Polyreactive antibodies developing amidst humoral rejection of human kidney grafts bind apoptotic cells and activate complement.

Antibody mediated rejection (AMR) is associated with a variety of graft-reactive antibodies following kidney transplant. To characterize these antibodies, we immortalized 107 B cell clones from a patient with AMR. In a previous study, we showed that six clones were reacting to multiple self-antigens as well as to HLA and MICA for two of them, thus displaying a pattern of polyreactivity. We show here that all six polyreactive clones also reacted to apoptotic but not viable cells. More generally we observed a nearly perfect overlap between polyreactivity and reactivity to apoptotic cells. Functionally, polyreactive antibodies can activate complement, resulting in the deposition of C3d and C4d at the surface of target cells. Testing the serum of 88 kidney transplant recipients revealed a significantly higher IgG reactivity to apoptotic cells in AMR patients than in patients with stable graft function. Moreover, total IgG purified from AMR patients had increased complement activating properties compared to IgG from non-AMR patients. Overall, our studies show the development of polyreactive antibodies cross-reactive to apoptotic cells during AMR. Further studies are now warranted to determine their contribution to the detection of C4d in graft biopsies as well as their role in the pathophysiology of AMR.

The role of performance indicators in changing the autonomy of the general practice profession in the UK.

Performance indicators (PIs) are widely used across the UK public sector, but they have only recently been applied to clinical care. In doing so, they challenge a previously guarded aspect of clinical autonomy-the assessment of work performance. This "challenge" is specific to a primary care setting and in the general practice profession. This paper reviews the qualitative findings from an empirical study within one English primary care group on the response to a set of clinical PIs relating to general practitioners (GPs) in terms of the effect upon their clinical autonomy. Prior to interviews with GPs, primary care teams received feedback on their clinical performance as judged by indicators. Five themes were crucial in understanding GPs responses: the credibility of PIs, the growing need to demonstrate competence, perceptions of autonomy, the ulterior purpose of PIs, and the identity of the assessor of their performance. PIs are playing a key role in changing the locus of performance assessment along two dimensions: location and expertise. As the locus helps to determine the nature of clinical autonomy, it is likely to have implications for the nature of the general practice profession.

Rates of cholesterol esterification and esterified cholesterol net mass transfer between high-density lipoproteins and apolipoprotein B-containing lipoproteins in Type 1 diabetes.

AIMS: Type 1 diabetes is associated with a high incidence of coronary heart disease (CHD) despite paradoxically normal or high high-density lipoprotein (HDL) cholesterol concentrations. Triglyceride (TG) concentrations have been shown to be important determinants of two aspects of HDL metabolism: cholesterol esterification rate and esterified cholesterol (EC) net mass transfer rate between HDL and the apolipoprotein B-containing lipoproteins. In order to try to explain the paradox, we aimed to assess the relationships between plasma TG and these two processes in Type 1 diabetic compared with non-diabetic subjects. METHODS: Rates of cholesterol esterification and EC net mass transfer between HDL and the apolipoprotein B-containing lipoproteins were assessed by incubating whole plasma at 37 degrees C; intra-assay coefficients of variation were 6% and 30%, respectively. RESULTS: Ten Type 1 diabetic and 10 non-diabetic subjects, with similar ages, sex distributions, body mass indices and total cholesterol and TG concentrations, were assessed. Apolipoprotein A1, HDL unesterified cholesterol, and HDL phospholipid concentrations were greater in the Type 1 diabetic subjects. There were no significant differences in the rates of cholesterol esterification or EC net mass transfer between the groups. There were strong associations between plasma TG and the rate of cholesterol esterification and between plasma TG and the rate of EC net mass transfer in Type 1 diabetic subjects (r = 0.83, P = 0.0027 and r = 0.88, P = 0.0009, respectively) and in non-diabetic subjects (r = 0.91, P = 0.0002 and r = 0.79, P = 0.0070, respectively). However, the slopes of the associations with plasma TG were significantly steeper in the Type 1 diabetic subjects (analyses of covariance P = 0.0053 and P = 0.0146, respectively). CONCLUSIONS: Increases in TG may therefore promote more EC enrichment of atherogenic apolipoprotein B-containing lipoproteins in Type 1 diabetes while also promoting more cholesterol esterification, thereby maintaining HDL cholesterol concentrations. This could contribute to the paradox of high CHD incidence despite normal or high HDL cholesterol concentrations in Type 1 diabetes.

High-density lipoprotein composition and paraoxonase activity in Type I diabetes.

Type I diabetes is associated with a high incidence of coronary heart disease (CHD), despite a normal or even increased concentration of high-density lipoprotein (HDL) cholesterol. This paradox may be explained by changes in the antioxidant capacity of HDL, related to paraoxonase (PON1) activity. HDL compositional changes in subjects with Type I diabetes may result in changes in PON1 activity that are associated with a higher incidence of CHD. Single-vertical-spin density-gradient ultracentrifugation was used to isolate seven HDL fractions from serum according to density. PON1 activity was measured in serum and in the HDL fractions using phenyl acetate as substrate. The mean recovery of PON1 activity in the HDL fractions was 87% (S.D. 12%). CHD risk was assessed using B-mode ultrasound to measure carotid artery intima-media thickness (IMT). Groups of 35 subjects with Type I diabetes [duration of diabetes 18 years (12-32 years) [median (interquartile range)]; glycated haemoglobin 7.67% (1.17%)] and 24 non-diabetic control subjects were studied. Carotid IMT was greater in the diabetic subjects [0.60 (0.55-0.70) compared with 0.55 (0.45-0.64) mm; P=0.042] and HDL cholesterol concentration was higher [1.53 (0.36) compared with 1.32 (0.34) mmol/l; P=0.031]. There were qualitative differences in HDL in subjects with Type I diabetes: HDL particles were triacylglycerol-deplete, and there were greater numbers of the larger, more buoyant HDL particles. These properties were not those found to determine PON1 activity. PON1 activity increased as HDL particle density increased and particle size decreased; the increase in PON1 activity was associated with an increase in the ratio of the two HDL surface lipid components, phospholipid and unesterified cholesterol, as particle density increased. PON1 activity was similar in diabetic and non-diabetic subjects [121 (28) and 120 (36) micromol x min(-1) x ml(-1) respectively; P=0.887]. PON1 activity was not associated with carotid IMT in either group. Our results suggest that the PON1 activities of HDL particles relate to the density, size and composition of the particles. However, PON1 activity does not appear to contribute to the greater risk of CHD in subjects with Type I diabetes.

Total antioxidant status and coronary artery calcification in type 1 diabetes.

OBJECTIVE: Type 1 diabetes is associated with a high risk of coronary heart disease (CHD), despite the absence of dyslipidemia. Oxidative modification may render LDLs more atherogenic. We aimed to assess antioxidant status in type 1 diabetes and its association with coronary artery calcification (CAC). RESEARCH DESIGN AND METHODS: Total antioxidant status (TAS) of serum was measured using the Trolox equivalent antioxidant capacity assay in 48 type 1 diabetic and 25 nondiabetic subjects. The presence of CAC was assessed in the diabetic subjects using electron beam computed tomography. RESULTS: TAS was reduced in type 1 diabetic subjects compared with nondiabetic subjects (Mann-Whitney U test, P < 0.0001). There were associations between TAS and HbA(1c) (r = -0.43; P = 0.0026) and duration of diabetes (r = -0.35; P = 0.0157). Significant CAC was considered present if the Agatston score was >10. The diabetic subjects with significant CAC were older (P < 0.0001); had longer duration of diabetes (P = 0.0002); were more likely to have high blood pressure (P = 0.040); had higher total cholesterol concentration (P = 0.039), serum creatinine concentration (P = 0.003), and urinary albumin-to-creatinine ratio (P = 0.022); and had lower serum TAS (P = 0.018) compared with those without significant calcification. In logistic regression with CAC as the dependent variable, TAS was entered as a predictor, and the effects on its predictive value of adding other explanatory variables in bivariate analyses were assessed. The power of TAS to predict CAC was independent of many of the traditional CHD risk factors. Whereas TAS as a predictor was no longer statistically significant when age or duration of diabetes were entered into the model, the odds ratio for a TAS concentration above the median value predicting significant CAC only increased from 0.19 to 0.26 and 0.32, respectively. CONCLUSIONS: TAS is reduced in type 1 diabetes and is associated with the presence of CAC.

Clinical governance in primary care groups: the feasibility of deriving evidence-based performance indicators.

OBJECTIVES: To test the feasibility of deriving comparative indicators in all the practices within a primary care group. DESIGN: A retrospective audit using practice computer systems and random note review. SETTING: A primary care group in southern England. SUBJECTS: All 18 general practices in a primary care group. MAIN OUTCOME MEASURES: Twenty six evidence-based process indicators including aspirin therapy in high risk patients, detection and control of hypertension, smoking cessation advice, treatment of heart failure, raised cholesterol levels in those with established cardiovascular disease, and the treatment of atrial fibrillation. Feasibility was tested by examining whether it was possible to derive these indicators in all the practices; the problems and constraints incurred when collecting data; the variations in indicator values between practices in both their identification of diseases and in the uptake of various interventions; the possible reasons for these variations; and the cost of generating such indicators. RESULTS: It was possible to derive eight indicators in all practices and in three practices all 26 indicators. The median number of indicators derived was 12 with two practices able to generate eight. There was considerable variation in the use of computers between practices and in the ability and ease of various practice computer systems to generate indicators. Practices varied greatly in the identification of diseases and in the uptake of effective interventions. Variation in identification of ischaemic heart disease could not be explained by a higher prevalence in practices with a more deprived population. The cost of generating these indicators was 5300 Pounds. CONCLUSION: Comparative evidence-based indicators, used as part of clinical governance in primary care groups, could have the potential to turn evidence into everyday practice, to improve the quality of patient care, and to have an impact on the population's health. However, to derive such indicators and to be able to make meaningful comparisons primary care groups need greater conformity and compatibility of computer systems, improved computer skills for practice staff, and appropriate funding.

Reactions to the use of evidence-based performance indicators in primary care: a qualitative study.

OBJECTIVES: To investigate reactions to the use of evidence-based cardiovascular and stroke performance indicators within one primary care group. DESIGN: Qualitative analysis of semi-structured interviews. SETTING: Fifteen practices from a primary care group in southern England. PARTICIPANTS: Fifty two primary health care professionals including 29 general practitioners, 11 practice managers, and 12 practice nurses. MAIN OUTCOME MEASURES: Participants' perceptions towards and actions made in response to these indicators. The barriers and facilitators in using these indicators to change practice. RESULTS: Barriers to the use of the indicators were their data quality and their technical specifications, including definitions of diseases such as heart failure and the threshold for interventions such as blood pressure control. Nevertheless, the indicators were sufficiently credible to prompt most of those in primary care teams to reflect on some aspect of their performance. The most common response was to improve data quality through increased or improved accuracy of recording. There was a lack of a coordinated team approach to decision making. Primary care teams placed little importance on the potential for performance indicators to identify and address inequalities in services between practices. The most common barrier to change was a lack of time and resources to act upon indicators. CONCLUSION: For the effective implementation of national performance indicators there are many barriers to overcome at individual, practice, and primary care group levels. Additional training and resources are required for improvements in data quality and collection, further education of all members of primary care teams, and measures to foster organisational development within practices. Unless these barriers are addressed, performance indicators could initially increase apparent variation between practices.

Inhibiting protein-protein interactions: a model for antagonist design.

Protein-protein interactions (PPI) are a ubiquitous mode of transmitting signals in cells and tissues. We are testing a stepwise, generic, structure-driven approach for finding low molecular weight inhibitors of protein-protein interactions. The approach requires development of a high-affinity, single chain antibody directed specifically against the interaction surface of one of the proteins to obtain structural information on the interface. To this end, we developed a single chain antibody (sc1E3) against hIL-1beta that exhibited the equivalent affinity of the soluble IL-1 receptor type I (sIL-1R) for hIL-1beta and competitively blocked the sIL-1R from binding to the cytokine. The antibody proved to be more specific for hIL-1beta than the sIL-1R in that it failed to bind to either murine IL-1beta or human/murine IL-1alpha proteins. Additionally, failure of sc1E3 to bind to several hIL-1beta mutant proteins, altered at receptor site B, indicated that the antibody interacted preferentially with this site. This, coupled with other surface plasmon resonance and isothermal titration calorimetry measurements, shows that sc1E3 can achieve comparable affinity of binding hIL-1beta as the receptor through interactions at a smaller interface. This stable single chain antibody based heterodimer has simplified the complexity of the IL-1/IL-1R PPI system and will facilitate the design of the low molecular weight inhibitors of this interaction.

Myocardial injury in major aortic surgery.

PURPOSE: The purpose of this study was to examine the effects of major aortic surgery and its associated oxidative stress and injury on the myocardium. METHODS: Plasma from 27 patients who underwent thoracoabdominal aortic aneurysm (TAAA) repair and 17 patients who underwent infrarenal aortic aneurysm (AAA) repair was collected at incision, aortic crossclamping, and reperfusion and 1, 8, and 24 hours thereafter. Samples were assayed for the myocardial specific protein troponin-T, total antioxidant status, and lipid hydroperoxides. RESULTS: Ten patients experienced cardiac dysfunction in the first 24 hours after surgery (eight patients in the TAAA group and two patients in the AAA group). Immediately after reperfusion, total antioxidant status levels dropped in all patients with TAAA and with AAA; this was more marked in patients with TAAA, leading to a significant difference between the two groups at this time point and for up to 1 hour thereafter (P <.01). Patients with TAAA showed a sharp rise in lipid hydroperoxide levels immediately after reperfusion, and levels were significantly higher than in patients with AAA (P =.0007). In patients with AAA, no significant change in troponin-T was observed throughout the study period; whereas in patients with TAAA, levels were significantly elevated at 8 and 24 hours after reperfusion (P <.01). Troponin-T levels significantly correlated with total antioxidant status (r = -0.5) and lipid hydroperoxides (r = 0.78) but not with systolic blood pressure. CONCLUSION: Supracoeliac aortic crossclamping is associated with a significant release of the myocardial injury marker troponin-T. This seems to correlate with the severity of oxidative rather than hemodynamic stresses. Ameliorating oxidative injury during TAAA surgery may therefore have a cardioprotective effect.

Spontaneous alpha-N-6-phosphogluconoylation of a "His tag" in Escherichia coli: the cause of extra mass of 258 or 178 Da in fusion proteins.

Several proteins expressed in Escherichia coli with the N-terminus Gly-Ser-Ser-[His]6- consisted partly (up to 20%) of material with 178 Da of excess mass, sometimes accompanied by a smaller fraction with an excess 258 Da. The preponderance of unmodified material excluded mutation, and the extra masses were attributed to posttranslational modifications. As both types of modified protein were N-terminally blocked, the alpha-amino group was modified in each case. Phosphatase treatment converted +258-Da protein into +178-Da protein. The modified His tags were isolated, and the mass of the +178-Da modification estimated as 178.06 +/- 0.02 Da by tandem mass spectrometry. As the main modification remained at +178 Da in 15N-substituted protein, it was deemed nitrogen-free and possibly carbohydrate-like. Limited periodate oxidations suggested that the +258-Da modification was acylation with a 6-phosphohexonic acid, and that the +178-Da modification resulted from its dephosphorylation. NMR spectra of cell-derived +178-Da His tag and synthetic alpha-N-d-gluconoyl-His tag were identical. Together, these results suggested that the +258-Da modification was addition of a 6-phosphogluconoyl group. A plausible mechanism was acylation by 6-phosphoglucono-1,5-lactone, produced from glucose 6-phosphate by glucose-6-phosphate dehydrogenase (EC 1.1.1.49). Supporting this, treating a His-tagged protein with excess d-glucono-1,5-lactone gave only N-terminal gluconoylation.

Plasma antioxidants: evidence for a protective role against reactive oxygen species following cardiac surgery.

Total plasma antioxidant status (TPAS), lipid peroxide concentration (LPX) and cardiac troponin T (cTnT) were measured in 24 patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Samples were obtained preoperatively and at 1.5 h, 6 h, 24 h and 72 h after CPB. The absolute TPAS values were significantly lower at 1.5 h, 6 h, 24 h and 72 h after CPB than were preoperative values (P < 0.05). The LPX concentration was significantly elevated at 1.5 h after CPB (P < 0.05). Cardiac troponin T concentrations were significantly elevated at all time points postoperatively (P < 0.05). Preoperative TPAS values were significantly correlated with the magnitude of fall in TPAS at 1.5 h (P < 0.05). The greater the fall in TPAS between 0 and 1.5 h, the less LPX was formed between 0 and 1.5 h. The LPX at 1.5 h displayed a significant correlation with cTnT release from myocardial myocytes (P < 0.05). These data provide evidence for the first time that the consumption of antioxidants during CABG surgery with CPB protects against the production of reactive oxygen species and subsequent myocyte necrosis. Furthermore, the availability of protective antioxidants is dependent upon preoperative TPAS.

Improving health outcomes--a review of case studies from English health authorities.

We review a series of case studies from English health authorities that have tackled the assessment and improvement of health outcomes. We reflect their concerns and difficulties and the lessons they learnt. We identified case studies from a telephone survey of 91 representatives of the 100 English health authorities (61 were directors of public health). We edited 26 structured case studies which described how they had used population health outcome assessments or indicators. The health outcome assessments included service reviews, needs assessment projects, case-control studies, small area variations analyses, action research, and the use of focus groups. Many case studies highlighted inequalities in health service delivery. Health authorities chose some topics because they were outliers on national indicators, others had found unacceptable inequalities within their district, and others had been concerned that clinicians were not using the most effective interventions. Public health departments played a major role in these population-based health outcome assessments. The case studies highlighted the strengths and weakness of national population-based health outcome indicators, the difficulties of using information on effectiveness, the role of evidence-based process proxies for outcome, the need to extend information sources, the involvement of patients and carers, and the difficulty of changing clinical behaviour. We make recommendations as to how the Department of Health and NHS Executive could help health authorities improve the health outcomes of the populations they serve.

Hip fracture incidence and mortality in an English Region: a study using routine National Health Service data.

BACKGROUND: We investigated the validity of routine hospital and mortality hip fracture data in one English Region and estimated trends in hip fracture between 1978-1981 and 1993-1995. METHODS: We identified from Hospital Episode System (HES) data for 1993-1995 all hip fracture episodes relating to individual patients aged over 65 years resident in Wessex. We determined from the discharge method code whether an individual had died during that admission. The number of individual regional and district admissions and deaths were compared with those presented in the Public Health Common Data Set. We compared regional admission rates with data for 1978-1981 from a previous study. RESULTS: National comparative indicators for hip fracture overestimated individual admissions in Wessex by 17 per cent (in health authorities by 1-56 per cent). National comparative indicators for hip fracture mortality underestimated individual deaths in Wessex by 48 per cent. Between 1978-1981 and 1993-1995 the age-sex-standardized hip fracture rates rose from 1.90 to 2.63 per 1000 per year for men and from 5.70 to 7.70 per 1000 per year for women. Rates increased in all age groups except those aged 65-69 years. There was also a small fall in absolute mean annual numbers in this age group. The rates also fell in females aged 70-74. CONCLUSIONS: It is possible to adjust routine national HES data to take account of multiple episodes within a single admission. These methods should be applied to national comparative indicators for hip fracture admission and deaths. Hip fracture rates continue to rise in those aged over 70 years. There may be a cohort effect with those born after 1925 showing stable rates which needs further investigation.

What do health authorities think of population based health outcome indicators?

OBJECTIVES: To determine the role of population based indicators of health outcome in local health outcome assessments; the constraints of using such indicators; how they could be made more useful; and whether health authorities had developed their own indicators of health outcome. DESIGN: A structured telephone interview with representatives of 91 of the 100 English health authorities. RESULTS: Interviewees, asked to give details on two clinical areas in which population health outcome assessments had been of most value, nominated 147 examples in over 30 clinical areas. They chose 50 (34%) of the examples because of an outlying national indicator, and 20 (14%) because of local variations in a national indicator. The main perceived constraints in the use of population based indicators of health outcome were: data validity and timeliness; the attributability of these health outcomes to the quality of health care; the difficulties of changing clinical behavior; and organisational change within health authorities. To make these indicators more useful interviewees wanted an increased use of process indicators as proxies for health outcome, indicator trend data, and indicator comparisons of districts with similar population structures. Some recent publications have started to consider some of these issues. 27 (30%) health authorities had developed their own indicators, mostly provider based process indicators. 10 of these used their own indicators to manage the performance of local provider units. CONCLUSIONS: Population based indicators of health outcome had an important role in prompting districts to undertake population health outcome assessments. Health authorities also used these indicators to examine local variations in health outcome. They helped to highlight areas for further investigation, initiated data validation, and enabled the monitoring of changes to services. Comparative population based indicators of health outcome may have an increasing part to play in assessing the performance of health authorities.

General practitioner's perceptions of the route to evidence based medicine: a questionnaire survey.

OBJECTIVES: To determine the attitude of general practitioners towards evidence based medicine and their related educational needs. DESIGN: A questionnaire study of general practitioners. SETTING: General practice in the former Wessex region, England. SUBJECTS: Randomly selected sample of 25% of all general practitioners (452), of whom 302 replied. MAIN OUTCOME MEASURES: Respondents' attitude towards evidence based medicine, ability to access and interpret evidence, perceived barriers to practising evidence based medicine, and best method of moving from opinion based to evidence based medicine. RESULTS: Respondents mainly welcomed evidence based medicine and agreed that its practice improves patient care. They had a low level of awareness of extracting journals, review publications, and databases (only 40% knew of the Cochrane Database of Systematic Reviews), and, even if aware, many did not use them. In their surgeries 20% had access to bibliographic databases and 17% to the world wide web. Most had some understanding of the technical terms used. The major perceived barrier to practising evidence based medicine was lack of personal time. Respondents thought the most appropriate way to move towards evidence based general practice was by using evidence based guidelines or proposals developed by colleagues. CONCLUSION: Promoting and improving access to summaries of evidence, rather than teaching all general practitioners literature searching and critical appraisal, would be the more appropriate method of encouraging evidence based general practice. General practitioners who are skilled in accessing and interpreting evidence should be encouraged to develop local evidence based guidelines and advice.

ETTIN patterns the Arabidopsis floral meristem and reproductive organs.

ettin (ett) mutations have pleiotropic effects on Arabidopsis flower development, causing increases in perianth organ number, decreases in stamen number and anther formation, and apical-basal patterning defects in the gynoecium. The ETTIN gene was cloned and encodes a protein with homology to DNA binding proteins which bind to auxin response elements. ETT transcript is expressed throughout stage 1 floral meristems and subsequently resolves to a complex pattern within petal, stamen and carpel primordia. The data suggest that ETT functions to impart regional identity in floral meristems that affects perianth organ number spacing, stamen formation, and regional differentiation in stamens and the gynoecium. During stage 5, ETT expression appears in a ring at the top of the floral meristem before morphological appearance of the gynoecium, consistent with the proposal that ETT is involved in prepatterning apical and basal boundaries in the gynoecium primordium. Double mutant analyses and expression studies show that although ETT transcriptional activation occurs independently of the meristem and organ identity genes LEAFY, APETELA1, APETELA2 and AGAMOUS, the functioning of these genes is necessary for ETT activity. Double mutant analyses also demonstrate that ETT functions independently of the 'b' class genes APETELA3 and PISTILLATA. Lastly, double mutant analyses suggest that ETT control of floral organ number acts independently of CLAVATA loci and redundantly with PERIANTHIA.

Lipid peroxidation, antioxidant status and troponin-T following cardiopulmonary bypass. A comparison between intermittent crossclamp with fibrillation and crystalloid cardioplegia.

OBJECTIVE: Intermittent crossclamp with fibrillation affords equivalent myocardial protection to cold crystalloid cardioplegia in patients undergoing elective coronary artery surgery. This study is a direct comparison between the two techniques with regards to free radical activity. METHODS: The study design was part of a prospective randomised trial. We studied 24 consecutive patients with ejection fraction of 30% or greater undergoing elective coronary artery surgery. Patients were randomised into two groups. In group 1 (n = 13) the myocardium was protected by intermittent aortic cross clamping with fibrillation and group 2 (n = 11) by antegrade cold crystalloid cardioplegia. The determinants of free radical activity were serial peripheral venous samples for lipid peroxidation and plasma antioxidant status (before and at 1, 6, 24 and 72 h after the end of cardiopulmonary bypass). The determinant of the efficacy of myocardial protection was serial peripheral venous samples of cardiac troponin-T taken at the same time intervals. RESULTS: The groups were similar with respect to age, sex distribution, preoperative ventricular function, left main stem disease, number of grafts and bypass times. Lipid peroxidation measurements at the 1 h time point were higher than preoperative values (7.24 +/- 1.19 vs. 4.48 +/- 0.69 and 9.36 +/- 1.46 vs. 4.98 +/- 1.02 (mean +/- S.E) in groups 1 and 2, respectively (units in mmol/l) thereafter values decreased to near preoperative values by 72 h. There was no significant difference between the groups (P = 0.42). Total plasma antioxidant status values at the 1 h time point were lower than the preoperative values for all patients (1.33 +/- 0.07 vs. 1.63 +/- 0.06 and 1.42 +/- 0.07 vs. 1.63 +/- 0.05 (mean +/- standard error) in groups 1 and 2, respectively, (units in mmol/l) and thereafter at the subsequent time points increased but never attained their preoperative value. There was no statistically significant difference between the two groups (P = 0.59). Troponin-T measurements showed no significant difference between the two groups at all time points (P = 0.2217). CONCLUSIONS: This study shows that lipid peroxidation is initially elevated and the defence mechanisms against oxygen free radicals-antioxidant status'-are depressed following cardiopulmonary bypass. The degree of oxygen free radical activity produced during ischaemia and reperfusion was similar in both types of myocardial protection employed in this study.