Biomedical subjects

Kenneth M Taylor

Publications and source records attributed to Kenneth M Taylor.

At least 19 recordsLinked to original sources

PubMed2006

Coronary artery size and disease in UK South Asian and Caucasian men.

OBJECTIVE: South Asian patients in the UK have a higher mortality rate after coronary artery bypass grafting (CABG) than Caucasian patients. As coronary artery size has been shown to correlate to outcome from bypass grafting, it has been suggested that smaller coronary arteries in South Asians as compared to Caucasians could contribute to a poorer outcome in the Asian population. We aimed to measure coronary artery size and disease in matched South Asian and Caucasian men undergoing first time coronary artery bypass grafting. METHODS: Coronary arteriograms from 53 matched first generation South Asian and Caucasian men were examined. The patients had no history of myocardial infarction, coronary revascularisation, familial dyslipidaemia, diabetes or renal disease. They were individually matched for age, height, weight, body mass index and body surface area. Thereafter, coronary artery diameters and significant (> or =50%) diameter stenoses were measured in a blinded fashion using quantitative coronary angiography (QCA). RESULTS: In South Asian men, diameters of the left main stem (LMS) and the proximal left anterior descending, the circumflex and the right coronary arteries were 4.6+/-0.9 mm, 3.5+/-0.8 mm, 3.4+/-0.8 mm and 3.5+/-0.8 mm, respectively. The corresponding arterial diameters among Caucasian men (4.5+/-0.9 mm, 3.5+/-0.7 mm, 3.5+/-0.8 mm and 3.8+/-0.8 mm) did not differ from those in South Asians. There was no difference in the number of significant coronary artery stenoses between the two groups and no difference in bypass and cross-clamp times or in adverse outcome (one from each group died after coronary artery bypass grafting). CONCLUSION: Proximal coronary artery size and number of significant coronary stenoses did not differ between matched pairs of South Asian and Caucasian men using strict inclusion/exclusion criteria.

Aged↗

PubMed2006

Effect of aprotinin and recombinant variants on platelet protease-activated receptor 1 activation.

BACKGROUND: Thrombin generated during cardiopulmonary bypass activates the high-affinity thrombin receptor, protease-activated receptor 1 (PAR1), causing platelet dysfunction and excessive bleeding. The serine protease inhibitor aprotinin protects platelets against thrombin-mediated PAR1 activation in vitro and in vivo. Here we have investigated three novel recombinant aprotinin variants with specific modifications to the active site lysine at amino acid position 15 (arginine-15, arginine-15-alanine-17, and valine-15-leucine-17) for their effect on PAR1-mediated platelet aggregation in vitro. METHODS: Aggregation studies were carried out using washed human platelets (n = 9) or platelet rich plasma (n = 7) from healthy volunteers activated with 1 or 5 nM thrombin. Recombinant aprotinin variants were used at the molar equivalent to 50 KIU/mL of the parent compound. The PAR1-specific antagonist peptide, FLLRN, was used at 500 microM. RESULTS: Platelet aggregation at low concentrations of thrombin (1 nM) was mediated exclusively through PAR1, as shown by inhibition of aggregation in the presence of FLLRN. At 1 nM thrombin, the mean percentage +/- SD aggregation of washed platelets was 68.6% +/- 12.3%. This was suppressed by each aprotinin variant at the 50 KIU/mL equivalent dose: arginine-15 (23.0% +/- 17.5%, p < 0.001); arginine-15-alanine-17 (33.3% +/- 22.9%, p < 0.01); aprotinin (37.5% +/- 19.4%, p < 0.05); valine-15-leucine-17 (50.0% +/- 16.1%, not significant)). At 5 nM thrombin, which activates both high (PAR1) and low-affinity (PAR4) thrombin receptors on platelets, FLLRN and aprotinin failed to block aggregation: this finding indicates that aprotinin selectively targeted PAR1. In platelet-rich plasma, aggregation at 1 nM thrombin was 77.1% +/- 10.0%, and this was inhibited in the following order: arginine-15 (30.1% +/- 9.6%, p < 0.001); arginine-15-alanine-17 (52.3% +/- 9.7%, p > 0.001); aprotinin (55.9% +/- 6.2%, p > 0.001); valine-15-leucine-17 (73.7% +/- 7.1%, not significant). CONCLUSIONS: Aprotinin variants differentially inhibit PAR1-mediated platelet aggregation. With more understanding of the mechanisms of action of aprotinin and its derivatives, safer and more efficacious aprotinin variants may become available for clinical use.

Aprotinin↗

PubMed2006

Pexelizumab reduces death and myocardial infarction in higher risk cardiac surgical patients.

BACKGROUND: Morbidity and mortality after coronary artery bypass graft surgery are directly related to specific preoperative risk factors. We assessed the influence of preoperative risk factors on the effect of pexelizumab, a C5 complement inhibitor, to reduce postoperative morbidity and mortality in this post hoc analysis of the Pexelizumab for Reduction in Myocardial Infarction and MOrtality in Coronary Artery Bypass Graft surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The composite endpoint of death or myocardial infarction or both through postoperative day 30 was examined in subpopulations of patients with pre-specified risk factors, which included diabetes mellitus, prior coronary artery bypass graft, urgent intervention, female sex, history of neurologic event, history of congestive heart failure, and two or more previous myocardial infarctions or a recent myocardial infarction. Stratified post hoc analyses were also performed on patients presenting with two or more and three or more of those risk factors. RESULTS: Pexelizumab significantly reduced the incidence of the composite endpoint of death or myocardial infarction through postoperative day 30 by 28% in patients with two or more risk factors (p = 0.004) and 44% in patients with three or more risk factors (p < 0.001). CONCLUSIONS: The C5 complement inhibitor, pexelizumab, reduced morbidity and mortality among high-risk patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Antibodies, Monoclonal↗

PubMed2006

Aprotinin inhibits proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1.

OBJECTIVE: Thrombin is generated in significant quantities during cardiopulmonary bypass and mediates adverse events, such as platelet aggregation and proinflammatory responses, through activation of the high-affinity thrombin receptor protease-activated receptor 1, which is expressed on platelets and endothelium. Thus antagonism of protease-activated receptor 1 might have broad therapeutic significance. Aprotinin, used clinically to reduce transfusion requirements and the inflammatory response to bypass, has been shown to inhibit protease-activated receptor 1 on platelets in vitro and in vivo. Here we have examined whether aprotinin inhibits endothelial protease-activated receptor 1 activation and resulting proinflammatory responses induced by thrombin. METHODS: Protease-activated receptor 1 expression and function were examined in cultured human umbilical vein endothelial cells after treatment with alpha-thrombin at 0.02 to 0.15 U/mL in the presence or absence of aprotinin (200-1600 kallikrein inhibitory units/mL). Protease-activated receptor 1 activation was assessed by using an antibody, SPAN-12, which detects only the unactivated receptor, and thrombin-mediated calcium fluxes. Other thrombin-dependent inflammatory pathways investigated were phosphorylation of the p42/44 mitogen-activated protein kinase, upregulation of the early growth response 1 transcription factor, and production of the proinflammatory cytokine interleukin 6. RESULTS: Pretreatment of cultured endothelial cells with aprotinin significantly spared protease-activated receptor 1 receptor cleavage (P < .0001) and abrogated calcium fluxes caused by thrombin. Aprotinin inhibited intracellular signaling through p42/44 mitogen-activated protein kinase (P < .05) and early growth response 1 transcription factor (P < .05), as well as interleukin 6 secretion caused by thrombin (P < .005). CONCLUSIONS: This study demonstrates that endothelial cell activation by thrombin and downstream inflammatory responses can be inhibited by aprotinin in vitro through blockade of protease-activated receptor 1. Our results provide a new molecular basis to help explain the anti-inflammatory properties of aprotinin reported clinically.

Aprotinin↗

PubMed2006

Feasibility and safety of delivering xenon to patients undergoing coronary artery bypass graft surgery while on cardiopulmonary bypass: phase I study.

BACKGROUND: Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system. METHODS: Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery. RESULTS: Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100beta levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout. CONCLUSIONS: Xenon was safely and efficiently delivered to coronary artery bypass grafting patients while on cardiopulmonary bypass. Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial.

Aged↗

PubMed2005

Generic, simple risk stratification model for heart valve surgery.

BACKGROUND: Heart valve surgery has an associated in-hospital mortality rate of 4% to 8%. This study aims to develop a simple risk model to predict the risk of in-hospital mortality for patients undergoing heart valve surgery to provide information to patients and clinicians and to facilitate institutional comparisons. METHODS AND RESULTS: Data on 32,839 patients were obtained from the Society of Cardiothoracic Surgeons of Great Britain and Ireland on patients who underwent heart valve surgery between April 1995 and March 2003. Data from the first 5 years (n=16,679) were used to develop the model; its performance was evaluated on the remaining data (n=16,160). The risk model presented here is based on the combined data. The overall in-hospital mortality was 6.4%. The risk model included, in order of importance (all P<0.01), operative priority, age, renal failure, operation sequence, ejection fraction, concomitant tricuspid valve surgery, type of valve operation, concomitant CABG surgery, body mass index, preoperative arrhythmias, diabetes, gender, and hypertension. The risk model exhibited good predictive ability (Hosmer-Lemeshow test, P=0.78) and discriminated between high- and low-risk patients reasonably well (receiver-operating characteristics curve area, 0.77). CONCLUSIONS: This is the first risk model that predicts in-hospital mortality for aortic and/or mitral heart valve patients with or without concomitant CABG. Based on a large national database of heart valve patients, this model has been evaluated successfully on patients who had valve surgery during a subsequent time period. It is simple to use, includes routinely collected variables, and provides a useful tool for patient advice and institutional comparisons.

Cardiac Surgical Procedures↗

PubMed2005

Assessment of magnetic field (4.7 T) induced forces on prosthetic heart valves and annuloplasty rings.

PURPOSE: To assess the magnetic field interactions on 11 heart valve prostheses and 12 annuloplasty rings subjected to a 4.7 T MR system. MATERIALS AND METHODS: Ex vivo testing was performed to evaluate translational and rotational forces using previously described techniques. RESULTS: Seventeen out of 23 prostheses showed zero interaction with the magnetic field. Translational forces with deflection angles of 2-20 degrees were demonstrated in six prostheses. Only two heart valves and two annuloplasty rings demonstrated rotational forces. The Carpentier Edwards (CE) Physio Ring, which contains Elgiloy, demonstrated deflection angles three times greater than those previously measured at 1.5 T. Furthermore, there was a direct relationship between increasing prosthesis size and increasing translational force. All heart valve prostheses attracted to the magnetic field were slightly paramagnetic/weakly ferromagnetic. CONCLUSION: Twenty-three heart valve prostheses evaluated for MRI are considered safe in static fields up to 4.7 T based on current safety criteria. However, the CE Physio Ring appeared to develop an increasing magnetism upon re-entry into the MR system. We conclude that prostheses made from Elgiloy may not be acceptable for patients in an MR environment of > or =4.7 T. Further investigations are required to confirm the safety of Elgiloy.

Bioprosthesis↗

PubMed2005

Mechanical testing of human cardiac tissue: some implications for MRI safety.

PURPOSE: The effects of aging on tissue strength and its ability to withstand forces associated with MRI have not been investigated. This study aimed to determine the forces required to cause partial or total detachment of a heart valve prosthesis in patients with age-related degenerative diseases exposed to MRI. METHODS: Eighteen tissue samples excised during routine heart valve replacement surgery were subjected to a suture pull-out test using a tensile materials testing machine. Five preconditioning cycles were applied before commencing the final destructive test. The test was complete when the sample ruptured and the suture was pulled completely free from the tissue. Results were compared with previously calculated magnetically induced forces at 4.7 T. RESULTS: All tissue samples displayed a basic failure pattern. Mean forces required to cause initial yield and total rupture were 4.0 N (+/- 3.3 N) and 4.9 N (+/- 3.6 N), respectively. Significant factors determining initial yield were stenosed calcific tissue (p < .01), calcific degeneration (single pathology) (p < .04) and tissue stiffness (p < .01). Calcific degeneration (p < .03) and tissue stiffness (p < .03) were also significant in determining maximum force required to cause total rupture. CONCLUSION: Specific age-related degenerative cardiac diseases stiffen and strengthen tissue resulting in significant forces being required to pull a suture through valve annulus tissue. These forces are significantly greater than magnetically induced < 4.7 T. Therefore, patients with degenerative valvular diseases are unlikely to be at risk of valve dehiscence during exposure to static magnetic field < or = 4.7 T.

Adult↗

PubMed2004

Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial.

CONTEXT: Inflammation and ischemia-reperfusion injury during coronary artery bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with postoperative myocardial infarction (MI) and mortality. OBJECTIVE: To determine the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing perioperative MI and mortality in CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial, including 3099 patients (> or = 18 years) undergoing CABG surgery with or without valve surgery at 205 hospitals in North America and Western Europe from January 2002 to February 2003. INTERVENTIONS: Patients were randomly assigned to receive intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours; n = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure. MAIN OUTCOME MEASURES: The primary composite end point was the incidence of death or MI within 30 days of randomization in those undergoing CABG surgery only (n = 2746). Secondary analyses included the intent-to-treat analyses of death or MI composite at days 4 and 30 in all 3099 study patients. RESULTS: After 30 days, 134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of patients receiving placebo (relative risk, 0.82; 95% confidence interval, 0.66-1.02; P =.07) died or experienced MI in the CABG surgery only population. In the intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving pexelizumab vs 215 (14.0%) of 1535 receiving placebo died or experienced MI (relative risk, 0.82; 95% confidence interval, 0.68-0.99; P =.03). The trial was not powered to detect a reduction in mortality alone. CONCLUSIONS: Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction 30 days after the procedure among all 3099 patients undergoing CABG with or without valve surgery.

Aged↗

PubMed2004

Postoperative infection with meticillin-resistant Staphylococcus aureus and socioeconomic background.

Infectious disease can be linked to social deprivation. We investigated whether postoperative infection with meticillin-resistant Staphylococcus aureus (MRSA) is related to socioeconomic background. Patients were stratified by social deprivation according to postcode. In a consecutive series of 1739 UK residents undergoing isolated coronary artery bypass grafting, 23 (1.3%) were infected with MRSA. We noted a graded relation between incidence of infection and social deprivation. Patients from the most deprived areas had a seven-fold higher infection rate (13 of 579 [2.2%]) than those from the least deprived areas (two of 580 [0.3%]; p=0.0040). Patients with MRSA infection had a six-fold higher mortality rate and a longer hospital stay than patients with no such infection. Our findings suggest that patients from deprived areas might be especially susceptible to postoperative infection with MRSA.

Coronary Artery Bypass↗

PubMed2004

Monocyte Fc gamma receptor expression in patients undergoing coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass is associated with an inflammatory response with potential deleterious effects. The white cell subpopulation mostly investigated so far is the neutrophil. To date very little has been investigated regarding the role of the monocyte/macrophage. This study focuses on the expression of Fc gamma receptors I, II, and III by monocytes in patients undergoing cardiopulmonary bypass. METHODS: We studied the surface expression of Fc gamma receptors I, II, and III by flow cytometry on gated monocyte subpopulations in the whole blood of adult patients undergoing elective coronary artery bypass grafting. Blood samples were drawn preoperatively and at 15 minutes, 1, 2, 4, 24, 48, and 72 hours, and 6 days postoperatively. A second group of patients undergoing lung resection surgery were studied in a similar fashion. RESULTS: Neither Fc receptor I nor receptor II expression were significantly changed throughout the time points studied. Fc receptor III expression was reduced at 2 and 4 hours (p = 0.016 and 0.002) and increased at 24, 48, and 72 hours after commencement of CPB on a selected subpopulation (15%-35%) of monocytes (p = 0.004, < 0.001, and < 0.001, respectively). This expression returned to preoperative levels by the sixth postoperative day. There were no statistically significant changes in the lung resection group. CONCLUSIONS: Our study demonstrated that cardiopulmonary bypass is associated with a biphasic Fc gamma receptor III expression on a subpopulation of peripheral blood monocytes up to 3 days postoperatively.

Aged↗

PubMed2004

Cardiac surgery risk modeling for mortality: a review of current practice and suggestions for improvement.

Risk models play a vital role in monitoring health care performances. Despite extensive research and widespread use of risk models in cardiac surgery, there are methodologic problems. We reviewed the methodology used for risk models for short-term mortality. The findings suggest that many risk models are developed in an ad hoc manner. Important aspects such as selection of risk factors, handling of missing values, and size of the data used for model development are not dealt with adequately. Methodologic details presented in publications are often sparse and unclear. Model development and validation processes are not always linked to the clinical aim of the model, which may affect their clinical validity. We make some suggestions in this review for improvement in methodology and reporting.

Cardiac Surgical Procedures↗

PubMed2003

Outcomes in nonagenarians after heart valve replacement operation.

BACKGROUND: Changes in the age profile of the United Kingdom population and improvements in preoperative and postoperative care have resulted in increasing numbers of very elderly patients undergoing heart valve replacement (HVR) operations. Although HVR operations in nonagenarians are relatively uncommon, the demand for cardiac operations in this age group may increase over time. Outcomes after HVR operations in nonagenarians have not been well described yet. Therefore, the aim of this study was to determine outcomes in terms of early mortality and long-term survival in 35 nonagenarians after HVR operation. METHODS: Data from the United Kingdom Heart Valve Registry were analyzed and nonagenarian patients were identified. Additional analyzed data include gender, valve position, valve type, valve size, operative priority, follow-up time, and date and cause of death. Kaplan-Meier actuarial curves were calculated to determine accurate 30-day mortality and long-term survival. RESULTS: On average five HVR operations are performed annually in the United Kingdom in nonagenarians with equal numbers of males and females. Aortic valve replacement with a bioprosthetic valve was the most common operation and 86% were elective admissions. Fourteen patients died within the review period; mean time to death was 402 days. Overall 30-day mortality was 17%, which was higher for males compared with females; females also displayed better long-term survival. CONCLUSIONS: HVR operations in nonagenarians carry a significantly higher risk of early mortality and reduced long-term survival. Despite increases in the age profile of the population, elective HVR operation with patients aged 90 years or older is likely to remain an infrequent surgical procedure reserved for very carefully selected patients.

Aged↗

PubMed2003

Is 30-day mortality an adequate outcome statistic for patients considering heart valve replacement?

BACKGROUND: In-hospital mortality is widely used by clinicians as a benchmark measure of outcome for determining risks/benefits of cardiac surgery. Patients, however, may wish to have information on estimated longer-term outcomes. Mortality risk by 1 year after the operation may be a more meaningful outcome statistic. We therefore undertook to determine 30-day and 365-day postoperative mortality rates in a large series of consecutive patients who have undergone heart valve replacement (HVR) surgery in the United Kingdom since 1986. METHODS: Data on 80,757 patients registered on the UK Heart Valve Registry were analyzed. Kaplan-Meier actuarial survival analysis was calculated to determine 30-day (group 1) and 365-day (group 2) mortality. Cox proportional hazards were calculated for each group to identify significant risk factors for mortality less than 1 year. RESULTS: Thirty-day mortality represents around half (56%) of the 365-day mortality. This ratio was robust for most subdivisions of the total population. Cox proportional hazards demonstrated female sex, age older than 70 years, single tricuspid valve replacement, multiple valve replacement regardless of type of valve, and subsequent valve operation as significant risk factors of early mortality (group 1). However, men were at significantly greater risk of late mortality (group 2). All other factors remained significant with the exception of subsequent valve operation, which was dropped from the model (group 2). CONCLUSIONS: The robustness of these data would allow cardiologists and cardiac surgeons to provide preoperative patients with a reasonably accurate estimate of survival rates at 1 year after valve replacement surgery in addition to the customary short-term 30-day outcome.

Adolescent↗

PubMed2003

Use of flexibility tests in the manufacturing process of 60 degrees Björk-Shiley convexo-concave valves and the risk of outlet strut fracture.

OBJECTIVES: Outlet strut fracture remains a concern for 30,000 patients living with a Björk-Shiley convexo-concave heart valve (Shiley, Inc, Irvine, Calif, a subsidiary of Pfizer, Inc). Previous studies (Netherlands and United Kingdom) investigating valve manufacturing aspects identified multiple performance of the hook deflection test as a risk factor for 60 degrees valves. The present study validated this finding using new data with a greater number of valves implanted worldwide. Risks of outlet strut fracture associated with other manufacturing aspects were also investigated. METHODS: A matched case-control study design was used including 416 outlet strut fracture cases and 803 controls. RESULTS: Analyses similar to that of the Dutch and United Kingdom studies produced odds ratios of 3.4 (95% confidence interval [CI]: 1.1-10.3) and 2.8 (95% CI: 1.1-7.3), respectively, for multiple hook deflection tests. Load deflection test, which replaced the hook deflection test, showed a statistically significant association with outlet strut fracture: odds ratio of 5.0 (95% CI: 2.1-11.8) and 6.2 (95% CI: 2.2-18.0) for single and multiple load deflection tests, respectively. An analysis where hook deflection tests were separated from load deflection tests showed significantly elevated odds ratios with performance of any type of flexibility test, and the highest odds ratio was observed with a combined performance of load and hook deflection tests. CONCLUSIONS: Multiple hook deflection tests can now be considered for inclusion in the risk model used for guidelines on explant surgery to improve prediction of outlet strut fracture and provide patient reassurance. Load deflection tests and combined performance of hook and load deflection tests were found to be significant risk factors. No outlet strut fractures were reported for valves manufactured after March 1984 when the load deflection test was still in place. Examining manufacturing documents for these valves may identify new risk factors that could be responsible for the outlet strut fractures risk that remains unexplained to date.

Heart Valve Prosthesis↗

PubMed2003

The effect of haemodilution on blood-biomaterial contact-mediated CD11b expression on neutrophils: ex vivo studies.

Modern cardiopulmonary bypass (CPB) systems are getting smaller, both in terms of the exposed surface area of biomaterials and the priming volume. In a series of studies utilizing a rat recirculation model, we demonstrated that the magnitude of the inflammatory response seen under these conditions is proportional to the surface area of exposed material, a finding that supports the use of miniature systems in terms of moderating the inflammatory response. However, the second impact of miniature perfusion systems, the reduced priming volume with concomitant reduction in haemodilution, was not investigated with reference to inflammation. The present study was designed to determine whether this change in CPB haematocrit profile has any effect on the inflammatory response. In common with previous studies by this group, we employed the expression of the integrin CD11b on neutrophils as a marker of neutrophil activation, and hence the inflammatory response, in a rat recirculation biomaterial testing model, containing di-(2-ethyl-hexyl)-phthalate plasticized polyvinyl chloride of the type commonly employed in CPB circuits. The results demonstrated that neutrophil activation is influenced by haemodilution. We studied five groups of animals, each with different mean induced haematocrit: Group 1 (41.3 +/- 1.27%); Group 2 (30.93 +/- 2.85%); Group 3 (24.83 +/- 1.36%); Group 4 (20.60 +/- 3.47%); Group 5 (20.48 +/- 1.31%). Groups 1 and 5 animals were controls, neither of which underwent the period of recirculation. Rather, these controls were employed to isolate the noncontact effect of haemodilution on CD11b expression. We found that there were differences in per cent change in CD11b expression from start to end of the recirculation period between Group 1 (109.54 +/- 49.53%), Group 2 (189.1 +/- 18.68%), Group 3 (224.28 +/- 43.97), Group 4 (368.97 +/- 24.28%) and Group 5 (127 +/- 57.8%). There were intergroup statistically significant differences (p < 0.05). These results confirm that there is a relationship between haematocrit level and biomaterial contact-mediated activation of neutrophils. Furthermore, these studies confirm that haemodilution alone has no effect on neutrophil activation. One possible explanation for this outcome is that with higher levels of haemodilution, neutrophils have a greater opportunity to contact surface 'receptor' sites on the biomaterial, resulting in more neutrophil activation. Whatever the mechanism, these data tend to support the modern trend towards lower circuit surface area and higher haematocrit.

Animals↗

PubMed2003

Leucocyte depletion in cardiopulmonary bypass: a comparison of four strategies.

Leucocytes have been shown to play a fundamental role in the pathophysiology of inflammation. This prospective, randomized, controlled study was designed to identify the most advantageous leucocyte depletion technique in terms of reduction in systemic inflammatory response syndrome and myocardial ischaemia reperfusion injury associated with cardiopulmonary bypass (CPB). Forty consecutive patients undergoing elective coronary artery bypass graft (CABG) surgery were randomly allocated to one of four groups. The four groups consisted of a control group, a systemic leucocyte depletion (SLD) group, a cardioplegic leucocyte depletion (CLD) group and a total leucocyte depletion (TLD) group. There were 10 patients in each group. Lactoferrin (marker of neutrophil activation) and troponin-I (marker of myocardial ischaemia reperfusion injury) were measured at six time points: post induction, 5 min on CPB, 5 min before releasing the aortic crossclamp, 15 min after releasing the clamp and 1 and 24 hours after the discontinuation of CPB. Plasma lactoferrin levels increased rapidly in every group after the commencement of CPB, subsequently reached a peak after releasing the aortic crossclamp and gradually declined after the discontinuation of CPB. The lowest lactoferrin concentration was observed in the TLD (range 2.15-141.9 ng/mL) and CLD groups (7.469-114.6 ng/mL). Regarding myocardial injury, plasma cardiac troponin-I levels did not differ significantly between groups; but troponin-I concentrations rose dramatically after releasing the aortic crossclamp in all groups. Nevertheless, the CLD group had the lowest troponin-I level (1.37-5.55 ng/mL). In conclusion, it is believed that myocardial ischaemia is probably a major contributor to the inflammatory response. Although there is no clear statistical significance shown in this pilot study, the data tend to support the cardioplegic leucocyte depletion strategy as the optimal method for attenuating neutrophil activation and myocardial ischaemia reperfusion injury.

Aged↗

PubMed2002

Preoperative haemoglobin concentration and mortality rate after coronary artery bypass surgery.

We did an observational study in 2059 patients undergoing coronary artery bypass surgery to assess the effect of haemoglobin concentration on in-hospital mortality. We noted that individuals with a preoperative haemoglobin concentration of 100 g/L or less had a five-fold higher in-hospital mortality rate after surgery than those with a higher haemoglobin concentration, despite having had blood transfusions or the pump primed with blood preoperatively as a routine precaution. Our findings suggest that a low haemoglobin concentration is a marker of disease severity or comorbidity that has a major effect on survival rate.

Aged↗