INSERTION OF AN INTRAAORTIC BALLOON THROUGH A LIMB OF AN AORTOFEMORAL GRAFT AFTER AORTIC VALVE REPLACEMENT, DOUBLE CORONARY ARTERY BYPASS, AND RESECTION OF AN ABDOMINAL AORTIC ANEURYSM

This case report describes a useful and unusual route for insertion of an intraaortic balloon in 63-year-old man who was operated upon for calcific aortic stenosis, coronary atherosclerosis involving the left anterior descending and right coronary arteries, and a large abdominal aortic aneurysm. Aortic valve replacement was accomplished with a porcine heterograft prosthesis. Bypasses to the left anterior descending and right coronary arteries were constructed with reversed saphenous vein grafts, and the abdominal aneurysm was resected and repaired with a bifurcated woven Dacron vascular graft. An electively placed intraaortic balloon was inserted through the right limb of the aortic graft prosthesis and used to assist the patient during the immediate postoperative period. Uneventful recovery ensued.     

Dynamic modelling of prosthetic chorded mitral valves using the immersed boundary method

Current artificial heart valves either have limited lifespan or require the recipient to be on permanent anticoagulation therapy. In this paper, effort is made to assess a newly developed bileaflet valve prosthesis made of synthetic flexible leaflet materials, whose geometry and material properties are based on those of the native mitral valve, with a view to providing superior options for mitral valve replacement. Computational analysis is employed to evaluate the geometric and material design of the valve, by investigation of its mechanical behaviour and unsteady flow characteristics. The immersed boundary (IB) method is used for the dynamic modelling of the large deformation of the valve leaflets and the fluid-structure interactions. The IB simulation is first validated for the aortic prosthesis subjected to a hydrostatic loading. The predicted displacement fields by IB are compared with those obtained using ANSYS, as well as with experimental measurements. Good quantitative agreement is obtained. Moreover, known failure regions of aortic prostheses are identified. The dynamic behaviour of the valve designs is then simulated under four physiological pulsatile flows. Experimental pressure gradients for opening and closure of the valves are in good agreement with IB predictions for all flow rates for both aortic and mitral designs. Importantly, the simulations predicted improved physiological haemodynamics for the novel mitral design. Limitation of the current IB model is also discussed. We conclude that the IB model can be developed to be an extremely effective dynamic simulation tool to aid prosthesis design.     

Prevention of Vascular Graft Infection by Sisomicin Incorporated into Fibrin Glue

To examine the efficacy of sisomicin (SISO) incorporated into fibrin glue (FG) for the prevention of graft infection in animal models, the susceptibility to infection of Dacron grafts (control) and SISO-FG Dacron grafts following the inoculation of Staphylococcus aureus or S. epidermidis was compared. The results showed that SISO-FG Dacron grafts displayed resistance to graft infection.     

Measurement of steady-flow instability and turbulence levels in Dacron vascular grafts.

Fluid dynamic properties of Dacron vascular grafts were studied under controlled steady-flow conditions over a Reynolds number range of 800 to 4500. Knitted and woven grafts having nominal diameters of 6 mm and 10 mm were studied. Thermal anemometry was used to measure centerline velocity at the downstream end of the graft; pressure drop across the graft was also measured. Transition from laminar flow to turbulent flow was observed, and turbulence intensity and turbulent stresses (Reynolds normal stresses) were measured in the turbulent regime. Knitted grafts were found to have greater pressure drop than the woven grafts, and one sample was found to have a critical Reynolds number (Rc) of less than one-half the value of Rc for a smooth-walled tube.     

A novel servo-control system that imposes desired aortic input impedance on in situ rat heart

To clarify the pathophysiological role of dynamic arterial properties in cardiovascular diseases, we attempted to develop a new control system that imposes desired aortic impedance on in situ rat left ventricle. In 38 anesthetized open-chest rats, ascending aortic pressure and flow waveforms were continuously sampled (1,000 Hz). Desired flow waveforms were calculated from measured aortic pressure waveforms and target impedance. To minimize the difference between measured and desired aortic flow waveforms, the computer generated commands to the servo-pump, connected to a side branch of the aorta. By iterating the process, we could successfully control aortic impedance in such a way as to manipulate compliance and characteristic impedance between 60 and 160% of their respective native values. The error between desired and measured aortic flow waveforms was 70 +/- 34 microl/s (root mean square; 4.4 +/- 1.4% of peak flow), indicating reasonable accuracy in controlling aortic impedance. This system enables us to examine the importance of dynamic arterial properties independently of other hemodynamic and neurohumoral factors in physiological and clinical settings.     

Clinical experience in 1040 patients with double-velour knitted Dacron vascular prostheses: With particular reference to dilatation and aneurysm formation

Recent reports of dilatation and aneurysm formation in Dacron fabric grafts have prompted us to review our experience with 1040 patients who received Meadox-Cooley double-velour knitted grafts over a 47-month period. Bifurcation grafts were used in 398 patients with aorto-femoral occlusive disease and in 203 patients with aortoiliac occlusive disease. Straight tube grafts were implanted in 310 patients with abdominal aortic aneurysms. Small caliber straight tube grafts were used for femoral-femoral bypass in 112 patients. The remaining 17 patients received double-velour grafts for restoration of the renal (14) and superior mesenteric (3) artery circulation. In a review of patients, no dilatation or aneurysm formation was disclosed by clinical examination, sonography or aortography.     

Establishment of animal model of dual liver transplantation in rat

The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we successfully established a novel rat model of dual right upper liver lobe transplantation.     

Prophylaxis of local vascular graft infection with levofloxacin incorporated into albumin-sealed dacron graft (LVFX-ALB Graft).

An animal model was used to assess the efficacy of levofloxacin (LVFX) incorporated into albumin (ALB)-sealed Dacron (LVFX-ALB) graft for the prevention of vascular graft infections caused by Staphylococcus aureus. Under general anesthetic, an interposition graft was placed into dog carotid artery. On completion of the operation, 0.1 ml of normal saline containing 10(7) colony-forming units (CFU) of a slime-producing S. aureus was inoculated directly onto the graft. After 1 day, the samples were sterilely harvested. The antibacterial activity of LVFX into the LVFX-ALB graft was evaluated by colony counting in bacterial cultures and by the fluorescent antibody method staining bacteria adhesion to the grafts. LVFX-ALB grafts had a lower infection rate than the control grafts (1/4, 10(2) CFU vs 4/4, 1.50 x 10(5)+/-1.38 x 10(5)CFU (mean+/-SE)). In an immunostaining study, LVFX-ALB grafts had small fluorescent areas showing S. aureus adhesion, while fluorescence was observed over the entire surface of the control grafts. Therefore, LVFX-ALB presumably had a bactericidal action and adhesive prevention against inoculated S. aureus. LVFX-ALB may be useful in preventing graft infections during and immediately after vascular reconstruction.     

THE DIFFICULT PROXIMAL CORONARY ANASTOMOSIS

Two patients are presented in whom severe calcific aortitis made performance of satisfactory proximal coronary anastomosis impossible. Endarterectomy of the ascending aorta after aortic valve replacement, combined with aortocoronary bypass prior to performance of the proximal anastomoses, was successfully employed in one patient. The second patient underwent resection of an anterior segment of aorta, which was replaced by a woven Dacron patch into which the vein grafts were sewn.     

Mechanistic insight into the physiological relevance of helical blood flow in the human aorta: an in vivo study

The hemodynamics within the aorta of five healthy humans were investigated to gain insight into the complex helical flow patterns that arise from the existence of asymmetries in the aortic region. The adopted approach is aimed at (1) overcoming the relative paucity of quantitative data regarding helical blood flow dynamics in the human aorta and (2) identifying common characteristics in physiological aortic flow topology, in terms of its helical content. Four-dimensional phase-contrast magnetic resonance imaging (4D PC MRI) was combined with algorithms for the calculation of advanced fluid dynamics in this study. These algorithms allowed us to obtain a 4D representation of intra-aortic flow fields and to quantify the aortic helical flow. For our purposes, helicity was used as a measure of the alignment of the velocity and the vorticity. There were two key findings of our study: (1) intra-individual analysis revealed a statistically significant difference in the helical content at different phases of systole and (2) group analysis suggested that aortic helical blood flow dynamics is an emerging behavior that is common to normal individuals. Our results also suggest that helical flow might be caused by natural optimization of fluid transport processes in the cardiovascular system, aimed at obtaining efficient perfusion. The approach here applied to assess in vivo helical blood flow could be the starting point to elucidate the role played by helicity in the generation and decay of rotating flows in the thoracic aorta.     

Fluid-structure interaction of deformable aortic prostheses with a bileaflet mechanical valve

Two different aortic prostheses can be used for performing the Bentall procedure: a standard straight graft and the Valsalva graft that better reproduces the aortic root anatomy. The aim of the present work is to study the effect of the graft geometry on the blood flow when a bileaflet mechanical heart valve is used, as well as to evaluate the stress concentration near the suture line where the coronary arteries are connected to graft. An accurate three-dimensional numerical method is proposed, based on the immersed boundary technique. The method accounts for the interactions between the flow and the motion of the rigid leaflets and of the deformable aortic root, under physiological pulsatile conditions. The results show that the graft geometry only slightly influences the leaflets dynamics, while using the Valsalva graft the stress level near the coronary-root anastomoses is about half that obtained using the standard straight graft.     

Experimental investigation of steady flow through a model of the human aortic arch

Steady flow through a model of the human aortic arch has been studied with hot-film anemometry. A three sensor hot-film velocity probe was inserted into an acrylic flow chamber fabricated from the in situ casting of a human aorta, and the axial, radial and tangential velocity profiles were determined for steady flows in the region of the aortic arch. These studies demonstrated the presence of a potential core throughout the arch region, with a concomitant boundary layer adjacent to the inner wall of curvature of the arch. Trapped secondary flows in this fluid layer along the inner wall were quantitatively determined. Our steady flow studies in the model human aortic arch suggests that a shear-dependent mass transfer mechanism may play a significant role in the development and propagation of atherosclerotic lesions in this segment of the human cardiovascular system.     

Differential PDGF secretion by graft and aortic SMC in response to oxidized LDL

Smooth muscle cells (SMC) from prosthetic vascular grafts constitutively secrete higher levels of platelet-derived growth factor-AA (PDGF-AA) than aortic SMC. Lipid oxidation products accumulate in grafts and may stimulate PDGF production. The effect of oxidized low-density lipoprotein (oxLDL) on PDGF-AA secretion by aortic and graft SMC was compared. SMC isolated from canine thoracic aorta or Dacron thoracoabdominal grafts (n = 10) were incubated with native LDL or oxLDL (0-400 microg/ml) for 72 h. PDGF-AA in the conditioned medium was measured with enzyme-linked immunosorbent assay. OxLDL increased PDGF-AA production by graft SMC from 78 +/- 2 to 256 +/- 16 pg PDGF/microg DNA and aortic SMC from 21 +/- 1 to 40 +/- 2 pg PDGF/microg DNA. Native LDL had no effect. N-acetylcysteine inhibited oxLDL-induced PDGF increase. Both superoxide and H(2)O(2) stimulated PDGF secretion by graft SMC had little effect on aortic SMC. Our results suggest that PDGF production by graft (synthetic) SMC is more sensitive to stimulation by oxidative stress than aortic (contractile) SMC. Lipid oxidation products that accumulate in prosthetic vascular grafts can cause an oxidative stress, which stimulates PDGF production by graft SMC. PDGF can induce migration of aortic SMC onto the graft, contributing to the development of intimal hyperplasia.     

Patient-specific simulation of a stentless aortic valve implant: the impact of fibres on leaflet performance

In some cases of aortic valve leaflet disease, the implant of a stentless biological prosthesis represents an excellent option for aortic valve replacement (AVR). In particular, if compared with the implant of mechanical valves, it provides a more physiological haemodynamic performance and a reduced thrombogeneticity, avoiding the use of anticoagulants. The clinical outcomes of AVR are strongly dependent on an appropriate choice of both prosthesis size and replacement technique, which is, at present, strictly related to surgeon's experience and skill. This represents the motivation for patient-specific finite element analysis able to virtually reproduce stentless valve implantation. With the aim of performing reliable patient-specific simulations, we remark that, on the one hand, it is not well established in the literature whether bioprosthetic leaflet tissue is isotropic or anisotropic; on the other hand, it is of fundamental importance to incorporate an accurate material model to realistically predict post-operative performance. Within this framework, using a novel computational methodology to simulate stentless valve implantation, we test the impact of using different material models on both the stress pattern and post-operative coaptation parameters (i.e. coaptation area, length and height). As expected, the simulation results suggest that the material properties of the valve leaflets affect significantly the post-operative prosthesis performance.     

Drug releasing systems in cardiovascular tissue engineering

Heart disease and atherosclerosis are the leading causes of morbidity and mortality worldwide. The lack of suitable autologous grafts has produced a need for artificial grafts; however, current artificial grafts carry significant limitations, including thrombosis, infection, limited durability and the inability to grow. Tissue engineering of blood vessels, cardiovascular structures and whole organs is a promising approach for creating replacement tissues to repair congenital defects and/or diseased tissues. In an attempt to surmount the shortcomings of artificial grafts, tissue-engineered cardiovascular graft (TECVG), constructs obtained using cultured autologous vascular cells seeded onto a synthetic biodegradable polymer scaffold, have been developed. Autologous TECVGs have the potential advantages of growth, durability, resistance to infection, and freedom from problems of rejection, thrombogenicity and donor scarcity. Moreover polymers engrafted with growth factors, cytokines, drugs have been developed allowing drug-releasing systems capable of focused and localized delivery of molecules depending on the environmental requirements and the milieu in which the scaffold is placed. A broad range of applications for compound-releasing, tissue-engineered grafts have been suggested ranging from drug delivery to gene therapy. This review will describe advances in the development of drug-delivery systems for cardiovascular applications focusing on the manufacturing techniques and on the compounds delivered by these systems to date.     

Simulation of transcatheter aortic valve implantation: a patient-specific finite element approach

Until recently, heart valve failure has been treated adopting open-heart surgical techniques and cardiopulmonary bypass. However, over the last decade, minimally invasive procedures have been developed to avoid high risks associated with conventional open-chest valve replacement techniques. Such a recent and innovative procedure represents an optimal field for conducting investigations through virtual computer-based simulations: in fact, nowadays, computational engineering is widely used to unravel many problems in the biomedical field of cardiovascular mechanics and specifically, minimally invasive procedures. In this study, we investigate a balloon-expandable valve and we propose a novel simulation strategy to reproduce its implantation using computational tools. Focusing on the Edwards SAPIEN valve in particular, we simulate both stent crimping and deployment through balloon inflation. The developed procedure enabled us to obtain the entire prosthetic device virtually implanted in a patient-specific aortic root created by processing medical images; hence, it allows evaluation of postoperative prosthesis performance depending on different factors (e.g. device size and prosthesis placement site). Notably, prosthesis positioning in two different cases (distal and proximal) has been examined in terms of coaptation area, average stress on valve leaflets as well as impact on the aortic root wall. The coaptation area is significantly affected by the positioning strategy ( ? 24%, moving from the proximal to distal) as well as the stress distribution on both the leaflets (+13.5%, from proximal to distal) and the aortic wall ( ? 22%, from proximal to distal). No remarkable variations of the stress state on the stent struts have been obtained in the two investigated cases.     

Dacron fabric-enveloped hydroxyapatite prosthesis for sternal tumor defect: an autopsy report

A 38-year-old housewife with solitary plasmacytoma of the manubrium who underwent a subtotal sternectomy treated by resection of the lesion is reported. This was followed by replacement with a Dacron fabric-enveloped hydroxyapatite prosthesis. The Dacron fabric was sutured to the surrounding tissues, and then the clavicle was passed through the cylindrical-shaped Dacron fabric to form a sternoclavicular joint capsule. The patient returned to her daily life 3 months after the operation. She had no trouble in her daily living, without any dislocation of the sternoclavicular joints or any displacement of the artificial sternum. The autopsy examination about 1 year after the operation showed that the Dacron fabric enveloping the artificial sternum became stronger with time. The sternoclavicular joint also was stably fixed, and the Dacron fabric fulfilled its function as an artificial articular capsule and biologic fixation of the surrounding supporting tissues.     

T-cadherin as a receptor regulating angiogenesis and blood vessel remodeling

The search for a membrane receptor responsible for hormone-like effects of low density lipoproteins (LDL) has revealed two proteins (Mol. wt. 105 and 130 kDa) in the membrane fraction of human aortic smooth muscle cells. These proteins were identified as mature T-cadherin and its unprocessed precursor. T-cadherin was originally cloned from chick embryo brain, where it was implicated in axon guidance in the developing nervous system. Our study on the T-cadherin distribution in human organs and tissues has indicated that T-cadherin is specifically expressed in nervous and cardiovascular system. However, physiological significance of T-cadherin expression in the vasculature, as well as intracellular signaling pathways mediating its effects remain obscure. This review summarizes our current knowledge about intracellular signaling utilized by T-cadherin and discusses possible functions of T-cadherin in the vasculature.     

A comparison of oxidized LDL-induced collagen secretion by graft and aortic SMCs: role of PDGF

Smooth muscle cells (SMCs) from prosthetic vascular grafts constitutively secrete higher levels of collagen than aortic SMCs. Lipid oxidation products accumulate in grafts, and we postulated that they stimulate SMC production of collagen. The effect of oxidized low-density lipoprotein (oxLDL) on type I collagen secretion by aortic and graft SMCs was compared. SMCs isolated from the canine thoracic aorta or Dacron thoracoabdominal grafts (n = 10) were incubated with native LDL or oxLDL (0-400 microg cholesterol/ml) for 72 h. Type I collagen in the conditioned medium was measured by ELISA. OxLDL increased collagen production by graft SMCs from 4.1 +/- 0.3 to 11.0 +/- 0.4 ng/microg DNA and by aortic SMCs from 2.3 +/- 0.1 to 3.5 +/- 0.2 ng/microg DNA. Native LDL had little effect. LY-83583, a superoxide generator, stimulated a dramatic increase in collagen secretion by graft SMCs and a smaller but significant elevation by aortic SMCs. OxLDL has been shown to increase PDGF production by graft SMCs, and PDGF can stimulate collagen production. Anti-PDGF antibody inhibited the increase in collagen production by graft SMCs that was stimulated by oxLDL, implicating PDGF as one mechanism of oxLDL-induced collagen production. Lipid oxidation products that accumulate in prosthetic vascular grafts can cause an oxidative stress that stimulates PDGF production by graft SMCs that in turn stimulates collagen production, contributing to the progression of intimal hyperplasia.     

Prosthetic vascular grafts engineered to combat calcification: Progress and future directions

Calcification in prosthetic vascular conduits is a major challenge in cardiac and vascular surgery that compromises the long-term performance of these devices. Significant research efforts have been made to understand the etiology of calcification in the cardiovascular system and to combat calcification in various cardiovascular devices. Novel biomaterial design and tissue engineering strategies have shown promise in preventing or delaying calcification in prosthetic vascular grafts. In this review, we highlight recent advancements in the development of acellular prosthetic vascular grafts with preclinical success in attenuating calcification through advanced biomaterial design. We also discuss the mechanisms of action involved in the designs that will contribute to the further understanding of cardiovascular calcification. Lastly, recent insights into the etiology of vascular calcification will guide the design of future prosthetic vascular grafts with greater potential for translational success.