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Biomedical subjects

David B Ross

Publications and source records attributed to David B Ross.

At least 19 recordsLinked to original sources
PubMed2006

Glutaraldehyde-fixed bioprosthetic heart valve conduits calcify and fail from xenograft rejection.

BACKGROUND: Glutaraldehyde fixation (G-F) decreases but likely does not eliminate the antigenicity of bioprosthetic heart valves. Rejection (with secondary dystrophic calcification) may be why G-F xenograft valves fail, especially in young patients, who are more immunocompetent than the elderly. Therefore, we sought to determine whether rejection of G-F xenograft occurs and to correlate this with graft calcification. METHODS AND RESULTS: Ascending aortas/valves (from rats [syngeneic] or guinea pigs [xenogeneic]) were transplanted (fresh or after 48 hour of G-F) into the infrarenal aortas of young rat recipients for 20 days. A xenogeneic group was also treated with steroids until graft harvest. The valves and media/adventitia were scored blindly for inflammation (0 to 4). Percent graft infiltration by T cells/macrophages was determined (immunohistochemistry), and rat IgG ELISAs were performed. There was >3 times more valve inflammation, >10 times more valve T-cell/macrophage infiltrate, and >3 times antibody rise in the G-F xenogeneic groups compared with the fresh syngeneic or the G-F syngeneic groups (P<0.05). There was >2 times more adventitial inflammation and T-cell/macrophage infiltrate in the xenogeneic groups (P<0.05). Steroid treatment decreased inflammation and antibody rise in the xenogeneic groups (P<0.05). Correlation analysis revealed media/adventitia inflammation (P=0.02) and percent macrophage (P=0.01) infiltration to be predictors of calcification. CONCLUSIONS: G-F xenografts have cellular/humoral rejection and calcify secondarily.

Animals↗
PubMed2006

Comparison of aortic valve allograft decellularization techniques in the rat.

Rodent models have been essential to understanding the immune-mediated failure of aortic valve allografts (AVAs). Decellularization has been proposed to reduce the immunogenicity of AVAs. The objective of this study was to determine the most effective method to decellularize AVAs for use in a rat model. Three different decellularization techniques were compared in Lewis aortic valves. Detergent decellularization involved a series of hypotonic and hypertonic Tris buffers at 4 degrees C for 48 h/buffer containing 0.5% Triton X-100 followed by a 72 h washout in phosphate-buffered saline. Osmotic decellularization was performed in similar manner to the detergent-based technique except without the addition of Triton X-100. Enzymatic decellularization consisted of trypsin/EDTA at 37 degrees C for 48 h. Assessment was performed with light microscopy (H&E, Movat's pentachrome), immunohistochemistry for residual cellular elements, and hydroxyproline assays. Detergent-based methodology effected near-complete decellularization of both the leaflets and aortic wall in addition to preservation of the extracellular matrix (ECM). Osmotic lysis was associated with preservation of ECM and moderate decellularization. Enzymatic decellularization resulted in complete decellularization but extensive degeneration and fragmentation of the ECM. When implanted into the infrarenal aorta of allogeneic rats for 1 week, valves decellularized with detergent-based and osmotic methodology failed to stimulate an allogeneic immune response as evidenced by an absence of T cell infiltrates. Osmotic lysis protocols with low dose detergent appear to be most effective at both removing antigenic cellular elements and preserving ECM.

Animals↗
PubMed2006

The rapid prototyping of anatomic models in pulmonary atresia.

OBJECTIVE: The goal of this study was to assess the utility and accuracy of solid anatomic models constructed with rapid prototyping technology for surgical planning in patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. METHODS: In 6 patients with pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, anatomic models of the pulmonary vasculature were rapid prototyped from computed tomographic angiographic data. The surgeons used the models for preoperative and intraoperative planning. The models' accuracy and utility were assessed with a postoperative questionnaire completed by the surgeons. An independent cardiac radiologist also assessed each model for accuracy of major aortopulmonary collateral artery origin, course, and caliber relative to conventional angiography. RESULTS: Of the major aortopulmonary collateral arteries identified during surgery and conventional angiography, 96% and 93%, respectively, were accurately represented by the models. The surgeons found the models to be very useful in visualizing the vascular anatomy. CONCLUSION: This study presents the novel vascular application of rapid prototyping to pediatric congenital heart disease. Anatomic models are an intuitive means of communicating complex imaging data, such as the pulmonary vascular tree, which can be referenced intraoperatively.

Biomedical Engineering↗
PubMed2006

Intermediate-term outcomes of the arterial switch operation for transposition of great arteries in neonates: alive but well?

OBJECTIVES: This interprovincial inception cohort study outlines the operative and intermediate outcomes of all neonates at a single institution with a broad referral area who underwent the arterial switch operation for transposition of great arteries, including complex types. Predictors of outcome are explored. METHODS: A total of 88 consecutive neonates underwent the arterial switch operation between 1996 and 2004 with full-flow (150 mg/kg/min) cardiopulmonary bypass with selective deep hypothermic circulatory arrest. Overall and event-free survivals were calculated. Health and neurodevelopment (Bayley Scales of Infant Development II) were assessed at 18 to 24 months of age. Univariate and multivariate analyses, sensitivity, and specificity were determined to identify preoperative, intraoperative, and postoperative factors associated with mental and/or motor delay. RESULTS: There was 1 operative mortality (1.1%). At the average 4-year follow-up, survival was 98.9% and freedom from reintervention was 93.2%. Eighty-five children were assessed. Three were excluded because of unrelated postoperative diagnoses. For the remaining 82, mean scores were 89 +/- 17 (49-118) for mental skills and 92 +/- 15 (49-125) for motor skills. Anatomic complexity, cardiopulmonary bypass, and deep hypothermic circulatory arrest times were not associated with developmental outcome. Preoperative variables of low gestational age and high preoperative lactate correctly classified 84.1% of mentally and/or motor-delayed children. CONCLUSION: Transposition of great arteries, including complex types, can be corrected with low surgical risk and good intermediate survival; however, neurodevelopmental outcome is a concern. These data suggest that although anatomic complexity may not affect late outcome, there may be potentially modifiable preoperative factors that can be optimized to improve developmental outcomes.

Cardiac Surgical Procedures↗
PubMed2006

Inbred or outbred? An evaluation of the functional allogenicity of farm sheep used in cardiac valve studies.

OBJECTIVE: Cryopreserved allograft cardiovascular tissue elicits a strong cellular and humoral response in recipients; this may accelerate the deterioration of the allograft and complicate future heart transplantation. Juvenile sheep are the standard model for in vivo valve research and have been used to investigate the allogeneic immune response to cardiac valve and vascular tissue transplantation. Studies to date have not considered the extent of allogenicity of sheep used in transplantation studies. METHODS: Functional allogenicity was assessed by standard one-way mixed lymphocyte reaction assay using peripheral blood mononuclear cells. Responder cells were stimulated with irradiated stimulator cells and cultured at 37 degrees C in 95% air and 5% carbon dioxide for 3, 4, 5, and 6 days. Cultures were pulsed with tritiated thymidine for 24 hours and harvested onto filtermats. RESULTS: The allogeneic response, measured as counts per minute, demonstrated a bimodal distribution. Fifty-nine (36.9%) of 160 pairs fell within the first peak (counts per minute < 10,000) and were defined as weak responders. The remaining 101 (63.1%) of 160 pairs of animals demonstrated a strong allogeneic response (counts per minute > or = 10,000) that followed a normal distribution. CONCLUSIONS: More than 1 in 3 pairs of sheep is too closely related to elicit an immune response when cross-reacted. This finding may alter the interpretation of studies that base their findings on allogeneic transplantations in sheep without ascertaining the genetic similarities of the animals. Valve transplantation studies in a sheep model should assess the extent of allogenicity of donor and recipient sheep.

Animals↗
PubMed2006

Q fever endocarditis: a case report and review of the literature.

The case of a 31-year-old man from Alberta diagnosed with Q fever endocarditis is presented. To the authors' knowledge, this is the first case of Q fever endocarditis diagnosed in the province of Alberta. The patient had undergone open valvulotomy for congenital aortic stenosis as an infant. He presented with congestive heart failure secondary to severe aortic regurgitation and underwent mechanical aortic valve replacement. Early failure of the mechanical prosthesis and numerous laboratory abnormalities prompted an investigation for endocarditis, which was initially negative. Markedly positive serology eventually established the diagnosis of chronic Q fever. The patient subsequently underwent a second aortic valve replacement following initiation of appropriate antimicrobials directed against Coxiella burnetii. The present report reviews the clinical presentation and diagnosis of Q fever endocarditis. It highlights the insidious and nonspecific nature of the presenting symptoms, and emphasizes the use of serology for diagnosis. Increased awareness and earlier diagnosis can significantly decrease the morbidity and mortality associated with this disease.

Adult↗
PubMed2006

Treating the right patient at the right time: Access to cardiac catheterization, percutaneous coronary intervention and cardiac surgery.

The Canadian Cardiovascular Society Access to Care Working Group was formed with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for cardiac catheterization and revascularization procedures for patients with stable angina, and access benchmarks for cardiac catheterization and surgery for patients with valvular heart disease. Literature on standards of care, wait times and wait list management was reviewed. A survey of cardiac centres in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommends the following medically acceptable wait times for access to cardiac catheterization: 14 days for symptomatic aortic stenosis and six weeks for patients with stable angina and other valvular disease. For percutaneous coronary intervention in stable patients with high-risk anatomy, immediate revascularization or a wait time of 14 days is recommended; six weeks is recommended for all other patients. The target for bypass surgery in those with high-risk anatomy or valve surgery in patients with symptomatic aortic stenosis is 14 days; for all others, the target is six weeks. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. There is an ongoing need to continually reassess current risk stratification methods to limit adverse events in patients on waiting lists and assist clinicians in triaging patients for invasive therapies.

Angioplasty, Balloon, Coronary↗
PubMed2005

Is mitral valve surgery safe in octogenarians?

OBJECTIVE: To evaluate the outcomes of mitral valve surgery in octogenarians. METHODS: Data were collected prospectively from January 1996 to March 2004 at two surgical centers. Of 1386 consecutive patients with mitral valve surgery, 58 (4.2%) were aged > or = 80 years. Survival data were analyzed using Cox proportional hazards modeling and Kaplan-Meier actuarial log rank statistics. RESULTS: Octogenarians were similar to younger patients for the presence of pre-operative hypertension, hyperlipidemia, diabetes mellitus, and smoking history. Octogenarians had a higher incidence of cerebrovascular disease (19.0 versus 7.8%, P = 0.003), urgent in-hospital surgery (55.2 versus 28.6%, P < 0.001), and presence of ischemic disease requiring combined mitral valve plus revascularization surgery (72.4 versus 41.0%, P < 0.001). Mitral valve repair was performed in a similar proportion of octogenarians and younger patients (44.8 versus 45.6%). Thirty-day mortality for octogenarians was significantly higher than younger patients (15.5 versus 5.6%, P = 0.002), and actuarial survival of octogenarians was significantly decreased (P = 0.009). However, 52.3% of the octogenarians were alive at 7-years following surgery. Independent predictors of mortality from multivariate risk adjusted modeling of the entire cohort were: emergency surgery (hazards ratio [HR] = 2.94, P < 0.001), combined mitral valve plus revascularization surgery (HR = 2.27, P < 0.001), mitral valve replacement (HR = 1.85, P < 0.01), and age > or = 80 years (HR = 1.80, P = 0.02). CONCLUSIONS: Octogenarians undergoing mitral valve surgery have significantly greater incidence of urgent surgery, ischemic disease requiring combined revascularization surgery, and have decreased rates of survival. While caution is required when operating on these higher risk elderly patients, overall 52.3% of the octogenarians are alive at 7-years following surgery, which is greater than the survival of octogenarians in the community. The greatest survival benefit within octogenarians occurred when mitral valve repair was possible over replacement. Further study will more clearly define subgroups of octogenarians with potentially greater benefit from mitral valve surgery.

Adolescent↗
PubMed2005

Pediatric poststernotomy mediastinitis.

BACKGROUND: Mediastinitis results in significant morbidity in pediatric cardiac patients. It is not clear whether delayed sternal closure is a risk factor for these infections. Management of mediastinitis remains controversial. METHODS: Cases of mediastinitis at the Stollery Children's Hospital from January 1, 1991, to June 30, 2004, were reviewed. RESULTS: There were 29 cases of mediastinitis in 2,675 open cardiac procedures for an overall incidence of 1.1%. Infection was diagnosed 5 to 27 days after the original surgical procedure (median, 10 days). The odds ratio for infection with delayed sternal closure versus primary sternal closure was 1.88 (95% confidence interval, 0.63 to 5.60). Signs at the onset of infection included fever (86%), incisional erythema (69%), purulent drainage from the incision or pacer wire sites (83%), and wound dehiscence (23%). Debridement was followed by primary sternal closure in all but three cases in which the sternum had not been closed before debridement and rotational muscle flaps were not used. Continuous irrigation systems were used only in the first 7 patients. One patient died of mediastinitis complicated by infective endocarditis, and 2 patients died of multiorgan failure. CONCLUSIONS: Delayed sternal closure was not a major risk factor for mediastinitis, especially if primary skin closure was used with delayed sternal closure. Excellent results were attained with debridement and primary closure of these infections.

Adolescent↗
PubMed2005

Use of an allograft patch in repair of hypoplastic left heart syndrome may complicate future transplantation.

OBJECTIVE: Cryopreserved allograft tissue used in the Norwood procedure for infants with hypoplastic left heart syndrome (HLHS) has the potential to cause marked immunologic sensitization which may complicate potential future heart transplantation, if required. The purpose of this study was to assess the anti-HLA antibody response to allograft patches used in the initial repair of HLHS. METHODS: A prospective cohort study was conducted comparing the panel-reactive antibody levels (PRA) in 12 infants undergoing repair of HLHS with cryopreserved allograft patch to 10 infants undergoing arterial switch for transposition of the great arteries (no allograft tissue used). PRA for Class I (HLA-A, B, C) and Class II (HLA-DR, DQ) antibodies were assessed preoperatively and postoperatively using flow cytometry. RESULTS: The two groups were well matched at the time of surgery (age, weight, gender). Infants in both groups received blood from multiple donors; however, the allograft group received significantly more (12+/-10 vs. 5+/-1 units; P<0.001). By 4 months, most infants receiving allograft tissue had become highly sensitized for both Class I PRA (62+/-40 vs. 0; P=0.002) and Class II PRA (49+/-42 vs. 2+/-3; P=0.022). This response continued to increase at 12 months: Class I PRA (79+/-21 vs. 0; P=0.008) and Class II PRA (66+/-27 vs. 5+/-6; P=0.008). Specificity analysis confirmed antibodies were specific for the donor allograft HLA type. In addition, infants who were coincidently HLA-matched with their allograft did not develop an elevated PRA. CONCLUSIONS: Allograft tissue used in the repair of HLHS is associated with profound donor specific immunologic sensitization in the majority of recipients and may complicate or jeopardize future transplantation. Methods to reduce the immunogenicity of cryopreserved allograft tissue used for arch reconstruction requires further investigation.

Adolescent↗
PubMed2005

Decellularization reduces the immune response to aortic valve allografts in the rat.

OBJECTIVES: Cryopreserved valve allografts used in congenital cardiac surgery are associated with a significant cellular and humoral immune response. This might be reduced by removal of antigenic cellular elements (decellularization). The aim of this study was to determine the immunologic effect of decellularization in a rat allograft valve model. METHODS: Brown Norway and Lewis rat aortic valves were decellularized with a series of hypotonic and hypertonic buffers, protease inhibitors, gentle detergents (Triton X-100), and phosphate-buffered saline. Valves were implanted into Lewis rats in syngeneic and allogeneic combinations. Cellular (CD3 and CD8) infiltrates were assessed with morphometric analysis, and the humoral response was assessed with flow cytometry. RESULTS: Morphometric analysis identified a significant reduction in CD3 + cell infiltrates (cells per square millimeter of leaflet tissue) in decellularized allografts compared with that seen in nondecellularized allografts at 1 (79 +/- 29 vs 3310 +/- 223, P < .001), 2 (26 +/- 11 vs 109 +/- 20, P = .004), and 4 weeks (283 +/- 122 vs 984 +/- 145, P < .001). Anti-CD8 staining confirmed the majority of infiltrates were cytotoxic T cells. Flow cytometric mean channel fluorescence intensity identified a negative shift (abrogated antibody formation) for decellularized allografts compared with nondecellularized allografts at 2 (19 +/- 1 vs 27 +/- 3, P = .033), 4 (35 +/- 2 vs 133 +/- 29, P = .001), and 16 weeks (28 +/- 2 vs 166 +/- 54, P = .017). CONCLUSIONS: Decellularization significantly reduces the cellular and humoral immune response to allograft tissue. This could prolong the durability of valve allografts and might prevent immunologic sensitization of allograft recipients.

Animals↗
PubMed2005

Declining need for permanent pacemaker insertion with the bicaval technique of orthotopic heart transplantation.

BACKGROUND: The bicaval technique of orthotopic heart transplantation, in contrast to the standard biatrial technique, may better preserve right atrial anatomy and, thus, may be associated with less sinus node dysfunction and less atrioventricular valve dysfunction. OBJECTIVES: To compare the requirement for permanent pacemaker insertion and the incidence of atrioventricular valve dysfunction following heart transplantation with either the standard or the bicaval technique. PATIENTS AND METHODS: A retrospective analysis was conducted of a consecutive cohort of 105 patients, older than 18 years of age, undergoing heart transplantation with either the standard (n=48) or the bicaval (n=57) technique from December 1998 to December 2001. RESULTS: Cross-clamp (100 min versus 112 min; P=0.012) and donor ischemic (222 min versus 276 min; P=0.005) times were significantly prolonged in the bicaval group. Perioperative morbidity and mortality were statistically similar between the groups. Bicaval transplantation resulted in a significant decrease in the requirement for permanent pacemaker insertion at 30 days (13% versus 0%; P=0.008) and 90 days (17% versus 1.8%; P=0.01) after transplantation. There was a nonsignificant trend toward a decreased degree of tricuspid valve regurgitation (mean 1.81 versus 1.36; P=0.141) and mitral valve regurgitation (mean 1.04 versus 0.79; P=0.348) with the bicaval technique. CONCLUSIONS: Although associated with longer cross-clamp and donor ischemic times, the data demonstrated a significant reduction in the need for permanent pacemaker insertion at 30 and 90 days post-transplantation with the bicaval technique. There was no statistically significant difference in the degree of mitral and tricuspid valve regurgitation between the two groups.

Age Factors↗
PubMed2004

Posterior annular plication: tricuspid valve repair in Ebstein's anomaly.

BACKGROUND: Nonneonatal Ebstein's anomaly is a rare congenital anomaly for which numerous operative techniques have been described to repair the aberrant tricuspid valve, exclude the atrialized right ventricle, and address right heart dysfunction. We reviewed short-term outcomes in surgical patients treated by a simplified operative technique. METHODS: Our operative approach to Ebstein's anomaly is approximation of the anteroposterior commissure to the remnant septal leaflet with closure of the cul-de-sac longitudinally. Plication of the atrialized right ventricle (1 patient) and a bidirectional cavopulmonary connection (2 patients) were performed only if necessary. All patients were followed postoperatively by their cardiac surgeon and cardiologist. RESULTS: Seven patients with a mean age of 39 years (range, 3.6 to 63.8 years) underwent repair. Preoperatively all patients had 4+ tricuspid valve regurgitation and were New York Heart Association class III. Mean postoperative hospital stay was 7 +/- 2 days (range, 4 to 11 days). Mean follow-up is 42 +/- 18 months (range, 7 to 58 months). At last follow-up 5 patients are New York Heart Association class I and average tricuspid valve regurgitation is mild. CONCLUSIONS: Plication of the posterior annulus without plication of the atrialized right ventricle, resiting the tricuspid valve, or performing prophylactic cavopulmonary connection appears to be a reasonable operative approach to nonneonatal Ebstein's anomaly. Long-term follow-up of this cohort is necessary to determine the durability of such a surgical approach.

Adolescent↗
PubMed2003

Human leukocyte antigen-DR and ABO mismatch are associated with accelerated homograft valve failure in children: implications for therapeutic interventions.

OBJECTIVE: This study examines the incidence and factors associated with the failure of homograft valves and identifies those factors that are modifiable. METHODS: From 1990 to 2001, 96 homograft valves were implanted in the right ventricular outflow tract of 83 children (mean age 5.1 +/- 5.6 years). Clinical and blinded serial echocardiographic follow-up was performed on all 90 valves in the 77 survivors. RESULTS: Eighteen homograft valves were replaced as the result of pulmonary insufficiency (3), stenosis (9), or both (6). Freedom from reoperation was 71% at 9 years (95% confidence interval, 58%-84%). Forty-eight valves developed progressive pulmonary insufficiency of at least 2 grades, 26 valves developed transvalvular gradients of 50 mm Hg or greater, and 14 of these valves were also insufficient. The freedom from echocardiographic failure (progressive pulmonary insufficiency >or=2 grades or >or=50 mm Hg gradient) was only 27% at 5 years (95% confidence interval, 17%-37%). In a multivariate analysis (Cox regression), use of an aortic homograft (P =.001) and short antibiotic preservation time (P =.04) were associated with reoperation. Younger age (P =.01), ABO mismatch (P =.04), and diagnosis (P =.005) were associated with echocardiographic failure. In the subanalysis of patients with human leukocyte antigen typing, age (P =.002), aortic homograft (P =.04), and human leukocyte antigen-DR mismatch (P =.03) were associated with echocardiographic valve failure. CONCLUSION: Many homografts rapidly become insufficient and require replacement. In our analysis of both reoperation and echocardiographic failure, several immunologic factors are consistently associated with homograft failure. Matching for human leukocyte antigen-DR, blood group, and avoiding short preservation times (thus minimizing antigenicity) offers the potential to extend the life of these valves.

ABO Blood-Group System↗