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Comparison of anesthetic techniques in patients undergoing heart valve replacement.

A prospective study of 324 adult patients undergoing operations requiring cardiopulmonary bypass for heart valve replacement was undertaken to determine the effect of anesthetic technique on outcome. Patients received one of three primary techniques: fentanyl (40-100 micrograms/kg), sufentanil (4-8 micrograms/kg), or diazepam (0.4-1 mg/kg) with ketamine (3-6 mg/kg). Supplemental inhalation anesthesia with enflurane, halothane, or isoflurane was used in 43.8% of cases. Patients in these anesthetic groupings had similar perioperative demographic and risk classifications. Although there were differences in the requirements for vasopressors postoperatively among the intravenous anesthetic agents, neither mortality rates, length of ICU stay, nor incidence of postoperative heart failure showed the advantage of any intravenous or inhalational agent. There were also no significant differences in the incidences of serious pulmonary, renal, or neurologic morbidity among primary anesthetic techniques nor among supplemental inhalation agents. Multivariate discriminant analysis of these data suggests that many factors are significantly more important than anesthetic technique as determinants of outcome after heart valve replacement.

Analysis of Variance↗

Tissue engineering heart valves: valve leaflet replacement study in a lamb model.

BACKGROUND: Valve replacements using either bioprosthetic or mechanical valves have the disadvantage that these structures are unable to grow, repair, or remodel and are both thrombogenic and susceptible to infection. These characteristics have significantly limited their durability and longevity. In an attempt to begin to overcome these shortcomings, we have tested the feasibility of constructing heart valve leaflets in lambs by seeding a synthetic polyglycolic acid fiber matrix in vitro with fibroblasts and endothelial cells. METHODS: Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted ovine arteries. Endothelial cells were selectively labeled with an acetylated low-density lipoprotein marker and separated from the fibroblasts using a fluorescent activated cell sorter. A synthetic biodegradable scaffold constructed from polyglycolic acid fibers was seeded with fibroblasts, which grew to form a tissue-like sheet. This tissue was subsequently seeded with endothelial cells, which formed a cellular monolayer coating around the leaflet. Using these constructs, autologous (n = 3) and allogenic (n = 4) tissue engineered leaflets were implanted in 7 animals. In each animal the right posterior leaflet of the pulmonary valve was resected and replaced with an engineered valve leaflet. RESULTS: All animals survived the procedure. Postoperative echocardiography demonstrated no evidence of stenosis and trivial pulmonary regurgitation in the autografts and moderate regurgitation in the allogenic valves. Collagen analysis of the constructs showed development of an extracellular matrix. Histologic evaluation of the constructs demonstrated appropriate cellular architecture. CONCLUSIONS: This preliminary experiment showed that a tissue engineered valve leaflet constructed from its cellular components can function in the pulmonary valve position. Tissue engineering of a heart valve leaflet is feasible, and these preliminary studies suggest that autograft tissue will probably be superior to allogenic tissue.

Animals↗

[Immunological indices in acquired heart defects after heart valve replacement with bioprostheses].

The indices of cellular and humoral immunity were studied in 46 patients with heart diseases of rheumatic origin prior to and alter operation for replacement of the heart valves with synthetic prostheses (in 19) and pig aortic valves treated with glutaraldehyde and methaperiodate solutions ater Karpantje (in 27). The indirect fluorescence method and the leukocyte migration inhibition test to the myocardial antigens showed that the operation for valve prosthetics causes an increase in the content of antibodies and activation of specific leukocyte sensitization to the antigens of the myocardium and heart valves. These changes do not depend on the type of the valve prosthesis and are normalized by the 6th month. The activation of immunological processes encountered in some patients in late periods after the operation (1-8 years) corresponded to an aggravation of their clinical condition which in most cases was not associated with impaired functioning of the biological prosthesis. The implantation of xenogenous valve prostheses treated by Karpantje's method did not cause the development of immunological processes which could have induced destruction of the prostheses.

Antibodies↗

[Reoperation in patients with heart valve prostheses. Analysis of risk factors affecting perioperative mortality].

Sixty-two patients with at least one prosthetic heart valve each underwent a total of 70 reoperations. Their cases were analysed with special regard to the risk of perioperative mortality and to the factors affecting that risk. The age of the patients studied was 47 +/- 14.6 years (mean +/- 1 SD), and 4.75 +/- 4 years had elapsed since their previous operation. A total of 85 prostheses were implanted at the time of initial surgery. Forty-nine of those were mitral, 28 were aortic, and 8 were tricuspid prostheses. There were 48 mechanical valves, 24 bioprostheses and 13 Carpentier rings (9 of the latter being mitral and 4 tricuspid). At reoperation (n = 70) 95 valves required treatment. Eighteen patients died following their first reoperation (18/62, 29%), and two more died after a second reoperation (2/8, 25%). Actuarial probability of hospital survivors being alive 8-9 years following reoperation was 47 +/- 15%. It was found by multiple regression analysis that the duration of cardiopulmonary bypass (p less than 0.01), surgical priority (p less than 0.05) and the patient's age (p less than 0.05) were the only independent predictors of hospital death. A review of the literature and our own results suggest that surgical problems encountered with reoperation have unfavourably affected surgical results in the past. Objective risk factors are currently more related to the operative outcome. For these to be neutralised, patients with dysfunctioning prosthetic heart valves should be operated at an early stage before they reach a critical one. Only patients with stable, mild dysfunction unlikely to worsen acutely may probably be followed-up safely.

Actuarial Analysis↗

Prevention of calcification in bioprosthetic heart valves: challenges and perspectives.

Surgical replacement with artificial devices has revolutionised the care of patients with severe valvular diseases. Mechanical valves are very durable, but require long-term anticoagulation. Bioprosthetic heart valves (BHVs), devices manufactured from glutaraldehyde-fixed animal tissues, do not need long-term anticoagulation, but their long-term durability is limited to 15 - 20 years, mainly because of mechanical failure and tissue calcification. Although mechanisms of BHV calcification are not fully understood, major determinants are glutaraldehyde fixation, presence of devitalised cells and alteration of specific extracellular matrix components. Treatments targeted at the prevention of calcification include those that target neutralisation of the effects of glutaraldehyde, removal of cells, and modifications of matrix components. Several existing calcification-prevention treatments are in clinical use at present, and there are excellent mid-term clinical follow-up reports available. The purpose of this review is to appraise basic knowledge acquired in the field of prevention of BHV calcification, and to provide directions for future research and development.

Calcinosis↗

In vivo behavior of epoxy-crosslinked porcine heart valve cusps and walls.

Calcification limits the long-term durability of xenograft glutaraldehyde-crosslinked heart valves. In this study, epoxy-crosslinked porcine aortic valve tissue was evaluated after subcutaneous implantation in weanling rats. Non-crosslinked valves and valves crosslinked with glutaraldehyde or carbodiimide functioned as control. Epoxy-crosslinked valves had somewhat lower shrinkage temperatures than the crosslinked controls, and within the series also some macroscopic and microscopic differences were obvious. After 8 weeks implantation, cusps from non-crosslinked valves were not retrieved. The matching walls were more degraded than the epoxy- and control-crosslinked walls. This was observed from the higher cellular ingrowth with fibroblasts, macrophages, and giant cells. Furthermore, non-crosslinked walls showed highest numbers of lymphocytes, which were most obvious in the capsules. Epoxy- and control-crosslinked cusps and walls induced lower reactions. Calcification, measured by von Kossa-staining and by Ca-analysis, was always observed. Crosslinked cusps calcified more than walls. Of all wall samples, the non-crosslinked walls showed the highest calcification. It is concluded that epoxy-crosslinked valve tissue induced a foreign body and calcification reaction similar to the two crosslinked controls. Therefore, epoxy-crosslinking does not represent a solution for the calcification problem of heart valve bioprostheses.

Animals↗

FDA's requirements for in-vitro performance data for prosthetic heart valves.

The Center for Devices and Radiological Health, Food and Drug Administration, has recently revised its "Replacement Heart Valve Guidance". That document lists the data FDA deems necessary to support the approval of new prosthetic heart valves of all designs, and which should be contained in Premarket Approval Applications for these devices. The Guidance covers detailed data requirements for in vitro, animal, and clinical data. This paper is intended to briefly summarize FDA's requirements for in vitro data, and, for those cases where it may not be obvious, to provide an overview of the significance of these data and how FDA interprets them in the approval decision process.

Biomechanical Phenomena↗

Development, manufacturing and validation of a single-leaflet mechanical heart valve prosthesis.

A new single-leaflet mechanical heart valve prosthesis was developed and evaluated in vitro and in vivo. The basic design of the closing body is S-shaped, with the leading and trailing edges parallel to the flow direction. This closing body has an additional cross camber and a fixed axis of rotation. The bearing pins of the disc are guided within oblong through bores of the housing, resulting in a self-cleaning effect. The valve housing has a nozzle-shaped configuration in order to avoid flow separation at the inlet and to reduce the associated pressure loss. Development and optimization studies were carried out by means of upscale valve models. After manufacturing of the closing body from pyrolytic carbon and of the orifice from titanium final hydrodynamic evaluation was carried out according to ISO 5840. The results were comparable or better than for bileaflet valves, the cavitation threshold was above a left ventricular dP/dt of 5500 mmHg/sec. The excellent in vitro results were confirmed by in vivo animal studies in calves and sheep with implantation times of 12 months and six months, respectively. These studies were carried out at the RWTH Aachen and at the NIH, Washington. Without any anticoagulation treatment the valves showed excellent results, confirming the concept of a valve design based on advanced engineering techniques.

Animals↗

Pregnancy outcome in women with prosthetic heart valves.

The pregnancy outcome of 59 pregnancies in 38 women with prosthetic heart valves, managed at a tertiary referral centre from 1989-98 were reviewed. Ten women underwent valve replacement during pregnancy. The main outcome measures were major maternal complications and perinatal outcome. The maternal mortality rate for pregnancies following valve replacement surgery was 6.1%, with a 21% pregnancy loss before viability and a perinatal loss of 8%. Major morbidity in this group was as follows: haemorrhage 29.8%, cardiac failure 12.8%, thromboembolism 8.5%, infective endocarditis 6.4% and valve thrombosis 4.3%. No maternal mortality occurred among those who underwent valve replacement during pregnancy but their perinatal loss was 25%. We conclude that although maternal mortality and morbidity rates in women with prosthetic heart valves who became pregnant were high, the perinatal outcome was good except for women who underwent valve replacement during pregnancy who experienced a high perinatal loss rate.

Journal Article↗

Histogenesis of the semilunar valves: an immunohistochemical analysis of tenascin and type-I collagen distribution in developing chick heart valves.

The development of the semilunar valves takes place in association with septation of the outflow tract in the embryonic heart. Although numerous studies have focused on this process, the causal mechanisms of valvular development remain obscure. This paper reports an immunohistochemical analysis of tenascin and type-I collagen distribution in developing chick heart valves. Tenascin is a glycoprotein that is present on some embryonic extracellular matrices. It plays several significant roles in tissue differentiation, cell growth, and tissue interactions; it is also important for the formation of specific zones of connective tissue that fulfill mechanical functions. Our results show that tenascin is present during valvular morphogenesis and histogenesis, and that its distribution is associated with zones specialized in bearing mechanical loads.

Animals↗

Beta-actin cannot be used as a control for gene expression in ovine interstitial cells derived from heart valves.

BACKGROUND AND AIM OF THE STUDY: In gene expression studies, endogenous controls that are constitutively expressed (housekeeping genes) are commonly used to normalize for variations in cDNA synthesis efficiency. In the present study, a frequently used control gene, beta-actin, was examined in ovine heart valves to evaluate its applicability as a housekeeping gene for this tissue. METHODS: Interstitial cells (IC) of the four heart valves were isolated using the outgrowth explant method. Cells were cultured under different serum conditions (10% or 20% fetal bovine serum or 20% sheep serum) up to passage (P) 5. mRNA from fresh tissue and from cells at P0 and P5 was isolated, and expression of beta-actin determined using reverse transcription-polymerase chain reaction (RT-PCR). An identical control sample was used for each PCR and each gel electrophoresis. Data were expressed as a relative value of this control sample. RESULTS: beta-Actin expression in the aortic valve was significantly lower than in other valves. The mRNA level of beta-actin was four-fold lower in freshly isolated IC than in cultured IC. Once up-regulated by in-vitro culturing conditions, beta-actin expression did not change from P0 to P5. An important increase in the variation of beta-actin expression was observed in cultured cells as compared to fresh cells. Different serum conditions did not lead to different beta-actin levels. CONCLUSION: Due to the variation in expression, beta-actin cannot be used as a reference for gene expression of ovine-derived heart valve IC in culture.

Actins↗

Polyurethane: material for the next generation of heart valve prostheses?

OBJECTIVES: The prospects for a durable, athrombogenic, synthetic, flexible leaflet heart valve are enhanced by the recent availability of novel, biostable polyurethanes. As a forerunner to evaluation of such biostable valves, a prototype trileaflet polyurethane valve (utilising conventional material of known in vitro behaviour) was compared with mechanical and bioprosthetic valves for assessment of in vivo function, durability, thromboembolic potential and calcification. METHODS: Polyurethane (PU), ATS bileaflet mechanical, and Carpentier-Edwards porcine (CE) valves were implanted in the mitral position of growing sheep. Counting of high-intensity transient signals (HITS) in the carotid arteries, echocardiographic assessment of valve function, and examination of blood smears for platelet aggregates were undertaken during the 6-month anticoagulant-free survival period. Valve structure and hydrodynamic performance were assessed following elective sacrifice. RESULTS: Twenty-eight animals survived surgery (ten ATS; ten CE; eight PU). At 6 months the mechanical valve group (n=9) showed highest numbers of HITS (mean 40/h, P=0.01 cf. porcine valves), and platelet aggregates (mean 62.22/standard field), but no thromboembolism, and no structural or functional change. The bioprosthetic group (n=6) showed low HITS (1/h) and fewer aggregates (41.67, P=1.00, not significant), calcification and severe pannus overgrowth with progressive stenosis. The PU valves (n=8) showed a small degree of fibrin attachment to leaflet surfaces, no pannus overgrowth, little change in haemodynamic performance, low levels of HITS (5/h) and platelet aggregates (17.50, P<0.01 cf. mechanical valves, P=0.23 cf. porcine valves), and no evidence of thromboembolism. CONCLUSIONS: In the absence of valve-related death and morbidity, and retention of good haemodynamic function, the PU valve was superior to the bioprosthesis; lower HITS and aggregate counts in the PU valve imply lower thrombogenicity compared with the mechanical valve. A biostable polyurethane valve could offer clinical advantage with the promise of improved durability (cf. bioprostheses) and low thrombogenicity (cf. mechanical valves).

Analysis of Variance↗

Libman-Sacks endocarditis in the antiphospholipid syndrome: immunopathologic findings in deformed heart valves.

OBJECTIVE: To examine the potential immunologic mechanism and involvement of antiphospholipid antibodies in the pathogenesis of heart valve lesions in patients with the antiphospholipid syndrome (APS). METHODS: Immunoperoxidase and immunofluorescence staining methods were used to evaluate 13 heart valve specimens derived from eight patients with the APS, either primary or secondary to systemic lupus erythematosus. Primary antibodies to human immunoglobulins, complement components, serum albumin and a monoclonal anti-idiotypic antibody to human anticardiolipin antibodies (aCL) were employed. Various tissue specimens from a patient with the APS as well as deformed and normal valves from subjects without the APS were used as controls. RESULTS: Linear subendothelial deposition consisting of immunoglobulins with complement components but not of a non-specific serum protein was found in deformed valves from patients with the APS. None of the control valves or tissues disclosed similar deposition. The same pattern and location of staining was obtained by the anti-idiotypic antibody to aCL. A significant amount of IgG immunoglobulins that bound to cardiolipin was eluted from a valve of a patient with secondary APS. CONCLUSION: Deposits of immunoglobulins including aCL, and of complement components, are common in affected valves of patients with primary and secondary APS. Such deposits may be involved in the pathogenesis of valvular lesions.

Adult↗

Regurgitant flow field characteristics of the St. Jude bileaflet mechanical heart valve under physiologic pulsatile flow using particle image velocimetry.

The regurgitant flow fields of clinically used mechanical heart valves have been traditionally studied in vitro using flow visualization, ultrasound techniques, and laser Doppler velocimetry under steady and pulsatile flow. Detailed investigation of the forward and regurgitant flow fields of these valves can elucidate a valve's propensity for blood element damage, thrombus formation, or cavitation. Advances in particle image velocimetry (PIV) have allowed its use in the study of the flow fields of prosthetic valves. Unlike other flow field diagnostic systems, recent work using PIV has been able to relate particular regurgitant flow field characteristics of the Bjork-Shiley Monostrut valve to a propensity for cavitation. In this study, the regurgitant flow field of the St. Jude Medical bileaflet mechanical heart valve was assessed using PIV under physiologic pulsatile flow conditions. Data collected at selected time points prior to and after valve closure demonstrated the typical regurgitant jet flow patterns associated with the St. Jude valve, and indicated the formation of a strong regurgitant jet, in the B-datum plane, along with twin vortices near the leaflets. Estimated ensemble-average viscous shear rates suggested little potential for hemolysis when the hinge jets collided. However, the vortex motion near the occluder tips potentially provides a low-pressure environment for cavitation.

Blood Flow Velocity↗

The collagen of heart valve.

A hydroxylysine-rich type I collagen has been isolated from pepsin-digested porcine heart valve. The ratio of alpha1 to alpha2 in the isolated molecule was 2:1. The component alpha chains exhibited unusual chromatographic behavior in comparison to corresponding chains from human dermis and lathyritic rat skin collagen. The composition of component cyanogen bromide peptides identified the alpha chains as authentic type I chains and demonstrated hydroxylysine enrichment throughout the length of the chain. delta6-Dehydro-5,5'dihydroxylysinonorleucine, a collagen cross-link derived from two hydroxylysyl residues and ordinarily found in hard tissue collagens was found to be the predominant cross-link in heart valve.

Amino Acids↗