Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.

The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.

Arachidonic acid and docosahexaenoic acid supplementation increases coronary flow velocity reserve in Japanese elderly individuals.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important components of phospholipids and cell membranes. There has, however, been no clinical report on the direct effects of ARA and DHA on coronary circulation. OBJECTIVE: To evaluate the effects of ARA and DHA on coronary circulation using the measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography (TTDE). METHODS: A double-blind, placebo-matched study of 28 Japanese elderly individuals (19 men, mean age 65 years) conducted to compare the effects of polyunsaturated fatty acids (PUFA; ARA 240 mg/day, DHA 240 mg/day) and placebo on CFVR. Coronary flow velocity (CFV) of the left anterior descending coronary artery was measured at rest and during hyperaemia by TTDE to determine CFVR. RESULTS: There were no significant differences in CFV at rest or during hyperaemia in CFVR at baseline in the two groups (PUFA versus placebo 17 (7 SD) versus 16 (6), 62 (20) versus 59 (12), and 3.85 (1.04) versus 3.98 (0.83) cm/s, respectively). After three months' supplementation, CFV during hyperaemia was significantly higher in the PUFA than in the placebo group (73 (19) versus 64 (12) cm/s, p<0.01) although no significant difference was found between the two groups in CFV at rest (17 (7) versus 16 (4) cm/s). CFVR thus significantly increased after PUFA consumption (3.85 (1.04) versus 4.46 (0.95), p = 0.0023). CONCLUSION: Three months' supplementation of PUFA increased CFVR in Japanese elderly individuals, which suggests beneficial effects of PUFA on the coronary microcirculation.

Polymorphisms of norepinephrine transporter and adrenergic receptor alpha1D are associated with the response to beta-blockers in dilated cardiomyopathy.

Recent clinical trials have clearly demonstrated that the administration with beta-blockers decreases the mortality in the patients with chronic heart failure (CHF). However, significant heterogeneity exists in the effectiveness of beta-blockers among individual cases. We focused on 39 polymorphisms in 16 genes related to adrenergic system and investigated their association with the response to beta-blockers among 80 patients with CHF owing to idiopathic dilated cardiomyopathy. The polymorphisms of NET T-182C (P=0.019), ADRA1D T1848A (P=0.023) and ADRA1D A1905G (P=0.029) were associated with the improvement of left ventricular fractional shortening (LVFS) by beta-blockers. Furthermore, combined genotype analysis of NET T-182C and ADRA1D T1848A revealed a significant difference in LVFS improvement among genotype groups (P=0.011). These results suggest that NET (T-182C) and ADRA1D (T1848A and A1905G) polymorphisms are predictive markers of the response to beta-blockers. Genotyping of these polymorphisms may provide clinical insights into an individual difference in the response to the beta-blocker therapy in CHF.

Tissue Doppler-derived index of left ventricular filling pressure, E/E', predicts survival of patients with non-valvular atrial fibrillation.

OBJECTIVES: To investigate whether the ratio of early transmitral flow velocity (E) to early diastolic mitral annular velocity (E') predict prognosis in patients with non-valvular atrial fibrillation. METHODS: 230 patients with non-valvular atrial fibrillation were enrolled and studied. According to E/E' value, patients were divided into groups with lower (group A with E/E' 15) E/E'. RESULTS: During follow up (average 245 days), 21 (9.1%) deaths were documented. All cause death (15/90 (16.7%) v 6/140 (4.3%)), cardiac death (10 (11.1%) v 2 (1.4%)) and congestive heart failure (16 (17.8%) v 8 (5.7%)) were more common in group B than in group A (all p < 0.01). A Kaplan-Meier survival curve showed that the cumulative survival rate was significantly lower in group B than in group A (log rank p = 0.0013). By multivariate logistic regression analysis, E/E' (chi(2) = 4.47, odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.11, p = 0.03) and age (chi(2) = 6.45, OR 1.06, 95% CI 1.01 to 1.11, p = 0.02) were independent predictors of mortality. CONCLUSION: The Doppler-derived index of left ventricular filling pressure, E/E', is a powerful predictor of the clinical outcome of patients with non-valvular atrial fibrillation.

Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia.

OBJECTIVE: To examine the effects of microbubble destruction with ultrasound (MB) combined with bone marrow derived mononuclear cell transplantation (BMT) into ischaemic tissues in rat hind limb ischaemia. METHODS AND RESULTS: Unilateral hind limb ischaemia was surgically induced in Lewis rats. At postoperative day 7, rats were randomly divided into three groups: a vehicle treated group, an ultrasound treated group, and an MB treated group. MB treatment increased vascular endothelial growth factor mRNA as assessed by real time polymerase chain reaction (3.0-fold, p < 0.05). At four weeks, the MB group had increases in laser Doppler blood flow index (LDBFI; 1.2-fold, p < 0.05), angiographically detectable collateral vessels (angiographic score: 1.4-fold, p < 0.01), and capillary to muscle fibre ratio (1.4-fold, p < 0.01) in ischaemic limbs compared with the vehicle treated group. No differences were seen between the vehicle and ultrasound treated groups. Secondly, rats were allocated to vehicle treatment, BMT (5 x 10(6) cells/rat), or a combination of MB and BMT (MB+BMT) at seven days after hind limb ischaemia. BMT treatment significantly increased LDBFI, angiographic score, and capillary to muscle fibre ratio compared with vehicle treatment. Interestingly, MB+BMT treatment produced significantly greater LDBFI (1.2-fold, p < 0.01), angiographic score (1.5-fold, p < 0.01), and capillary to muscle fibre ratio (1.5-fold, p < 0.05) than BMT treatment alone. CONCLUSIONS: MB may be a useful technique to enhance BMT induced neovascularisation.

Relation between aortic stiffness and coronary flow reserve in patients with coronary artery disease.

OBJECTIVES: To investigate the relation between aortic stiffness and coronary flow reserve (CFR) in patients with coronary artery disease (CAD). DESIGN: Observational study. SETTING: Coronary care unit of a primary care hospital. PATIENTS: 192 consecutive patients who underwent coronary angiography. MAIN OUTCOME MEASURE: Brachial-ankle pulse wave velocity (ba-PWV), CFR, and severity of CAD. RESULTS: According to the angiographic findings, patients were divided into four subgroups: patients without significant stenosis (normal coronary artery (NCA) group, n = 28) and those with one vessel disease (1VD group, n = 92), two vessel disease (2VD group, n = 50), or three vessel disease (3VD group, n = 22). ba-PWV increased with the number of diseased vessels and was significantly correlated with the number of diseased vessels (NCA group v 1VD group v 2VD group v 3VD group: 1481 (252) v 1505 (278) v 1577 (266) v 1727 (347) cm/s, p < 0.001). CFR had a significant negative correlation with ba-PWV (r = -0.45, p < 0.0001). The diastolic to systolic velocity ratio obtained in 45 patients also was significantly correlated with ba-PWV (r = -0.35, p < 0.05). Multiple regression analysis showed that ba-PWV was an independent determinant of CFR (p < 0.01). CONCLUSIONS: Coronary flow is altered with aortic stiffening in patients with CAD. These results suggest one possible mechanism for recent reports that aortic stiffness is a key cardiovascular risk factor.

A case-control study of bronchial asthma associated with ulcerative colitis: role of airway microvascular permeability.

BACKGROUND: Recent attention has been devoted to the respiratory manifestations that may be associated with diseases of distant organs. The most prevalent and distinctive pattern of respiratory involvement in ulcerative colitis (UC) is airway inflammation. OBJECTIVE: This study was designed to examine the contribution of airway microvascular permeability to the pathophysiological association of asthma with UC. METHODS: Sputum induction and methacholine provocation test were performed in 27 asthmatic patients (15 without UC and 12 with UC), nine patients with UC and 15 normal controls. Inflammatory indexes, vascular endothelial growth factor (VEGF) levels in induced sputum, airway vascular permeability index and exhaled nitric oxide (NO) levels were examined in all subjects. RESULTS: The percentage of eosinophils and concentration of eosinophil cationic protein in induced sputum were similar in all four groups. Though exhaled NO levels were significantly higher in asthmatics with or without UC than in normal controls or UC patients, these levels were comparable in asthmatics with and without UC. VEGF levels in induced sputum and airway vascular permeability index were significantly higher in asthmatics without UC (VEGF: 1920 (990) pg/mL; airway vascular permeability index: 0.018 (0.008)) and asthmatics with UC (6570 (1000) pg/mL; 0.040 (0.006)) than in normal controls (950 (700) pg/mL; 0.009 (0.003)), whose levels were comparable to those of UC patients (900 (600) pg/mL; 0.011 (0.003)). In particular, these parameters were markedly increased in asthmatics with UC than in asthmatics without UC. VEGF level was significantly correlated with airway vascular permeability index in asthmatics with UC. Moreover, VEGF level and airway vascular permeability index was inversely correlated with degree of airway obstruction and airway hyper-reactivity to methacholine in these asthmatics. CONCLUSION: Airway microvascular hyper-permeability induced by VEGF may have a profound effect on airway function and can explain the heightened airway hyper-responsiveness characteristic of asthma associated with UC.

Effect of one or more co-morbid conditions on diagnostic accuracy of coronary flow velocity reserve for detecting significant left anterior descending coronary stenosis.

OBJECTIVE: To determine the effect of one or multiple co-morbid conditions on the diagnostic accuracy of coronary flow velocity reserve (CFVR) in a heterogeneous patient population. METHODS: CFVR was measured in the left anterior descending coronary artery (LAD) by transthoracic Doppler echocardiography (TTDE) in 318 consecutive patients before elective coronary angiography. CFVR was calculated as the average peak diastolic velocity during intravenous ATP infusion divided by baseline flow velocity. All patients underwent coronary angiography within 48 hours. Significant LAD stenosis was defined as > 50% luminal narrowing. Diagnostic accuracy of CFVR was analysed according to the type and number of risk factors that may adversely affect microvascular function. RESULTS: CFVR was measured in 309 patients, of whom 105 were found to have significant LAD stenosis based on coronary angiography. CFVR < 2.0 had a sensitivity of 86% and a specificity of 77% for predicting significant LAD stenosis. Left ventricular hypertrophy (LVH) was the only factor that significantly lowered diagnostic accuracy (61% with LVH v 84% without LVH, p < 0.001). Diagnostic accuracy was not affected by increasing number of risk factors. CONCLUSIONS: The diagnostic accuracy of CFVR by TTDE for detecting significant LAD stenosis remains high in a more clinically relevant population with multiple cardiovascular co-morbidities. Only the presence of LVH adversely affected diagnostic accuracy.

Oxidized phosphatidylcholine in alveolar macrophages in idiopathic interstitial pneumonias.

It has been suggested that oxidative stress plays a pathogenic role in idiopathic interstitial pneumonias. Macrophage- or neutrophil-derived oxidants seem to be important sources of oxidative stress in this group of inflammatory disorders. Recent experimental studies have revealed that oxidative injury during inflammation or apoptosis can change phosphatidylcholine of cell membrane into its oxidized form, which serves as a ligand for macrophage scavenger receptor CD36. Recently, we developed a monoclonal antibody against oxidized phosphatidylcholine. Using this novel antibody, we performed an immunohistochemical investigation to clarify the localization of oxidized phosphatidylcholine in lung tissues of idiopathic interstitial pneumonias and a relationship between oxidized phosphatidylcholine localization and CD36 expression. Lung specimens obtained from patients with desquamative (n = 8) or usual interstitial pneumonia (n = 15) were studied. Thirteen normal lung tissues were also examined as controls. Antibodies against oxidized phosphatidylcholine, CD36, epithelial cells, macrophages, and neutrophils were used as primary antibodies. The positive cell number was counted by computer-aided morphometry. While there were no oxidized phosphatidylcholine-positive cells in normal lungs, lungs of desquamative or usual interstitial pneumonia contained large numbers of oxidized phosphatidylcholine-positive cells in the alveolar spaces. Double-staining analysis revealed that most oxidized phosphatidylcholine-positive cells were macrophages. The oxidized phosphatidylcholine-positive cells were increased in association with the increase in the densities of macrophages (Rs = 0.87, p < 0.0001) and neutrophils (Rs = 0.89, p < 0.0001). Accumulated macrophages also showed distinct CD36 expression. These findings suggest that oxidative stress and the related product, oxidized phosphatidylcholine, play an important role in the pathophysiology of idiopathic interstitial pneumonias.

Angiotensin converting enzyme inhibitor prevents left ventricular remodelling after myocardial infarction in angiotensin II type 1 receptor knockout mice.

BACKGROUND: It is well known that angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 (AT1) receptor blockers (ARBs) prevent left ventricular (LV) remodelling after myocardial infarction (MI). However, it is still not clear whether inhibition of the AT1 receptor is enough to prevent LV remodelling after MI. OBJECTIVE: To elucidate the effects of ACE inhibitors that are not mediated by the AT1 receptor on LV remodelling, MI was experimentally induced in wild-type (WT-MI) mice and AT1 receptor knockout (KO-MI) mice. METHODS: Mice were divided into six groups: WT-control, KO-control, WT-MI, KO-MI, WT-MI treated with an ACE inhibitor, and KO-MI treated with an ACE inhibitor. Four weeks after MI, cardiac function was assessed by Doppler echocardiography and non-infarcted myocardial mRNA expression by northern blot analysis. RESULTS: Cardiac function decreased significantly in the MI groups compared with the sham operated groups. Additionally, in the MI groups end diastolic dimension, E wave velocity, the ratio of peak velocity of E wave to A wave, deceleration rate of E wave, and mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and collagens I and III increased significantly compared with the sham groups. LV remodelling after MI was prevented in KO-MI mice compared with WT-MI mice. ACE inhibitor administration significantly attenuated progressive LV remodelling in both WT and KO-MI groups. CONCLUSION: ACE inhibitors can prevent the LV remodelling process that accompanies cardiac dysfunction after MI, even in AT1 KO mice. These findings suggest that ACE inhibitors prevent LV remodelling after MI by mechanisms other than inhibition of angiotensin AT1 receptor mediated effects.

Intravenous myocardial contrast echocardiography predicts regional and global left ventricular remodelling after acute myocardial infarction: comparison with low dose dobutamine stress echocardiography.

OBJECTIVE: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE). METHODS: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2-4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months' follow up. Percentage increase in LV end diastolic volume (%DeltaEDV) was also calculated. RESULTS: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %DeltaEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%DeltaEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72). CONCLUSION: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling.

Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction.

OBJECTIVE: To examine the effects of eplerenone, a selective aldosterone blocker, on cardiac function after myocardial infarction (MI) and myocardial remodelling related transcriptional factors and mRNA expression in non-infarcted myocardium. METHODS: MI was induced by ligation of the coronary artery in Wistar rats. Rats were randomly assigned to a vehicle treated group or an eplerenone treated group (100 mg/kg/day). RESULTS: At four weeks after MI, left ventricular (LV) end diastolic pressure, LV weight, and LV end diastolic dimension were increased in MI rats. Eplerenone significantly reduced the increase in LV end diastolic pressure, LV weight, and LV end diastolic dimension. In the MI rats the decreased ejection fraction indicated systolic dysfunction and the increased E wave to A wave ratio and E deceleration rate indicated diastolic dysfunction. Eplerenone significantly attenuated this systolic and diastolic dysfunction. Myocardial interstitial fibrosis, transcriptional activities of activator protein 1 and nuclear factor kappaB, and mRNA expression of monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, atrial natriuretic peptide, brain natriuretic peptide, and collagen types I and III were significantly increased at four weeks after MI. Eplerenone significantly attenuated interstitial fibrosis and suppressed transcriptional activity and mRNA expression of these genes. CONCLUSIONS: When administered after MI, eplerenone prevents cardiac remodelling accompanied by systolic and diastolic dysfunction and inhibits abnormal myocardial transcriptional activities and gene expression.

Left ventricular hypertrophy and angiotensin II receptor blocking agents.

Angiotensin II plays a significant role in cell growth and proliferation in model systems and in humans. Numerous studies have shown that left ventricular hypertrophy (LVH) increases the risk of coronary heart disease, congestive heart failure, stroke or transient ischemic attack; all-cause deaths, and sudden death. The use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has provided beneficial effects on LVH regression and on cardiac remodeling in the presence of hypertension and heart failure. The new class of ARBs appears to provide cardioprotective effects that are similar to those of the ACE inhibitors. Most of the beneficial effects provided by these agents appear to be related to a more complete blockade of the angiotensin II type 1 (AT1) receptor. However, costimulation of the angiotensin II type 2 (AT2) receptor appears to increase nitric oxide and thus causes some bradykinin-like effects. Evidence for the role of angiotensin II in promoting LVH as well as abnormal regulation of the angiotensin II signal transduction pathways in model systems and in humans has been reviewed. Secondly, the mechanisms for the beneficial effects of angiotensin II receptor blockers studied in model systems and in humans, including possible involvement in the formation of reactive oxygen species by mononuclear cells, are presented. Finally, results from large-scale interventions such as the Losartan Intervention For Endpoint reduction (LIFE) study, as well as an overview of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial involving the use of ARB in high-risk patients, are presented.

Acute improvement of atrial mechanical stunning after electrical cardioversion of persistent atrial fibrillation: comparison between biatrial and single atrial pacing.

OBJECTIVE: To evaluate the acute effects of atrial pacing at different pacing sites on mechanical stunning after cardioversion of atrial fibrillation (AF). SETTING: Tertiary referral centre. PATIENTS: 20 patients with persistent AF were studied. INTERVENTIONS: Spontaneous echo contrast (SEC), left atrial appendage emptying velocity (LAAEV), and left atrial appendage emptying fraction (LAAEF) were assessed by transoesophageal echocardiography (TOE) during AF, after conversion to sinus rhythm, and during atrial pacing from the right atrial appendage, left lateral atrium, and both atria simultaneously. Transmitral inflow velocity of the atrial wave (TMIF-A) by TOE and the maximum P wave duration in 12 lead ECG were also measured during sinus rhythm and atrial pacing. MAIN OUTCOME MEASURES: Comparison of atrial mechanical function and P wave duration in 12 lead ECG during atrial pacing from different sites after cardioversion of AF. RESULTS: Compared with sinus rhythm, atrial pacing at 80 beats/min increased LAAEV from mean (SD) 14.6 (10.1) to 33.4 (19.8) cm/s (p = 0.001), LAAEF from 13.8 (8.5) to 32.1 (11.2)% (p < 0.001), and TMIF-A from 24.6 (11.9) to 45.6 (21.0) cm/s (p < 0.001) and reduced SEC grade from 2.6 (1.0) to 1.6 (0.9) (p < 0.001). These effects had a positive force-frequency relation. Biatrial pacing produced the shortest P wave duration and resulted in the most significant improvement in atrial function (LAAEV, 33.2 (19.3) v 53.7 (23.9) cm/s, p = 0.0001; LAAEF, 31.9 (11.1) v 46.2 (12.6)%, p < 0.0001; TMIF-A, 37.7 (18.3) v 54.1 (21.2) cm/s, p < 0.001; SEC grade, 1.4 (1.1) v 0.8 (0.9), p = 0.001, right atrial appendage versus biatrial pacing). CONCLUSIONS: Atrial pacing at increased rates can improve atrial mechanical function after cardioversion of persistent AF. Biatrial pacing may be the most effective technique to reverse atrial mechanical stunning.

Early detection of cardiac involvement in patients with sarcoidosis by a non-invasive method with ultrasonic tissue characterisation.

OBJECTIVES: To clarify the value of cycle dependent variation of myocardial integrated backscatter (CV-IB) analysis, which non-invasively measures acoustic properties of the myocardium, for early detection of cardiac involvement in patients with sarcoidosis. METHODS: The study population consisted of 22 consecutive patients with biopsy proven sarcoidosis who did not have any abnormal findings on conventional two dimensional echocardiogram. Cardiac sarcoidosis was diagnosed by radionuclide testing including thallium-201 scintigraphy, gallium-67 scintigraphy, and cardiac fluorine-18-deoxyglucose positron emission tomography. The magnitude and delay of the CV-IB were analysed in the basal mid septum and the basal mid posterior wall of the left ventricle of all patients. RESULTS: The patients were divided into two groups: 8 patients with cardiac involvement and 14 patients without cardiac involvement. In the basal septum, a major reduction in the magnitude (mean (SD) 1.8 (4.4) v 6.6 (1.3), p = 0.012) and an increase in the time delay (1.3 (0.5) v 1.0 (0.1), p = 0.038) of CV-IB were observed in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. The sensitivity for detecting cardiac involvement was such that the magnitude of CV-IB in the basal septum discriminated 75% of patients with cardiac sarcoidosis from those with non-cardiac sarcoidosis, whereas two dimensional echocardiographic parameters did not discriminate between these two groups. CONCLUSIONS: The CV-IB is decreased in the basal septum in patients with cardiac sarcoidosis even in the absence of two dimensional echocardiographic abnormalities. Analysis of CV-IB may be a useful method to detect early myocardial involvement in patients with sarcoidosis.

Implications of plasma concentrations of adiponectin in patients with coronary artery disease.

OBJECTIVE: To investigate whether concentrations of plasma adiponectin constitute a significant coronary risk factor, with particular focus on the relation between plasma concentrations of adiponectin and the development of acute coronary syndrome (ACS). SUBJECTS AND METHODS: Plasma concentrations of adiponectin were measured in 123 patients with coronary artery disease (CAD) and in 17 control participants. Patients were divided into three groups according to condition type: acute myocardial infarction (AMI) group (n = 59), unstable angina pectoris (UAP) group (n = 28), and stable angina pectoris (SAP) group (n = 36). RESULTS: Plasma concentrations of adiponectin correlated negatively with body mass index (r = -0.18, p < 0.05), serum triglyceride (r = -0.25, p < 0.01), and fasting glucose concentrations (r = -0.21, p < 0.05), but correlated positively with age (r = 0.26, p < 0.01), high density lipoprotein cholesterol concentrations (r = 0.35, p < 0.01), and low density lipoprotein particle size (r = 0.37, p < 0.01). Plasma concentrations of adiponectin in patients with ACS, in both the AMI and UAP groups, were significantly lower than those in patients with SAP and in the control group (ACS, 6.5 (3.0) microg/ml; SAP, 11.3 (5.9) micro g/ml; control 12.8 (4.3) microg/ml; p < 0.01). Additionally, plasma concentrations of adiponectin in patients with CAD (7.9 (4.6) microg/ml, p < 0.01) were significantly lower than in the control group. There were, however, no significant differences between patients with SAP and the control group (p = 0.36). Multiple logistic regression analysis showed that smoking, fasting glucose concentration, and low log adiponectin concentration correlated independently with the development of an ACS. CONCLUSIONS: The findings suggest that measurement of plasma concentrations of adiponectin may be of use for assessing the risk of CAD and may be related to the development of ACS.