>1</sub>-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α<sub>1D</sub>-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α<sub>1</sub>-ARs proteins were evaluated. α<sub>1D</sub>-AR increased at 30 and 60 min post Ang II exposure, the α<sub>1A</sub>-AR diminished from 1 to 4 h, while α<sub>1B</sub>-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α<sub>1D</sub>-AR at short times, and BMY-7378 protected α<sub>1D</sub>-AR from desensitization.
文摘Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α<sub>1D</sub>-adrenergic receptor (α<sub>1D</sub>-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α<sub>1D</sub>-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α<sub>1D</sub>-AR antagonist) or 5-methylurapidil (α<sub>1A</sub>-AR antagonist) was used to identify the α<sub>1</sub>-AR involved in the response, or BMY-7378 to protect the α<sub>1D</sub>-AR from desensitization. Results showed that α<sub>1D</sub>-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α<sub>1D</sub>-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α<sub>1A</sub>-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α<sub>1B</sub>-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α<sub>1D</sub>-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α<sub>1D</sub>-AR in the cultured aorta, and the α<sub>1D</sub>-AR is protected by BMY-7378.
文摘BACKGROUND Postoperative aortobronchial fistula(ABF)is a rare complication that can occur in 0.3%-5.0%of patients over an extended period of time after thoracic aortic surgery.Direct visualization of the fistula via imaging is rare.AIM To investigate the relationship between computed tomography(CT)findings and the clinical signs/symptoms of ABF after thoracic aortic surgery.METHODS Six patients(mean age 71 years,including 4 men and 2 women)with suspected ABF on CT(air around the graft)at our hospital were included in this retrospective study between January 2004 and September 2022.Chest CT findings included direct confirmation of ABF,peri-graft fluid,ring enhancement,dirty fat sign,atelectasis,pulmonary hemorrhage,and bronchodilation,and the clinical course were retrospectively reviewed.The proportion of each type of CT finding was calculated.RESULTS ABF detection after surgery was found to have a mean and median of 14 and 13 years,respectively.Initial signs and symptoms were asymptomatic in 4 patients,bloody sputum was found in 1 patient,and fever was present in 1 patient.The complications of ABF included graft infection in 2 patients and graft infection with hemoptysis in 2 patients.Of the 6 patients,3 survived,2 died,and 1 was lost to follow-up.The locations of the ABFs were as follows:1 in the ascending aorta;1 in the aortic arch;2 in the aortic arch leading to the descending aorta;and 2 in the descending aorta.ABFs were directly confirmed by CT in 4/6(67%)patients.Peri-graft dirty fat(4/6,67%)and peri-graft ring enhancement(3/6,50%)were associated with graft infection,endoleaks and pseudoaneurysms were associated with hemoptysis(2/6,33%).CONCLUSION Asymptomatic ABF after thoracic aortic surgery can be confirmed on chest CT.CT is useful for the diagnosis of ABF and its complications.
基金Supported by a grant from the National Natural Science Foundation of China(Grant No.81070219)
文摘Objective:To investigate the expression of phosphorylated peroxisome proliferators-activated receptor y(p-PPARY) in the aging thoracic aorta of spontaneously hypertensive rat(SHR) and the inhibitory effect of rosiglitazone on the phosphorylation of PPART.Methods:16,32 and 64 week-old Wistar-Kyoto rats(WKY) and SHR were randomly and respectively divided into WKY,SHR and SHR+rosiglitazone group(9 in each group).The rats in SHR+rosiglitazone group were treated with rosiglitazone(5 mg/kg,intragastrically) for 56 d,whereas normal saline was applied in WKY and SHR groups.Systolic blood pressure(SBP)of rats was measured by tail cuff method.Histopathological damage of thoracic aorta was analyzed using Hematoxylin-Eosin(HE) staining.Immunohistochemical staining and western blot were performed to test the level of p-PPARY protein in the thoracic aorta arising from each group.Results:The SBP in 16,32 and 64 week-old SHR were significantly higher as compared with those in matched WKY rats(P【0.05,respectively).HE staining showed increased content of smooth muscle cell,wrinkled lining endothelium and increased thickness of internal elastic lamina in the thoracic aorta of SHR.Immunohistochemical staining and western blot indicated that the levels of p-PPARY in the thoracic aorta arising from SHR were obviously higher than those in the thoracic aorta arising from WKY rats(P【0.05,respectively).Importantly,the high SBP,histopathological abnormalities of the thoracic aorta and elevated p-PPARY expression were prominently abrogated by rosiglitazone treatment in SHR(P【0.05,respectively).Furthermore,the SBP,histopathological abnormalities of the thoracic aorta and p-PPARY expression were positively correlated with age in SHR(P【0.05,respectively).Conclusions:The PPARY phosphorylation was observed in the thoracic aorta of SHR and its expression was increased by the increase of age.Furthermore,rosiglitazone inhibited the PPARY phosphorylation and suppressed vascular aging in SHR.
基金This project was supported by a grant from Hubei Scien-tific and Technological Comm ittee (No. 96 2 9110 1)
文摘In order to study the effect of and mechanism of lysophosphatidylcholine (LysoPC) on proliferation of the calf thoracic aorta smooth muscle cells (ASMCs), the ASMCs were used to observe the effects of LysoPC induced endothelial cell conditioned medium on the DNA content and proliferating cell nuclear antigen (PCNA) expression in the calf thoracic ASMCs by flow cytometry and Western Blot technique. It was found that LysoPC induced endothelial cell conditioned medium could significantly promote PCNA expression of the calf ASMCs, induce the converting of ASMCs from G 0 /G 1 phase to S phase of DNA synthesis, and increase the tyrosine phosphorylation protein expression. Tyrosine protein kinase inhibitor (TPKi) RG50864 could obviously inhibit proliferation of LysoPC induced ASMCs in a dose dependence manner. The results indicated that the effect of LysoPC promoting the proliferation of ASMCs is partly evoked by endothelial cell derived growth factors such as PDGF and so on.
文摘Background:Extracellular matrix (ECM) plays a very important role in the development ofrestenosis after PTCA The MMPs,enymes specialized in degradation of ECM,probably partciptesin extracelular matrix remodeling after balloon injury,but the factors that regulates MMPs activity arenot completely understood Basic fibroblast growth factor (bFGF),as a mitogen for a variety of cellstypes,influences metabolism of ECM.However,if effects on MMPs are not known.Methodsand Results:24 male Wistar rats were divided randomly into control group,balloon-injuried group andbFGF-treated group.The rats of control group were not treated.The rats in balloon-injuried group weredamaged by balloon and the thoracic aortas were harvested after two weeks.In the bFGF-treated grorp,balloon injury and the injuried vessels were collected after two weeks.The northern blot was used toinvestigate the MMP1,MMP2 and MMP9 mRNA expression of vesss.At the same time,the effectsof differet dose bFGF (0ng/ml,40ng/ml,80ng/ml and 120ng/ml) on the MMPs expression of culturedVSMCs were examined The results showed the bFGF can selectively increase the expression ofMMP1 and MMP9 mRNA without effect on the MMP2 on the injuried rat thoracic aorta,and dosedependently increase the MMP1 mRNA expression of cultured VSMCs without MMP2 and MMP9expression Conclusion:bFGF selectively increased MMPs mRNA expression on both injuried ratthoracic aorta and cultured VSMCs.This effect may be related to the degradation of ECM,remodelingof vessel after injuty.
文摘Clonidine is a classically categorized α2-adrenoceptor (α2-AR) agonist that produces vascular contractions by stimulating arterial smooth muscle α2-ARs. However, clonidine inhibits α1-AR-mediated arterial contractions. Recently, it was suggested that repeated stimulation with clonidine induces desensitization of α2-ARs, thus inhibiting noradrenaline-induced smooth muscle contractions. In the present study, we examined whether clonidine-mediated inhibition of α1-AR contractions involves interactions with α2-ARs in rat thoracic aortae. 1) Clonidine and guanfacine inhibited electrical field stimulation-induced contractions in a concentration-dependent, yohimbine-sensitive manner in isolated rat vas deferens preparations. 2) Clonidine almost completely suppressed phenylephrine-induced sustained contractions of rat thoracic aortae. 3) Clonidine competitively inhibited phenylephrine-induced contractions with a pA2 value of 6.77 at concentrations between 10-7 and 10-6 M. At 10-5 M, clonidine inhibited phenylephrine-induced contractions and dramatically reduced maximum contractions. 4) In contrast, clonidine did not inhibit contractions produced by high KCl or prostaglandin F2α. 5) Inhibition of phenylephrine-induced sustained contractions by clonidine was also produced in the presence of yohimbine. However, guanfacine did not inhibit phenylephrine-induced sustained contractions. These findings suggest that clonidine inhibits phenylephrine-induced contraction of rat thoracic aortae by competitive antagonism of α1-ARs, which is mediated through a mechanism independent of α2-AR stimulation.
基金the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine (2017-XK-A36)the Key Research and Development Program of Zhejiang Province (2019C03076).
文摘BACKGROUND:Fatal aortic rupture caused by esophageal foreign body(EFB),is associated with a high mortality,but can be prevented by thoracic endovascular aorta repair(TEVAR)that performed increasingly as technology improves.This study aims to investigate the cause,management and prognosis of suspected penetrating aortoesophageal foreign body injury.METHODS:Twelve cases who met the criteria were enrolled in this study.The demographic and clinical data were reviewed for evaluating the characteristics of EFB.RESULTS:Among 12 cases enrolled,7 were males and 5 were females,with an age 27–86 years.The distance of EFB from aorta(DFA)of 7 cases were less than or equal to 0 mm,5 cases were 0–2 mm.Eleven cases were managed with TEVAR,only one case was with open surgery standby but finally treated by flexible endoscopy(FE)successfully,without TEVAR.In group with TEVAR,EFB of 7 cases were successfully removed by rigid endoscopy(RE),and one of them was failed at the first RE treatment.EFB of 2 cases were successfully removed by open surgery with TEVAR,and other 9 cases were managed by endoscopies with TEVAR.The mean length of stay of hospitalization(LOS)and length of ICU stay of patients treated by open surgery with TEVAR(18.50±2.12 days and 5.50±0.71 days)was significantly longer than those of patients treated by endoscopy with TEVAR(7.00±2.74 days and 1.33±1.12 days,P<0.001 and P=0.001,respectively).Five cases had severe complications.CONCLUSION:Rational application of TEVAR can be a life-saving management for aortoesophageal foreign body injury,and jointed with endoscopy is safe and effective with a shorter length of ICU or total hospital stay.
文摘AIM: To investigating the relationship between thoracic and cardiac <sup>18</sup>F-Natrium-Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors.METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F-NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to-background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta.RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 ± 0.76 vs 1.07 ± 0.3, P < 0.001), but also between MR and HR-LR (1.4 ± 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively).CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients’ risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination.
文摘<strong>Objectives:</strong> To describe our technique for the implantation of the Thoraflex Hybrid prosthesis for replacement of the aortic arch in a safe and reproducible way. <strong>Materials:</strong> Thoraflex<span style="font-size:12.0pt;line-height:107%;font-family:;" "="">™</span> Hybrid Plexus Device (Terumo Aortic).<strong> Design:</strong> Drawing on our own experience over the past 4 years in the management of acute type A aortic dissection, we have distilled the essentials of our “Frozen Elephant Trunk” technique which have led us through our own learning curve to the improved management of this taxing condition. <strong>Method/ Results:</strong> Small extension of the median sternotomy incision along the medial border of sternocleidomastoid muscle. End to side graft anastomosis near the origin of the left subclavian artery during cooling on bypass towards 20 degrees. Attention to cardiac protection and maintenance of cerebral perfusion during the shortened corporeal arrest period. Excellent results in 24 consecutive AAAD patients with just one hospital mortality. <strong>Conclusions:</strong> We believe we are entering a new phase in the treatment of AAAD, facilitated by the availability of a hybrid prosthesis which combines expanding stent technology with familiar surgical graft material. Our particular management of the left subclavian artery and of the cerebral circulation during implantation has contributed to an expeditious and reproducible method of treating dissection within the arch of the aorta and beyond.
文摘Backgroud Thoracic aortic aneurysm (TAA) disease is a serious condition with both high mortality and morbidity rates associated with surgical therapy. Further understanding of the formation and progression of TAAs may provide novel, less invasive therapeutic strategies in patients with this devastating disease. Aneurysm formation is a complicated, dynamic process involving both cellular and extracellular processes. The mechanisms of TAA formation are poorly understood, mainly due to the lack of a useful and reproducible model. In 2003, Ikonomidis in South Carolina developed a murine model of TAA.The mouse model was less satisfactory because the small size of the murine aorta. The rat model has the advantage of larger aorta and the ability to do more research. Proper animal models are useful to understand the aetiology and evolution and they can be used to evaluate the efficacy of new treatments.Objective The goal of this study was to test the hypothesis that abluminal calcium chloride application could creat TAAs in the SD rats.MethOds Eight-week-old male Sprague-Dawley(SD) rats(n=60) were divided into two groups equally. All rats were anesthetized. An angiocath was then advanced through the mouth into the trachea under direct vision and connected to a rodent ventilator set at a respiratory rate of 180 breaths per minute. And their thoracic aortas were exposed via left thoracotomy. In the experiment group,a sponge soaked in 0.5 mol/L CaCl2 was placed on the distal half of the exposed descending thoracic aorta under direct vision. As control group, 0.5 mol/L CaCl2 was instead of 0.9% NaCl. After 15 min, the sponge was removed. Then the chest was closed. At 4,8,12 weeks, all animals undergoing fixation and aortic harvest were reanesthetized and the thorax was then opened beneath the xiphoid process. Potassium chloride was injected into the left ventricle under direct vision to arrest the heart. Then it was perfusion program and the entire animal was immersed in formalin. Seven days after fixation, the animal was removed from formalin, and the aorta was carefully harvested from its root to the renal arteries. The aorta was then immersed in an individually labeled jar containing a mixture of 80% methanol and 20% dimethyl sulfoxide (Dent’s solution).Diameter measurements were made using Axioplan 2 imaging system. Hematoxylin and eosin staining and Van Gieson and Verhoeff staining showed the elastic architecture and collagen structure. Immunohistochemical staining was performed to evaluate the presence of lymphocytes and macrophages. Results 12 weeks of CaCl2 treatment resulted in visually obvious dilation of the exposed distal descending thoracic aortic segment.The distal descending thoracic aortic diameter at 4,8,12 weeks was (0.82±0.13), (1.12±0.43), (1.65±0.58)μm respectively. The control group at 4,8,12 weeks was (0.81±0.04) , (0.94±0.12), (1.09±0.03)μm respectively. The diameter of the ascending aorta (used as an internal control) were not significantly different between groups. Hematoxylin and eosin stained slides showed disruption of the normal elastic lamellar architecture of the CaCl2-exposed aortic wall compared to the contralateral wall or untreated control. Van Gieson-stained sections showed decreased collagen content in the exposed region of aortic wall. Immunohistochemical study indicated significantly more CD3+cells and CD68+ cells in the aortas of CaCl2 treated groups than in control aortas. CD3+ cells were located in the media and surrounding the vasa vasorum in the adventitia. Conclusion We conclude that abluminal application of CaCl2 to the thoracic aorta reliably produces dilation, wall-thinning, and disruption of mural architecture, the hallmark signs of aneurysm formation. These results suggest that the rat is a useful and technically feasible model for the study of TAAs. To our knowledge, these findings describe for the first time the generation of a reproducible model of isolated TAA formation in SD rat.
文摘The human body has been the subject of thorough researches—not only from medical perspective but from a technical one as well—are very rich, amongst them we find blood circulation system comprising: the heart, the arteries and the veins. The overriding role of these researches is to explain some cardiovascular pathology and provide an aid tool for the endoprothesis positioning in blood vessels while treating them. In this study we have developed a digital pattern using the common (engineering technique of the) finite element method (FEM) to simulate the mechanical behavior of the thoracic aorta and the abdominal aorta below the kidney under blood pressure effect. This pattern calculates the displacements, the stresses (constraints) and the deformations of the two arteries’ walls enabling us to know their experimentally determined mechanical and geometric properties. This pattern could be applied to detect the aneurysm and dissection phenomena.
基金supported by Grants-in-Aid from the National Natural Science Research Foundation of China,No.30670517,10632010
文摘Object To elucidate the physiological significance of the spiral flow in the arterial system from the viewpoint of atherogenic lipid transport,an ex vivo experimental comparative