Healing and remodeling of bioengineered pulmonary artery patches implanted in sheep.

PURPOSE: We hypothesized that cell-seeded patches implanted into sheep pulmonary artery would undergo progressive and complete healing into a viable structure well integrated with the arterial wall. METHODS: Autologous ovine blood-derived endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (MSCs) were isolated and cultured in vitro. MSCs and EPCs were seeded onto poly-4-hydroxybutyrate (P4HB)-coated polyglycolic acid (PGA) nonwoven biodegradable mesh scaffolds (10x20 mm) and cultured for 5 days in a laminar fluid flow system. Seeded patches were implanted into the wall of sheep pulmonary artery for 1-2 weeks (n=4) or 4-6 weeks (n=3). Preimplant and postexplant specimens were analyzed by histology and immunohistochemistry. RESULTS: Unimplanted constructs contained alpha-smooth muscle actin (SMA)-positive cells and early extracellular matrix formation (primarily glycosaminoglycans). One week after implantation, seeded patches had surface thrombus formation and macrophage infiltration. Seeded patches implanted for 2 weeks showed granulation tissue, early pannus formation, macrophages, foreign body giant cells around disintegrating polymer, and early angiogenesis (microvessel formation). After 4 weeks in vivo, seeded patches contained glycosaminoglycans, collagen, and coverage of the luminal surface by host artery-derived pannus containing alpha-SMA-positive cells and laminated elastin; polymer scaffold degradation was almost complete with replacement by fibrous tissue containing viable cells. CONCLUSIONS: This study shows that cell-seeded patches implanted in sheep pulmonary artery remodel to layered and viable tissue well integrated into the native arterial wall. The key remodeling processes included (1) intimal overgrowth at the luminal surface (pannus formation; neointima) and (2) granulation tissue formation and fibrosis with foreign body reaction.     

Dysfunction of an ATS valve in the aortic position: the first reported case caused by pannus formation

A 64-year-old woman underwent aortic valve replacement with a 21-mm Advancing The Standard (ATS) open-pivot mechanical heart valve for bicuspid aortic valve stenosis. In addition to the appearance of a new cardiac murmur, echocardiography performed 3 years after surgery showed a high pressure gradient across the ATS valve and a reduction in the valve orifice area. Cineradiography of the valve revealed restricted leaflet opening. Subsequent multidetector-row computed tomography clearly demonstrated pannus overgrowth on the inflow aspect of the ATS valve. During a repeat operation, subvalvular overgrown pannus was confirmed and the ATS valve was replaced with a bioprosthetic valve. This is the first reported case of prosthetic valve dysfunction resulting from pannus formation in a patient with an ATS valve in the aortic position.     

Prevalence of pannus formation after aortic valve replacement: clinical aspects and surgical management

Pannus formation after aortic valve replacement is not common, but obstruction due to chronic pannus is one of the most serious complications of valve replacement. The causes of pannus formation are still unknown and effective preventive methods have not been fully elucidated. We reviewed our clinical experience of all patients who underwent reoperation for prosthetic aortic valve obstruction due to pannus formation between 1973 and 2004. We compared the initial 18-year period of surgery, when the Björk–Shiley tilting-disk valve was used, and the subsequent 13-year period of surgery, when the St. Jude Medical valve was used. Seven of a total of 390 patients (1.8%) required reoperation for prosthetic aortic valve obstruction due to pannus formation. All seven patients were women; four patients underwent resection of the pannus and three patients needed replacement of the valve. The frequency of pannus formation in the early group was 2.4% (6/253), whereas it was 0.73% (1/137) in the late group (P < 0.05). Pannus was localized at the minor orifice of the Björk–Shiley valve in the early group and turbulent transvalvular blood flow was considered to be one of the important factors triggering its growth. We also consider that small bileaflet valves have the possibility of promoting pannus formation and that the implantation of a larger prosthesis can contribute to reducing the occurrence of pannus.     

Retrieval and analysis of a clinical total artificial heart

Examination by light microscopy, scanning electron microscopy (SEM), and x-ray microanalysis of a clinical total artificial heart (TAH) implanted for 112 days revealed no evidence of calcification, pannus, or vegetative thrombus. A macroscopic thrombus was seen along the suture line in the right atrium but did not obstruct blood flow or valve function. Microscopic thrombi (less than 0.1 mm) and evidence of microemboli were observed on the pumping diaphragm using SEM. Characterization of selected polyetherurethane (PEU) samples from the pumping bladders and housing by Curie-point pyrolysis mass spectrometry (Py-MS) revealed unexpected differences between postmortem retrieved ventricles. Although the origin of these differences could be traced back to batch-to-batch variations in the original PEU material (Biomer), the precise nature of the observed differences in chemical structure and/or composition is still unknown. Numerical comparison between pyrolysis mass spectra from PEU samples exposed to blood or tissue and unexposed samples from the same ventricles did not detect evidence of biodegradation. Continual improvements in fabrication and quality control should minimize surface imperfections and ensure polymer reproducibility; however, existing materials and design parameters appear to be adequate for continued clinical implantation.     

In vitro testing of a new driver for the pneumatic total artificial heart with inherent cardiac output measuring system

Based upon the Utah pneumatic driver, a new model for use in animal experiments was designed. It enabled measurement of cardiac output, optimal percentage of systole as well as diagnosis of some of the causes of the decrease of cardiac output of the pneumatic total artificial heart, such as valvular stenosis due to pannus formation. This driver is based on the expansion of a known amount of 'driving-air' during the systolic period. In the calculation of the cardiac output, the in vitro experiments yielded an error range of +/- 3.5%. The analysis of the driving-air pressure tracing during its decompression (systolic period) gave accurate information about the optimal percentage of systole for each frequency and the inflow and outflow resistances.     

Flow through a defective mechanical heart valve: a steady flow analysis

Approximately 250,000 valve replacement operations occur annually around the world and more than two thirds of these operations use mechanical heart valves (MHV). These valves are subject to complications such: pannus and/or thrombus formation. Another potential complication is a malfunction in one of the valve leaflets. Although the occurrence of such malfunctions is low, they are life-threatening events that require emergency surgery. It is, therefore, important to develop parameters that will allow an early non-invasive diagnosis of such valve malfunction. In the present study, we performed numerical simulations of the flow through a defective mechanical valve under several flow and malfunction severity conditions. Our results show that the flow upstream and downstream of the defective valve is highly influenced by malfunction severity and this resulted in a misleading improvement in the correlation between simulated Doppler echocardiographic and catheter transvalvular pressure gradients. In this study, we were also able to propose and test two potential non-invasive parameters, using Doppler echocardiography and phase contrast magnetic resonance imaging, for an early detection of mechanical heart valve malfunction. Finally, we showed that valve malfunction has a significant impact on platelet activation and therefore on thrombus formation.     

光学相干断层成像在肺动脉介入诊疗中的应用

目的 评价光学相干断层成像(OCT)在肺血管病的鉴别诊断与针对性治疗中的可行性和有效性.方法 采用美国Lightlab公司的OCT系统,对10例经肺动脉造影证实为狭窄和(或)闭塞(先经介入血管重建)的16条直径在2～6 mm的肺血管进行OCT扫描检查,并用该系统自带的分析测量软件进行分析测量.结果 对10例患者的16支肺血管进行了66次OCT检查,全部获取有特征性的清晰图像,无并发症发生.OCT表现为,肺动脉血栓栓塞(5例):动脉壁不增厚,内膜上附着红或白血栓,管腔狭窄;特发性肺动脉高压(3例):肺动脉直径在2～6mm,血管壁正常的3层结构消失,内膜粗糙、增厚,反光增强,管腔狭窄程度超过50%,最小管腔内径≤1 mm;不明原因的肺动脉狭窄(2例):内膜正常或增厚,纤维样增生,厚0.17～0.60 mm,管状附着在内膜上,致管腔狭窄60%～80%.肺动脉闭塞和(或)狭窄介入血管重建后:内膜不完整,内膜下脂质斑块,多处病变伴有斑块破裂,内膜碎片,红白血栓,局部夹层形成.结论 OCT可以在肺动脉疾病的各个发展阶段安全进行,能显示不同肺血管病变血管壁特征性的组织学改变,有助于肺动脉疾病的诊断、鉴别诊断及指导治疗.     

Development of an ambulatory artificial lung in an ovine survival model

We are developing an artificial lung (AL) as an eventual bridge to lung transplant or recovery. The device is rigidly housed, noncompliant, and has a very low resistance to blood flow. In eight sheep, arterial cannulae were anastomosed end-to-side to the proximal and distal main pulmonary artery, and attached to the AL. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the AL. Eight of eight sheep survived the preparation. Mean pressure gradient across the AL was 8 mm Hg (3 Wood units; 8 mm Hg/2.8 L/min). Four of eight sheep tolerated immediate full diversion of blood flow and died at 24 and 40 hours (exsanguination) or 168 and 168 hours (elective sacrifice). Four of eight sheep were intolerant of full flow: two died of right heart failure at <8 hours with full flow through the device (full snare); the other two survived with partial device flow (partial snare), but the device clotted. These two then underwent successful closed-chest cannula thrombectomy and device change-out at 53 and 75 hours, and subsequently tolerated full flow. Long-term (up to 7 day) survival with complete diversion of pulmonary blood flow through a non-compliant, low-resistance AL is possible. Initial right heart failure in this model was 50% (4 of 8).     

Pannus formation in aortic valve prostheses in the late postoperative period

We present three patients who underwent repeat aortic valve replacement for prosthetic valve dysfunction caused by tissue ingrowth in the late postoperative period. These patients (three women aged 48–51 years, mean 49.3 ± 1.53 years) underwent operations for restriction of prosthetic valve leaflet movement by pannus in the left ventricular outflow tract. The interval from the previous operation ranged from 8.0 to 9.6 years (mean 9.6 ± 2.0 years). The symptoms of the patients were New York Heart Association functional class I, II, and IV in one patient each. Diagnosis was made by cinefluoroscopy in two patients and aortography in one patient. The operative procedures consisted of aortic valve replacement (n = 1) and aortic valve replacement with mitral valve replacement (n = 2). Pannus was found at the left ventricular aspect of the prosthetic valve in all patients. In two patients, the pannus directly restricted movement of the leaflet and also severely narrowed the inflow orifice of the prosthetic valve. In the other patient, the pannus had grown at a distance of 7mm from the valve and narrowed the left ventricular outflow tract circularly. The postoperative course was uneventful and all three patients were discharged in a good condition. One patient died of pneumonia 8 months after surgery and the other two patients have remained well and have been followed up for one and a half years. In conclusion, there may be a discrepancy between the clinical symptoms and the grade of subvalvular stenosis caused by pannus. Therefore, it is essential for satisfactory operative results that early diagnosis be made by various means.     

Immunohistochemical analysis of hepatocyte growth factor in human coronary atherectomy specimens: comparison with transforming growth factor beta isoforms

The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-β1, -β2, and -β3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-β isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.     

Osteopontin expression in pulmonary tumor thrombotic microangiopathy caused by gastric carcinoma

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles in patients with metastatic carcinoma. Osteopontin (OPN) is a multifunctional cytokine and adhesive protein, and has been demonstrated to be implicated in fibrosis, neointima formation, arterial occlusion by thrombus, and tumor metastases in cooperation with platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Herein is described an autopsy case of gastric adenocarcinoma with severe pulmonary hypertension due to PTTM. Histologically, tumor cell emboli markedly induced both fibromuscular intimal thickening and thrombosis, resulting in luminal stenosis and occlusion of small pulmonary arteries and arterioles. Tumor cells, both in the PTTM lesions and primary gastric carcinoma, had positive immunoreactivity for OPN, PDGF, and VEGF. In addition, proliferating fibromuscular intimal cells also showed expression of OPN, PDGF, and VEGF. These findings suggest that OPN may be involved in fibrocellular intimal proliferation and thrombus formation in PTTM together with PDGF and VEGF. To the best of the authors' knowledge this is the first report to demonstrate the possible involvement of OPN in PTTM. It is postulated that OPN is one of the candidate molecules for the development of PTTM.     

A SAM valve prosthesis in the mitral position: report of a case of long-term survival

No long-term survivals over 20 years after valve replacement with SAM (Sakakibara-Arai-Mera) valve prostheses have been described. We report a 57-year-old woman who survived for 31 years after mitral valve replacement with the SAM valve (Type M, 5M). Echocardiography revealed remarkable dilatation of the left atrium and moderate tricuspid regurgitation. Cineradiography, however, showed no restricted or asymmetric disc movement of the SAM valve. Cardiac catheterization revealed moderate pulmonary hypertension (64/30mmHg), with a mean pulmonary capillary wedge pressure of 25mmHg and a mean transprosthetic pressure gradient of 13mmHg. The mitral valve area was calculated to be 0.9 cm². No findings of pannus overgrowth around the SAM valve were confirmed on echocardiograms or left ventriculograms. Although the diagnosis of prosthetic valve obstruction resulting from pannus formation was suspected, the patient strongly refused replacement of the SAM valve because of her poor prognosis with bilateral breast cancer with systemic metastases. We believe that this patient may be the last living patient with the SAM valve.     

Novel "biomechanical" polymeric valve prostheses with special design for aortic and mitral position: a future option for pediatric patients?

In children, systemic heart valve replacement with bioprostheses is associated with accelerated valve degeneration, and mechanical prostheses require permanent anticoagulation. Novel "biomechanical" polymeric valve prostheses ("bio" = flexible, "mechanical" = synthetic), solely made of polycarbonate urethane (PCU), were tested in vitro and in a growing animal (calf) model with the aim of improved durability without permanent anticoagulation. The trileaflet aortic prosthesis has diminished pressure loss and reduced stress and strain peaks. The asymmetric bileaflet mitral valve mimics natural nonaxial inflow. The valves underwent long-term in vitro testing and in vivo testing in growing calves for 20 weeks [mitral (7), aortic (7)] with comparison to different commercial bioprostheses [mitral (7), aortic (2)]. In vitro durability of PCU valves was proved up to 20 years. Survival of PCU valves versus bioprostheses was 7 versus 2 mitral and 5 versus 0 aortic valves, respectively. Two animals with PCU aortic valves died of pannus overgrowth causing left ventricular outflow tract obstruction. Degeneration and calcification were mild (mitral) and moderate (aortic) in PCU valves but were severe in biological valves. There was no increased thrombogenicity of the PCU valves compared to bioprostheses. The novel polymeric valve prostheses revealed superior durability compared to current bioprostheses in growing animal model without permanent anticoagulation and thus, may be a future option for pediatric patients.     

Pathology of myocardial infarction,coronary artery disease,plaque disruption,and the vulnerable atherosclerotic plaque

Despite scientific advances, cardiovascular disease remains the leading cause of death in developed countries. The pathologic process responsible for the majority of this mortality is atherosclerosis. Human atherosclerosis is characterized by the transition of arteries through distinct pathologic stages. Initially, there is vascular wall activation, characterized by the formation of a smooth muscle cell rich intimal hyperplasia/thickening. The thickened intima promotes the lipid and macrophage accumulation characteristic of atherosclerosis. In some patients, the atherosclerotic plaque becomes disrupted stimulating formation of luminal thrombus and acute clinical events. Understanding the pathology of such vulnerable plaques has been a challenging and controversial area of investigation. Recent prospective longitudinal imaging studies of human coronary arteries have confirmed earlier pathologic observations reporting pathologic features that predispose to acute events in some patients include plaques with a thin fibrous cap overlying a large lipid-rich necrotic core as well as plaques with severe stenosis.     

Hemodynamic effect of Neuroform stent on intimal hyperplasia and thrombus formation in a carotid aneurysm

Stents play an important role in management of cerebral aneurysms. A stent reconstructs the parent artery, assists coil embolization, and decreases flow activity within an aneurysm. However, an in-stent stenosis often occurs within the stented artery and compromises the circulation at the parent artery. Hemodynamic basis of re-stenoses from aneurysm stenting is not fully understood. An 8mm cavernous carotid aneurysm with a wide neck was treated by a Neuroform stent first and by coils five weeks later. A comparison of the difference in morphology during this five-week period reveals the presence of intimal hyperplasia in the internal carotid artery, 1.3mm thick at the proximal end and 1mm at the distal end of the stent, and 1mm thick thrombus at the postero-inferior side of the aneurysm. Computational fluid dynamic analyses show that the site of intimal hyperplasia is exposed to low wall shear with high oscillatory shear index (OSI), and the location of thrombus is subject to high OSI. Intimal hyperplasia and thrombus occur at comparable rates, but at different hemodynamic conditions; however, both prefer regions with high OSIs.     

Pulmonary artery fibrous bands: report of a case with extensive lung infarction and superinfection with Coccidioides immitis, Pseudomonas, and acid-fast bacilli

A 46-year-old woman presented with shortness of breath and frequent lower respiratory tract infections. A ventilation-perfusion scan showed markedly reduced perfusion of the right lung, and pulmonary arteriogram showed stenosis of the right pulmonary artery. A right pneumonectomy revealed dense white fibrous bands partially occluding the pulmonary artery branches and two large abscess cavities filled with pus in the upper and lower lobes. Microscopic examination revealed extensive necrosis of lung parenchyma, suppurative granulomatous inflammation with Coccidioides immitis organisms and rare acid-fast bacilli. Pulmonary artery fibrous bands were originally believed to be congenital; however, they are now known to be sequelae of thromboembolic phenomena.     

Pulmonary hyperplasia in the Fraser cryptophthalmos syndrome

We report on 2 sibs with the Fraser cryptophthalmos syndrome who had pulmonary hyperplasia and laryngeal stenosis. A third unrelated patient with Fraser syndrome had laryngeal stenosis, renal agenesis, and normal lung development, rather than the expected pulmonary hypoplasia. Three additional cases of pulmonary hyperplasia in the Fraser syndrome were ascertained from a review. In all of these cases the likely mechanism for pulmonary hyperplasia is retention of fetal lung fluid by laryngeal or tracheal obstruction. © 1994 Wiley-Liss, Inc.     

生物型与骨水泥型人工股骨头置换治疗高龄股骨颈骨折

背景：随着人工关节材料、工艺及技术的成熟和发展,人工股骨头置换治疗股骨颈骨折尤其是老年患者有移位的股骨颈骨折日渐普及。 目的：观察生物型与骨水泥型人工股骨头置换治疗合并心脏病老年性股骨颈骨折的临床疗效。 方法：选择2004年1月至2009年12月天津疗养院骨科中心收治合并心脏病的股骨颈骨折患者35例,其中合并心绞痛型冠心病16例,心肌梗死型冠心病8例,无症状冠心病8例,缺血性心肌病冠心病3例。18例采用生物型人工股骨头置换,17例采用骨水泥型人工股骨头置换。 结果与结论：35例患者除1例在术中死亡外,34例均获得随访,随访时间8-36个月,置换过程中出现3例并发症均为骨水泥型组,其中1例在手术过程中经抢救无效死亡,2例在置换过程中血压下降,呼吸困难,经过抢救后生命特征恢复正常。在随访过程中发现生物型组中2例骨质疏松较严重的患者有部分假体下沉,生物型组优良率89%(16/18),骨水泥型组优良率94%(16/17),提示对于合并严重心脏病的患者适合运用生物型人工股骨头置换,而有骨质疏松的患者适合运用骨水泥型人工股骨头置换。     

The Ross procedure--valvular pathology of synchronous pulmonary autograft and homograft insufficiency

We report the morphological changes in a patient with combined pulmonary autograft and homograft dysfunction after 9 years of implantation. The case highlights long-term adaptive changes in the autograft to withstand systemic blood pressure with formation of exuberant pannus rich in elastic tissue. In the homograft, maturation of pannus had produced shortening of the 3 cusps with resultant incompetence.