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Background: Cardiopulmonary bypass is associated with impaired platelet macroaggregation. Heparin contributes to platelet dysfunction before extracorporeal circulation. In vitro heparinization of whole blood does not impair macroaggregation. Heparin releases several endothelial proteins; thus heparin may inhibit macroaggregation indirectly., Methods: Patients undergoing operations using cardiopulmonary bypass and ABO blood group compatible volunteers were studied. Whole blood impedance aggregometry assessed macroaggregation in response to collagen (0.6 microg ml(-1)) in blood diluted either with normal saline or with platelet poor plasma, obtained from patients at different stages of cardiopulmonary bypass., Results: Before heparinization, blood diluted with its own platelet poor plasma recorded an impedance change of 13.0 (4.7 to 15.6) Ohms. Platelet poor plasma obtained after heparinization or during extracorporeal circulation reduced this response to 3.7 (1.1 to 8.4) and 2.0 (1.1 to 3.3) Ohms, respectively (both p < 0.0001 versus pre-heparin; n = 13). Macroaggregation in blood from volunteers was similarly inhibited by patients' platelet poor plasma (n = 30). The macroaggregatory response in blood sampled after heparinization for cardiopulmonary bypass, decreased gradually from 11.4 (8.2 to 15.9) Ohms immediately after sampling to 1.7 (1.4 to 4.1) Ohms 2 hours later (p < 0.0001; n = 11)., Conclusions: In vivo heparinization induces plasma changes that inhibit platelet macroaggregation. This is an indirect, delayed inhibition that is transferable in vitro to normal platelets.

Unlabelled: Cardiopulmonary bypass (CPB) is associated with both neutrophil activation and failure of platelets to form large stable aggregates. We aimed to determine the effects of heparin and of neutrophil activation on platelet aggregation in whole blood. Fourteen patients undergoing routine aortocoronary bypass grafting and NSAID-free for over 7 days were studied before and after heparinisation, and at end-CPB. Whole blood, anticoagulated with rHirudin, was stirred for 3 minutes, and macroaggregation in response to collagen (0.6 microg. mL(-1)) or the neutrophil stimulant fMLP (10(-7)M) was determined by whole blood impedance aggregometry. Microaggregation was measured by counting unaggregated single platelets (corrected for haemodilution). The blood of volunteers was studied in vitro., Patients: Before CPB, heparin effectively abolished platelet macroaggregation induced by collagen (20.5 to 1.4 Ohms) or fMLP (3.9 to 0 Ohms (p<0.0001). CPB had no additional effect. Heparinisation also reduced the platelet count from 127 (110-170) to 95 (64-117). The inhibition of macroaggregation could not be reversed by ex vivo heparinase., Volunteers: In vitro, the same heparin concentration, as measured in vivo (4 micromL(-1)), inhibited collagen-induced macroaggregation (20.3 to 14.7 Omega), but this effect was less than that observed ex vivo and was reversed by heparinase. In vitro heparin promoted fMLP macroaggregation (2.9 to 8.6 Omega). The inhibition of macroaggregation resulted from heparinisation, per se, rather than CPB and was insensitive to heparinase. There was less inhibition by in vitro heparin, which was reversible by heparinase, indicating a direct effect of heparin in vitro. The disparate findings are suggestive of an indirect action by heparin in vivo on macroaggregation, although heparin had a small direct stimulatory action on microaggregation.

Background and Aim of the Study: There is renewed interest in the pericardial heart valve as an alternative to the porcine bioprosthesis. The long-term results of a randomized trial comparing a second-generation pericardial valve against a well-tested porcine bioprosthesis are presented. Seven-year follow up has been reported previously. Production of the Bioflo pericardial prosthesis used in this trial was discontinued due to fears related to bovine spongiform encephalopathy., Methods: Between February 1987 and March 1990, 170 patients undergoing aortic (AVR) or mitral (MVR) valve replacement were assigned randomly to receive either the Bioflo pericardial bioprosthesis or the Carpentier-Edwards (CE) supra-annular porcine bioprosthesis. Eighty-five patients received 93 Bioflo valves (46 AVR, 31 MVR, eight AVR+MVR), and the remaining 85 received 99 CE valves (48 AVR, 23 MVR, 14 AVR+MVR). Mean patient age was 61.0 years (range: 38-77 years) for the Bioflo group and 62.1 years (range: 41-77 years) for the CE group. Current follow up is 100% complete and totals 1,391 patient-years; mean +/- SD follow up was 8.2 +/- 3.4 years (maximum 12.2 years)., Results: The operative mortality rate was 4.12%. There were 70 patients still at risk at 11 years (31 Bioflo, 39 CE); of these, 91.4% were in NYHA classes I/II. No significant difference in survival or valve-related complications was seen between the groups. Mean (+/- SEM) survival at 11 years was 41.4 +/- 6.8% in the Bioflo group and 55.3 +/- 6.8% in the CE group (p = 0.15). There were 16 valve-related deaths (nine in the Bioflo group, seven in the CE group). At 11 years, freedom from valve-related mortality was 89.5 +/- 3.9% for the Bioflo group and 91.0 +/- 3.5% for the CE group (p = 0.4). Valve position had no impact on survival. At 11 years, freedom from structural valve deterioration was 83.9 +/- 5.4% and 87.5 +/- 4.2% in the Bioflo and CE groups, respectively (p = 0.9)., Conclusion: Over the 11-year period of follow up, clinical performance of the Bioflo pericardial valve was comparable with that of the Carpentier-Edwards supra-annular porcine bioprosthesis. No difference was apparent between the two valve types when implanted in either the aortic or the mitral position.

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).

Objective: Although the decline in the pulmonary transfer factor (TL(CO)) following heart transplantation is well documented, the causes and mechanisms of this decline remain unknown. The aim of this study was to determine the relative contribution of each of TL(CO) components (the diffusing capacity of the alveolar-capillary membrane (D(M)), the pulmonary capillary blood volume (V(C)) and haemoglobin concentration) to TL(CO) reduction in heart transplant recipients., Methods: TL(CO) and its components were measured in 75 heart transplant recipients (mean age 48 years, range 19-61) between 6 weeks and 36 months after transplantation using the Roughton and Forster method and the single-breath technique. Results were compared with data from 38 heart transplant candidates (mean age 51 years, range 34-61) and 26 normal subjects (mean age 47 years, range 27-62)., Results: The mean percentage predicted TL(CO) was reduced in recipients compared to candidates (56.9 and 69.9%, respectively, P<0. 001) and both were lower than normal controls (97.7%, P<0.001). The mean percent predicted V(C) was also reduced in recipients compared to candidates (52.8% vs. 80.2 (4.2)%, P<0.001) which was also lower than normal subjects (102%, P<0.001). D(M) was equally reduced in recipients and candidates (77.7 and 81.4%, respectively, P=0.48) compared to normal subjects (100.0%, P<0.001). Correction for haemoglobin concentration increased TL(CO) in recipients to 63.5% (P<0.001), but it remained lower than haemoglobin-corrected TL(CO) in candidates (71.1%, P<0.001). In recipients, the intra-capillary resistance (1/thetaV(C)) formed 60% of the total resistance to CO transfer (1/TL(CO)) compared to 50% in candidates and normal subjects., Conclusions: TL(CO) decline following heart transplantation is due to an increase in the intra-capillary resistance, and this appears to be due to a combination of anaemia and reduced pulmonary capillary blood volume, with the diffusing capacity of the alveolar-capillary membrane remaining unchanged.

Artificial blood pumps play an increasingly important role in the treatment of end-stage cardiac failure. The fluid dynamics of blood flow through such devices crucially affects their clinical effectiveness. Specifically, if the flow of blood stagnates or slowly re-circulates thrombus formation can occur and the avoidance of such flow features is a primary consideration in the design of pumps. The present study concerns the development of a fluorescent particle visualisation technique and its application to investigate the flow environments in four prototype blood pump designs. The procedure involves recording video images of eight illuminated cross sections through the pumping chambers as the pumps operate in a mock circulatory loop using a test fluid seeded with fluorescent particles. The technique enabled a semi-quantitative characterisation of the entire flow field, throughout the pumping cycle, to be performed for each pump design. Flow features were then related to design properties of the individual pumps and recommendations made for design optimisation.

Objectives: To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TL(CO)) in heart transplant candidates, as this is the most common lung function abnormality., Setting: Regional cardiopulmonary transplant centre., Methods: TL(CO) and its components (the diffusing capacity of the alveolar-capillary membrane (D(M)) and the pulmonary capillary blood volume (V(C))) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62)., Results: Mean per cent predicted TL(CO), D(M), and V(C) were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p < 0.001). The relative contribution of the two components of TL(CO) in patients was similar to that of normal subjects, with each component accounting for approximately 50% of the total resistance to diffusion (1/TL(CO))., Conclusions: TL(CO) impairment in patients with severe chronic heart failure awaiting heart transplantation results from a proportionate reduction in both D(M) and V(C), suggesting a significant disturbance of the pulmonary vascular bed.

Platelet counting detects lesser degrees of platelet aggregation than conventional aggregometry. In order to prevent progressive platelet aggregation or disaggregation after sampling it is customary to fix blood samples. However fixation may introduce other artefacts. We first compared stability of platelet counts in EDTA-, citrate- and r-hirudin-anticoagulated blood from healthy volunteers. Second, the stability of platelet counts in unfixed EDTA- and hirudin-anticoagulated blood was compared with glutaraldehyde-fixed blood in the same anticoagulants. Third, the effect of in vivo heparin administration on platelet counts in EDTA- and hirudin-anticoagulated blood was studied. Platelet counts within 2 h of collection were significantly higher in EDTA- than in hirudin- or citrate-anticoagulated blood (P = 0.002 vs. hirudin and P = 0.001 vs. citrate). Twenty-four hour counts in hirudin and EDTA were unchanged (P = 0.3 and P = 0.2, respectively, vs. earlier counts). Counts in citrate increased significantly (P = 0.007; n = 10). Platelet counts in fixed blood did not differ significantly from those in unfixed blood. Heparin administered for cardiopulmonary bypass reduced platelet counts in hirudin-anticoagulated blood from (mean +/- 1 standard deviation) 180 +/- 45 to 162 +/- 30 x 10(9) l-1 (P = 0.01; n = 14), without significantly lowering counts with EDTA-anticoagulation, consistent with increased platelet aggregation. Hirudin and EDTA provided stable platelet counts, suggesting that fixation is unnecessary.

Artificial blood pump assistance of the failing human heart can allow it to recover. Analysis of blood pump fluid flow is a useful tool for design development and thrombosis minimization. The aim of this study was to investigate fluid flow, particularly ventricular clearance rate and stagnation areas, in four different blood pump geometries and to determine the best design. The blood pumps consisted of a polyurethane ventricle, and combinations of inlet/outlet pipe angles and compression plate shapes. A video camera recorded the motion of fluid labelled with an optical tracer (Methyl Blue histological dye). A novel processing method was developed to produce colour maps of tracer concentration, experimentally calibrated. An overall picture of fluid flow in each pump geometry was generated by considering clearance curves, tracer concentration maps and inflow jet animations. Overall and local mixing coefficients are calculated for each pump. The best geometry featured straight inlet/outlet pipes and a domed compression plate. This optical tracer technique has proven convenient, economical, sensitive to low concentrations of tracer and provides instantaneous pictures of tracer distribution in a ventricle.

Background: There are no prospective methods available to quantify the myocyte injury in hearts prior to transplantation. The potential of the isotope labeled infarct marker 99m Technetium pyrophosphate (TcPPT) being used in this role was investigated., Methods: Brain death was induced by creating an extradural space occupying lesion in young adult swine after which hemodynamic changes were monitored and myocyte injury was quantified by histochemistry. TcPPT was administered 5 hours after induction of intracranial hypertension, and after hearts were harvested myocardial uptake was measured. These latter measurements were related to the histochemical assessment of myocyte injury., Results: Sham animals (n = 4) maintained cardiovascular stability and experienced minimal myocyte injury, grades 0 to 3. BD animals (n = 10) exhibited varying patterns of hemodynamic change and myocyte injury, the latter was significant in 6, graded 4 to 11, p less than 0.05. Uptake of TcPPT by BD hearts was greater than twice the 90th centile sham value in 6. The sensitivity and specificity of greater uptake indicating the presence of myocyte injury was 83.3% and 75% respectively., Conclusions: TcPPT has the potential to quantify myocardial injury induced by brain death and its potential utility merits further investigation.

Background and Aims of the Study: The composition of microemboli detected as high-intensity transient signals (HITS) by Doppler ultrasound in patients with prosthetic heart valves is still debated. Here, platelet aggregation and HITS were investigated in a sheep model., Methods: Insonation of the carotid artery was performed in 20 sheep with either a mechanical or a biological mitral valve prosthesis in place. The effect of ICI 170809, a 5HT2a antagonist, on the frequency of HITS and on platelet aggregates, counted in arterial blood smears per nine high-power fields, was assessed at three and six months after valve implantation. The mitral transvalvular gradient was measured by transthoracic echocardiography at three and six months., Results: Data are expressed as median and interquartile range. At three months, there were 36 (20-114) HITS/h in the mechanical group, and 0 (0-15) HITS/h in the biological group. At six months, there were 21 (0-82) and 0 (0-2) HITS/h, respectively. The occurrence of HITS was unaffected by either ICI 170809, or by duration of implant in either group. Platelet aggregate counts were higher with the mechanical than with the biological valve at three months, but not at six months. ICI 170809 reduced platelet aggregate counts in both valve types; the reduction was not significant in the bioprosthetic valve group. The pressure gradient across the bioprosthesis increased during the study from 2 (2-3) mmHg to 7.5 (6-10) mmHg, but was unchanged in the mechanical valve., Conclusions: (i) It was confirmed that the frequency of HITS is higher with the mechanical prosthesis than the bioprosthesis; (ii) circulating platelet aggregates in the bioprosthetic valve group tended to increase as structural valve deterioration occurred; (iii) the frequency of HITS was not influenced by either an increase or a decrease in circulating platelet aggregates; and (iv) HITS detected in patients with prosthetic valves are unlikely to be due to circulating platelet aggregates.

Polyurethane heart valves can be functionally durable with minimal calcification, in vitro. In vivo, these characteristics will depend on the resistance of the polyurethane to thrombogenesis and biodegradation. Surface modification may improve the polyurethane in these respects, but may adversely affect calcification and durability. This study investigates the effects of surface modifications of two polyurethane heart valves (PEU and PEUE) on their in vitro fatigue and calcification behaviour. Modifications included heparin, taurine, 3-aminopropyltriethoxysilane and polyethylene oxide (PEO). Neither hydrodynamic function nor leaflet thickness distribution was significantly altered by surface modification. PEO-modification was detrimental to valve fatigue durability and calcification. Heparin, taurine or aminosilane modifications of PEU valves increased durability. Aminosilane modification of PEUE valves increased durability compared with PEO modification. Appropriate surface modification may be useful to improve blood compatibility of implantable polyurethanes, and may also be advantageous as regards fatigue durability of flexing materials in longterm applications.

Aim: To establish the diagnostic value of in situ hybridisation and the nested polymerase chain reaction (PCR) in detecting clinically relevant cytomegalovirus (CMV) infection in upper gastrointestinal biopsies from heart transplant patients., Methods: Test sensitivity and specificity for detection of CMV early gene RNA by in situ hybridisation and CMV intermediate early gene by PCR were established and then compared with haematoxylin and eosin (H&E) and immunocytochemical detection of CMV in order to establish the best pathological diagnostic approach. All investigations were carried out on formalin fixed, paraffin embedded tissue., Results: Nested PCR had the highest test sensitivity, followed by in situ hybridisation and immunocytochemistry with the same sensitivity; H&E had the lowest. H&E and immunocytochemistry were the most specific but both had a significant false negative rate which was less of a problem with PCR. However, PCR gave no other diagnostic information, and in situ hybridisation was no better than immunocytochemistry. Both in situ hybridisation and PCR were technically complex and more expensive., Conclusions: H&E and immunocytochemistry represent the best initial screen for CMV and other diseases in upper gastrointestinal biopsies from heart transplant patients. If H&E and immunocytochemistry were negative, nested PCR could significantly increase the diagnostic yield of clinically relevant CMV infection. In situ hybridisation appeared to have no advantages and some drawbacks compared with immunocytochemistry and PCR.

Polyurethanes have proven durable materials for the manufacture of flexible trileaflet heart valves, during in vitro tests. The response of two polyurethanes of differing primary structure to parameters of blood compatibility has now been investigated, using an in vitro test cell. Platelet (beta-thromboglobulin) release, complement (C3a) activation, the activation of free plasma and surface-bound factor XII were studied using fresh, human blood (no anticoagulant) or citrated plasma in control and surface-modified polyurethane. Surface modifications were designed to affect material thrombogenicity and included covalent attachment of heparin, taurine, a platelet membrane glycoprotein fragment, polyethylene oxide (PEO), 3-aminopropyltriethoxysilane, and glucose or glucosamine. Unmodified control polyurethanes caused platelet release and complement activation. High molecular weight (2000 D) polyethylene oxide reduced platelet release slightly but only glucose attachment to the surface produced a significant reduction in platelet activation. All modifications reduced C3 activation compared with controls, but the greatest reduction was achieved with polyethylene oxide attachment or glycosylation. Most surface modifications were more activating of factor XII, both in plasma and on the material surfaces, than the control polyurethanes. Heparin and high molecular weight PEO produced the greatest activation of factor XII in the free plasma form, but low molecular weight PEO and glucosamine produced the greatest activation of surface-bound factor XIIa. The least activating surfaces, affecting both free plasma and surface-bound factor XIIa, were those treated with platelet membrane glycoprotein fragment and glucose. PEO surfaces performed relatively well, compared with controls and most surface modifications. The best overall surface, however, was the glucose-modified surface which was least activating considering all parameters of blood compatibility.

In contrast to the standard single-breath transfer factor for carbon monoxide (TLCO), there are no specific guidelines or recommendations for the measurement of its components, the pulmonary capillary blood volume (VC) and membrane component (DM), by the Roughton and Forster method. Ten randomly selected heart transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age range 24-55 years) were assessed on two occasions using either the standard or high-oxygen mixture as the first inspired gas in random order. Ten normal subjects (all non-smokers, age range 23-54 years) were assessed on two occasions using either a long protocol (30 min waiting time between repeat measurements in an individual set) or a short protocol (5 min waiting time). Two technically acceptable results of TLCO were used to derive a mean value for DM and VC for each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different sequences of gas mixtures produced no significant differences between the values obtained in ten heart transplant patients for mean TLCO (mmol min-1 kPa-1) (standard first 5.13 +/- 1.15, high-oxygen first 5.14 +/- 1.12; limits of agreement -0.57 to 0.59 for DM or for VC. The long or short protocol produced no significant differences between the means of TLCO (mmol min-1 kPa-1) (long 8.0 +/- 1.9, short 8.0 +/- 1.9; limits of agreement -0.5 to 0.5), DM or VC. This allows the development of a standard test protocol of short duration (about 40 min) making it practical for clinical use without compromising the precision or reproducibility of the results obtained.

Background: This study was designed to investigate renal microvascular changes during cardiopulmonary bypass., Methods: Kidneys were harvested from each of four groups of 6 pigs. Group A were anesthetized and heparinized only. The remaining three groups underwent cardiopulmonary bypass at 28 degrees C, group B for 30 minutes and groups C and D for 120 minutes; group D had an additional 30 minutes of normothermic perfusion at the end of the experiment. Renal cortical blood flow was measured using radiolabeled microspheres. Microvascular morphology was defined by corrosion casting and scanning electron microscopy., Results: In group A, renal vascular resistance was 61+/-5.1 mm Hg x mL(-1) x min(-1). This value decreased to 28+/-7.8 in group B and 25+/-4.0 in group C (p < 0.05), and increased in group D to 40+/-4.1 (p < 0.05 versus groups A, B, and C). Cortical thickness, as measured by microvascular casts in groups A, B, and C, was 33, 34, and 31 mm, respectively, with equal distribution of the resin to the superficial and deep cortex but was significantly reduced in group D to 22 mm (p < 0.05 versus groups A, B, and C), with failure of the resin to fill the superficial cortical layer. Diameters of glomeruli as seen on the casts were 111+/-10.38 microm in group A, 100+/-9.24 microm in group B, and 82+/-4.4 microm in group C (p < 0.05 group A versus group C). The glomeruli from group D were still significantly smaller than group A (93+/-10.35 microm, p < 0.05). Mean glomerular capillary diameters were 4.65+/-0.26 microm in group A, 3.9+/-0.16 microm in group B, 3.6+/-0.19 microm in group C, and 3.65+/-0.3 microm in group D (p < 0.05 group A versus groups B, C, and D)., Conclusions: Hypothermic nonpulsatile cardiopulmonary bypass decreased renal vascular resistance, but the superficial and deep layers of the cortex were perfused equally. Glomeruli were reduced in size because of capillary narrowing. This was consistent with diversion of blood through bypass channels. With restoration of normothermia, underperfusion of the superficial cortex occurred, with potential for damage to these nephrons during the increased metabolic demands of rewarming.

Objective: The pulmonary transfer factor for carbon monoxide (TLCO) has been reported to decline following heart transplantation, but the time course of this decline is not well documented. The aim of this study was to define the longitudinal changes in TLCO after heart transplantation., Methods: Single breath TLCO, lung volumes and expiratory flow rates were prospectively measured in 57 patients (mean age 49 years, range 19-61) before and at least once after heart transplantation. Thirty seven of the 57 patients had four post-transplant assessment which were performed at 6 weeks, 3, 6 and 12 months in 26 patients and at 12, 18, 24 and 36 months in 11 patients. Results were compared with data from 28 normal subjects (mean age 40 years, range 19-61)., Results: Before transplantation there was a mild impairment of lung volumes and expiratory flow rates. At 6 weeks after transplantation, there was a further reduction in the forced expiratory volume in one second, forced vital capacity, residual volume and total lung capacity, but all of these increased in the subsequent measurements to exceed their pre-transplant values at about 1 year after transplantation. Haemoglobin-corrected TLCO was also reduced before transplantation compared to normal controls (74.3% and 98.6% of predicted respectively, P < 0.001). Although TLCO per unit alveolar volume (KCO) was relatively preserved in heart transplant candidates, it was still significantly lower than that of normal controls (92.6% and 105.3% of predicted respectively, P < 0.05). After transplantation, mean haemoglobin-corrected TLCO and KCO declined by 12% and 20% of predicted respectively) with the majority of patients having reductions greater than 10% of predicted. The decline in TLCO and KCO was evident at 6 weeks after transplantation with no further changes in the subsequent measurements., Conclusions: TLCO is reduced in heart transplant candidates and declines further after heart transplantation despite improvement in lung volumes and airway function. The early and non-progressive nature of TLCO decline suggests an aetiology exerting its effect on TLCO within the first 6 weeks after transplantation.

Characterization of flow properties of an artificial ventricle may aid development of designs to minimize thrombosis. Techniques for determining two such flow properties, viz. ventricular clearance rate and ejection fraction, are compared and validated here for polyurethane and silicone rubber ventricles operated in a mock circulatory loop at various stroke volumes and pulse rates. Ventricular clearance rats were measured both by clinical radionuclide tracer techniques and by an optical tracer method. Ejection fractions were measured by radionuclide imaging and validated by direct measurements of flow rate and ventricular volume. Results from the two methods for ventricular clearance are in close agreement. The optical tracer method is superior in spatial resolution, convenience and economy, but the radionuclide tracer method for ejection fraction gives excellent agreement with the absolute measurements.

Laser profiling techniques have been used to examine the 2-dimensional and 3-dimensional patterns of leaflet motion in functioning bovine pericardial heart valves (1 normal valve and 1 fatigued/calcified). In the normal valve the general patterns of opening and closing were similar for all leaflets; however, localised variations such as areas of high curvature, retarded motion and high speed motion were identified. In the fatigued/calcified valve significant differences from the normal leaflet motion were observed e.g. increased crimping, gross leaflet lag and irregular deformation. The laser profiling technique was able to reveal changes in the functional dynamics of pericardial valve leaflets not otherwise detectable by conventional hydrodynamic measurements of valve performance.

Avascular necrosis affects 3% of transplant recipients. In the lower limb, the femoral heads or condyles may be involved. We report the hitherto unrecorded complication of avascular necrosis of the calcaneum. Conservative management resulted in resolution without long-term complications.

Background: The role of Helicobacter pylori in the pathogenesis of nonautoimmune gastritis and peptic ulceration is well recognized. H. pylori is widely prevalent in the general population, but the incidence among heart transplant recipients has not been reported. Furthermore, the natural history of this infection may be modified by immunosuppression., Methods: Gastric and duodenal biopsy specimens from 47 heart transplant recipients were examined over a period of 44 months., Results: Twenty-three (49%) patients had H. pylori infection (15 men, 8 women; mean age 49 [range 35 to 59] years). Eight of the 23 (35%) had symptoms. These eight patients were treated for H. pylori with bismuth, metronidazole, and amoxicillin, followed by maintenance H2-receptor antagonists. Dyspepsia continued in six of these patients, with persistence or recurrence of H. pylori being demonstrated in four., Conclusions: This study shows that although histologically diagnosed H. pylori infection is widely prevalent among heart transplant recipients, this prevalence is very similar to the general population. Immunosuppression may play a role in the recurrence or persistence of this infection and may diminish the mucosal inflammatory response to the organism.

A case is reported of dissecting aneurysm of the donor ascending aorta and root 4 years after orthotopic cardiac transplantation. The pathology raises the possibility of Marfan's syndrome in the donor.

A flexible trileaflet polyurethane valve has been made by dip-moulding leaflets directly onto an injection-moulded frame. The durability of this value is, in part, determined by the thickness of its leaflets. Leaflet thickness is also a major determinant of hydrodynamic function. This study examines valves (n = 31) with leaflets made of a polyetherurethane (PEU, n = 22) or a polyetherurethaneurea (PEUE, n = 9), of varying thickness distributions. The valves were subjected to accelerated fatigue test at 37 degrees C and failure monitored. Leaflet thicknesses ranged from 60 to 200 microns. PEU leaflet thickness bore no relationship to durability, which was less than 400 million cycles. PEUE valves, in contrast, exceeded 800 million cycles. Durability in PEUE valves was directly related to leaflet thickness (r = 0.93, p < 0.001), with good durability achieved with median leaflet thicknesses of approximately 150 microns. Thus polyurethane valves can be made with good hydrodynamic properties and with sufficient durability to consider potential clinical use.

Six flexible-leaflet prosthetic heart valves, fabricated from a polyetherurethaneurea (PEUE), underwent long-term fatigue and calcification testing. Three valves exceeded 800 million cycles without failure. Three valves failed at 775, 460, and 544 million cycles, respectively. Calcification was observed with and without associated failure in regions of high strain. Comparison with similar valves fabricated from a polyetherurethane (PEU) suggests that the PEU is likely to fail sooner as a valve leaflet. Localized calcification developed in PEUE leaflets at the primary failure site of PEU leaflets, close to the coaptation region of the three leaflets. The failure mode in PEU valves had the appearance of abrasion wear associated with calcification. High strains in the same area may render the PEUE leaflets vulnerable to calcification. Intrinsic calcification of this type, however, is a long-term phenomenon unlikely to cause early valve failure. Both polymers performed similarly during static in vitro and in vivo calcification testing and demonstrated a much lesser degree of calcification than bioprosthetic types of valve materials. Polyurethane valves can achieve the durabilities required of an implantable prosthetic valve, equaling the fatigue life of currently available bioprosthetic valves.

Objectives: Despite laboratory evidence of leucocyte involvement in reperfusion injury, cardiac surgical clinical trials do not support the therapeutic effectiveness of leucocyte filtration. Furthermore, the direct effects of crystalloid cardioplegia and reperfusion on the capillaries of the heart have yet to be elucidated. We tested the effects of cardioplegic arrest and reperfusion both with and without leucocyte depletion, in a model of cardiopulmonary bypass that mimics clinical cardiac surgical conditions., Methods: Four groups of Landrace pigs were studied. Group A (n = 6) underwent 30 min of hypothermic (28 degrees C) cardiopulmonary bypass. Groups B (n = 6), C (n = 6) and D (n = 6) also had 90 min of cardioplegic arrest. Group C was then reperfused with whole blood, while Group D was reperfused with leucocyte-depleted blood. Microvascular methylmethacrylate corrosion casts were made at the end of the experimental period. Myocardial vascular anatomy was defined by electron microscopy and capillary abundance derived from this and from the weight of casts from representative areas. Leucocyte deposition was assessed using radioisotope-labelled leucocytes. Ischaemic damage to tissues was graded according to light and electron microscopic findings., Results: In Group A the mean (+/- S.D.) vascular cast weight/volume of myocardium (density) was 125 +/- 9 mg/mm3. After cardioplegic arrest (Group B), it fell to 74 +/- 7 mg/mm3 (P < 0.0001) due to absence of capillaries, although arterioles, venules and non-nutritive bypass vessels remained patent. Following reperfusion with whole blood (Group C), capillary numbers partially recovered but luminal diameters were reduced with a cast density of 94 +/- 5 mg/mm3 (P < 0.0001 versus Group A and B). Leucocyte-depleted (87-92%) reperfusion in Group D did not affect cast density (90 +/- 3 mg/mm3; P = 0.17). Coronary vascular resistances in Groups C and D rose slightly, but not significantly, during reperfusion., Conclusions: Following cardioplegic arrest, microvascular changes are marked. These changes are partially reversed by 30 min reperfusion. Leucocyte depletion does not ameliorate these effects in this model.

We report the coexistence of symptomatic viral, bacterial, and fungal infection of the upper gastrointestinal tract in a heart transplant recipient. Endoscopic findings were normal at all levels but, because of severe symptoms and recent conversion to positive serology for Cytomegalovirus, biopsies were taken. These showed esophageal candidiasis and gastric Helicobacter infection that has hitherto been unreported in cardiac transplant recipients.

In light of the thrombogenicity of mechanical valves and the limited durability of bioprosthetic valves, alternative designs and materials are being considered for prosthetic heart valves. A new tri-leaflet valve, made entirely from polyurethane, has been developed. The valve comprises three thin polyurethane leaflets (approximately 100 microns thick) suspended from the inside of a flexible polyurethane frame. The closed leaflet geometry is elliptical in the radial direction and hyperbolic in the circumferential direction. Valve leaflets are formed and integrated with their support frame in a single dip coating operation. The dipping process consistently gives rise to tolerably uniform leaflet thickness distributions. In hydrodynamic tests, the polyurethane valve exhibits pressure gradients similar to those for a bioprosthetic valve (St Jude Bioimplant), and levels of regurgitation and leakage are considerably less than those for either a bi-leaflet mechanical valve (St Jude Medical) or the bioprosthetic valve. Six out of six consecutively manufactured polyurethane valves have exceeded the equivalent of 10 years function without failure in accelerated fatigue tests. The only failure to date occurred after the equivalent of approximately 12 years cycling, and three valves have reached 527 million cycles (approximately 13 years equivalent). The simplicity of valve manufacture, combined with promising results from in vitro testing, indicate that further evaluation is warranted.

While flexible-leaflet, central-flow prosthetic heart valves promise relief from anticoagulation therapy, they continue to be restricted by inadequate durability. In consequence, a novel trileaflet valve, made entirely from polyurethane, has been developed. A batch of 6 consecutively manufactured polyurethane valves was subjected to hydrodynamic function and accelerated fatigue testing. Computerized data acquisition and control systems have been introduced to improve valve testing methodologies. In terms of hydrodynamic function, the polyurethane valve demonstrates transvalvular pressure gradients similar to those for a bioprosthetic valve (Carpentier-Edwards) and levels of retrograde flow significantly less than those for either the bioprosthetic valve or a bileaflet mechanical valve (St Jude Medical). The equivalent of 10 years of cycling without failure has been exceeded by all 6 polyurethane valves in accelerated fatigue tests with 2 valves remaining intact after 674 million cycles (equivalent to approximately 17 years) in continuing tests. Highspeed photography revealed considerable differences in leaflet motion between valves cycled at accelerated and physiological rates.

Background and Aims of the Study: Flexible trileaflet polyurethane heart valves can be designed which have good hydrodynamic function in vitro. The choice of polyurethane for fabrication of such valves is not simple; several similar polyurethanes are available, but relatively minor differences in their structure and composition may have profound effects on long term fatigue behavior with little effect on their short term mechanical properties., Methods: The relative functional characteristics of flexible trileaflet polyurethane valves made from two different polyetherurethanes were compared before and after long term fatigue testing. The polyetherurethanes had similar gross mechanical properties, differing in that one was chain-extended with butanediol (PEU) and the other with ethylene diamine (PEUE). Six valves of each type, with similar leaflet thickness distributions, were studied., Results: Hydrodynamic function of both valve types was similar to a similarly sized porcine aortic valve. Mean pressure drop across the open valve was higher in PEU valves than in PEUE valves, although PEUE valves had greater energy losses during closure and when closed. Reverse flow decreased with time in the fatigue tester. In long term fatigue tests, all six PEU valves failed by 307 million cycles, with failure primarily by development of holes at the coaptation region of the leaflets associated with localized calcification. Three PEUE valves exceeded 800 million cycles without failure and all PEUE valves exceeded 450 million cycles., Conclusions: A combination of good phase separation of polyurethane soft and hard segments with good rubbery characteristics can explain the better results achieved in the PEUE valves compared with similar PEU valves. These results suggest the general type of polyurethane structure suitable for heart valve fabrication and have implications for development of novel polyurethanes for this application.

A 43-year-old orthotopic heart transplant recipient had coagulase-negative staphylococcus endocarditis 26 weeks after the operation. A diagnosis of endocarditis was confirmed and followed up by serial transoesophageal echocardiography. Treatment with intravenous gentamycin and vancomycin cured her endocarditis, and a 2.5 cm vegetation regressed significantly. She has been well since and, at 14 months after transplantation, was back to her normal activities. Although repeated blood culture yielded only intermittent light growths of coagulase-negative staphylococci, there were several positive samples. In a setting of infective features, light growths of coagulase-negative staphylococcus should be taken seriously if repeatedly positive in heart transplant recipients or other immunocompromised patients. Transesophageal echocardiography offers significant advantages over the transthoracic modality in suspected endocarditis.

Cardiopulmonary bypass is known to activate both white cells and platelets. The aim of this study was to investigate whether the use of bubble and membrane oxygenators results in different degrees of deposition in the filter and oxygenator of the bypass circuit. Dual-isotope imaging techniques were employed, with white cells labelled with 99Tcm and platelets with 111In, and with subsequent imaging of the filters and oxygenators on a gamma camera fitted with a medium-energy, parallel-hole collimator, relative to a known standard. The percentage white cell oxygenator deposition ranged from 0.011 to 4.91% in the bubble group (n = 20) and was not different from the membrane group (0.001 to 4.22%). Similarly, no difference in platelet deposition was found, with 0.605-45.17% deposited in the bubble oxygenators and 0.001-15.26% deposited in the membrane oxygenators. Filter deposition of both types of cell was substantially lower in both membrane and bubble groups with no difference between groups. The striking feature of the data is the non-normal distribution of the deposition in both types of oxygenator. This study demonstrated that both white cell and platelet deposition in the cardiopulmonary bypass circuit can be quantified using radiolabelled cells. No differences in oxygenator or filter deposition were found in patients randomly allocated to membrane or bubble oxygenation.

The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).

Doppler ultrasound detection of abnormally high-pitched signals within the arterial waveform offers a new method for diagnosis, and potentially for prediction, of embolic complications in at-risk patients. The nature of Doppler "microembolic" signals is of particular interest in patients with prosthetic heart valves, where a high prevalence of these signals is observed. Monitoring the middle cerebral artery with 2-MHz transcranial Doppler ultrasound (TC-2000, Nicolet Biomedical; Warwick, UK), we looked for microemboli signals in 150 patients (95 women and 55 men), and found 1 or more signals during a 30-min recording in 89% of 70 patients with Bjork-Shiley valves (principally monostrut), 54% of 50 patients with Medtronic-Hall valves, and 50% of 30 patients with Carpentier-Edwards valves (p < 0.001, chi 2). In the patients with Bjork-Shiley valves, the mean number of signals per hour was 59 (range, 42-86; 95% confidence interval), which was significantly higher than the mean in patients with Medtronic-Hall and Carpentier-Edwards valves (1.5[range, 0.5-2.5] and 1 [range, 0-5.3], respectively; both p < 0.04, multiple comparisons. Bonferroni correction). In the patients undergoing serial pre- and postoperative studies, the causative role of the valve implant was emphasized. There was no correlation between the number of emboli signals and a prior history of neurologic deficit, cardiac rhythm, previous cardiac surgery, or the intensity of oral anticoagulation, in patients with prosthetic heart valves. In Bjork-Shiley patients, dual (mitral and aortic) valves were associated with more signals than were single valves. In Medtronic-Hall patients, the signal count was greater for valves in the aortic position than it was for valves in the mitral position. Comparative studies of Doppler emboli signals in other clinical settings suggest a difference in composition or size of the underlying maternal between prosthetic valve patients and patients with carotid stenosis. These studies also suggest that the signals are of gaseous origin in valve patients. The clinical significance of continuing microembolism remains to be determined.

Objective: Cardiopulmonary bypass induces respiratory dysfunction postoperatively, with activation of both the complement system and white cells implicated. This study compared the effects of bubble and membrane oxygenators for cardiopulmonary bypass in terms of respiratory dysfunction and markers of white cell activation and endothelial damage., Methods: Fifty patients undergoing cardiopulmonary bypass were randomly allocated either membrane or bubble oxygenation. Respiratory function was assessed serially by arterial oxygen tension and alveolar-arterial oxygen gradient. Complement activation was measured by serial sampling of serum C3a levels. White cell activation was assessed by serial measurement granulocyte elastase; other markers investigated were levels of thromboxane B2, von Willebrand factor and malondialdehyde. All sample measurements were made preoperatively, early and late during bypass, 4-6 h postoperatively and then on the 1st, 2nd and 6th postoperative day. All samples were corrected for haemodilution, and differences between groups tested non-parametrically., Results: In both groups of patients there was a highly significant fall (P < 0.001) in arterial oxygen tension accompanied by a highly significant rise (P < 0.0001) in aleveolar-arterial oxygen gradient at 18 h compared to preoperative values persisting until 6 days postoperatively. Levels of C3a increased significantly in both groups at 10 min post bypass, increased further at 60 min peaking at 4-6 h post bypass. Granulocyte elastase serum levels increased significantly at 10 min postoperatively in both groups compared to control levels, remaining elevated till 48 h, but returning to control levels by 6 days. There was a small difference (P < 0.04) between the groups at 4-6 h only. Levels of von Willebrand factor increased significantly at 60 min post bypass in both groups, remaining elevated 6 days postoperatively. Levels of malondialdehyde increased at 10 min post bypass, remaining elevated until 6 days post bypass. Thromboxane levels showed no significant changes. For all markers measured, there were no significant differences between the groups other than those already indicated., Conclusions: This study demonstrated marked respiratory dysfunction, complement activation and white cell activation in patients undergoing cardiopulmonary bypass with either bubble or membrane oxygenators. There was marked variability in the response of individual patients with either oxygenation technique, but overall no significant differences between the groups.

Transcranial Doppler ultrasound has revealed the existence of cerebrovascular microemboli in asymptomatic patients with prosthetic heart valves. We investigated the relation between the presence and number of emboli signals and valve type. Patients with six types of prosthetic valves (Björk-Shiley monostrut, Medtronic-Hall, Carbomedics, ATS, Carpentier-Edwards standard, Carpentier-Edwards supraannular) were examined using transcranial Doppler ultrasound in two centers. The monitoring time was 30 min over the right middle cerebral artery. All patients were stabilized on warfarin at the time of study. Microemboli signals were identified by their characteristic audiovisual signal and on subsequent spectral analysis, based on accepted criteria. A standard neurologic questionnaire was completed by all patients. The prevalence of microemboli signals varied between 49% (Medtronic Hall) and 97% (Björk-Shiley monostrut), while their number varied between 1 [0-3] (Carpentier-Edwards standard) and 187 [136-240] (Björk-Shiley monostrut) per hour (median and 95% CI). Both parameters were significantly higher in patients with Björk-Shiley monostrut valves compared to the other patient groups. There were no significant differences in the prevalence of neurologic complications among the groups examined (overall 16%), or in emboli numbers between symptomatic and asymptomatic patients. The prevalence and quantity of microemboli signals in patients with prosthetic heart valves, as detected by transcranial Doppler, is dependent upon valve type. The clinical significance of these microemboli signals remains to be further evaluated.

Application of transcranial Doppler ultrasonography to asymptomatic prosthetic heart valve patients can result in the detection of transient high intensity signals, similar to those induced by the passage of emboli. However, the origin of these signals is unknown. An in vitro study has been undertaken to investigate the capacity of prosthetic heart valves to generate high intensity Doppler signals in the absence of blood. A pulse duplicator, filled with a seeded saline solution, was used to function prosthetic heart valves under mock-physiological conditions. A Björk-Shiley Monostrut valve was mounted in the aortic port while a tri-leaflet control valve was fixed in the mitral port. At stations upstream and downstream from the Björk-Shiley valve, flow was monitored using pulsed wave Doppler ultrasound (Nicolet TC-2000, 2 MHz probe). The effect of damping the harsh closure of the mechanical valve was investigated by applying a thin layer of soft adhesive tape between the valve occluder and outer ring. For all valve configurations, transient high intensity Doppler signals, characteristic of microemboli and similar to those observed in clinical studies of prosthetic heart valve patients, were detected downstream from the aortic port. The number of microemboli signals did not change significantly between sites at 20 cm and 40 cm downstream from the aortic valve. Damping the Björk-Shiley valve closure greatly reduced (by 80%) the number of microemboli signals detected. It is concluded that Doppler microemboli signals can be generated by prosthetic heart valves while functioning in the absence of the formed elements of blood, and that the number of microemboli signals produced depends upon the rate of energy dissipation at valve closure.

A detailed understanding of the stresses and strains developed in functioning flexible-leaflet valves is necessary if a durable, non-thrombogenic heart valve replacement is to be realized. A new experimental tool, laser profiling, is presented for the study of flexible-leaflet heart valve dynamics. Profiles of moving leaflet surfaces are obtained by projecting parallel sheets of laser light onto valve leaflets as the valves open and close in a mock circulatory loop. Two versions of laser profiling have been developed. In two-dimensional mode multiple profiles are generated on a fixed plane in space but at discrete intervals in time, whereas in three-dimensional mode multiple profiles are generated across the leaflet surface at (effectively) a single instant in time. Highlighted leaflet profiles are captured by camera and transferred to an image processing system for analysis. A simple algorithm permits digitized profiles to be reconstructed within a computer-aided design software package, providing detailed visualization and quantification of valve motion. Extensive validation studies have been performed using the Medtronic-Hall mechanical prosthetic heart valve. Laser profiling enables computer reconstruction of the rigid occluder to an accuracy of +/- 200 microns from a 0.7 ms exposure taken during the period at which the occluder moves with greatest velocity. The technique has been applied to investigate the leaflet dynamics of a bovine pericardial heart valve prosthesis.

The application of transcranial Doppler (TCD) ultrasonography to asymptomatic prosthetic heart valve patients can result in detection of localized bursts of high intensity signals, similar to those caused by the passage of emboli. The origin of these signals is not known. In order to investigate this phenomenon in a simplified, more controllable environment, a TCD machine was used to record flow downstream from mechanical prosthetic heart valves in a mock circulatory loop. The model, which uses a saline solution seeded with silk particles (< 15 micrometers) as the circulatory fluid, recreates the principal hydrodynamic characteristics of the left heart and systemic circulation. Reproducibility of the system was established through repeated testing of a Monostrut valve. Three different mechanical valve types, (Monostrut, Medtronic Hall, St. Jude Medical) were tested over a range of simulated cardiac outputs, and the effect of valve size was investigated with four Omniscience tilting disc valves (21, 23, 25 and 29 mm). Average energy of the reflected Doppler signal was used to quantify the amount of high intensity Doppler signal, QTCD. TCD signals recorded in vitro were visually and aurally similar to those found in prosthetic heart valve patients. All valve types generated exponentially more QTCD with increasing simulated cardiac output. Differences amongst valve types were only significant at higher flow outputs, with the Monostrut valve producing the greatest QTCD. Larger valves consistently generated greater QTCD than smaller valves. In conclusion, TCD signals found in prosthetic heart valve patients can be reproduced, at least qualitatively, using a mock circulatory loop which does not incorporate the formed elements of blood.(ABSTRACT TRUNCATED AT 250 WORDS)

The prosthetic heart valves were fabricated from a polyurethane containing a 4,4'-diphenylmethane diisocyanate hard segment, chain-extended with butanediol and with a polyether soft segment. The rate of calcification of these polyurethane heart valves was much slower in a dynamic in vitro test system than similar bioprosthetic heart valves. The calcified deposits were located exclusively at regions of material failure. Fourier transform infrared (FTIR) spectroscopy indicated the involvement of the polyether soft segments of the polymer directly in the calcification process. Calcification of polymer fractions also suggested that small molecular weight extractable components are accelerating factors in the calcification process.

Between 2 February 1987 and 20 March 1990, 170 patients were randomly allocated to receive a new pericardial heart valve (the Bioflo) or the Carpentier-Edwards supra-annular porcine bioprosthesis. Eighty-five patients (mean age 61 years, range 38-77) received 93 Bioflo valves, 46 having aortic valve replacement (AVR), 31 mitral valve replacement (MVR) and 8 aortic and mitral valve replacement (A+MVR); 85 patients (mean age 62.1 years, range 41-77) received 99 Carpentier-Edwards porcine valves (48 AVR, 23 MVR and 14 A+MVR). Cumulative follow-up totals 926 patient-years (mean 5.45 +/- 1.93, median 6.03, maximum 7.47 years). The overall operative mortality rate for the Bioflo group was 2.4%, and 5.9% for the Carpentier-Edwards group. At 7 years, there was no statistically significant difference in survival or in any prosthesis-related complication between the pericardial and porcine valve recipients overall, or when the data were analysed according to valve implant position. The actuarial survival rate at 7 years for the Bioflo group was 80.1 +/- 5.1% and 72.3 +/- 5.9% for the Carpentier-Edwards group. Freedom from structural valve deterioration (SVD) at 7 years for Bioflo patients was 98.5 +/- 1.5% and for Carpentier-Edwards patients 91.2 +/- 4.1%. No patient in the Bioflo group has required reoperation for SVD. The randomised prospective trial has proven practical and effective and has shown the pericardial valve to perform at least as well as the porcine valve up to 7 years when all of the standard outcome measures of valve performance are assessed.

Despite considerable investigation, the mechanism of laser assisted vascular anastomosis remains unknown. Indications suggest that bonding is the result of thermal action, particularly the thermal denaturation of tissue proteins. However, our own work has led us to conclude that dehydration is an important factor. Hence, we have proposed that laser anastomosis is the result of dehydration at the apposed tissue faces, induced by laser irradiation. This was investigated by comparing the properties of bonds created by dehydration with those created by laser. The bonds were created using parameters consistent with laser anastomoses created in vivo. Results revealed that anastomoses created by dehydration were equivalent to those created by laser, with little difference in strength, histology or response to rehydration. The only significant difference (p < 0.02) was mean bond strength created at temperatures above the denaturation temperature of the tissue (548 g cm(-2) by laser, 994 g cm(-2) by dehydration). Given the similarity of bonds created by the two methods, we conclude that the same mechanism (i.e. dehydration) is likely to be responsible for bonding in both cases and therefore that argon laser bonding is mediated by dehydration.

Previous work in our laboratory has demonstrated a simple, dynamic in vitro calcification method for studying bovine pericardial heart valves. The calcification produced closely resembled that found in clinical explant valves. The current study extends this technique to the porcine aortic bioprosthesis. Five Carpentier-Edwards porcine aortic bioprostheses were calcified in vitro in a modified wear tester. All valves calcified to a similar degree as bovine pericardial valves. Calcification predominated on the ribbed tissue structures near the commissures on the outflow surfaces. The same calcification pattern was seen in clinical explant valves. A number of anti-calcification modifications of porcine aortic valves were also investigated. These had all previously inhibited calcification of bovine pericardium in a rat subdermal implant model but had failed to reduce calcification in whole pericardial valves calcified in vitro under dynamic conditions. The modified porcine valves produced similar results: no modification achieved reduction of calcification on exposure to the functional valve calcification model. The dynamic in vitro calcification test has been shown to be useful for the study of both main types of bioprostheses, bovine pericardial and porcine aortic valves, and for the assessment of alterations to these biomaterials.

Background and Purpose: Doppler emboli detection is an established technique, but the nature of the underlying embolic material remains unclear. The intensity and spectral distribution of emboli signals could help to distinguish between signals arising from formed and gaseous emboli. We undertook this study to develop and evaluate a differentiation algorithm based on the spectral characteristics of emboli signals. Subsequently the algorithm was applied to patients with mechanical prosthetic cardiac valves., Methods: Emboli signals detected in patients with carotid disease, acute stroke, and atrial fibrillation were used as formed emboli data, and signals detected in patients undergoing cardiac catheterization studies were used as gaseous emboli data. For each embolus signal, the maximal amplitude, the sum of amplitudes, and the spectral intensity distribution were calculated. Two hundred emboli signals from each category were used to develop a differentiation algorithm, which was subsequently evaluated on 501 additional solid and 995 gaseous emboli signals. The same algorithm was used to analyze 5958 emboli signals detected in 60 patients with mechanical prosthetic valves., Results: The best results were obtained with an algorithm based on both the maximal amplitude and the sum of amplitudes (sensitivity, 99%; specificity, 96.5%). On subsequent evaluation, the sensitivity and specificity of the algorithm were 99.6% and 89.8%, respectively. Of the 5958 emboli signals detected in prosthetic valve patients, 92.4% were classified as gaseous., Conclusions: Differentiation between gaseous and formed emboli signals, as detected by transcranial Doppler in vivo, is feasible by means of spectral analysis. Application of the differentiation algorithm in prosthetic valve patients suggests that the embolic material in these patients is gaseous. The possibility of distinguishing between different formed embolic materials with this technique remains to be evaluated.

Calcification of bioprosthetic heart valves is a major factor limiting their long-term function. Current methods of microscopic examination of calcific deposits require dehydration and processing of the leaflet material, e.g. wax embedding, sectioning, gold coating. Confocal laser scanning microscopy is a new technique which allows serial optical sectioning of thick biological specimens in their normal hydrated state. The current study has examined bovine pericardium and porcine aortic valve materials calcified in vitro under static and dynamic conditions. A series of clinical explants of bovine pericardial and porcine aortic valve types has also been examined. The calcium-specific stain, Alizarin Red S, has been used as a fluorescent marker for calcium deposits. Fluorescent images, generated by Argon ion laser light at 488nm, have been obtained at varying depths into samples. These have been reconstructed to demonstrate the relationship between calcium deposits and autofluorescent collagen fibers. The patterns of calcification were similar in both in vitro and explant valve material. The calcification was of three main patterns: calcium depositing longitudinally on collagen fiber bundles; calcium forming a banded pattern perpendicular to the fiber direction and large, dense, focal deposits obliterating the underlying collagen structure. Involvement of collagen fibers in the calcification pattern was a consistent finding in all sample types. The method is a useful addition to the tools available for study of calcification processes. The potential exists for three-dimensional reconstruction of leaflet architecture and its inter-relationship with calcium deposition, in a normally hydrated state.

Between 1st Jan 1992 and 1st Sept 1993 164 patients were referred as candidates for heart transplantation in Scotland. 79 were accepted for transplantation and 39 of these received orthotopic heart transplants. 30 day mortality was zero. Mean time on intensive care post operatively was 46.35 hrs and mean time to hospital discharge was 17.03 days. Cumulative actuarial survival (survival at 18 months post operatively) was 87%. There were three deaths, two from infection at six and 19 weeks and one from neoplasia at 37 weeks. Mean time to rejection was 38.54 days. Linear rejection rates at 0-3, 3-6, 6-9, 9-12, 12-15 and 15-18 months were 1.86, 0.94, 0.6, 0.04, 0 and 0 events per 100 pt-days respectively. Linear infection rates at 0-3, 3-6, 6-9, 9-12, 12-15 and 15-18 months were 1.81, 0.17, 0.1, 0, 0.05 and 0.18 events per 100 pt-days respectively. The heart transplant programme in Scotland has been successful in terms of operative mortality and short to medium term survival.

The biocompatibility of artificial organs is recognised as an area presenting difficulties in terms of the complexity of the situation. The nature of the blood response involving interactions of systems, pattern and extent of change, patient status and the influence of the whole device contribute to the complexity. Recognising these, the profile of the blood response to cardiopulmonary bypass (CPB), with respect to type of device, mode of blood flow, duration of the procedure and patient status, has been evaluated by monitoring contact phase activation [Factor XII-like activity (FXIIA)], fibrinolytic activity [Fibrin degradation products (X-FDP's)], complement activation (C3a, C5a), leucocyte activation [Granulocyte elastase (GE)] and platelet and white cell imaging. FXIIA, X-FDP's, and GE rose gradually during CPB, with levels remaining elevated post-operatively for up to 48 h. In contrast, C3a levels rose sharply with no significant elevation in the post-operative period, while C5a did not show significant changes during bypass. The use of pulsatile perfusion resulted in lesser activation of the parameters, although these were significantly less only for GE. The alterations in FXIIA, X-FDP's, C3a and GE correlated positively with the duration of CPB, with this effect pronounced in the post-operative period for FXIIA, X-FDP's and GE. However, these changes had no apparent influence on clinical outcome and the majority of patients had uncomplicated post-operative recoveries. With respect to the use of bubble/membrane oxygenators, platelet and white cell deposition and the patterns of change for FXIIA and C3a were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)