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Biomedical subjects

A J Bogers

Publications and source records attributed to A J Bogers.

At least 19 recordsLinked to original sources

Prognosis after aortic valve replacement with a bioprosthesis: predictions based on meta-analysis and microsimulation.

BACKGROUND: Bioprostheses are widely used as an aortic valve substitute, but knowledge about prognosis is still incomplete. The purpose of this study was to provide insight into the age-related life expectancy and actual risks of reoperation and valve-related events of patients after aortic valve replacement with a porcine bioprosthesis. METHODS AND RESULTS: We conducted a meta-analysis of 9 selected reports on stented porcine bioprostheses, including 5837 patients with a total follow-up of 31 874 patient-years. The annual rates of valve thrombosis, thromboembolism, hemorrhage, and nonstructural dysfunction were 0.03%, 0.87%, 0.38%, and 0.38%, respectively. The annual rate of endocarditis was estimated at 0.68% for >6 months of implantation and was 5 times as high during the first 6 months. Structural valve deterioration was described with a Weibull model that incorporated lower risks for older patients. These estimates were used to parameterize, calibrate, and validate a mathematical microsimulation model. The model was used to predict life expectancy and actual risks of reoperation and valve-related events after implantation for patients of different ages. For a 65-year-old male, these figures were 11.3 years, 28%, and 47%, respectively. CONCLUSIONS: The combination of meta-analysis with microsimulation enabled a detailed insight into the prognosis after aortic valve replacement with a bioprosthesis for patients of different ages. This information will be useful for patient counseling and clinical decision making. It also could serve as a baseline for the evaluation of newer valve types.

Adolescent↗

[Surgical treatment of hypoplastic left heart syndrome: limited success].

OBJECTIVE: To inventory the treatment of hypoplastic left heart syndrome (HLHS) in the Netherlands and its results. DESIGN: Retrospective. METHOD: Data were collected from all patients (n = 117) diagnosed with HLHS in the Wilhelmina Children's Hospital-University Medical Center Utrecht and the University Hospital Rotterdam-Sophia Children's Hospital and born in the period 1 March 1988-31 May 2000. Type and time of intervention, and mortality were recorded and cumulative survival was analysed by Kaplan-Meier analysis. Cumulative survival was compared between early and late series and between the two hospitals. RESULTS: The study group comprised 68 boys and 49 girls, all neonates. At the time of the investigation, the mean duration of follow-up was 185 days (range: 0-3855). Fifty-eight children had received no treatment; all of these had died. Fifty-nine children were scheduled for the Norwood procedure; six of them died before operation. The 53 patients who underwent the first stage of the Norwood procedure had 1-month, 1-year, 2-year, and 5-year survival chances of 55%, 30%, 27%, and 24% respectively. Survival chances between the two time periods and the two hospitals showed no significant differences. CONCLUSION: The Norwood procedure was performed in almost half of the children with HLHS. It is only moderately successful; however, it seems the only realistic choice in the management.

Cardiac Surgical Procedures↗

Right ventricular outflow tract reconstruction with an allograft conduit.

BACKGROUND: Allograft conduits are used for reconstruction of the right ventricular outflow tract in patients with congenital heart disease and in the pulmonary autograft procedure. A retrospective evaluation of our experience with the use of allograft conduits for reconstruction of the right ventricular outflow tract was conducted. METHODS: Between August 1986 and March 1999, 316 allografts (246 pulmonary, 70 aortic) were implanted in 297 patients for reconstruction of the right ventricular outflow tract. Main diagnostic groups were aortic valve pathology (n = 112, 35%), tetralogy of Fallot (n = 71, 22%), and pulmonary atresia with ventricular septal defect (n = 46, 14%). Kaplan-Meier analyses were done for survival, valve-related reoperation, and valve-related events. In addition, Cox regression analysis was used for evaluation of potential risk factors. RESULTS: Mean age at operation was 18 years (range, 7 days to 61 years). Mean follow-up was 4 years (range, 2 days to 12 years). Twelve patients (4%) died within 30 days after operation. Patient survival was 90% (95% confidence interval [CI], 86% to 94%) at 5 years and 88% (95% CI, 83% to 94%) at 8 years. Twenty-four reoperations were required for allograft dysfunction in 23 patients; 21 allografts were replaced. Freedom from valve-related reoperation was 91% (95% CI, 86% to 95) at 5 years and 87% (95% CI, 81% to 93%) at 8 years. Twenty-nine valve-related events were reported (2 deaths, 24 reoperations, 2 balloon dilatations, and 1 endocarditis). Freedom from valve-related events was 90% (95% CI, 85% to 94%) at 5 years after implantation, and 84% (95% CI, 77% to 91%) at 8 years. Risk factors for accelerated allograft failure were extra-anatomic position of the allograft (p = 0.03; hazard ratio, 9.7) and the use of an aortic allograft (p = 0.02; hazard ratio, 2.4). CONCLUSIONS: Right ventricular outflow tract reconstruction with an allograft conduit has good medium-term results, although progression of allograft degeneration is noted. Aortic allografts should preferably not be used for reconstruction of the right ventricular outflow tract.

Adolescent↗

Estimated event-free life expectancy after autograft aortic root replacement in adults.

BACKGROUND: Autograft aortic root replacement is an established therapeutic option for young adults with aortic valve disease. Unfortunately, most series are small with a limited follow-up. Meta-analysis and microsimulation modeling were used to predict long-term outcome based on currently available midterm data. METHODS: We combined our center's experience with autograft aortic root replacement in 85 adult patients in a meta-analysis with reported results of three other hospitals. The outcomes of this meta-analysis were entered in a microsimulation model, calculating (event-free) life expectancy after autograft aortic root replacement. RESULTS: The pooled results comprised 380 patients with a total follow-up of 1,077 patient-years. Mean age was 37 years (range 16 to 68 years). Male/female ratio was 2.7. Operative mortality was 2.6% (n = 10); during follow-up 6 more patients died. Linearized annual risk estimates were 0.5% for thromboembolism, 0.3% for endocarditis, and 0.4% for nonstructural valve failure. Structural autograft failure requiring reoperation occurred in 5 patients, and a Weibull function was constructed accordingly. Using this information, the microsimulation model predicted age- and gender-specific mean, reoperation-free, and event-free life expectancy. CONCLUSIONS: Based on current evidence the calculated average autograft-related reoperation-free life expectancy is 16 years. The combination of meta-analysis and microsimulation provides a promising and powerful tool for estimating long-term outcome after aortic valve replacement.

Adolescent↗

Immunological aspects of fresh and cryopreserved aortic valve transplantation in rats.

BACKGROUND: The influence of immune activation on valve allograft degeneration remains unclear. We studied the combined effect of major histocompatibility complex (MHC)-incompatibility and cryopreservation on valve performance, histomorphology, and tissue antigenicity in rats. METHODS: Fresh or cryopreserved allogeneic aortic valves from WAG (RT1u) rats were transplanted to DA (RT1a) recipients and syngenic transplants served as controls. After 7 or 21 days, valves were examined for competence and morphology. Immune reactivity of the recipient was measured by concanavalin A (conA) stimulation and analysis of donor-reactive Helper T-lymphocyte frequencies (HTLf) in peripheral blood and spleen. RESULTS: Syngenic grafts demonstrated normal competence and structure. Allografts lost their competence over time caused by destruction of the leaflets combined with cellular infiltration in the vascular wall. Cryopreservation induces early loss of competence and retrovalvular thrombosis. Cryopreserved allografts were also heavily infiltrated. ConA stimulation indices and HTLf were higher in allogeneic recipients compared to syngenic recipients (p < 0.03). Cryopreserved allografts elicited a lower immune response compared with fresh allografts (p < 0.03). CONCLUSIONS: Aortic valve allografts are able to induce a donor-reactive immune response that is related to early graft destruction and incompetence. Cryopreservation appears to diminish but not eliminate the antigenicity of the allograft.

Animals↗

Is the use of albumin in colloid prime solution of cardiopulmonary bypass circuit justified?

BACKGROUND: Albumin in the priming solution precoats the surface of the cardiopulmonary bypass circuit, supposedly causing delayed adsorption of fibrinogen and reduced activation and adhesion of platelets. This action may result in lower transoxygenator resistance. Because our institution uses a colloidal prime solution (Gelofusine), questions were raised about the value of albumin in the prime solution. We decided to focus on the clinical effects of transoxygenator resistance. METHODS: Sixty adults undergoing elective cardiac operations were randomly divided into three groups: a group with 20-g albumin (n = 20), a group with 2-g albumin (n = 20), and a group with no albumin (n = 20) in the 1,600-mL colloidal prime. Patients older than 75 years and patients with a preoperative serum albumin level of 30 g/L or less were excluded. The transoxygenator resistance was measured throughout cardiopulmonary bypass. Beta-thromboglobulin levels were used to study contact activation of platelets. Measures of prothrombin F1,2 fragments were used as a marker of thrombin generation. Body surface area, age, preoperative albumin, hematocrit, hemoglobin, fibrinogen, platelet count, and colloid osmotic pressure levels were compared between groups. RESULTS: Base line characteristics and chosen control measurements were similar for all three populations. When comparing the observed transoxygenator resistance among the three different groups, no significant differences were noted. Prothrombin F1.2 fragments remained low for all the groups without significant differences. In the no-albumin group the level of beta-thromboglobulin appeared to be higher, but the difference was not statistically significant. CONCLUSIONS: Addition of albumin to prime solution in a cardiopulmonary bypass circuit that already contains colloids does not affect the transoxygenator resistance of the COBE Duo flat sheet oxygenator and does not affect prothrombin F1.2 and beta-thromboglobulin levels. Therefore additional costs for the albumin are not justified. Measurement of transoxygenator resistance is a reliable, simple method to determine the effects of a prime solution on the oxygenator surface in vivo.

Aged↗

Different behavior of sequential versus single left internal mammary artery to left anterior descending area grafts(1).

To study echo Doppler characteristics of sequential versus single left internal mammary artery (LIMA) to left anterior descending (LAD) area grafts transthoracic echo Doppler at the LIMA origin and angiography were performed pre- and postoperatively. In 17 patients single LIMA to LAD (group I) and in 45 patients sequential LIMA to LAD area (group II) bypass grafting was performed. All patients show an early postoperative shift towards diastolic coronary Doppler velocity spectra. Only group II shows a further significant late increase in diastolic, velocity time integral and some systolic echo Doppler parameters at rest. Diastolic peak and diastolic as well as total mean and velocity time integral maximal values are significantly higher in group II in late postoperative hyperemic response. Preoperative and late control angiography showed no significant differences in overall grading of native LAD stenosis between both groups. The large coronary reserve in LIMA sequential grafts may contribute to an improved long-term patency.

Aged↗

Is there a place for pediatric valvotomy in the autograft era?

OBJECTIVE: Valvotomy and the autograft procedure are the most common surgical treatment options for children with valvular aortic stenosis. We evaluated the results of these surgical procedures in our institution. METHODS: Retrospective analysis was done of all patients presenting with aortic stenosis and operated upon before the age of 18. In 11 patients a valvotomy was performed and in 36 an autograft procedure. RESULTS: There was no hospital mortality. Mean follow-up in the valvotomy group was 4.8 years (SD 3.3), in the autograft group 4.5 years (SD 3.3). During follow-up one patient died suddenly 2 months after valvotomy. Two patients in the autograft group died (not valve-related). After valvotomy three patients underwent a balloon valvotomy, in one followed by an autograft procedure and one patient had a repeat valvotomy. In the autograft group one patient was reoperated for severe aortic regurgitation and moderate pulmonary stenosis. At last echocardiography after valvotomy (eight remaining patients) in only two patients (25%) no aortic stenosis or regurgitation was present. In the remaining six patients aortic stenosis is mild in two and moderate in three, including one with moderate aortic regurgitation. In one patient without stenosis, moderate aortic regurgitation was seen. No pulmonary stenosis or regurgitation is present. Echocardiography after autografting (33 remaining patients) showed no aortic stenosis. Aortic regurgitation was mild in seven patients, moderate in two, severe in one. Pulmonary stenosis was present in two patients (16%). Pulmonary regurgitation was mild in three patients and moderate in one. CONCLUSIONS: In selected patients with valvular aortic stenosis who are beyond infancy, valvotomy may be adequate and may postpone further surgery for a significant length of time. After valvotomy the main problem is residual aortic stenosis while after autografting a shift occurs to aortic regurgitation and problems related to the pulmonary valve. Careful clinical and echocardiographic follow-up is therefore warranted in young patients after the autograft procedure.

Adolescent↗

Differences in LIMA Doppler characteristics for different LAD perfusion areas.

OBJECTIVES: To correlate supraclavicular left internal mammary artery (LIMA) to left anterior descending artery (LAD) area Doppler characteristics with angiographically perfused area. METHODS: Sixty patients (50 male, mean age 62+/-7.3 years) with LIMA to LAD area grafting were prospectively entered in a follow up study. Supraclavicular echo Doppler of the LIMA was studied at the LIMA origin preoperatively, and at 4.8+/-3.8 months and 1.8+/-0.9 years postoperatively. The potential area to be revascularized judged from preoperative angiography was called the 'target' area. Control angiography (native and LIMA) was done at 1.5+/-0.9 years. The perfused area % was classified into group I < or =17.0% (n=16), group II >17.0% and <22.50% (n=17), and group III > or =22.50% (n=18) and related to LIMA Doppler characteristics. Multivariate linear regression analyses (MLRA) were performed to assess the relations between Doppler variables and the perfused area, target area and ratio of perfused/target area. RESULTS: At MLRA perfused area was significantly related to the natural logarithm of diastolic peak velocity (DPV) (P=0.013) and diastolic mean velocity (P=0.048) and the ratio only to the degree of LAD stenosis (P=0.004). In hyperaemic response maximal DPV (DPV max) showed significant correlation to the perfused area (P=0.005) as well as to the ratio (P=0.017). When analyzing the additive power of both investigations, only DPV max (P=0.005) correlated significantly to the perfused area and for the ratio only the degree of stenosis of the LAD emerged as significant (P=0.004). CONCLUSIONS: At MLRA the diastolic flow pattern at rest and the maximal DPV in hyperaemic response correlated significantly with the LIMA run-off area whereas the last variable is the strongest predictor of the LIMA run-off area.

Coronary Angiography↗

Cognitive, and behavioural and emotional functioning of young children awaiting elective cardiac surgery or catheter intervention.

AIMS: To assess the cognitive, and behavioural and emotional functioning of children aged 3 months to 7 years shortly before elective cardiac surgery or elective interventional catheterisation. METHODS: We used the Bayley Scales of Infant Development, and the McCarthy Scales of Children's Abilities, to measure cognitive functioning. The Child Behavior Checklist was used to assess behavioural and emotional problems. RESULTS: We found no significant differences in mean cognitive scores for children scheduled for cardiac surgery or interventional catheterisation when compared with reference groups. This was also the case for children awaiting cardiac surgery as opposed to those awaiting interventional catheterisation, and for those below as compared to those above the age of 2.5 years. Overall, our results regarding behavioural and emotional functioning were comparable to those of normative reference groups. The only difference found was that the children scheduled for cardiac surgery and aged from 2 to 3 years had significantly higher scores on the Child Behavior Checklist than did peers from normative groups. CONCLUSION: Cognitive, and behavioural and emotional functioning, both for young children awaiting elective cardiac surgery and interventional catheterisation, can be considered as quite favourable.

Age Factors↗

Increased numbers of circulating donor-specific T helper lymphocytes after human heart valve transplantation.

Implantation of cryopreserved human donor heart valves for either congenital or acquired cardiac disease has been performed since the last three decades. Although the clinical outcome is good, long-term valve degeneration resulting in dysfunction has been observed. A specific immunological response of the recipient against the allograft has been proposed as one of the factors involved in this process. Helper T lymphocytes play an important intermediate role in cellular and humoral immune response. Increasing numbers of circulating donor-specific helper T lymphocytes precursors (HTLp) correlate with graft rejection after organ transplantation. To investigate whether cryopreserved human donor heart valves are able to induce a donor-specific T helper response, we monitored the HTLp frequencies (HTLpf) in peripheral blood samples of 13 patients after valve allograft transplantation by use of a limiting dilution assay followed by an interleukin-2 bioassay. Prior to transplantation, HTLpf specific for donor and third-party antigens showed individual baseline levels. After allografting, the antidonor frequencies significantly increased in 11 of the 13 patients (P = 0.02). This was not found for stimulation with third-party spleen cells (P = 0.68), which indicates a donor-specific response. Maximal donor-specific HTLpf were already found at 1--2 months after operation. Valve allograft transplantation induces an increase in the numbers of donor-specific HTLp in peripheral blood of the patients. Analogous to organ transplantation, these HTLp may play a crucial role in events that lead to valve damage. Therefore, monitoring of HTLp in peripheral blood samples might be informative for donor valve degeneration (rejection) and subsequently valve allograft failure.

Adult↗

Altered arterial expression patterns of inducible and endothelial nitric oxide synthase in pulmonary plexogenic arteriopathy caused by congenital heart disease.

Flow-associated pulmonary hypertension leads to pulmonary plexogenic arteriopathy (PPA), a specific pulmonary vascular disease that includes vascular lesions characterized by abnormal vasodilatation and endothelial cell proliferation. Increased local production of NO has been suggested in this condition. Because reported data on the expression of endothelial NO-synthase (ecNOS) have been contradictory, we speculated that the expression of the inducible isoform of NOS (iNOS) is enhanced in this form of pulmonary hypertension. We investigated immunohistochemically the expression of ecNOS and iNOS in lung tissue of patients with flow-associated pulmonary hypertension (n = 18) and compared the findings with those in patients with increased pulmonary blood flow but normal pulmonary artery pressure (n = 10), with congestive vasculopathy (n = 6) and control subjects (n = 4). Immunoreactivity for ecNOS and iNOS was present both in normal and diseased pulmonary arteries. Marked immunoreactivity to both isoforms was present within the advanced lesions of PPA, including plexiform lesions. Semiquantitative analysis of immunoreactivity, both for ecNOS and iNOS, showed no correlation with the severity of morphologic vascular lesions (p = 0.29 and p = 0.23, respectively). In contrast to ecNOS, immunoreactivity for iNOS was increased in patients with flow-associated pulmonary hypertension compared with other patients (p = 0.02). The present study has demonstrated enhanced expression of iNOS in patients at risk for advanced PPA, but not in patients with other forms of pulmonary arteriopathy. Moreover, high expression of both ecNOS and iNOS were present in advanced lesions of PPA. These data suggest differentiated roles for different isoforms of NOS in the pathogenesis of this specific pulmonary arteriopathy.

Analysis of Variance↗

Craniovascular selectivity of eletriptan and sumatriptan in human isolated blood vessels.

BACKGROUND: Eletriptan is a 5-HT(1B/1D) receptor agonist with proven efficacy in the acute treatment of migraine. OBJECTIVE: To assess the craniovascular selectivity of eletriptan and sumatriptan in blood vessels predictive of therapeutic efficacy (human middle meningeal artery) and adverse coronary side effects (human coronary artery and human saphenous vein). METHOD: The authors obtained coronary artery from organ donors (n = 9), middle meningeal artery from patients (n = 11) undergoing craniotomy, and saphenous vein from patients (n = 9) undergoing coronary bypass surgery. Concentration-response curves to eletriptan and sumatriptan were constructed to obtain measurements of efficacy (maximum contraction, E(max)) and potency (concentration eliciting 50% of E(max), EC(50)). The contraction that is likely to be induced at the maximal free plasma concentration (C(max)) was determined by calculating C(max)/EC(50) ratios and by interpolation of the concentration-response curves. RESULTS: Eletriptan and sumatriptan induced concentration-dependent contractions of meningeal artery, coronary artery, and saphenous vein. Eletriptan was less potent than sumatriptan in coronary artery, whereas both compounds had similar potency in meningeal artery and saphenous vein. However, the potency of eletriptan and sumatriptan was higher in meningeal artery than in coronary artery (86-fold for eletriptan and 30-fold for sumatriptan) or saphenous vein (66- and 25-fold). The efficacy of eletriptan and sumatriptan was similar within tissues. The predicted contraction by eletriptan (40 mg and 80 mg) and sumatriptan (100 mg) at free C(max) observed in clinical trials was similar in meningeal artery, whereas in coronary artery and saphenous vein it was lower for 40 mg eletriptan than for sumatriptan. CONCLUSIONS: At therapeutic concentrations both eletriptan and sumatriptan contract middle meningeal artery more than coronary artery. This suggests that in patients with healthy coronary arteries, they have a limited propensity to cause adverse coronary side effects. However, both drugs remain contraindicated in patients with coronary artery disease.

Aged↗

Pharmacological analysis of contractile effects of eletriptan and sumatriptan on human isolated blood vessels.

Eletriptan, a second-generation triptan with high affinity for 5-HT(1B/1D) receptors, is highly effective in migraine, with or without aura. We compared the effects of eletriptan and sumatriptan on the human isolated middle meningeal and coronary arteries and saphenous vein, used as models for therapeutic efficacy and potential side effects, and have investigated the role of 5-HT(1B/1D) receptors in contractions induced by these triptans. Concentration-response curves to eletriptan and sumatriptan were constructed in the absence or presence of a selective 5-HT(1B/1D) receptor antagonist, N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-py rid yl) benzamide (GR125743). All three blood vessels constricted in response to eletriptan and sumatriptan, but the middle meningeal artery relaxed following the highest concentration (100 microM) of eletriptan. In the middle meningeal artery, GR125743 antagonised the contractions induced by both eletriptan (pEC(50): 7.34+/-0.13) and sumatriptan (pEC(50): 6.91+/-0.17) to a similar degree (pA(2): 8. 81+/-0.17 and 8.64+/-0.21, respectively). In the human coronary artery and saphenous vein, sumatriptan-induced contractions (pEC(50): 6.24+/-0.14 and 6.19+/-0.12, respectively) were also potently antagonised by GR125743 (pA(2): 8.18+/-0.27 and 8.34+/-0.12, respectively). The eletriptan-induced contractions of the human saphenous vein (pEC(50): 6.09+/-0.13) were antagonised less effectively by GR125743 (pK(B): 7.73+/-0.18), and those of the human coronary artery (pEC(50): 5.54+/-0.22) remained unaffected by GR125743 up to a concentration of 100 nM. These results suggest that (i) based on the differences in pEC(50) values, the cranioselectivity of eletriptan (63-fold) is higher than that of sumatriptan (5-fold) in coronary artery, (ii) the contractile effects of sumatriptan and eletriptan (lower concentrations) in the three blood vessels are mediated via the 5-HT(1B) receptor, and (iii) additional mechanisms seem to be involved in coronary artery and saphenous vein contractions and middle meningeal artery relaxation following high concentrations of eletriptan.

Adult↗

Enhanced expression of vascular endothelial growth factor in pulmonary plexogenic arteriopathy due to congenital heart disease.

Congenital heart disease (CHD) leading to increased pulmonary blood pressure and flow is an important cause of pulmonary plexogenic arteriopathy (PPA). This type of arteriopathy tends to progress to an irreversible stage, hallmarked histologically by the emergence of a number of characteristic lesions, which include concentric laminar intimal proliferation and fibrosis, and plexiform lesions. The pathogenesis of these lesions, which connote a very poor prognosis, is not well understood. Since endothelial cell proliferation has been demonstrated in these lesions, it was hypothesized that vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, might play a role in their pathogenesis. Thirty-nine patients with various types of CHD, who underwent cardiac catheterization and subsequent cardiac surgery, were studied prospectively. On the basis of a detailed assessment of the type of cardiac defect, the haemodynamic abnormalities, and the histopathological features evident from open lung biopsies, taken in all instances, patients were histologically grouped into cases with moderate PPA (n=18), advanced PPA (n=7), pulmonary congestive vasculopathy (PCV, n=5), and controls lacking pulmonary hypertension or increased pulmonary blood flow (n=4). Five patients were excluded from analysis because of inadequate sample size or quality. The presence of VEGF was assessed immunohistochemically using standard procedures and was correlated with haemodynamic and histological data. Immunoreactive VEGF was detected in pulmonary arterial smooth muscle cells and endothelial cells in 13 out of 34 cases and was more frequent and more pronounced in patients with the histological lesions of advanced PPA than in those with moderate PPA (p<0.01). VEGF positivity was particularly prominent in the lesions characteristic of advanced PPA. No difference in VEGF expression was observed between controls, PVC, and moderate PPA cases. Measured haemodynamic parameters did not differ significantly between VEGF-positive and VEGF-negative cases. We conclude that VEGF may play a role in the angioproliferative changes of advanced PPA.

Child↗

Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model.

Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde competence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.

Animals↗

Smoking cessation reduces mortality after coronary artery bypass surgery: a 20-year follow-up study.

OBJECTIVES: The goal of this study was to determine the influence of smoking cessation on mortality after coronary artery bypass graft surgery (CABG), which has still not been established clearly. BACKGROUND: Cigarette smoking is one of the known major risk factors of coronary artery disease. METHODS: One thousand and forty-one patients underwent CABG between 1971 and 1980. The preoperative and postoperative smoking habits of 985 patients (95%) could be retrieved and were analyzed in a multivariate Cox analysis. RESULTS: The median follow-up was 20 years (range 13 to 26 years). Smoking status before surgery did not entail an increased risk of mortality: patients who had smoked before surgery and those who had not smoked in the year before surgery had a similar probability of survival. However, smoking cessation after surgery was an important independent predictor of a lower risk of death and coronary reintervention during the 20-year follow-up when compared with patients who continued smoking. In analyses adjusted for baseline characteristics, the persistent smokers had a greater relative risk (RR) of death from all causes (RR 1.68 [95% confidence interval 1.33 to 2.13]) and cardiac death (RR 1.75 [1.30 to 2.37]) as compared with patients who stopped smoking for at least one year after surgery. The estimated benefit of survival for the quitters increased from 3% at five years to 14% at 15 years. The quitters were less likely to undergo repeat CABG or a percutaneous coronary angioplasty procedure (RR 1.41 [1.02 to 1.94]). CONCLUSIONS: Patients who continued to smoke after CABG had a greater risk of death than patients who stopped smoking. They also underwent repeat revascularization procedures more frequently. Cessation of smoking is therefore strongly recommended after CABG. Clinicians are encouraged to start or to continue smoking-cessation programs in order to help smokers to quit smoking, especially after CABG.

Angioplasty, Balloon, Coronary↗