Increased CD40 ligand expression on platelets is associated with cardiovascular events after total hip arthroplasty.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
M J Ray
Publications and source records attributed to M J Ray.
Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab.
BACKGROUND: Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention (PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention. METHODS: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration. These were tested for platelet activation markers by flow cytometry. Cardiac troponin I levels were assayed at baseline and at 24 h post PCI. RESULTS: Compared to healthy controls, patients with coronary artery disease had elevated markers of platelet activation including platelet-monocyte aggregates, P-selectin and PAC-1 (a marker specific for activated glycoprotein IIb/IIIa) prior to PCI. Increased levels of platelet-monocyte aggregates before PCI were associated with increased expression of P-selectin on the platelet surface. Abciximab therapy reduced platelet-monocyte aggregate levels but had no effect on P-selectin expression. The high levels of expression of activated glycoprotein IIb/IIIa (PAC-1) on platelets prior to PCI was reduced with abciximab therapy. Patients with higher levels of platelet-monocyte aggregates prior to PCI were more likely to develop an elevation of cardiac troponin I during the 24 h after PCI. CONCLUSIONS: Increased levels of platelet-monocyte aggregates may predict patients at risk for troponin elevation following PCI and identify those most likely to benefit from abciximab.
Abciximab↗
Heparin monitoring during cardiac surgery. Part 1: Validation of whole-blood heparin concentration and activated clotting time.
There is limited published data on the agreement between techniques for monitoring heparin levels. The aim of this study was to validate the Hepcon/HMS, with particular focus on the agreement with laboratory anti-Xa assay. The performances of two ACT instruments--Hemochron and HemoTec--were also evaluated, including an assessment for interchangeability. Blood samples from 42 adult cardiopulmonary bypass (CPB) patients were analysed for activated clotting time (ACT), whole-blood heparin concentration (Hepcon/HMS) and anti-factor Xa (anti-Xa) plasma heparin concentration. Agreement between measures was determined using the method of Bland and Altman. Simple analysis of agreement between the Hepcon and anti-Xa heparin revealed the Hepcon has a mean bias of -0.46 U/mL, with the limits of agreement +/- 1.12 U/mL. The comparison between ACT instruments indicated a mean difference of -96 seconds for the HemoTec, with limits of +/- 265 seconds. The Hepcon/ HMS instrument displayed satisfactory agreement with anti-Xa plasma heparin concentration, as the expected variation would not be expected to cause problems in the clinical setting. Agreement between the two measurements of ACT may be satisfactory, provided each is assigned a different target value.
Aged↗
Heparin monitoring during cardiac surgery. Part 2: Calculating the overestimation of heparin by the activated clotting time.
Activated clotting time (ACT) values were converted to heparin concentration, enabling an assessment of the accuracy of the ACT and a quantification of the prolongation imposed by bypass. Blood samples were obtained from 42 adult cardiopulmonary bypass (CPB) patients before and during bypass surgery. Samples were analysed for ACT (HemoTec ACT) and anti-factor Xa (anti-Xa) plasma heparin concentration. The mean heparin concentration calculated before bypass was an accurate reflection of plasma heparin; however, calculated values rose to around 170% of anti-Xa values upon connection to bypass. By adjusting for this rise, for 95% of cases the calculated heparin concentration would vary between 0.60 and 1.65 times anti-Xa values. Without accounting for artificial prolongation or individual sensitivities, the ACT may give values between 0.8 and 3.0 times that indicated by the anti-Xa assay. When both individual heparin sensitivities and the effects of bypass are considered, the ACT may provide a more suitable indication of heparin levels; however, typical use may overestimate heparin up to threefold.
Aged↗
Remifentanil and controlled hypotension; comparison with nitroprusside or esmolol during tympanoplasty.
PURPOSE: To determine whether remifentanil, combined with propofol, could induce controlled hypotension, reduce middle ear blood flow (MEBF) measured by laser-Doppler flowmetry, provide a "dry" operative field, and could be compared with nitroprusside or esmolol combined with alfentanil and propofol. METHODS: Thirty patients undergoing tympanoplasty and anesthetized with 2.5 mg x kg(-1) propofol iv followed by a constant infusion of 120 microg x kg(-1) x min(-1), were randomly assigned in three groups to receive either 1 microg x kg(-1) remifentanil iv followed by a continuous infusion of 0.25 to 0.50 microg x kg(-1) x min(-1), or nitroprusside iv, or esmolol iv combined for the latter two groups with alfentanil iv. RESULTS: Controlled hypotension was achieved at the target pressure of 80 mmHg within 107 +/- 16, 69 +/- 4.4, 53.3 +/- 4.4 sec for remifentanil, nitroprusside and esmolol respectively. MEBF decreased by 24 +/- 0.3, 22 +/- 3.3, 37 +/- 3% and preceded the decrease in SABP, within 30 +/- 6.1, 11.2 +/- 3.1, 15 +/- 2.8 sec for remifentanil, nitroprusside and esmolol respectively. Remifentanil, and nitroprusside decreased MEBF autoregulation less than esmolol (0.36 +/- 0.1, 0.19 +/- 0.2, -0.5 +/- 0.2). Controlled hypotension was sustained in all three groups throughout surgery, and the surgical field rating decreased in a range of 80% in all three groups. Nitroprusside decreased pH and increased PaCO2. There were no postoperative complications in any of the groups. CONCLUSIONS: Remifentanil combined with propofol enabled controlled hypotension, reduced middle ear blood flow and provided good surgical conditions for tympanoplasty with no need for additional use of a potent hypotensive agent.
Adjuvants, Anesthesia↗
Comparison of epsilon aminocaproic acid and low-dose aprotinin in cardiopulmonary bypass: efficiency, safety and cost.
BACKGROUND: In this study we compared the clinical efficiency, safety, and economic benefit of low-dose aprotinin with epsilon aminocaproic acid (EACA) in reducing bleeding after cardiopulmonary bypass operation. METHODS: In a double-blind, randomized study, 100 patients received low-dose aprotinin (2 x 10(6) kallikrein inhibitor units) or EACA (20 g). The surgical procedure was single- or double-valve replacement with or without coronary artery bypass grafts. RESULTS: Mediastinal chest drainage and transfusion requirements with both therapies were similar. There were no urgent reoperations to secure hemostasis in either group. Similar levels of D-dimer with both therapies indicate a similar inhibition of fibrinolysis. Release of troponin I was less in the low-dose aprotinin group 1 and 4 hours after bypass, although electrocardiographic measurements did not reflect this difference. Levels of S-100beta and neuron-specific enolase were similar with both therapies, confirming that there was no difference in the occurrence of any adverse neurologic events in either group. CONCLUSIONS: Low-dose aprotinin and EACA showed similar effects on the reduction of intraoperative and postoperative bleeding. The lower cost of EACA with no change in safety outcome suggests it is the preferred treatment.
Aminocaproic Acid↗
Postoperatively administered aprotinin or epsilon aminocaproic acid after cardiopulmonary bypass has limited benefit.
BACKGROUND: Intraoperative antifibrinolytic treatment with aprotinin and epsilon aminocaproic acid (EACA) has been shown to be effective prophylaxis in the reduction of excessive bleeding after cardiopulmonary bypass operations. This study investigated the effectiveness of both drugs when used as a postoperative treatment of patients showing early signs of increased bleeding. METHODS: In a double-blind, randomized study, 69 patients with chest drainage of 100 mL or more 1 hour after bypass were treated with aprotinin, EACA, or placebo. RESULTS: In the first 24 hours postoperatively, neither drug significantly reduced chest drainage or blood transfusion requirements compared with placebo. Median (interquartile) cumulative chest drainage volumes for the first 24 hours postoperatively for the aprotinin, EACA, and placebo groups were 525 (340, 750), 575 (450, 762), and 650 (550, 800) mL, respectively. Among the study patients, 4 undergoing valve operation and treated with aprotinin showed a trend toward less bleeding during the first 12 hours postoperatively compared with 5 valve operation patients who received placebo (p = 0.06). Among all patients, the treatment with aprotinin or EACA failed to reduce levels of D-dimer compared with placebo after treatment, indicating that fibrinolysis was not significantly inhibited. CONCLUSIONS: Aprotinin or EACA administered in the early postoperative period was ineffective in reducing postoperative bleeding with the exception of a small group of patients having valve operations in whom aprotinin treatment may have shown some benefit.
Aged↗
Epsilon-aminocaproic acid promotes the release of alpha2-antiplasmin during and after cardiopulmonary bypass.
This double-blind, randomized study compared the mechanisms by which low-dose aprotinin and epsilon-aminocaproic acid (EACA) inhibited fibrinolysis during cardiopulmonary bypass surgery. D-dimer levels during and after bypass were similar, indicating an equivalent inhibition of fibrinolysis. Effects on tissue plasminogen activator release were not associated with the inhibition of fibrinolysis by either drug. Treatment with EACA was associated with a substantial release of endogenous alpha2-antiplasmin, particularly 1 h after bypass. Compared with the aprotinin group, higher levels of the plasmin-alpha2-antiplasmin complex in the EACA group confirmed an increased inhibition of plasmin by alpha2-antiplasmin. In conclusion, it is hypothesized that EACA inhibited fibrinolysis by stimulating the release of the patients' own alpha2-antiplasmin.
Aminocaproic Acid↗
Economic evaluation of high-dose and low-dose aprotinin therapy during cardiopulmonary bypass.
BACKGROUND: Aprotinin therapy is now widely used during cardiac surgery. This study examined the clinical and economic effectiveness of high-dose or low-dose aprotinin in comparison to placebo. METHODS: In a double blind, randomized study, three groups of 50 patients received high-dose aprotinin costing AUS$614 per patient (AUS$ = Australian dollars), low-dose aprotinin costing AUS$220 per patient or placebo. Resource use influenced by aprotinin therapy was measured. RESULTS: Both doses were effective in reducing chest drainage and postoperative transfusion requirements, high-dose being more effective than low-dose. Both doses reduced the rate of reoperations for hemostasis. A base case of statistically significant differences associated with the high-dose and low-dose aprotinin showed cost savings of AUS$77 and AUS$348 per patient, respectively. If the demonstrated less significant reductions in operating room and ward stay are included, these savings become AUS$463 and AUS$715, respectively. Alternately, if cross-matches are replaced by group-and-hold and cell savers are not used, the savings per patient would be AUS$196 and AUS$467, respectively. CONCLUSIONS: While high-dose aprotinin is clinically more effective than low-dose aprotinin, low-dose therapy demonstrates greater cost savings.
Aprotinin↗
Structural analysis of apolipoprotein A-I: limited proteolysis of methionine-reduced and -oxidized lipid-free and lipid-bound human apo A-I.
The domain structures of lipid-free and lipid-bound apolipoprotein A-I (apo A-I) containing reduced and oxidized methionines were analyzed by limited proteolysis. Lipid-free apo A-I is cleaved primarily in the extreme carboxy-terminus and, to a much lesser extent, in the central region of the protein between residues 115 and 136. Oxidation of methionines 112 and 148 to the corresponding sulfoxides in putative amphipathic helices 4 (P99-E120) and 6 (P143-A164), respectively, causes helices 1 (L44-G65), 2 (P66-S87), and 7 (P165-G186) to become susceptible to protease digestion. These results are consistent with a discrete, globular tertiary structure for the lipid-free protein minimally formed from amphipathic helices 1, 2, 4, 6, and 7. In distinct contrast to lipid-free apo A-I, lipid-bound apo A-I is most susceptible to cleavage in the extreme amino-terminus and, to a lesser extent, in both the central and carboxy-terminal regions. The observed cleavage pattern for the reduced lipid-bound protein supports the existence of many of the turns between helices predicted by sequence analysis of the lipid-bound protein. Methionine oxidation of lipid-bound protein results in a decreased protease susceptibility in the extreme amino-terminus and a concomitant increase in protease susceptibility in the central and carboxy-terminal regions. The results from methionine oxidation indicate the oxidation state of the protein is an important determinant in defining the conformation of both lipid-free and lipid-bound apo A-I.
Amino Acid Sequence↗
Truncation of the amino terminus of human apolipoprotein A-I substantially alters only the lipid-free conformation.
An amino-terminal deletion mutant (residues 1-43) of human apolipoprotein A-I (apo hA-I) has been produced from a bacterial expression system to explore the structural and functional role of these amino acids, encoded by exon 3, in apo hA-I. Lipid binding of apo delta (1-43)A-I and lipid binding of apo hA-I are very similar as assessed by surface activity, lipid association with palmitoyloleoylphosphatidylcholine (POPC) vesicles, and lipid association with plasma lipoproteins. Preliminary kinetic measurements appear to show that the reactivity of lecithin:cholesterol acyltransferase (LCAT) with the mutant is slightly decreased compared to wild-type apo hA-I. Collectively, these results indicate that the N-terminal region is not necessary for lipid binding or activation of LCAT. In contrast, there are significant structural differences between lipid-free apo delta (1-43)A-I and apo hA-I, as judged by denaturant-induced unfolding, binding of the fluorescent probe 1-anilinonaphthalene-8-sulfonate, surface balance measurements, and far- and near-ultraviolet circular dichroic spectroscopy. All spectral and physical measurements indicate apo delta (1-43)A-I has a folded, tertiary structure, although it is significantly less stable than that of apo hA-I. It is concluded that the N-terminal 43 residues are an important structural element of the lipid-free conformational state of apo hA-I, the absence of which induces a fundamentally different fold for the remaining carboxy-terminal residues, compared to those in native apo hA-I.
Anilino Naphthalenesulfonates↗
Preoperative platelet dysfunction increases the benefit of aprotinin in cardiopulmonary bypass.
BACKGROUND: This study was designed to determine the benefit of aprotinin therapy in reducing bleeding during and after cardiopulmonary bypass in patients with preoperative platelet dysfunction. Platelet function involvement in the mechanism by which aprotinin acts was also investigated. METHODS: In a double-blind, randomized study, patients received high-dose aprotinin (n = 54) or placebo (n = 52). Whole blood aggregation was measured preoperatively. Platelet function and activation in both groups were assessed intraoperatively and postoperatively at five times. RESULTS: Aprotinin significantly reduced perioperative bleeding and postoperative blood transfusion. Placebo-treated patients with reduced preoperative platelet aggregation bled more postoperatively, but aprotinin reduced the bleeding in patients with normal or reduced platelet function to similar levels. Any cardiopulmonary bypass-induced changes in platelet aggregation, platelet activation as measured by P-selectin expression, and von Willebrand factor antigen and function were similar in aprotinin-treated and placebo-treated groups. CONCLUSIONS: The mechanism by which aprotinin reduced bleeding was independent of any effect on platelet function. However, aprotinin produced a greater reduction in bleeding among patients whose condition was hemostatically compromised by preoperative platelet dysfunction.
Aprotinin↗
A brief review of studies evaluating the adverse effects of aprotinin therapy in aortocoronary bypass surgery.
Explore the source record for details and available documents.
Aprotinin↗
Aprotinin reduces blood loss after cardiopulmonary bypass by direct inhibition of plasmin.
The effectiveness and mechanism of aprotinin reduced bleeding after cardiopulmonary bypass surgery was studied in a double blind randomised study of 106 patients undergoing valve replacement surgery. Aprotinin therapy was associated with significant reduction in perioperative bleeding and postoperative blood transfusion requirements. Although initially tissue plasminogen activator (t-PA) activity was lower in the aprotinin than placebo group, as surgery proceeded this difference was reversed due to less plasminogen activator inhibitor-1 release in the aprotinin group. This indicates that aprotinin-mediated suppression of fibrinolysis as demonstrated by reduced D-dimer concentration was not related to t-PA. Furthermore, similar perioperative reduction of plasminogen levels in aprotinin and placebo groups indicated a similar degree of conversion of plasminogen to plasmin. However, less plasmin bound with alpha 2-antiplasmin in the plasma in the aprotinin group as it was already complexed with aprotinin where it remained protected from the natural inhibitor on the intact fibrin surface. The reduced fibrinolytic activity of the aprotinin group was thus brought about by the complexing of aprotinin with the plasmin which was bound to the fibrin surface.
Adult↗
Erroneous D-dimer result on a paediatric citrated specimen.
Explore the source record for details and available documents.
Anticoagulants↗
A proposed model to monitor heparin therapy using the concentrated thrombin time which allows standardisation of reagents and improved estimation of heparin concentrations.
The concentrated thrombin time (CTT), a thrombin time performed with a high concentration of thrombin, was evaluated as an alternative to the activated partial thromboplastin time (APTT) for monitoring of heparin therapy. Forty-nine plasmas from patients receiving unfractionated heparin therapy were tested. It was first demonstrated that CTTs using three commercial reagents could be standardised against CTTs performed with a reference reagent, MRC reagent 66/305. For comparison, APTTs were performed on the plasmas. As a benchmark of the degree of heparinisation, the heparin concentration of the plasmas was determined by chromogenic anti-IIa heparin assays, therapeutic range being 0.2-0.4 units/ml. The optimal relationships of the CTTs and APTT with the heparin concentration were established. These were used to predict the heparin concentrations of the plasmas from the results of the APTT, CTT performed with the reference reagent, and transformed CTT performed with each of the three commercial reagents. In predicting the assayed plasma heparin concentrations, the accuracy of the APTT was only 53%, while the CTT was from 78 to 82%. The CTT can be standardised and, subject to results of clinical trials, could provide an improved method of monitoring heparin therapy.
Afibrinogenemia↗
The role of von Willebrand factor in haemostasis and blood loss during and after cardiopulmonary bypass surgery.
Excessive perioperative and postoperative bleeding continue to complicate cardiopulmonary bypass surgery (CPB). In this study we measured the von Willebrand factor antigen (vWF:Ag), collagen binding assay (CBA) and ristocetin cofactor assay (RiCo) in 52 patients undergoing CPB. The collagen binding assay employs the affinity of the high-molecular-weight multimers of vWF to collagen and was used in this study to demonstrate differences in the multimeric composition of vWF during and after CPB. The observed values for the vWF:Ag, CBA and RiCo were correlated to the amount of postoperative bleeding. Both the preoperative vWF:Ag and the CBA showed significant negative correlation with postoperative blood loss (r = -0.3046, P < 0.05 and r = -0.3228, P < 0.05 respectively). Higher blood loss figures correlated with lower vWF:Ag, CBA and RiCo during and after surgery with the strongest correlation 1 h post-op between both vWF:Ag and CBA and actual blood loss (r = -0.5061, P < 0.001 and r = -0.4942, P < 0.001 respectively). The strong negative correlations between vWF:Ag, CBA and RiCo before, during and after CPB and blood loss data verify the important role of vWF in primary haemostasis. Of particular note, the negative correlations between preoperative levels of vWF:Ag, CBA and postoperative blood loss provide valuable insight into another possible mechanism of excessive bleeding post CPB.
ABO Blood-Group System↗
Effects of posture, hypotension and locally applied vasoconstriction on the middle ear microcirculation in anaesthetized humans.
Studies by laser-Doppler flowmetry of middle ear microcirculation changes induced by physical and chemical stimuli in the animal have only recently been made. This prospective study, performed in humans, was designed to compare the effects of a postural manoeuvre (headup tilt 30 degrees), hypotension and locally applied vasoconstriction on middle ear blood flow during anaesthesia. Circulatory changes provoked by a headup tilt of 30 degrees, and successive intravenous boluses of potent vasodilators, were compared with circulatory changes provoked by locally applied adrenaline, in ten healthy patients in good physical states undergoing middle ear surgical repair. Heart rate and direct arterial pressure were continuously recorded via a radial artery cannula. Middle ear blood flow was continuously recorded via a laser-Doppler probe placed on the promontorium cavi tympani. Metabolic parameters (partial pressure of O2 and CO2 in arterial blood, pH, arterial lactate concentrations) and arterial concentrations of propofol were measured just before and just after the experiment. Headup tilt did not modify heart rate, mean arterial pressure or middle ear blood flow. Vasodilators (nicardipine, nitroprusside, nitroglycerin) provoked a fall in arterial pressure (P < 0.0001, P < 0.0001, P < 0.019, respectively), but did not induce any significant variations in heart rate; variations occurred in middle ear blood flow (P > 0.05, not significant) which were different according to patients and agents. Locally applied adrenaline provoked a fall in the middle ear blood flow (P < 0.0012), with no effect on heart rate and arterial pressure. There were no significant changes in metabolic values, or propofol serum concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗