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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
PubMed2006

Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial.

OBJECTIVE: To determine whether, in acute non-ST elevation coronary syndrome, the benefit from early invasive coronary intervention compared with a conservative strategy of later symptom-guided intervention varies over time. METHODS: In RITA 3 (Randomised Intervention Trial of unstable Angina 3) patients were randomly assigned to coronary angiography (median 2 days after randomisation) and appropriate intervention (n = 895) or to a symptom-guided conservative strategy (n = 915). RESULTS: In the first week patients in both groups were at highest risk of death, myocardial infarction (MI) or refractory angina (incidence rate 40 times higher than in months 5-12 of follow up). There were 22 MIs and 6 deaths in the intervention group (largely due to procedure-related events, 14 MIs and 3 deaths) versus 17 MIs and 3 deaths in the conservative group. In the rest of the year there were an additional 12 versus 27 MIs, respectively (treatment-time interaction p = 0.021). Over one year in the intervention group there was a 43% reduction in refractory angina; 22% of patients underwent coronary artery bypass surgery and 35% underwent percutaneous coronary intervention only, which reduced refractory angina but provoked some early MIs; and 43% were still treated medically, mostly because of a favourable initial angiogram. CONCLUSION: Any intervention policy needs to recognise the high risk of events in the first week and the substantial minority of patients not needing intervention. Intervention may be best targeted at higher risk patients, as the early hazards of the procedure are then offset by reduced subsequent events.

Adult↗
PubMed2006

Dynamic modelling of prosthetic chorded mitral valves using the immersed boundary method.

Current artificial heart valves either have limited lifespan or require the recipient to be on permanent anticoagulation therapy. In this paper, effort is made to assess a newly developed bileaflet valve prosthesis made of synthetic flexible leaflet materials, whose geometry and material properties are based on those of the native mitral valve, with a view to providing superior options for mitral valve replacement. Computational analysis is employed to evaluate the geometric and material design of the valve, by investigation of its mechanical behaviour and unsteady flow characteristics. The immersed boundary (IB) method is used for the dynamic modelling of the large deformation of the valve leaflets and the fluid-structure interactions. The IB simulation is first validated for the aortic prosthesis subjected to a hydrostatic loading. The predicted displacement fields by IB are compared with those obtained using ANSYS, as well as with experimental measurements. Good quantitative agreement is obtained. Moreover, known failure regions of aortic prostheses are identified. The dynamic behaviour of the valve designs is then simulated under four physiological pulsatile flows. Experimental pressure gradients for opening and closure of the valves are in good agreement with IB predictions for all flow rates for both aortic and mitral designs. Importantly, the simulations predicted improved physiological haemodynamics for the novel mitral design. Limitation of the current IB model is also discussed. We conclude that the IB model can be developed to be an extremely effective dynamic simulation tool to aid prosthesis design.

Biocompatible Materials↗
PubMed2005

Fish oil before cardiac surgery: neutrophil activation is unaffected but myocardial damage is moderated.

Could pre-operative dietary intervention with fish oil reduce neutrophil activation and myocardial damage associated with cardiopulmonary bypass (CPB)? Patients were randomised to receive either 8 g/day fish oil (n=22) or placebo (n=18) for 6 weeks. Neutrophil activation, apoptosis and cardiac damage were measured. Demographics and operative variables were similar. Fish oil diet decreased plasma VLDL from 0.69+/-0.34 to 0.51+/-0.24 mmol/l and triglycerides from 1.68+/-0.70 to 1.39+/-0.54 mmol/l. HDL cholesterol increased from 0.94+/-0.27 to 1.03+/-0.26 mmol/l demonstrating significant treatment effects (P=0.007, 0.02 and 0.0003, respectively) as well as compliance with treatment. There were no significant differences in ex vivo N-formyl-methionyl-leucyl-phenylalanine-stimulated neutrophil superoxide anion generation or myeloperoxidase release at recruitment, pre-operatively and at end-CPB. Apoptosis at end-CPB was equally reduced in both groups from 23+/-9% to 13+/-4% in the fish oil group (P<0.001) and 35+/-14% to 15+/-3% in the placebo group (P=0.001). At end-CPB overall troponin I levels averaged 0.91+/-0.60 ng/ml which clearly exceeded diagnostic levels (0.15 ng/ml). At 24h troponin I fell significantly in the fish oil group to 46+/-23% of end-CPB levels (P=0.0002) whereas it peaked in the placebo group to 107+/-72% (P=0.098 vs. end-CPB); this difference was significant: P=0.013. At 48 h the placebo-treated patients had higher troponins but not significantly so (P=0.059). Area-under-the-curve analysis did not conclusively support this (P=0.068). We conclude that fish oil did not significantly decrease post-CPB neutrophil activation (as detected ex vivo) but may moderate post-operative myocardial damage.

Apoptosis↗
PubMed2005

The future role of surgery in ischaemic heart disease.

The ability to restore myocardial perfusion in ischaemic heart disease has been one of the triumphs of surgery. Alternative, less invasive catheter-based methods have now taken the lead as favoured treatment. The resultant threat to surgical practice, as well as societal and organisational issues that impact on the life of surgeons, have caused many to question the future role of surgery in ischaemic heart disease. In spite of general awareness of risk factors, there is little to suggest that coronary disease will soon disappear; rather, obesity and unfavourable life-style of many will continue to recruit further patients and, additionally, an epidemic of heart failure is anticipated. At the same time, rapid advance in knowledge of the underlying disease is opening the prospect for more effective intervention for unstable coronary plaque. Of great relevance to the surgeon are recent advances in knowledge and technology that will lead to gene and cell-based therapy for ischaemic heart disease. The ability to modify or augment activity of myocytes in heart failure, and to promote angiogenesis, offers hope for repair of ischaemically damaged hearts undreamed of only a few years ago. Tissue engineering, encompassing gene and cell-based therapy, holds promise of reconstruction of the myocardium and its vasculature. Temporary cardiovascular support to enable application of these techniques will very likely provide one role for surgery. More importantly, the need to ensure optimal anatomic and functional repair will surely give rise to a new generation of surgeons with much expanded scientific and technical support to draw upon, and will ensure an important role for surgery in ischaemic heart disease for decades to come.

Biological Therapy↗
PubMed2003

Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses.

OBJECTIVE: To compare survival and outcome in patients receiving a mechanical or bioprosthetic heart valve prosthesis. DESIGN: Randomised prospective trial. SETTING: Tertiary cardiac centre. PATIENTS: Between 1975 and 1979, patients were randomised to receive either a Bjork-Shiley or a porcine prostheses. The mitral valve was replaced in 261 patients, the aortic in 211, and both valves in 61 patients. Follow up now averages 20 years. MAIN OUTCOME MEASURES: Death, reoperation, bleeding, embolism, and endocarditis. RESULTS: After 20 years there was no difference in survival (Bjork-Shiley v porcine prosthesis (mean (SEM)): 25.0 (2.7)% v 22.6 (2.7)%, log rank test p = 0.39). Reoperation for valve failure was undertaken in 91 patients with porcine prostheses and in 22 with Bjork-Shiley prostheses. An analysis combining death and reoperation as end points confirmed that Bjork-Shiley patients had improved survival with the original prosthesis intact (23.5 (2.6)% v 6.7 (1.6)%, log rank test p < 0.0001); this difference became apparent after 8-10 years in patients undergoing mitral valve replacement, and after 12-14 years in those undergoing aortic valve replacement. Major bleeding was more common in Bjork-Shiley patients (40.7 (5.4)% v 27.9 (8.4)% after 20 years, p = 0.008), but there was no significant difference in major embolism or endocarditis. CONCLUSIONS: Survival with an intact valve is better among patients with the Bjork-Shiley spherical tilting disc prosthesis than with a porcine prosthesis but there is an attendant increased risk of bleeding.

Animals↗
PubMed2002

Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina.

BACKGROUND: Current guidelines suggest that, for patients at moderate risk of death from unstable coronary-artery disease, either an interventional strategy (angiography followed by revascularisation) or a conservative strategy (ischaemia-driven or symptom-driven angiography) is appropriate. We aimed to test the hypothesis that an interventional strategy is better than a conservative strategy in such patients. METHODS: We did a randomised multicentre trial of 1810 patients with non-ST-elevation acute coronary syndromes (mean age 62 years, 38% women). Patients were assigned an early intervention or conservative strategy. The antithrombin agent in both groups was enoxaparin. The co-primary endpoints were a combined rate of death, non-fatal myocardial infarction, or refractory angina at 4 months; and a combined rate of death or non-fatal myocardial infarction at 1 year. Analysis was by intention to treat. FINDINGS: At 4 months, 86 (9.6%) of 895 patients in the intervention group had died or had a myocardial infarction or refractory angina, compared with 133 (14.5%) of 915 patients in the conservative group (risk ratio 0.66, 95% CI 0.51-0.85, p=0.001). This difference was mainly due to a halving of refractory angina in the intervention group. Death or myocardial infarction was similar in both treatment groups at 1 year (68 [7.6%] vs 76 [8.3%], respectively; risk ratio 0.91, 95% CI 0.67-1.25, p=0.58). Symptoms of angina were improved and use of antianginal medications significantly reduced with the interventional strategy (p<0.0001). INTERPRETATION: In patients presenting with unstable coronary-artery disease, an interventional strategy is preferable to a conservative strategy, mainly because of the halving of refractory or severe angina, and with no increased risk of death or myocardial infarction.

Angina Pectoris↗
PubMed2002

Are we negating the benefits of CABG by forgetting secondary prevention?

UNLABELLED: The objective of the study was to examine medically managed secondary prevention at one year after coronary artery bypass grafting (CABG). In all, 214 consecutive patients undergoing isolated elective CABG seen four weeks preoperatively and one year post-operatively. Preoperative systolic blood pressure averaged 135+/-20 mmHg, which increased to 148+/-25 mmHg (P<0.0001) as did diastolic pressure (81+/-12 to 87+/-13 mmHg; P<0.0001). Anginal symptoms were reported by 45.1% (P<0.0001) although median severity scored lower (4.0 [3.0-5.4] vs 0 [0-2.0]; P<0.0001). Breathlessness decreased from 93% to 64% (P<0.0001) and was scored less severely (4.0 [2.0-5.0] vs 2.0 [0-4.0]; P<0.0001. In all, 88% with postoperative angina reported dyspnoea against 44% of those without (P<0.0001). Calcium antagonist use was more common in patients with angina (27.2% vs 5.1%; P<0.0001), but not nitrates (P=0.8695), diuretics (P=0.4218), digoxin (P=0.2565), beta-blockers (P=0.0820), or ACE inhibitors (P=0.7256). Preoperatively 166 patients (80.2%) took aspirin vs 69.2% afterwards (P=0.0131). Twelve patients (6.5%) received warfarin after operation vs none preoperatively. Two took digoxin (0.97%) preoperatively and 14 (7.7%) postoperatively (P=0.001) for chronic atrial fibrillation. One of these took warfarin. Long-acting nitrate use fell from 63.4% to 15.8% (P <0.0001). Short-acting nitrate use fell similarly (P<0.0001). Preoperatively 37 patients (17.9%) took ACE inhibitors vs 44 postoperatively (24.2%); 39 had not received them before. Preoperatively 48 (23.2%) took diuretics vs 30 (16.5%) postoperatively (P=0.127); 24 had not previously taken diuretics. More patients took HMGCoA inhibitors postoperatively (P=0.0068) and total cholesterol was significantly reduced with a concomitant increase in HDL fraction. Smoking habit was virtually unchanged from 17.8% to 15.1% (P=0.5023). IN CONCLUSION: angina was common. Apart from statin prescribing, postoperative secondary prevention measures were poorly applied, less widespread and less effective than preoperatively. The implications are disturbing.

Angina Pectoris↗
PubMed2002

Coronary artery surgery at the dawn of the 21st century.

Since the 1970's coronary bypass surgery has evolved to become one of the commonest and most successful of all operative procedures. The symptomatic and survival benefit of this surgery is well recognised. However, developments in cardiological interventions, coupled with demographic and lifestyle changes, are altering the patient profile and referral pattern. Coronary surgery at the beginning of the new century frequently involves higher risk patients and more complex surgery as a result of changes in disease presentation and the success of competing cardiological interventional techniques for less extensive disease. Technological advances in endovascular devices are making significant inroads into traditional coronary surgical practice. Surgeons have responded by developing new strategies to maximise effectiveness of coronary surgery and minimise the injury associated with cardiopulmonary bypass. At the same time regulatory and media scrutiny is focussing attention on the cardiac surgeon, further adding to the stresses and complexity of cardiac surgical practice

Cardiac Surgical Procedures↗
PubMed2001

Platelet aggregatory responses to low-dose collagen are maintained in hirudin-anticoagulated whole blood for 24 h when stored at room temperature.

Whole blood from 15 volunteers was anticoagulated with hirudin (200U/l) and the response to a known submaximal concentration of collagen (0.6 microg/ml) was tested by impedance aggregometry. In 8 volunteers platelet counts were also taken before and after the maximum aggregatory response. These tests were repeated when the samples had rested for 24 h at room temperature. The median [interquartile range] aggregatory response immediately after sampling was 17.3 [16.7-18.4] ohms. At 24 h it was 17.7 [15.8-19.3] ohms (p = 0.88) although variance was increased (p = 0.006). The immediate platelet count before collagen exposure was 438 [381-510] x 10(9)/l and 258 [227-297] x 10(9)/l post-collagen. At 24 h the platelet count was 448 [443-473] x 10(9)/l (p = 0.224 versus immediate count) but variance was not increased (p = 0.215). After full aggregation the count fell to 284 [234-304] x 10(9)/l (p = 0.592 versus early post-collagen). Variances were similar (p = 0.558). Aggregate response ratios increased non-significantly after 24 h from 0.59 [0.53-0.62] to 0.64 [0.51-0.68] although variance was increased (p = 0.021). Full macroaggregatory responses by impedance aggregometry were seen after 24h storage of whole blood with hirudin at room temperature. This suggests both that distant assessment of platelet function using a standardized method is possible and a potential role of thrombin inhibition for platelet storage.

Anticoagulants↗
PubMed2001

The influence of general health status and social support on symptomatic outcome following coronary artery bypass grafting.

OBJECTIVES: To assess health status, level of social support, and presence of coronary artery disease risk factors before and after coronary artery bypass grafting (CABG); to assess symptomatic relief approximately 12 months postoperatively; and to examine the association between preoperative health status and recurrence of symptoms. DESIGN: Observational study. SETTING: Preoperatively, in hospital outpatient department (1995-1996); postoperatively, at home (1996-97). SUBJECTS AND METHODS: Patients awaiting elective CABG were recruited one month before the expected date of operation. Preoperative assessment included severity of symptoms, coronary artery disease risk factors, short form 36 (SF-36) questionnaire, and social activities questionnaire. The presence and severity of angina and breathlessness were reported postoperatively (mean 16.4 months). Multiple regression analysis was used to identify factors associated with improved outcome following CABG. MAIN OUTCOME MEASURE: Patient reported presence and severity of angina and breathlessness. RESULTS: 183 patients were followed for a mean of 16. 4 months after CABG. Angina and breathlessness were completely relieved in 55% and 36% of patients, respectively. In patients with residual symptoms, the severity was significantly reduced (angina p < 0.001; breathlessness, p = 0.02). Patients with low SF-36 scores and low social network scores preoperatively were less likely to be relieved of symptoms (p < 0.001). Health status and social support levels preoperatively were lower than in other reported coronary artery disease patients groups. Preoperatively, coronary artery disease risk factors were higher than recommended in current guidelines: 67.4% had raised plasma cholesterol, 39.0% were hypertensive, 80% were moderately obese, and 22.9% were smokers. CONCLUSIONS: Recurrence of symptoms exceeded other published studies. Patients' perception of general health, symptoms, and social support influences outcome.

Adult↗
PubMed2001

Nurse led shared care for patients on the waiting list for coronary artery bypass surgery: a randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a nurse led shared care programme to improve coronary heart disease risk factor levels and general health status and to reduce anxiety and depression in patients awaiting coronary artery bypass grafting (CABG). DESIGN: Randomised controlled trial. SETTING: Community, January 1997 to March 1998. STUDY GROUPS: 98 (75 male) consecutive patients were recruited to the study within one month of joining the waiting list for elective CABG at Glasgow Royal Infirmary University NHS Trust. Patients were randomly assigned to usual care (control; n = 49) or a nurse led intervention programme (n = 49). INTERVENTION: A shared care programme consisting of health education and motivational interviews, according to individual need, was carried out monthly. Care was provided in the patients' own homes by the community based cardiac liaison nurse alternating with the general practice nurse at the practice clinic. OUTCOME MEASURES: Smoking status, obesity, physical activity, anxiety and depression, general health status, and proportion of patients exceeding target values for blood pressure, plasma cholesterol, and alcohol intake. RESULTS: Compared with patients who received usual care, those participating in the nurse led programme were more likely to stop smoking (25% v 2%, p = 0.001) and to reduce obesity (body mass index > 30 kg/m(2)) (16.3% v 8.1%, p = 0.01). Target systolic blood pressure improved by 19.8% compared with a 10.7% decrease in the control group (p = 0.001) and target diastolic blood pressure improved by 21.5% compared with 10.2% in the control group (p = 0.000). However, there was no significant difference between groups in the proportion of patients with cholesterol concentrations exceeding target values. There was a significant improvement in general health status scores across all eight domains of the 36 item short form health survey with changes in difference in mean scores between the groups ranging from 8.1 (p = 0.005) to 36.1 (p < 0.000). Levels of anxiety and depression improved (p < 0.000) and there was improvement in time spent being physically active (p < 0.000). CONCLUSIONS: This nurse led shared care intervention was shown to be effective for improving care for patients on the waiting list for CABG.

Adult↗
PubMed2001

A new design for polyurethane heart valves.

BACKGROUND AND AIM OF THE STUDY: The synthetic flexible tri-leaflet heart valve offers considerable potential for improvement in both hydrodynamic and biomechanical performance of replacement heart valves. To date, success with the synthetic leaflet heart valve has been limited, partly due to limitations in the biostability of the polyurethanes used. With the synthesis of new biostable polyurethanes, the integration of advancing technology, and better knowledge of the functional and biomechanical design requirements necessary to increase the long-term durability of the polyurethane heart valve, novel clinical solutions are now in sight. METHODS: This study describes the design characteristics, hydrodynamic and biomechanical performance of a new design of polyurethane heart valve. The function and durability characteristics of this novel design of heart valve, manufactured using a proven durable non-biostable polyurethane, was compared with that of a single AorTech porcine bioprosthetic heart valve and a single tilting disc mechanical heart valve, the Björk-Shiley Monostrut valve (BSM), of similar size. RESULTS: For equivalent sizes of valve, the new polyurethane heart valve design had significantly lower pressure gradients compared with the porcine valve at all flow rates and to the BSM valve at the higher flow rates. The effective orifice area of the polyurethane valve was greater than the other two valves studied; regurgitation and total energy loss were less. The new polyurethane valve design reached over 360 million cycles in an accelerated durability tester, without failure. CONCLUSION: This new design of polyurethane heart valve showed improved hydrodynamic function in comparison with either the porcine bioprosthetic or the BSM mechanical heart valve. The pulsatile flow results showed a lower total energy loss associated with this valve, indicating improved potential patient benefit. The durability of this new design of polyurethane heart valve was demonstrated when manufactured using a medical-grade polyurethane.

Biomechanical Phenomena↗
PubMed2001

Hydrodynamic function of a biostable polyurethane flexible heart valve after six months in sheep.

Survival to six months for sheep with a non-biostable polyurethane mitral heart valve prosthesis has been reported previously, however, with surface degradation and accumulation of calcified fibrin/thrombus that impaired leaflet motion and compromised hydrodynamic function. Newly available biostable polyurethanes may overcome this problem. Six adult sheep with biostable polyurethane trileaflet heart valve prostheses of documented hydrodynamic performance, implanted in the mitral position, were allowed to survive for 6 months. Explanted valves were photographed, resubmitted to hydrodynamic function testing, and studied by light and electron microscopy. Explanted valves were structurally intact and differed little in appearance from their preimplant state. Hydrodynamic testing showed no deterioration in pressure gradient or energy losses compared with pre-implant values. Biostable polyurethanes demonstrated improved blood compatibility leaving leaflets flexible and valve function unimpaired. Biostable polyurethanes may thus improve prospects for prolonged function of synthetic heart valve prostheses.

Animals↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗