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Biomedical subjects

D J Wheatley

Publications and source records attributed to D J Wheatley.

At least 19 recordsLinked to original sources

Heparin, platelet aggregation, neutrophils, and cardiopulmonary bypass.

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.

Anticoagulants↗

Heparin-induced platelet dysfunction and cardiopulmonary bypass.

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.

Blood Platelet Disorders↗

Mechanisms of pulmonary transfer factor decline following heart transplantation.

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.

Adult↗

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

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

Analysis of Variance↗

Assessment of changes in general health status using the short-form 36 questionnaire 1 year following coronary artery bypass grafting.

OBJECTIVE: The problem addressed in the study was to gain a greater understanding of the health benefits of coronary artery bypass grafting (CABG). The purpose of the study was to assess general health status, using the short-form (SF)-36 questionnaire, approximately 12 months following CABG, and to document any associations between pre-operative health status, level of social support, coronary artery disease (CAD) risk factors, CAD symptom severity and post-operative health status. METHODS: The study was prospective and observational in design and included assessments at two time points, namely pre-operatively in a hospital outpatient department (1995-1996) and post-operatively at home (1996-1997). Two hundred and fourteen patients awaiting elective CABG were recruited a month before the expected date of operation. Pre-operative assessment included: (1), severity of symptoms; (2), CAD risk factors; (3), SF-36 questionnaire; and (4), social activities questionnaire. Post-operative assessment measured health status using the SF-36 instrument (mean, 16.4 months). Correlation and multiple linear regression analyses were used to identify factors associated with improved health status following CABG. RESULTS: Two hundred and fourteen patients were assessed pre-operatively and underwent CABG. There was a 4.8% 30-day mortality rate, and 183 patients were followed for a mean of 16.4 months after CABG. SF-36 scores following CABG were improved across all of the eight domains (P<0.001). A higher social network score and higher pre-operative health status were associated with improved health status. Patients with lower health levels (SF-36 scores) prior to CABG were less likely to gain improvement in health (SF-36 scores) following CABG. Lower SF-36 scores following operation were influenced by the presence of diabetes mellitus, cigarette smoking, younger age, a high socio-economic deprivation category and higher alcohol intake. Many patients had uncorrected CAD risk factors at pre-operative assessment. CONCLUSIONS: The SF-36 instrument was shown to be a useful and sensitive tool to assess differences and changes in the general health status of patients before and following CABG. High levels of social support were associated with improved health status post-operatively. Lower pre-operative general health status, the presence of diabetes mellitus and cigarette smoking were associated with poorer post-operative general health status.

Activities of Daily Living↗

Evaluation of four blood pump geometries: fluorescent particle flow visualisation technique.

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.

Anion Exchange Resins↗

The effects of heparin and extracorporeal circulation on platelet counts and platelet microaggregation during cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass is associated with platelet activation and reduced platelet counts. Platelet activation may artifactually lower platelet counts by causing aggregation. In vivo platelet activation may increase existent platelet microaggregation ex vivo. We studied platelet counts and existent platelet microaggregation at different stages of cardiopulmonary bypass. METHODS: Twenty-one patients were studied before and after heparinization (300 U. kg(-1)) and at the end of cardiopulmonary bypass. Unaggregated (or single) platelets were counted in hirudin-anticoagulated blood, and total platelets were counted in ethylenediaminetetraacetic acid-anticoagulated blood. RESULTS: The total platelet count, 198 +/- 61 x 10(9). L(-1), was unaffected by heparin and stayed at 197 +/- 60 x 10(9). L(-1) (P =.7) but fell during extracorporeal circulation; the hemodilution-corrected count was 163 +/- 52 x 10(9). L(-1) (P =.0004). Heparinization reduced the unaggregated platelet count from (mean +/- 1 SD) 178 +/- 62 x 10(9). L(-1) to 155 +/- 60 x 10(9). L(-1) (P =.0001). Extracorporeal circulation had little additional effect. The hemodilution-corrected count was 142 +/- 48 x 10(9). L(-1) (P =.6). CONCLUSIONS: Heparinization caused platelet activation and increased existent platelet microaggregation ex vivo. During extracorporeal circulation, there was a reduction in total platelets that was greater than could be explained by hemodilution alone, but the unaggregated platelet count did not change significantly when corrected for hemodilution. Furthermore, the increased platelet microaggregation observed after heparinization was no longer evident after this loss. These findings suggest that during extracorporeal circulation, the platelets that formed into microaggregates after heparinization were lost from the circulation in preference to single platelets.

Adult↗

Quantitative detection of platelet aggregates in whole blood without fixation.

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.

Adult↗

The alveolar-capillary membrane diffusing capacity and the pulmonary capillary blood volume in heart transplant candidates.

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.

Adult↗

Evaluation of four blood pump geometries: the optical tracer technique.

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.

Benzenesulfonates↗

Porcine versus pericardial bioprostheses: eleven-year follow up of a prospective randomized trial.

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.

Animals↗

Can technetium 99m pyrophosphate be used to quantify myocardial injury in donor hearts?

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.

Animals↗

Platelet aggregation and high-intensity transient signals (HITS) in a sheep model of mitral valve replacement.

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.

Animals↗

Digoxin use in patients awaiting heart transplantation for systolic left ventricular failure.

We reviewed the drug therapy of 83 patients who underwent cardiac transplantation for chronic left ventricular cardiac failure in Scotland from 1992-1996. Digoxin had been prescribed to 52% of patients in sinus rhythm, and 82% of those in atrial fibrillation (P=NS). This audit confirms that, in line with the clinical practice in the period between 1992 and 1996, digoxin was not widely used in patients with advanced chronic heart failure who were in sinus rhythm. The publication of the withdrawal trials in 1993 might have been expected to increase the use of digoxin but this could not be demonstrated. The management of patients on the cardiac transplantation waiting list should include the best symptomatic treatment possible. In view of the clinical and experimental evidence of symptomatic improvement by cardiac glycosides, it is to be hoped that publication of the results of the Digitalis Investigation Group trial will improve this situation.

Adult↗

Alterations in renal microcirculation during cardiopulmonary bypass.

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.

Anesthesia, Inhalation↗

In vitro blood compatibility of surface-modified polyurethanes.

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.

Biocompatible Materials↗