A decision aid for autologous pre-donation in cardiac surgery--a randomized trial.

OBJECTIVES: The objective of this randomized, controlled study was to determine the usefulness of a decision aid on pre-donation of autologous blood before elective open heart surgery. METHODS: The decision aid (DA) group received a tape and booklet which described the options for peri-operative transfusion in detail. The no decision aid (NDA) group received information usually given to patients about autologous donation. RESULTS: A total of 120 patients were randomized. The DA group rated themselves better prepared for decision making and showed significant improvements in knowledge (p = 0.001) and realistic risk perceptions (p = 0.001). In both groups there was an increase in the proportion of patients choosing allogeneic blood between baseline and follow-up (p = 0.001). Patients in the DA group were significantly more satisfied with the amount of information they received, how they were treated and with the decision they made, than patients in the NDA group. CONCLUSION: The decision aid is useful in preparing patients for decision making. PRACTICE IMPLICATIONS: The next stage is to explore strategies to make it available to all appropriate patients.

A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery.

BACKGROUND: We performed this study to determine the dose-response of hemoglobin raffimer administered in conjunction with intraoperative autologous donation in patients undergoing coronary artery bypass grafting surgery. A secondary objective was to evaluate hemoglobin raffimer for reducing the incidence of allogeneic red blood cell transfusions. METHODS: This was a phase II, single-blind, multicenter, placebo-controlled, open-label study. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation were randomized to receive a single dose of hemoglobin raffimer or control (10% pentastarch). Patients were sequentially enrolled in a dose block of 250, 500, 750, and 1000 mL. RESULTS: Sixty patients received hemoglobin raffimer (n = 30) or control (n = 30). Hemoglobin raffimer was well tolerated. Most (98%) adverse events were mild or moderate in severity. There was an expected dose-dependent increase in the incidence of blood pressure increases and jaundice in hemoglobin raffimer-treated patients. In a dose-pooled analysis of hemoglobin raffimer versus control, increased blood pressure (43% vs 17%), nausea (37% vs 33%), and atrial fibrillation (37% vs 17%) were the most frequently reported adverse events. All serious adverse events were considered unrelated or unlikely to be related to study drug. No hemoglobin raffimer-treated patient required an intraoperative allogeneic red blood cell transfusion, compared with 5 (17%) pentastarch-treated patients (P =.052). This advantage of hemoglobin raffimer was maintained at 24 hours after surgery (7% vs 37%; P =.010) and up to 5 days after surgery (10% vs 47%; P =.0034). CONCLUSIONS: Hemoglobin raffimer was not associated with any serious adverse events in patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation in a dose-response study up to 1000 mL. Hemoglobin raffimer was effective in facilitating decreased exposure or avoidance of allogeneic red blood cell transfusions when used in conjunction with intraoperative autologous donation.

Hospital accreditation and the surgeon: the Canadian experience.

Accreditation is an internationally recognised process through which healthcare organisations are able to improve the safety and quality of services delivered to patients. The focus of accreditation is to help organisations understand what they are doing well and what opportunities are available for improvement. The Canadian approach to accreditation is a rigorous peer review process comprised of a self-assessment against a set of standards, an on-site survey and follow-up action on recommendations that arise from the survey. The accreditation standards can be used effectively to guide the surgical teams in the transformation of the specialty. The 17 standards that are used to evaluate surgical teams relate to the activities that represent the continuum of clinical care as well as aspects related to learning. Within the subsections and standards are opportunities for surgeons and surgical teams to use the standards to effectively deliver services and to continuously improve patient care. In 38 recent Canadian Accreditation AIM surveys, that included at least one surgical team, there were a total of 75 recommendations made to the teams. Most recommendations related to process as opposed to outcome issues, implying that surgeons need to become more proactive in the functioning of the surgical team and to participate more effectively in management issues related to surgical care. Attention to these details will position surgical programmes to effectively deal with the rapid pace of change that is inherent in a modern surgical practice.

Counting the number of disulfides and thiol groups in proteins and a novel approach for determining the local pKa for cysteine groups in proteins in vivo.

X-ray Absorption Spectroscopy (XAS) is a powerful tool to investigate sulfur in biological molecules. The spectral features are sensitive to the local electronic and geometric environment of the atom; thus, they constitute a fingerprint of the different chemical forms in which the sulfur is present. This allows straightforward detection of the ratio between free thiols and disulfides. Intra- or inter-molecular disulfide bond formation between residues plays an important role in structural and conformational changes in proteins, and such changes can be investigated using sulfur XAS. Also, a thiolate-disulfide equilibrium is involved in the regulation of the redox potential in the cells by means of modulating the concentrations of the reduced (thiolate) and oxidized (disulfide) form of the tripeptide glutathione. Thus, we can monitor the redox state of a cell by means of sulfur XAS. Thiols also exhibit an acid-base equilibrium, and sulfur XAS can be used to determine the local pKa of the -SH group. Here we report examples of how sulfur XAS has been used for these applications.

Absence of Mn-centered oxidation in the S(2) --> S(3) transition: implications for the mechanism of photosynthetic water oxidation.

A key question for the understanding of photosynthetic water oxidation is whether the four oxidizing equivalents necessary to oxidize water to dioxygen are accumulated on the four Mn ions of the oxygen-evolving complex (OEC), or whether some ligand-centered oxidations take place before the formation and release of dioxygen during the S(3) --> [S(4)] --> S(0) transition. Progress in instrumentation and flash sample preparation allowed us to apply Mn Kbeta X-ray emission spectroscopy (Kbeta XES) to this problem for the first time. The Kbeta XES results, in combination with Mn X-ray absorption near-edge structure (XANES) and electron paramagnetic resonance (EPR) data obtained from the same set of samples, show that the S(2) --> S(3) transition, in contrast to the S(0) --> S(1) and S(1) --> S(2) transitions, does not involve a Mn-centered oxidation. On the basis of new structural data from the S(3)-state, manganese mu-oxo bridge radical formation is proposed for the S(2) --> S(3) transition, and three possible mechanisms for the O-O bond formation are presented.

S K- and Mo L-edge X-ray absorption spectroscopy to determine metal-ligand charge distribution in molybdenum-sulfur compounds.

Mo L-edge and S K-edge X-ray absorption spectroscopy were applied to investigate the charge distribution between Mo and S in a series of Mo thiolate compounds, which serve as amide-sulfur H-bonding models and exhibit different redox potentials arising from polar group effects and ligand hydrogen bonds near the redox center. For all oxidized complexes, the S K-edge spectra exhibit a thiolate-based pre-edge feature centered at 2470.2 eV and the inflection point oCCurs at 2472.0 eV. No intense pre-edge feature is observed in the spectra for the reduced Mo model compounds and the energy shift of the S K-edge position depends on the S-ligand. Correlations between ligand charge density and the redox potential of the Mo-S cores are observed.

High-resolution X-ray spectroscopy of rare events: a different look at local structure and chemistry.

The combination of large-acceptance high-resolution X-ray optics with bright synchrotron sources permits quantitative analysis of rare events such as X-ray fluorescence from very dilute systems, weak fluorescence transitions or X-ray Raman scattering. Transition-metal Kbeta fluorescence contains information about spin and oxidation state; examples of the characterization of the Mn oxidation states in the oxygen-evolving complex of photosystem II and Mn-consuming spores from the marine bacillus SG- are presented. Weaker features of the Kbeta spectrum resulting from valence-level and 'interatomic' ligand to metal transitions contain detailed information on the ligand- atom type, distance and orientation. Applications of this spectral region to characterize the local structure of model compounds are presented. X-ray Raman scattering (XRS) is an extremely rare event, but also represents a unique technique to obtain bulk-sensitive low-energy (<600 eV) X-ray absorption fine structure (XAFS) spectra using hard (approximately 10 keV) X-rays. A photon is inelastically scattered, losing part of its energy to promote an electron into an unoccupied level. In many cases, the cross section is proportional to that of the corresponding absorption process yielding the same X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) features. XRS finds application for systems that defy XAFS analysis at low energies, e.g. liquids or highly concentrated complex systems, reactive compounds and samples under extreme conditions (pressure, temperature). Recent results are discussed.

Mn K-edge XANES and Kbeta XES studies of two Mn-oxo binuclear complexes: investigation of three different oxidation states relevant to the oxygen-evolving complex of photosystem II.

Two structurally homologous Mn compounds in different oxidation states were studied to investigate the relative influence of oxidation state and ligand environment on Mn K-edge X-ray absorption near-edge structure (XANES) and Mn Kbeta X-ray emission spectroscopy (Kbeta XES). The two manganese compounds are the di-mu-oxo compound [L'2Mn(III)O2Mn(IV)L'2](ClO4)3, where L' is 1,10-phenanthroline (Cooper, S. R.; Calvin, M. J. Am. Chem. Soc. 1977, 99, 6623-6630) and the linear mono-mu-oxo compound [LMn(III)OMn(III)L](ClO4)2, where L- is the monoanionic N,N-bis(2-pyridylmethyl)-N'-salicylidene-1,2-diaminoethane ligand (Horner, O.; Anxolabéhère-Mallart, E.; Charlot, M. F.; Tchertanov, L.; Guilhem, J.; Mattioli, T. A.; Boussac, A.; Girerd, J.-J. Inorg. Chem. 1999, 38, 1222-1232). Preparative bulk electrolysis in acetonitrile was used to obtain higher oxidation states of the compounds: the Mn(IV)Mn(IV) species for the di-mu-oxo compound and the Mn(III)Mn(IV) and Mn(IV)Mn(IV) species for the mono-mu-oxo compound. IR, UV/vis, EPR, and EXAFS spectra were used to determine the purity and integrity of the various sample solutions. The Mn K-edge XANES spectra shift to higher energy upon oxidation when the ligand environment remains similar. However, shifts in energy are also observed when only the ligand environment is altered. This is achieved by comparing the di-mu-oxo and linear mono-mu-oxo Mn-Mn moieties in equivalent oxidation states, which represent major structural changes. The magnitude of an energy shift due to major changes in ligand environment can be as large as that of an oxidation-state change. Therefore, care must be exercised when correlating the Mn K-edge energies to manganese oxidation states without taking into account the nature of the ligand environment and the overall structure of the compound. In contrast to Mn K-edge XANES, Kbeta XES spectra show less dependence on ligand environment. The Kbeta1,3 peak energies are comparable for the di-mu-oxo and mono-mu-oxo compounds in equivalent oxidation states. The energy shifts observed due to oxidation are also similar for the two different compounds. The study of the different behavior of the XANES pre-edge and main-edge features in conjunction with Kbeta XES provides significant information about the oxidation state and character of the ligand environment of manganese atoms.

Is tranexamic acid safe in patients undergoing coronary endarterectomy?

BACKGROUND: Patients undergoing coronary endarterectomy during coronary artery bypass grafting (CABG) are at increased risk of perioperative myocardial infarction due to coronary intimal disruption. Data assessing the safety of the antifibrinolytic drug tranexamic acid (TA) in patients undergoing this procedure are lacking. METHODS: From September 1997 to December 1999, 221 patients underwent nonemergency primary CABG with endarterectomy of the right coronary artery alone in 149, the left anterior descending in 35, or both right and left anterior descending in 27. TA was administered intraoperatively to 87 patients (TA group: average total dose 62 +/- 4.4 mg/kg; range 20 to 109 mg/kg), and was not administered to 134 patients (No TA group). RESULTS: The patient characteristics of the 2 groups were similar. In-hospital mortality consisted of 2 patients in the TA group and 4 patients in the No TA group. Perioperative myocardial infarction rates were 2% and 5% in the TA and No TA groups, respectively (p = 0.49). The relative risk for any type of perioperative cardiac ischemic event in the TA group versus the No TA group was 0.77 (95% CI; 0.4, 1.2). Patients in the TA group had a significant reduction in postoperative chest tube drainage (685 versus 894 mL in the TA versus No TA groups, respectively) and in the use of fresh-frozen plasma (p = 0.03). CONCLUSIONS: These results suggest that the clinical effectiveness of tranexamic acid in reducing postoperative blood loss in patients undergoing coronary endarterectomy is not associated with a higher incidence of myocardial ischemia-related complications.

Evaluation of a decision aid for patients considering autologous blood donation before open-heart surgery.

BACKGROUND: Patients undergoing open-heart surgery frequently require one or more blood transfusions. Because of the risks of receiving blood from volunteer donors, some patients choose to donate their own blood before surgery. This reduces their risk of exposure to volunteer-donated blood, but it increases their chance of receiving any transfusion, either of self-donated or volunteer-donated blood. Also, preoperative hemoglobin levels tend to be lower in patients who donate their own blood, and surgeons may be more likely to give transfusions to patients with self-donated blood. To help patients decide whether to donate their blood before surgery, we designed a decision aid comprising a booklet and audiotape and assessed its effectiveness. METHODS: The 59 study subjects were a sample of consecutive patients referred to the Ottawa Heart Institute between Oct. 1, 1998, and Jan. 5, 1999, for future coronary artery bypass grafting, valve surgery or combined surgery. All were eligible to donate blood. Initial questionnaires were administered in the clinic by a physician or study nurse, and follow-up questionnaires were completed at home and mailed in after use of the decision aid. Outcome measures included patients' knowledge, values (importance ratings), preferences for transfusion methods, decisional conflict (the amount of uncertainty about the course of action to take), risk perception and acceptability of the decision aid. RESULTS: Mean knowledge scores on a 15-item test increased from 67% correct responses before the decision aid to 85% correct responses after use of the aid (p < 0.001); the effect was similar when the patients were divided into subgroups according to education level. The number of patients favouring donating their own blood increased from 41 (69%) before to 45 (76%) after use of the aid. Nine (64%) of 14 initially uncertain patients preferred autologous donation after use of the aid. The overall mean score for decisional conflict was unchanged, at 1.7, which indicated a low level of uncertainty. Risk perception improved, from 0%-14% correct responses on an 8-item test before the aid to 18%-60% correct responses after use of the aid. The decision aid was acceptable to the majority of patients, and 95% indicated that they would recommend it to others. INTERPRETATION: The decision aid improved knowledge and risk perceptions of blood donation and transfusion, and it helped uncertain patients to make choices.

A comparative study of peptide models of the alpha-domain of alpha-lactalbumin, lysozyme, and alpha-lactalbumin/lysozyme chimeras allows the elucidation of critical factors that contribute to the ability to form stable partially folded states.

alpha-Lactalbumin (alpha LA) forms a well-populated equilibrium molten globule state, while the homologous protein hen lysozyme does not. alpha LA is a two-domain protein and the alpha-domain is more structured in the molten globule state than is the beta-domain. Peptide models derived from the alpha-subdomain that contain the A, B, D, and 3(10) helices of alpha LA are capable of forming a molten globule state in the absence of the remainder of the protein. Here we report comparative studies of a peptide model derived from the same region of hen lysozyme and a set of chimeric alpha-lactalbumin--lysozyme constructs. Circular dichroism, dynamic light scattering, sedimentation equilibrium, and fluorescence experiments indicate that the lysozyme construct does not fold. Chimeric constructs were prepared to probe the origins of the difference in the ability of the two isolated subdomains to fold. The first consists of the A and B helices of alpha LA cross-linked to the D and C-terminal 3(10) helices of lysozyme. This construct is highly helical, while a second construct that contains the A and B helices of lysozyme cross-linked to the D and 3(10) helices of alpha LA does not fold. Furthermore, the disulfide cross-linked homodimer of the alpha LA AB peptide is helical, while the homodimer of the lysozyme AB peptide is unstructured. Thus, the AB helix region of alpha LA appears to have an intrinsic ability to form structure as long as some relatively nonspecific interactions can be made with other regions of the protein. Our studies show that the A and B helices plays a key role in the ability of the respective alpha-subdomains to fold.

Effects of charged amino acids at b and c heptad positions on specificity and stability of four-chain coiled coils.

An understanding of the balance of chemical forces responsible for protein stability and specificity of structure is essential for the success of efforts in protein design. Specifically, electrostatic interactions between charged amino acids have been explored extensively to understand the contribution of this force to protein stability. Much research on the importance of electrostatic interactions as specificity and stability determinants in two-stranded coiled coils has been done, but there remains significant controversy about the magnitude of the attractive forces using such systems. We have developed a four-stranded coiled-coil system with charged residues incorporated at b and c heptad positions to explore the role of charge interactions. Here, we test quantitatively the effects of varying sidechain length on the magnitude of such electrostatic interactions. We synthesized peptides containing either aspartate or ornithine at both b and c heptad positions and tested their ability to self-associate and to hetero-associate with one another and with peptides containing glutamate or lysine at the same positions. We find that interactions between glutamate and either lysine or ornithine are more favorable than the corresponding interactions involving aspartate. In each case, charged interactions provide additional stability to coiled coils, although helix propensity effects may play a significant role in determining the overall stability of these structures.

X-ray spectroscopy-based structure of the Mn cluster and mechanism of photosynthetic oxygen evolution.

The mechanism by which the Mn-containing oxygen evolving complex (OEC) produces oxygen from water has been of great interest for over 40 years. This review focuses on how X-ray spectroscopy has provided important information about the structure of this Mn complex and its intermediates, or S-states, in the water oxidation cycle. X-ray absorption near-edge structure spectroscopy and high-resolution Mn Kbeta X-ray emission spectroscopy experiments have identified the oxidation states of the Mn in the OEC in each of the intermediate S-states, while extended X-ray absorption fine structure experiments have shown that 2.7 A Mn-Mn di-mu-oxo and 3.3 A Mn-Mn mono-mu-oxo motifs are present in the OEC. X-ray spectroscopy has also been used to probe the two essential cofactors in the OEC, Ca2+ and Cl-, and has shown that Ca2+ is an integral component of the OEC and is proximal to Mn. In addition, dichroism studies on oriented PS II membranes have provided angular information about the Mn-Mn and Mn-Ca vectors. Based on these X-ray spectroscopy data, refined models for the structure of the OEC and a mechanism for oxygen evolution by the OEC are presented.

Feasibility of blinding in a randomized controlled trial comparing preoperative autologous blood donation and acute normovolemic hemodilution in adult cardiac surgery.

BACKGROUND: Acute normovolemic hemodilution and preoperative autologous donation have been shown to be effective techniques for decreasing the exposure of patients to allogeneic blood during cardiac surgery. They have not, however, been compared to each other, because of perceived difficulties in blinding in such a clinical study. The feasibility of blinding was tested in a pilot trial. STUDY DESIGN AND METHODS: Ten patients were randomly assigned to undergo preoperative autologous blood donation or acute normovolemic hemodilution during cardiac surgery. Patients were blinded during this process by shielding of the arm and by insertion of an intravenous line in each patient. Every attempt was made to blind the clinical staff during and after surgery. The effectiveness of this blinding was determined by using a questionnaire. RESULTS: In the 10 cases, six patients, four surgeons, and one anesthetist answered, "I do not know," with respect to whether preoperative autologous blood donation had occurred. The remaining people interviewed believed the blinding was unsuccessful. However, correct answers were given by 75 percent of the patients (95% CI, 19-99%), 83 percent of the surgeons (95% CI, 36-99.6%), and 66 percent of the anesthetists (95% CI, 29.9-92.5%). The frequency of correct answers did not differ significantly from the 50 percent expected by chance, but the CIs are wide. CONCLUSIONS: Blinding of patients and all members of the surgical team during both the preoperative donation process and acute normovolemic hemodilution in the operating theater was successful most of the time, as the frequency of correct answers did not differ significantly from the 50 percent expected by chance. However, more accurate estimates of the success of blinding require a study with a larger sample. It is possible that, with a larger series, the physician's ability to determine patient assignment would be significantly better than that by chance alone.

Structural analysis of the neuronal SNARE protein syntaxin-1A.

Intracellular trafficking depends on the docking and fusion of transport vesicles with cellular membranes. Central to docking and fusion is the pairing of SNARE proteins (soluble NSF attachment protein receptors) associated with the vesicle and target membranes (v- and t-SNAREs, respectively). Here, the X-ray structure of an N-terminal conserved domain of the neuronal t-SNARE syntaxin-1A was determined to a resolution of 1.9 A using multiwavelength anomalous diffraction. This X-ray structure, which is in general agreement with an NMR structure of a similar fragment, provides new insight into the interaction surface between the N-terminal domain and the remainder of the protein. In vitro characterization of the intact cytoplasmic domain of syntaxin revealed that it forms dimers, and probably tetramers, at low micromolar concentrations, with concomitant structural changes that can be detected by limited proteolysis. These observations suggest that the promiscuity characteristic of pairing between v-SNAREs and t-SNAREs extends to the formation of homo-oligomeric t-SNARE complexes as well. They also suggest a potential role for the neuronal Sec1 protein (nSec1) in preventing the formation of syntaxin multimers.

Rational modification of protein stability by the mutation of charged surface residues.

Continuum methods were used to calculate the electrostatic contributions of charged and polar side chains to the overall stability of a small 41-residue helical protein, the peripheral subunit-binding domain. The results of these calculations suggest several residues that are destabilizing, relative to hydrophobic isosteres. One position was chosen to test the results of these calculations. Arg8 is located on the surface of the protein in a region of positive electrostatic potential. The calculations suggest that Arg8 makes a significant, unfavorable electrostatic contribution to the overall stability. The experiments described in this paper represent the first direct experimental test of the theoretical methods, taking advantage of solid-phase peptide synthesis to incorporate approximately isosteric amino acid substitutions. Arg8 was replaced with norleucine (Nle), an amino acid that is hydrophobic and approximately isosteric, or with alpha-amino adipic acid (Aad), which is also approximately isosteric but oppositely charged. In this manner, it is possible to isolate electrostatic interactions from the effects of hydrophobic and van der Waals interactions. Both Arg8Nle and Arg8Aad are more thermostable than the wild-type sequence, testifying to the validity of the calculations. These replacements led to stability increases at 52.6 degrees C, the T(m) of the wild-type, of 0.86 and 1.08 kcal mol(-)(1), respectively. The stability of Arg8Nle is particularly interesting as a rare case in which replacement of a surface charge with a hydrophobic residue leads to an increase in the stability of the protein.

Local interactions and the role of the 6-120 disulfide bond in alpha-lactalbumin: implications for formation of the molten globule state.

Molten globule states are partially folded states of proteins which are compact and contain a high degree of secondary structure but which lack many of the fixed tertiary interactions associated with the native state. A set of peptides has been prepared in order to probe the role of local interactions in the vicinity of the Cys(6)-Cys(120) disulfide bond in stabilizing the molten globule state of human alpha-lactalbumin. Peptides derived from the N-terminal and C-terminal regions of human alpha-lactalbumin have been analyzed using nuclear magnetic resonance, circular dichroism, fluorescence spectroscopy and sedimentation equilibrium experiments. A peptide corresponding to the first helical region in the native protein, residues 1-13, is only slightly helical in isolation. Extending the peptide to include residues 14-18 results in a modest increase in helicity. A peptide derived from the C-terminal 12 residues, residues 112-123, is predominantly unstructured. Crosslinking the N- and C-terminal peptides by the native disulfide bond results in almost no increase in structure and there is no evidence for any significant cooperative structure formation over the range of pH 2.2-11.7. These results demonstrate that there is very little enhancement of local structure due to the formation of the Cys(6)-Cys(120) disulfide bond. This is in striking contrast to peptides derived from the region of the Cys(28)-Cys(111) disulfide.

Circuits with surface modifying additive alter the haemodynamic response to cardiopulmonary bypass.

OBJECTIVE: Blood contact with synthetic surfaces during cardiopulmonary bypass (CPB), inevitably results in the activation of a variety of interrelated pathways of inflammation and coagulation that may contribute to postoperative complications in cardiac surgery patients. The objective of this trial was to evaluate clinical events and complement activation related to the use of a novel biomaterial, into which a surface modifying additive had been incorporated into the polymer used to prepare the bypass circuit. METHODS: A prospective, double-blind trial was carried out with 34 patients randomized to surgery, with either a standard circuit or a circuit treated ('tip to tip') with the surface modifying additive. Variables recorded included perioperative haemodynamics, volume replacement, alpha-agonist and inotrope use. Terminal complement complex (SC5b-9) was measured using an ELISA. RESULTS: Upon initiation of bypass, there was a decrease in mean arterial pressure (MAP) in the control group, not seen in the test group (P = 0.0005, ANOVA). There was a decrease in the total volume of replacement fluid given intraoperatively in the test group as compared with the control group (total plus prime; control 5.3 +/- 1.2 L, test 4.4 +/- 1.9 L, P = 0.03, Mann-Whitney test). There was a trend to decreased need for inotrope infusion in the test group after CPB (test 1/17, control 6/17, Fisher exact test; P = 0.085). No difference was seen in the generation of terminal complement complex between the groups either during or after CPB. CONCLUSIONS: The decrease in blood pressure in the control group, upon the initiation of CPB, did not occur in patients undergoing CPB with the circuit prepared with the surface modifying additive. The decrease in blood pressure was likely associated with the increase in total administered fluids intraoperatively (approximately 1 l/patient) and perhaps the trend towards higher use of inotropes in the control patients as opposed to the test patients. These haemodynamic changes did not appear to be related to complement activation early in CPB.

Transfusion practices among patients who did and did not predonate autologous blood before elective cardiac surgery.

BACKGROUND: Preoperative autologous blood donation is commonly used to reduce exposure to allogeneic transfusions among patients undergoing elective cardiac surgery. However, this technique is associated with an overall increase in transfusions (allogeneic or autologous). The authors assessed the impact of transfusion decision-making on the effectiveness of preoperative autologous donation in reducing the frequency of allogeneic transfusions, and its impact on the increased transfusion rate associated with preoperative autologous donation in cardiac surgery. METHODS: This retrospective analysis compared transfusion practices among 176 patients who predonated autologous blood before elective cardiac surgery and 176 matched cardiac surgery patients who did not predonate blood. The impact of decision-making on transfusion exposure was determined using multivariate analyses to account for major perioperative interventions and complications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for exposure to allogeneic blood transfusion or any transfusion, before and after exclusion of transfusions not conforming with selected transfusion criteria. RESULTS: Exposure to allogeneic transfusion was more likely among patients who did not predonate blood than among those who did predonate blood (OR 14.0, 95% CI 5.8-33.8). This finding was still true after exclusion of transfusions not meeting the transfusion criteria (OR 19.3, 95% CI 6.7-55.7). The autologous blood donors were more likely than the nondonors to receive any transfusion (OR 10.8, 95% CI 5.7-20.3). However, this association was substantially attenuated after exclusion of transfusions not meeting the transfusion criteria (OR 1.9, 95% CI 1.1-3.2). INTERPRETATION: Patients who predonated blood before elective cardiac surgery were at lower risk of receiving allogeneic transfusions than the nondonors. This was not because of a deliberate withholding of allogeneic transfusions from autologous donors. However, more liberal transfusion criteria for autologous blood were largely responsible for the increased transfusion rate among the autologous donors.

Hematologic evaluation of cardiopulmonary bypass circuits prepared with a novel block copolymer.

BACKGROUND: To decrease the complications associated with cardiopulmonary bypass, novel biomaterials have been introduced that may be less thrombogenic than standard synthetic surfaces. METHODS: Thirty-four patients undergoing coronary artery bypass grafting were randomized to bypass using either a control circuit or a circuit prepared "tip-to-tip" with a triblock-copolymer (polycaprolactone-polydimethylsiloxane-polycaprolactone). RESULTS: There was a progressive increase in thrombin generation in the control group during bypass, which was not seen in the test group. The test surface decreased the release of tissue plasminogen activator and plasmin-alpha2-antiplasmin complex formation (p<0.005). There was also an increased platelet count and a decreased platelet activation in the test group, as detected by GMP-140 expression and beta-thromboglobulin release (p = 0.017). There was also significantly more debris that accumulated on the arterial filter in the control group, as confirmed by scanning electron microscopy. CONCLUSIONS: This clinical trial has demonstrated a significant difference in the hematologic effects of the test circuits, with evidence of platelet preservation, decreased fibrinolysis, and decreased thrombin generation. A larger trial would be necessary to establish the clinical relevance of these differences.