BACKGROUND:Electrical cardioversion is a common modality of therapy for persistent atrial fibrillation. Unfortunately even if the cardioversion is initially successful many patients revert to atrial fibrillation. It has been proposed that there may be an inflammatory component to this arrhythmia. It is interesting to speculate that this may have a role in determining the outcome following elective cardioversion.METHODS:The study group consisted of 81 patients with persistent atrial fibrillation undergoing elective external cardioversion. Blood samples were taken immediately prior to the procedure. Soluble E-Selectin, P-Selectin, intra-cellular adhesion molecule and vascular cell adhesion molecule were assayed using a commercially available enzyme linked immunosorbent assay technique (R&D systems) and high sensitivity C reactive protein was measured by rate nephelometry. Patients were reviewed at 8 weeks and bloods were taken at this time.RESULTS:At baseline patients who had an unsuccessful cardioversion (n=15) were compared to those who had a successful cardioversion (n=66). Thirty-two patients of the 66 initially successful patients reverted to atrial fibrillation during the follow-up period. There was no difference in the levels of baseline serum inflammatory markers measured between those with an unsuccessful cardioversion and those who were successful. When the group who reverted to atrial fibrillation were compared to those who remained in sinus rhythm again there was no difference in the levels of serum markers measured at baseline.CONCLUSION:There was no association between maintenance of sinus rhythm following cardioversion and serum inflammatory markers.

Atrial fibrillation (AF) remains the most common cardiac arrhythmia and is associated with an increase in both morbidity and mortality. Some data in both the surgical and non-surgical settings suggest that inflammation has a pivotal role in the onset and propagation of AF. As on pump coronary artery bypass surgery is associated with a significant inflammatory response and an incidence of AF between 11–40%, we decided to use this model to study if there was a potential association between perioperative response and the development of postoperative AF.1,2 The study was approved by the hospital ethics committee and all patients provided informed consent. This study complies with the Declaration of Helsinki. We recruited 149 non-diabetic patients undergoing first time non-emergency on pump coronary artery bypass grafting. The exclusion criteria were impaired left ventricular function (ejection fraction 200 μmol/l), malignancy, chronic inflammatory conditions, and concurrent infection. Patients’ cardiac rhythm was monitored continuously for 72 hours after surgery, which was reviewed by a cardiologist daily. The primary end point was defined as new onset AF that persisted for at least one hour or that required urgent treatment because of instability. High sensitivity C reactive protein was measured by rate nephelometry with a Dade Behring apparatus. The adhesion molecules P-selectin, E-selectin, soluble intercellular adhesion molecule …

As more data have become available demonstrating that percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) are equivalent in terms of myocardial revascularization, more attention is being paid to non-cardiac effects of the procedures such as the cognitive impairment that occurs following surgery [ 1 Schofield P.M. Indications for percutaneous and surgical revascularisation: how far does the evidence base guide us?. Heart. 2003 (May); 89: 565-570 Crossref PubMed Scopus (13) Google Scholar , 2 Newman M.F. Kirchner J.L. Philips-Bute B.S. et al. Longitudinal assessment of neurocognitive function after coronary artery bypass surgery. N. Engl. J. Med. 2001; 344: 395-402 Crossref PubMed Scopus (1647) Google Scholar ]. Pulmonary function and cardiac function are intimately related, with dyspnea being a recognized anginal equivalent. Pulmonary function, which is reduced in both acute and chronic heart failure, deteriorates following CABG but no published data are available after PCI [ [3] Braun S.R. Birnbaum M.L. Chopra P.S. Pre- and post-operative pulmonary function abnormalities in coronary artery revascularisation surgery. Chest. 1978; 73: 316-320 Crossref PubMed Scopus (110) Google Scholar ]. Potentially, PCI should offer advantages over surgery as there is no disruption of the chest wall or its vasculature (as occurs in internal mammary artery grafting), which have been proposed as being responsible for the post-surgical deterioration [ [4] Cohen A.J. Moore P. Jones C. et al. Effect of internal mammary harvest on post-operative pain and pulmonary function. Ann. Thorac. Surg. 1993; 56: 1107-1109 Abstract Full Text PDF PubMed Scopus (69) Google Scholar ].

Background: The acute coronary syndromes are associated with an intense inflammatory response and sustained leukocyte activation. This inflammatory state has been correlated with an adverse prognosis, but the source of this inflammation remains controversial, with evidence that it may arise either from the coronary vasculature or from the systemic endothelium. Methods: Levels of soluble cell adhesion molecules, and of their respective monocyte cell surface ligands, were measured in the peripheral serum of 21 patients presenting with acute coronary syndromes. Soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were measured by enzyme linked immunosorbent assay and expression of the monocyte integrins CD11b (Mac-1) and CD49d (VLA-4) was measured by direct immunofluorescence using flow cytometry. Results: High levels of the monocyte receptor CD11b (531 vs. 345 MFI, P<0.01), and its soluble intercellular adhesion molecule-1 (329 vs. 232 ng/ml, P<0.01), were noted in patients with acute coronary syndromes compared to healthy controls. Conclusions: Reciprocal activation of monocyte receptor ligands and endothelial adhesion molecules was found in the peripheral blood of patients with acute coronary syndromes. This may indicate a coordinated state of pro-inflammatory upregulation with widespread activation of both leukocytes and endothelium and suggests a systemic rather than local source for inflammation in acute coronary disease.

Background: Aortic stenosis is an inflammatory process, as evidenced by increased tissue expression and serum levels of various endothelial cellular adhesion molecules. Aortic stenosis and atherosclerosis have many risk factors in common, including hypercholesterolemia. In atherosclerosis, statins lower cholesterol and display some anti-inflammatory activity. We hypothesized that statins might also have anti-inflammatory effects in patients with aortic stenosis. Methods: This observational cross-sectional study measured levels of cellular adhesion molecules in 129 patients (88 male, mean age 68) with aortic stenosis (mean echo gradient 49 mm Hg, range 22 to 112) and compared levels in patients already on statin therapy for primary or secondary prevention of coronary artery disease, to those not on treatment. Concomitant conditions included hypertension (47%), diabetes (10%), and ischemic heart disease (54%). A comparison group consisted of 45 patients with stable ischemic heart disease. Results: Patients on statins (35) were more likely to have hypertension (62% vs 42%, P = .05), but no significant differences existed in sex, age, concomitant ischemic heart disease, or diabetes. Statin-treated patients had a 20% lower vascular cellular adhesion molecule level than those without (484 ± 143 ng/L vs 604 ± 245 ng/L, P = .006). The reduction in cellular adhesion molecule levels was consistent in patients with aortic stenosis alone, aortic stenosis and ischemic heart disease, or ischemic heart disease alone. There were no differences in the levels of the other adhesion molecules between the three groups, or related to statin therapy. Conclusion: Statin therapy is associated with reduced serum levels of vascular cellular adhesion molecules in patients with aortic stenosis. Vascular cellular adhesion molecule levels are similar in patients who have aortic stenosis, ischemic heart disease, or both. A prospective study is required to confirm this finding and to determine whether this suppression of endothelial inflammation translates into a slowing of the progression of aortic stenosis.

Inflammation is a critical pathogenic component in acute coronary syndromes. As a consequence the potential use of inflammatory markers as predictors of clinical outcome in acute coronary syndromes has been investigated. This review outlines the pathology underlying acute coronary syndromes and reviews the published data on inflammatory markers in acute coronary syndromes.

Extensive evidence supports a pathogenic role for both local and systemic inflammation in acute coronary syndromes. However, several important questions remain unanswered. Is the observed inflammatory process a precursor or a consequence of coronary plaque rupture? Is the inflammatory component of unstable coronary disease a potential therapeutic target? Finally, do infectious agents have a pathogenic role in coronary atherosclerosis and acute coronary syndromes?

Inflammation is now considered a critical pathogenic component of the atherosclerotic process. This is characterized histopathologically by leukocyte infiltration of the vascular endothelial wall. The vascular endothelium is a dynamic organ system, which has natural antiadhesive and anticoagulant properties. However, in response to injury the endothelium promotes coagulation and mediates the binding and transendothelial migration of activated leukocytes. These pathological processes are believed to be critical to the initiation and progression of atherosclerosis as well as the pathogenesis of acute coronary syndromes and are mediated by a group of molecules referred to collectively as cell adhesion molecules. Cell adhesion molecules are a diverse system of proteins and adhesive receptors, which orchestrate vital biological phenomena such as embryogenesis, cell growth and differentiation as well as inflammatory processes. Over the past decade there has been considerable progress in our understanding of adhesion molecules and their complex interactions. Among the many types of adhesion receptors on the cell surface, four main families are described (Fig.1).

Background: Despite recent refinements to thrombolysis for acute myocardial infarction, a significant minority of patients still fail to reperfuse. There is no reliable predictor of this state of ‘thrombolysis resistance’, but platelet and endothelial factors are believed to be important. Cell adhesion molecules are expressed by the endothelium when activated and their shed or soluble portion can be quantified in the peripheral serum, where they may be taken as a measure of endothelial activation. We sought to find a link between markers of endothelial inflammation at time of infarction and failure to reperfuse as measured by vessel occlusion at angiography. Methods: Patients presenting with their first acute myocardial infarction had levels of soluble adhesion molecules, C-reactive protein and monocyte chemotactic protein-1 measured prior to thrombolysis. An angiogram on day five after admission was performed to establish patency of the index vessel. Results: Levels of soluble vascular adhesion molecule-1 (sVCAM-1) taken prethrombolysis were significantly elevated compared to those with a patent vessel (620±90 vs. 418±28 ng/ml, P<0.03. The positive predictive value of sVCAM-1 for vessel patency was 88%. Conclusions: We found elevated serum levels of the adhesion molecule soluble vascular adhesion molecule-1 (sVCAM-1) at presentation in patients with acute myocardial infarction who did not respond to thrombolysis. Endothelial activation may be important in thrombolysis resistance.

Saint James' Hospital is a 650-bed tertiary referral hospital. An audit was performed of acute transmural myocardial infarctions for the years 1996 to 1999 inclusive. On average there were 2043 cardiology admissions annually, 9.8% of all hospital admissions. Acute transmural myocardial infarction was diagnosed in 178 patients annually, and was less common during the summer. The figure of 72% receiving revascularisation therapy (thrombolysis 67%, primary angioplasty 5%) compares favourably with 35% in 1992. The main reason for not receiving thrombolysis was late presentation (15%) with contraindications present in only 5%. The case fatality rate was 16% confirming the higher mortality in clinical practice than that of thrombolytic trials. The prescription of aspirin or warfarin (99%) and betablockers (67%) was in line with international trials. The use of angiotensin converting enzyme inhibitors (34%) and statins (28%) is similar to other studies but less than would be expected according to trial evidence.

Of 147 patients admitted with acute coronary syndromes, 17 were taking statins at the time of presentation. These were matched with 17 subjects not taking statins. We found that statin therapy was associated with lower levels of sP-selectin, a marker of platelet and vascular endothelial activation. This provides further insight into the extralipid effect of statins in clinical practice and may help explain the greater-than-expected benefits of statin therapy in ischemic heart disease.

OBJECTIVE To assess prospectively the prognostic value of soluble cellular adhesion molecules (CAMs) in patients with unstable angina and non-Q wave myocardial infarction and to compare their prognostic accuracy with that of C reactive protein (CRP). DESIGN AND SETTING Prospective observational study of patients presenting acutely with unstable angina and non-Q wave myocardial infarction to a single south Dublin hospital. METHODS Patients with Braunwald IIIA unstable angina and non-Q wave myocardial infarction had serum samples taken at presentation before initiation of antithrombotic treatment and were followed for six months. The primary end point was the occurrence of major adverse cardiovascular events (recurrent unstable angina, non-fatal myocardial infarction, and cardiovascular death) at six months. Concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble endothelial selectin, and soluble platelet selectin were measured using an enzyme linked immunosorbent assay technique. CRP was measured with an immunophelometric assay. RESULTS 91 patients (73 men and 18 women, mean (SD) age 61 (11) years) were studied; 27 patients (30%) had major adverse cardiac events during the six months of follow up. Concentration of CRP were significantly raised in patients who had an ischaemic event (mean (SEM) 11.5 (6.4) mg/l v5.4 (2.5) mg/l, p < 0.001). Concentrations of sVCAM-1 were also significantly raised in the ischaemic event group (979 (30) ng/mlv 729 (22) ng/ml, p < 0.001). Both sVCAM-1 and CRP concentrations correlated strongly with the occurrence of an adverse event. The sensitivity of CRP > 3 mg/l and sVCAM-1 > 780 ng/ml for predicting future events was > 90%. There was no difference in concentrations of sICAM-1, soluble endothelin selectin, or soluble platelet selectin between event and non-event groups. CONCLUSION Raised concentrations of sVCAM-1 and CRP are predictive of an increased risk of major adverse cardiovascular events six months after presentation with unstable angina and non-Q wave myocardial infarction. These findings suggest that the intensity of the vascular inflammatory process at the time of presentation is a determinant of clinical outcome in unstable coronary artery disease.

AIMS:Diabetes mellitus (DM) is associated with chronic endothelial dysfunction. Diabetic patients presenting with acute coronary syndromes have a worse prognosis than non-diabetics. An acute inflammatory reaction at the site of coronary plaque rupture and increased expression of surface and soluble cellular adhesion molecules (CAMs) are pathological features of acute coronary syndromes. We set out to characterize the expression of soluble CAMs in patients with and without diabetes presenting with unstable angina (UA) and non Q-wave myocardial infarction (NQMI). METHODS:Patients presenting with UA and NQMI had serum samples taken on presentation, after 72 h and then 3, 6 and 12 months after discharge. Levels of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and P-selectin were measured using an ELISA technique. RESULTS:We studied 15 diabetic patients and 15 age- and sex-matched non-diabetic patients presenting with either UA or NQMI. Levels of soluble E-selectin were elevated in the diabetic patients in comparison with the non-diabetic patients at all measured time points: 74 +/- 10 ng/ml vs. 47 +/- 3 ng/ml, P < 0.03 at t = 0 h, 55 +/- 5 ng/ml vs. 38 +/- 2 ng/ml, P < 0.02 at t = 72 h. However, levels of soluble P-selectin were lower in the diabetic cohort during follow-up: 134 +/- 15 ng/ml vs. 225 +/- 32 ng/ml, P < 0.02 at t = 3/12 and 112 +/- 8 ng/ml vs. 197 +/- 23 ng/ml, P < 0.02 at t = 6/12. There was no significant difference in levels of soluble ICAM-1 and VCAM-1 between diabetic and non-diabetic patients. CONCLUSIONS:Levels of soluble E-selectin are significantly elevated in diabetic patients presenting with UA and NQMI in comparison with non-diabetics. This finding may reflect enhanced endothelial activation which may contribute to the adverse prognosis of diabetic patients with acute coronary syndromes.

The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the occupancy of the internal and external pools of GPIIb/IIIa and platelet function following an abciximab bolus and infusion, 15 patients undergoing elective percutaneous transluminal coronary angioplasty were administered abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and TRAP-6 (20 microM)-activated samples (to expose the internal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhibition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupancy (range 82--99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 microM ADP (maximal, 11 +/- 2% of baseline), but less so to 5 microM TRAP-6 (maximal, 36 +/- 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappearance of abciximab from the platelet surface. Maximum inhibition of platelet function and receptor occupancy of the external pool of GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some internal receptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.

Background: Elevated levels of soluble cell adhesion molecules (sCAMs) have been reported in various coronary artery disease processes. The principle stimulus for expression of sCAMs is believed to he an inflamed atherosclerotic plaque within the coronary vessel. The relationship between levels of sCAMs in the coronary circulation and the peripheral circulation has not been defined. The primary aim of this study was to define the relationship between levels of sCAMs sampled from the systemic circulation and from the coronary circulation. We also set out to document the acute expression of soluble CAMs following coronary angioplasty with or without stent implantation. Methods: The coronary sinus Mas cannulated in patients undergoing LAD angioplasty. Samples were drawn from left coronary ostium (LCO) and coronary sinus (CS) and femoral vein simultaneously before, immediately after and 4 h after the PTCA procedure. Levels of sICAM-1, sVCAM-1. sE-selectin and sP-selectin were measured using ELISA technique. Results: 10 patients (7 male/3 female, 61 +/- 11 y) entered the study. There was no significant difference in the levels of sICAM-1. sVCAM-1, sE-selectin and sPselectin whether sampled from left coronary ostium, coronary sinus or femoral vein at all time points. There was no significant change in the acute expression of sICAM-1, sVCAM-1 and sE-selectin following coronary angioplasty. Levels of sP-selectin fell significantly during the PTCA procedure (142 +/- 7 ng/ml to 64 +/- 6 ng/ml, P < 0.001) but then rose again after 4 h and returned toward baseline levels at 24 h. Conclusion: Levels of soluble CAMs sampled In the systemic circulation directly reflect levels in the coronary circulation. Coronary angioplasty results in rapid fall in levels of sP-selectin which returns: to normal within 24 h following the procedure. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

OBJECTIVES We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery.BACKGROUND Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions.METHODS Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (LC normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls.RESULTS The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005).CONCLUSIONS Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively. (C) 2000 by the American College of Cardiology.