33 research outputs found

    The pathology of heart valve replacement by valvular prostheses.

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    Blood analogue for thrombogenicity assessment

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    The chief problem at present with artificial heart valves is their thrombogenicity, which requires the recipients to undergo dangerous anticoagulant therapy, which is not always successful. The present accepted method of testing valve thrombogenicity is implantation in experimental animals. This technique is unsatisfactory because of its high cost, the lack of control, the length of the experiments and because differences between the blood of various species render the results of dubious value. A more fundamental approach to the problem based on fluid mechanics'fails because of the complexity of the situation and because of the opposed effects of a given fluid mechanical phenomenon. The in vitro use of blood is not possible due to the need for a single pass system to avoid recirculating clots, necessitating some thirty gallons of blood for a run of only one hour. An analogue method using a fluid which does not have the disadvantages of the alternatives described above, therefore, seems worth exploring. Rennetized milk is a possible fluid for such a purpose and experiments were performed to ascertain whether it behaves in a manner analogous to blood in respect of its essential clotting properties. The first indications from the Lee-White inverted test tube test were very promising with milk behaving in a manner apparently identical to blood. Further experiments using the Stagnation Point Flow Chamber showed that there was a striking similarity in the microscopic appearance of the deposits forming at and around the stagnation point when a jet of milk/blood impinges normally onto a glass slide. A subsequent experiment, in which the fluids are pumped through a mesh, revealed that the sequence of clot growth as measured by the pressure variation upstream of the mesh is the same for both fluids. Finally, full scale tests of the clotting propensity of various heart valves were performed using an artificial heart system, which showed that the location and appearance of the clots forming on the valves with rennetized milk were similar to those found in humans and that the results were reproducible. It is, therefore, apparent that rennetized milk shows great potential as an analogue for the flow related clotting of blood and can be used for testing artificial heart valves provided care is taken in the choice of materials for construction

    A review of cardiac surgery in South Australia

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    An analysis of the outcome following cardiac valve surgery and coronary artery bypass grafting performed in the Royal Adelaide Hospital Cardiothoracic Surgical Unit over a 25 year period.Thesis (M.S.) -- University of Adelaide, Dept. of Surgery, 1993

    Antithrombogenic therapy after heart valve replacement - Effect of anti-platelet drug on aggregation-

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    人工弁置換患者の血栓塞栓症(TE)は,長期予後の成績を左右する。 TEを減少させるために凝固因子を抑制するwarfarinと抗血小板剤による抗血栓療法が行われている。人工弁置換患者103例を対象に,抗血小板剤であるtrapidil(TP)とdipyridamole(DP)の血小板凝集能に与える効果を検討した。36ヵ月間検討したが,warfarin単独群は血小板凝集能に変化がなく,TP,DP共にADP凝集能を抑制した。しかし有意差の見られたのは全経過ではなく,凝集能抑制は強力かつ持続的ではなかった。またコラーゲン誘導凝集能は変化を認めなかった。TPとDPの抗血小板効果は同等と思われる。期間中の血栓塞栓発生は,warfarin単独群9.5%,TP群4.3%,DP群7.7%であった。臨床的に抗血小板剤の併用は有効と思われるが,血小板凝集抑制には投与量の増量,あるいは他の薬剤の検討が必要であろう。To evaluate the effect of anti-thrombotic thrapy after valve replacement, serial platelet aggregation measurememnts were carried out in 103 patients. Patients were divided into three groups. e. i. warfarin alone (control), warfarin with trapidil (TP) of 300mg/day and dipyridamole (DP) of 300mg/day. The aggregation of platelet of the control group did not change through 36 months. TP group showed a decrease in platelet aggregation at 24 and 30 months from the pretreatment value. The aggregation of 24 month in TP was significantly lower than that of control. There was no difference of platelet aggregation between TP and DP group. The incidence of thromboembolism of control, TP and DP group were 9.5%, 4.3% and 7.7%, respectively. These data suggest that the supression of platelet aggregation .by TP and DP is not adequate to continue for long time and TP has similar anti-thrombotic effect to DP

    ECM STABILIZATION STRATEGIES FOR BIOPROSTHETIC HEART VALVES FOR IMPROVED DURABILITY

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    Abstract Approximately 85,000 heart valve replacement surgeries are performed every year in United States and about 300,000 surgeries worldwide. It is estimated that half of them are mechanical valve replacements and the other half bioprosthetic valve replacements. The use of bioprosthetic heart valves is slowly increasing. Bioprosthetic heart valves are made from porcine aortic valves or bovine pericardium. Commercially these bioprostheses are currently crosslinked using glutaraldehyde (GLUT) to prevent tissue degradation and reduce tissue antigenicity. GLUT crosslinks these bioprostheses by stabilizing the collagen present in the tissue via a Schiff base reaction of the aldehyde with the hydroxylysine / lysine residues of collagen. However, Glut crosslinked BHVs fail due to structural dysfunction or calcification and need second replacements. 10 years after surgery, 20-30% of these valves become dysfunctional, and more than 50% of them fail between 12 - 15 years postoperatively. GLUT is known to be a good fixative for the collagenous component of the heart valves. However, GLUT is known to cause cytotoxicity and it is one of the causes of calcification of BHVs. Several alternative fixatives have been researched for BHV stabilization. Physical methods of crosslinking include ultraviolet irradiation and dye mediated photo-oxidation (PhotoFix®, Carbomedics, Austin, TX). Alternative chemical fixatives include stabilization using epoxy compounds, diphenylphosphorylazide, acyl azides, cyanamide, diisocyanates, diglycidyl ether, polyethylene glycol (PEG), carbodiimide (Ultifix®, Medtronic, Minneapolis, MN), diamine bridges, triglycidylamine, sodium metaperiodate, reuterin and genepin. They have shown significantly lower calcification of BHVs, however none of the above mentioned crosslinker is proven successful in long-term clinical studies. Glutaraldehyde is still the only major crosslinker used for clinically used BHVs. Glycosaminoglycans (GAGs) and elastin the other two major components of heart valves apart from collagen are not stabilized by GLUT fixation. It has been shown that GAGs are lost during harvesting, fixation, storage, in vitro cyclic fatigue and after in vivo animal implantation. Clinically explanted BHVs also show GAG depletion. GAGs are an important component of the valves and they maintain a hydrated environment in the valves and help in absorbing compressive and shear stresses acting on the valve and resisting local tissue buckling. It has been hypothesized that loss of these important matrix elements might result in the accelerated degeneration of BHVs. Furthermore, fixation of these components in the valves may help in the better biomechanics of the valves and also improve in vivo durability of the valves. Better extracellular matrix (ECM) stabilization to prevent degeneration will determine the long-term success and durability of these valves. Crosslikers such as carbodiimide, triglycidylamine, and sodium metaperiodate were tried as GAG-targeted fixatives; however, they were unable to completely inhibit the enzyme mediated degradation of GAGs. The focus of this study is on using neomycin trisulfate, a hyaluronidase inhibitor, along with GAG-targeted fixative carbodiimide for stabilizing the GAGs present in the valves. Systematic approach is used in our studies to determine the tissue GAG content, resistance to enzymatic GAG degradation, collagen and elastin stability, in vitro cyclic fatigue, in vivo calcification, effect on biomechanical properties of valves as well as combination with anti-calcification treatments to prevent both degeneration and calcification. We show that neomycin based chemistry significantly stabilize GAGs in the BHVs against GAG degrading enzymes and such fixation would improve long-term durability of the prosthesis

    Volume 19, issue 3

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    The mission of CJS is to contribute to the effective continuing medical education of Canadian surgical specialists, using innovative techniques when feasible, and to provide surgeons with an effective vehicle for the dissemination of observations in the areas of clinical and basic science research. Visit the journal website at http://canjsurg.ca/ for more.https://ir.lib.uwo.ca/cjs/1140/thumbnail.jp

    STABILIZATION OF EXTRACELLULAR MATRIX COMPONENTS IN BIOPROSTHETIC HEART VALVES USING NEOMYCIN AND PENTAGALLOYL GLUCOSE ENHANCED CROSSLINKING

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    Bioprosthetic heart valves (BHVs) fail within 12-15 years of implantation due to limited durability. This limits their application to elderly population. Younger patients with contraindications for long-term anticoagulant therapy necessary for mechanical heart valves may also receive BHVs. Investigation into improving valve durability can lead to longer implant life, increased quality of life for patients receiving BHVs, and a broadened patient demographic. Current BHVs are chemically treated with glutaraldehyde (GLUT) to stabilize collagen via chemical crosslinking and to reduce tissue antigenicity. GLUT fails to adequately stabilize elastin and glycosaminoglycans (GAGs), essential extracellular matrix components for valve function and durability. Degradation of elastin also increases elastin-oriented calcification. Previous use of neomycin and carbodiimide crosslinking has improved GAG stability. Similarly, use of pentagalloyl glucose (PGG), a plant polyphenol, has previously improved elastin stability in aortic wall and abdominal aortic aneurysm. We have focused on long term GAG stability using neomycin and carbodiimide crosslinking to replace GLUT, and the use of neomycin and PGG along with GLUT to stabilize elastin. The first study shows improved long term GAG stability when tissue treated with neomycin and carbodiimide crosslinking is stored for ten months or implanted subdermally in rats for up to 15 weeks. The second study evaluated stabilization of all extracellular matrix components against enzymatic degradation in an in vivo model, mechanical properties, and calcification potential and extracellular matrix stability in a rat subdermal model. This study demonstrated a marked increase in extracellular matrix stability when compared to GLUT control. Further, the changes we saw to mechanical properties can be attributed to specific crosslinking modalities. Neomycin, PGG and GLUT crosslinked tissue also demonstrated increased calcification potential in a rat subdermal model when compared to GLUT controls. In these studies we present two viable heart valve fixation techniques. One replaces GLUT with carbodiimide based chemistry, to stabilize GAGs and remove negative effects caused by GLUT. The other adds neomycin and PGG to GLUT to stabilize elastin and GAGs in bioprosthetic heart valve leaflets. By stabilizing these components, in vivo tissue and valve mechanics may improve, accompanied by an increase in valve durability

    A sequential evaluation of left ventricular function in asymptomatic and symptomatic patients with chronic severe aortic regurgitation

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    The optimal timing of valve replacement surgery in chronic severe aortic regurgitation (AR) has remained a major clinical problem in the management of these patients. Although the onset of symptoms is the generally accepted indication for aortic valve replacement (AVR), the unpredictable development of pre-symptomatic left ventricular (LV) dysfunction as a result of prolonged volume overload has resulted in numerous reports attempting to formulate a risk profile for these patients. Although aortic root and LV cineangiography have been the "gold standard" for defining the severity of AR and its effect on LV performance, serial follow-up by these means is impractical. More recently numerous non-invasive measures of LV size (echocardiogram) and function both at rest and on exercise (echocardiogram and equilibrium radionuclide angiocardiography., ERNA) have been serially utilised~ In these endeavours, the thinking has been clouded by a tendency to equate these two measures and failing to appreciate that apparent preoperative LV dysfunction (particularly on exercise) may be rapidly reversible by AVR and the consequent changes in LV loading conditions. This study was a prospective, sequential evaluation of left ventricular function using both non-invasive and invasive techniques in symptomatic and asymptomatic patients with isolated chronic, severe (4+) AR at cardiac catheterisation. The aims of the study were to (I) Identify differences in the clinical, echocardiographic, resting and exercise haemodynamic and I radionuclide measures of left ventricular function in symptomatic and asymptomatic patients with chronic severe A.R. with particular reference to the incidence of presymptomatic development of left ventricular dysfunction. (II) Critically evaluate the role of exercise stress (both isotonic and isometric) in the assessment of patients with chronic severe A.R. (III) Evaluate the influence of time (sequential studies) on the haemodynamic burden in asymptomatic patients. (IV) Study the impact of successful aortic valve replacement on the reversibility of abnormal pre-operative LV function in an attempt to predict which patients would benefit from this therapeutic intervention and whether operation for symptoms alone is the correct clinical practice
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