Perioperative microemboli and platelet aggregation in patients undergoing carotid endarterectomy.

In carotid endarterectomy (CEA) patients, platelet aggregation is increased despite heparinization. We investigated whether this phenomenon correlates with the occurrence of perioperative microemboli. Of 27 CEA patients, 18 (67%) used aspirin and 9 also used clopidogrel. Blood was collected at multiple time points before, during, and after CEA. Platelet aggregation and P-selectin expression were determined. Transcranial Doppler monitoring was used to measure microemboli. Platelet aggregation showed a significant increase 5 minutes postheparinization compared with preheparinization (19.7 +/- 2.8% vs 8.9 +/- 0.9% in the aspirin group and 22.5 +/- 4.4% vs 8.7 +/- 1.2% in the clopidogrel group; p < .01 and p < .05, respectively). P-selectin expression showed a tendency to increase postheparinization in both groups (p = .07 and p = .09, respectively). The number of microemboli ranged from 0 to 50. Clopidogrel patients displayed fewer microemboli than aspirin patients (4.1 +/- 2.3 vs 17.6 +/- 18.2; p < .01). Patients with a high number of microemboli displayed had a tendency toward higher baseline platelet aggregation than patients with a low number of microemboli (p = .08). In conclusion, platelet aggregation is transiently increased during CEA despite the administration of antiplatelet agents. Clopidogrel is associated with a decreased number of perioperative microemboli. The exact relationships between these findings, postoperative microemboli formation, and the risk for thromboembolic complications after CEA remain to be determined.

Plasma matrix metalloproteinase-9 and ACE-inhibitor-induced improvement of urinary albumin excretion in non-diabetic, microalbuminuric subjects.

INTRODUCTION: Elevated plasma matrix metalloproteinase-9 (MMP-9) levels have been suggested to precede the development of microalbuminuria. As angiotensin-converting enzyme (ACE) inhibitors effectively reduce urinary albumin excretion (UAE), in the present study we have investigated the potential association of plasma MMP-9 levels with UAE and treatment effects of ACE-inhibition. MATERIAL AND METHODS: In a placebo-controlled randomised trial we determined plasma MMP-9 levels at baseline and after three months of randomisation to either placebo (n=202) or fosinopril (20 mg/day, n=204) treatment. RESULTS: Baseline plasma MMP-9 levels were not related to baseline UAE (r=-0.008, p=0.871). Three months of fosinopril treatment effectively reduced UAE compared to placebo treatment (-10.4+/-2.4 vs. 1.8+/-1.3 mg/24 hours, p<0.001, respectively). However, fosinopril treatment failed to significantly change plasma MMP-9 levels compared to placebo (-0.47+/-7.68 vs. 0.06+/-9.20, p=0.646, respectively). In addition, the change in UAE was not related with change in MMP-9 levels. CONCLUSION: The effective reduction of UAE with fosinopril was not related to plasma MMP-9 levels.

ACE I/D-corrected Z-scores to identify normal and elevated ACE activity in sarcoidosis.

BACKGROUND: The value of elevated serum angiotensin-converting enzyme (ACE) activity in the diagnosis and follow-up in sarcoidosis is a matter of ongoing debate. This may be at least related to the insertion (I)/deletion (D) polymorphism in the ACE gene (ACE I/D). ACE activity is influenced by the ACE I/D polymorphism. As a consequence, the use of one reference interval instead of three genotype-specific reference intervals for ACE activity may lead to a less precise interpretation of ACE activity. METHODS: In order to assess whether determination of ACE activity indeed requires the ACE I/D genotype to be taken into account, we established ACE I/D-corrected reference intervals in healthy, Caucasian volunteers (n=200). In addition, ACE activities in ACE I/D genotyped patients suspected of or having sarcoidosis (n=129) were expressed as the Z-score related to ACE I/D-corrected reference intervals. RESULTS: Comparison of the Z-score with ACE activity in which ACE I/D is ignored rendered 8.5% misclassification of 'elevated' versus 'normal' ACE or vice versa. CONCLUSIONS: Our data demonstrate a convenient way to circumvent the use of three reference intervals by introducing a Z-score for ACE activity. It also illustrates the need to re-investigating the possible clinical value of serum ACE activity in sarcoidosis by considering ACE I/D.

Expression of priming-associated cellular markers on neutrophils during an exacerbation of COPD.

Chronic inflammation of the airways is a hallmark of chronic obstructive pulmonary disease (COPD). We investigated the kinetics of priming of inflammatory cells in peripheral blood during exacerbations of COPD and during the resolution phase. Modulation of the leukocyte compartment as a consequence of systemic activation by cytokines/chemokines was determined by measuring the expression of priming-associated epitopes by novel antibodies designated A17 and A27. Furthermore, H2O2 was determined in breath condensate as a read out for local inflammation. Leukocytes were obtained from COPD patients (GOLD II-IV) during and after an exacerbation of their disease. During an exacerbation the expression of priming epitopes on leukocytes was increased. This priming phenotype disappeared upon treatment with intravenous corticosteroids. Similarly, H2O2 levels in breath condensate were also increased during an exacerbation and decreased upon treatment. We conclude that the activation status of neutrophils in the systemic compartment can be used as a read-out for systemic innate immune signals involved in the pathogenesis of COPD. The correlation between H2O2 in exhaled air with A27 priming on neutrophils showed that local inflammation has systemic effects on cells of the innate immune system.

Markers of inflammation and oxidative stress in exacerbated chronic obstructive pulmonary disease patients.

COPD is characterised by damage to small airways due to an inflammatory process as well as an imbalance between oxidants and antioxidants. Several cytokines and cell adhesion molecules enhancing a mainly neutrophilic inflammation have been associated with COPD. The aim of the study was to investigate whether inflammation or oxidative markers gave an indication of the course of COPD during an exacerbation. Fourteen patients with moderate to severe COPD admitted to the St. Antonius Hospital because of an exacerbation have been monitored during treatment with prednisolone 50 mg intravenously during 24 h at admission, reduced to 25 mg at day 3 and tapered off with oral prednisolone at day 7. On three separate occasions, day 1, 3 and 7, H2O2 in exhaled air, IL-8 and the soluble cell adhesion molecule sICAM and sE-selectin in serum were measured. We compared the patients at day 1 with healthy controls (in both non-smokers and smokers). Furthermore, we examined the changes from the study group in time during therapy. At admission all the markers were raised in comparison with the control groups. During treatment H2O2 concentrations in breath condensate declined significantly (P<0.001) as well as IL-8 and sICAM in serum (P=0.002, respectively, P<0.001). There was no significant change in sE-selectin (P=0.132). No significant improvement has been found in spirometry. These data suggest that the markers H2O2 in exhaled air, IL-8 and sICAM in serum are suitable markers in monitoring exacerbated COPD.

High-dose aspirin in addition to daily low-dose aspirin decreases platelet activation in patients before and after percutaneous coronary intervention.

BACKGROUND: Activated platelets play a major role in acute vessel closure after coronary angioplasty. Although aspirin is the routine therapy during angioplasty, it only incompletely prevents acute closure. This might be due to suboptimal dosing. OBJECTIVE: First, to study the effect of additional high-dose aspirin on platelet activation during coronary angioplasty. Second, to assess the potential of the new PFA-100 analyzer to evaluate the effect of different doses of aspirin in patients undergoing angioplasty. METHODS: Fifty-one patients on 100 mg aspirin/day for at least 1 month were randomized to continuation of 100 mg aspirin/day only (Group A=24 patients), or to this regime plus a bolus of 1000 mg of aspirin given 1 day before angioplasty (Group B=27 patients). Results were compared with 15 controls. Platelet function was measured before angioplasty by the PFA-100 analyzer; platelet activation was measured by flow cytometry just before and 1 h after angioplasty. RESULTS: At baseline, Group A had significantly more activated platelets than the control group (P<.001). High-dose aspirin in Group B resulted in significantly lower platelet activation as compared with both controls (P<.001) and Group A (P<.001). During angioplasty, the number of activated platelets decreased significantly in Group A (P<.001), while there was no change in Group B (P=.6). The PFA-100 analyzer was unable to detect differences between the two treatment groups. CONCLUSIONS: The addition of high-dose aspirin to daily low-dose aspirin, 1 day before coronary angioplasty, significantly reduced the platelet activation state before and after intervention. The PFA-100 analyzer did not detect differences in the effect of low- versus high-dose aspirin on platelet function.

Pretreatment with oral anticoagulants decreases platelet activation in patients before and after percutaneous coronary intervention.

BACKGROUND: Platelet activation plays a major role in acute vessel closure after coronary angioplasty. In the randomized Balloon Angioplasty and Anticoagulation Study (BAAS), pretreatment with oral anticoagulants in addition to aspirin resulted in a 47% reduction of acute complications as compared with aspirin alone. This result may suggest a direct effect of oral anticoagulants on platelet activation. METHODS AND RESULTS: Patients were randomized to aspirin alone (group A, n = 26) or to aspirin plus oral anticoagulants started one week before angioplasty (group B, n = 26). Platelet response tests were performed 1 hour before (baseline) and 1 hour after intervention and on day 1. Platelet activation was measured by flow cytometry, as the number of antibody-positive platelets per 10,000 counted. Platelet function was evaluated with use of the PFA-100 analyzer. In group B, the median number of P-selectin-positive platelets was lower before (28 vs. 54, P = 0.018) and after (13 vs. 24, P = 0.377) angioplasty than in group A. Also the median decrease in the number of P-selectin-positive platelets during angioplasty was lower in group B (delta = 4) than in group A (delta = 30, P = 0.022). No further significant change was observed in platelet activation on day 1 in the two groups. The ability of platelets to become stimulated as measured with the PFA-100 analyzer was not affected by oral anticoagulants. CONCLUSIONS: Pretreatment with oral anticoagulants resulted in less activated platelets before and after coronary angioplasty, which is in agreement with its clinical effect of reducing procedural complications. Platelet function was not affected by oral anticoagulants.