Epicardial and pericardial adipose tissue: physiological importance and role of imaging techniques.

Epicardial adipose tissue (EAT) is becoming a cardiovascular risk factor. Multiple imaging techniques are used to measure it, each one with its prons and cons. We will review the literature realizing that there is still a lot of work that needs to be done.

Investigating the signal transduction pathways underlying remote ischemic conditioning in the porcine heart.

BACKGROUND: The mechanism underlying remote ischemic conditioning (RIC) remains unclear. We investigated whether RIC protects the heart through the activation of the adenosine receptor and the PI3K-Akt pathway at the onset of myocardial reperfusion. METHODS AND RESULTS: Domestic pigs (27-35 kg) were subjected to in situ left anterior descending coronary artery ischemia (60 min) followed by reperfusion (180 min) and randomised to the following: (1) Control- No additional intervention; (2) Remote ischemic preconditioning (RIPC)- Four-5 min cycles of lower limb ischemia/reperfusion were administered prior to myocardial ischemia; (3) RIPC + Wort or 8-SPT: Wortmannin (Wort 20 µg/kg, a PI3K inhibitor) or 8-sulfophenyltheophylline (8-SPT 10 mg/kg, an adenosine receptor inhibitor) were administered intravenously 30 s before myocardial reperfusion to RIPC-treated animals; (4) Remote ischemic perconditioning (RIPerC)--Four-5 min cycles of lower limb ischemia/reperfusion were applied 1 min before myocardial reperfusion; (5) RIPerC + Wort or 8-SPT: Wort or 8-SPT were given 30 s before myocardial reperfusion to RIPerC-treated animals. Both RIPC and RIPerC reduced myocardial infarct size (13.3 ± 2.2% with RIPC, 18.2 ± 2.0% with RIPerC versus 48.8 ± 4.2% in control:P < 0.05:N ≥ 5/group). Wortmannin abolished the infarct-limiting effects of RIPC (33.2 ± 6% with RIPC + Wort versus 13.3 ± 2.2% with RIPC:P < 0.05:N ≥ 5/group) but not RIPerC (18.0 ± 3.4% with RIPerC + Wort versus 18.2 ± 2.0% with RIPerC:P > 0.05:N ≥ 5/group). 8-SPT did not influence the infarct-limiting effects of either RIPC or RIPerC. Western blot analysis confirmed Wortmannin-sensitive PI3K and Akt activation at myocardial reperfusion in RIPC-treated hearts. CONCLUSIONS: In the porcine heart, both RIPC and RIPerC both reduce myocardial infarct size and with RIPC but not RIPerC this cardioprotective effect is associated with the activation of the PI3K-Akt pathway at reperfusion.

Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages.

Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.

Incremental predictive value of carotid intima-media thickness to arterial stiffness for impaired coronary flow reserve in untreated hypertensives.

Coronary microcirculation is disturbed in patients with arterial hypertension. Carotid intima-media thickness (IMT) and arterial stiffness are markers of subclinical atherosclerosis with prognostic significance. We investigated whether the combination of increased carotid IMT and arterial stiffness has a greater predictive value for the presence of impaired coronary flow reserve (CFR) than each index alone in never-treated hypertensives. We studied 110 untreated patients (age: 54.5+/-12 years) with newly diagnosed arterial hypertension. We measured (1) carotid-to-femoral artery pulse wave velocity (PWV), (2) carotid IMT and (3) CFR by means of color-guided Doppler echocardiography after adenosine infusion. Among other confounders, arterial stiffness and IMT were independent determinants of CFR (coefficient B=-0.146 and B=-0.006, P<0.05). Arterial stiffness and IMT had an incremental value for the determination of CFR when added to a model including other confounders (chi(2) change=4.423, P for change=0.038 after addition of IMT; and chi(2) change=5.369, P for change=0.020 after addition of PWV). Receiver operating curve analysis showed that PWV>10.2 m s(-1) and IMT>1 mm were the optimal cutoff values to predict a CFR<2.5. Patients with IMT>1 mm, PWV>10.2 m s(-1) or their combination had an odds ratio of 3.5, 5.0 and 11.2, P<0.05, for a CFR<2.5, respectively. The combination of increased carotid IMT and arterial stiffness has a greater predictive value for impaired CFR than each index alone in never-treated hypertensives.

Hypertension and paroxysmal atrial fibrillation: a novel predictive role of high sensitivity C-reactive protein in cardioversion and long-term recurrence.

The role of inflammation in maintenance of paroxysmal atrial fibrillation (PAF) in patients with hypertension and no other heart disease has not been fully elucidated yet. We investigated the association of various inflammatory markers with cardioversion and recurrence of PAF in patients with hypertension. We studied 75 patients (44 male, mean age 67.9+/-9.9 years) with PAF (duration from onset of symptoms<24 h) secondary to hypertension. None had heart failure or any other ongoing inflammatory process. All patients received anticoagulation and intravenous amiodarone for cardioversion. High sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumour necrosis factor (TNF)-alpha were measured on admission and 48 h later. By 48 h from admission 61/75 patients (81.3%) regained sinus rhythm (cardioverted), whereas 14/75(18.7%) remained in AF (non-cardioverted). hsCRP, IL-6 and TNF-alpha serum levels on admission were similar between groups. hsCRP at 48 h was the most significant factor correlated with cardioversion outcome (OR: 0.06, 95% CI: 0.01-0.47, P=0.008). During a 1-year follow-up, AF recurred in 28/61(45.9%) patients. The strongest factor associated with AF recurrence was hsCRP at 48 h > or =2.27 mg l(-1) (hazard ratio: 6.2, 95% CI: 2.2-17.6, P=0.001). hsCRP at 48 h after admission correlates with cardioversion outcome and may predict long-term AF recurrence.

Remote postconditioning is more potent than classic postconditioning in reducing the infarct size in anesthetized rabbits.

PURPOSE: Postconditioning confers protection to the heart after a potentially lethal episode of prolonged ischemia. There is evidence that it may also be protective when applied at a distal artery. In the present study, we sought to determine whether remote postconditioning within the heart (local) or outside the heart (distal) is effective in salvaging the ischemic heart in vivo and to compare its effect with that of the classic postconditioning. METHODS: Twenty seven open chest New Zealand white anesthetized male rabbits were divided into four groups and were exposed to 30 min regional myocardial ischemia (isc), after ligation of a prominent coronary artery, followed by 3 h reperfusion (rep) after releasing the snare. Control group (n = 7) was subjected to no additional interventions, postC group (n = 6) was subjected to four cycles of 1 min isc/1 min rep of the same coronary artery at the beginning of reperfusion, remote local postC group (n = 7) to four cycles of 1 min isc/1 min rep of another coronary artery 30 s before the end of index isc and remote distal postC group (n = 7) to four cycles of 1 min isc/1 min rep of another (carotid) artery again 30 s before the end of index isc. Infarct size (I) and area at risk (R) were delineated with the aid of TTC staining and green fluorescent microspheres respectively and their ratio was expressed in percent (%I/R). RESULTS: Remote local and remote distal postC reduced the % I/R ratio (17.7 +/- 1.7% and 18.4 +/- 1.6%, respectively vs 47.0 +/- 2.5% in the control group, P < 0.01). Classic PostC had an intermediate protective effect (33.1 +/- 1.7%, P < 0.05 vs all the other groups). CONCLUSION: Remote postconditioning consisted of 1 min isc/1 min rep protects the ischemic rabbit heart in vivo, independently of the site of the remote artery. This intervention seems to confer a stronger protection than the classic postconditioning.

Molecular diagnosis of the viral component in cardiomyopathies: pathophysiological, clinical and therapeutic implications.

BACKGROUND: Myocarditis is defined as the inflammation of myocardium associated with cardiac dysfunction. Despite this clear-cut definition, diagnosis and etiologic treatment continue to create considerable debate. Viral infections are frequent causes of myocarditis and there is evidence that persistent viral infection is associated with poor prognosis in different subtypes of cardiomyopathy. OBJECTIVE: To review methods for diagnosis of viral myocarditis and present the use of polymerase chain reaction (PCR)-based protocols for evaluating viral infection in myocarditis/cardiomyopathies. METHODS: A review of published literature. RESULTS/CONCLUSION: There is increasing evidence that PCR-based protocols can provide reliable molecular evidence for the presence of viral infection in myocardium. Thus application of molecular techniques will allow collection and analysis of more information on the epidemiology of viral cardiomyopathies, patient risk stratification and appropriate medical treatment.

Usefulness of inflammatory and haemostatic markers to predict short-term risk for death in middle-aged ischaemic stroke patients.

OBJECTIVES: There is increasing evidence that inflammation and hypercoagulability play an important role in the pathophysiology of acute ischaemic stroke. We examined the in-hospital prognostic value on mortality of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), fibrinogen and D-dimer in middle-aged ischaemic stroke patients. MATERIALS AND METHODS: We recruited 231 consecutive patients <66 years with acute ischaemic stroke. CRP, TNF-alpha, fibrinogen and D-dimer levels were determined within 12 h from admission. RESULTS: Fifteen (6.5%) patients died during hospitalization. CRP, fibrinogen and D-dimer levels were significantly higher in patients who died compared with those who survived but only CRP and fibrinogen were independently associated with death, after adjusting for various confounding factors. For 1 mg/l increase in CRP there was a 20% higher risk of dying while for 10 mg/dl increase in fibrinogen the additive risk was 18%. CRP levels >18 mg/l and fibrinogen levels >490 mg/dl were the optimal points that discriminated those who died from the rest. CONCLUSIONS: CRP and fibrinogen levels can predict independently the risk of early death in middle-aged ischaemic stroke patients emphasizing the role of inflammation and coagulation in the evolution of ischaemic stroke.

Clinical and prognostic implications of self-rating depression scales and plasma B-type natriuretic peptide in hospitalised patients with chronic heart failure.

BACKGROUND: Depression is common among patients with chronic heart failure (CHF) and has been independently associated with a poorer prognosis. PURPOSE: This study evaluated the clinical and prognostic value of depression scales (Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (Zung SDS)) along with plasma B-type natriuretic peptide (BNP) in CHF. METHODS: 155 hospitalised CHF patients (ejection fraction 26.9% (SD 6.4%)) were studied by depression (BDI, Zung SDS) and functional questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI)), BNP and 6-minute walk test (6MWT). Patients were followed for 6 months for cardiovascular events, including death from any cause or rehospitalisation for CHF decompensation. RESULTS: Seventy-six (49%) patients with depressive symptoms, as estimated by both scales, had significantly lower DASI and KCCQ scores (13.2 (SD 9.9) vs 23.6 (SD 13.0) and 26.6 (SD 15.0) vs 45.0 (SD 17.0), respectively; p<0.001), higher BNP (921 (SD 889) vs 439 (SD 267) pg/ml, p = 0.001) and reduced 6MWT (270 (SD 130) vs 337 (SD 133); p<0.001). According to logistic regression analysis, Zung SDS and BNP were independently associated with adverse clinical outcomes; values of Zung SDS >or=40 and of BNP >or=290 pg/ml predicted future events with a sensitivity of 82% and 94% and a specificity of 45% and 46%, respectively. The combination of Zung SDS plus BNP had an additive prognostic value, predicting events with a sensitivity of 77% and a specificity of 70% (event-free survival: Zung <40 and BNP <290 pg/ml; 170 (SD 9) days; Zung >or=40 and BNP <290 pg/ml, 159 (SD 14) days; Zung <40 and BNP >or=290 pg/ml, 118 (SD 15) days; Zung >or=40 and BNP >or=290 pg/ml, 73 (SD 8) days, p<0.001). CONCLUSIONS: CHF patients with depressive symptoms have impaired physical activity, associated with excessive neurohormonal activation. Among the studied scales, Zung SDS seemed to independently predict clinical outcome, especially in patients with increased plasma BNP concentration. Hence, the combination of those two modalities provides a practical means for risk stratification in CHF.

Ischemic but not mechanical preconditioning attenuates ischemia/reperfusion induced myocardial apoptosis in anaesthetized rabbits: the role of Bcl-2 family proteins and ERK1/2.

OBJECTIVE: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study aimed first, to examine whether short mechanical stretch with acute pressure overload (MPC), which has been shown to reduce infarct size after ischemia/reperfusion, mimics IPC in attenuating myocardial apoptosis and second, to evaluate whether induced cardioprotection involves modulation of the expression of the Bcl-2 family proteins and phosphorylation of prosurvival kinases. METHODS AND RESULTS: A model of anaesthetized rabbit was used and the preconditioning protocol included one cycle of short ischemia/reperfusion, or short mechanical stretch with acute pressure overload. Preconditioning stimuli were equally effective in reducing the infarct size, determined after 4 h reperfusion. However, IPC but not MPC attenuated myocardial apoptosis. IPC restored the decreased expression of Bcl-2 and Bcl-xL observed in hearts subjected to ischemia and reperfusion only. Bax levels were not different among the groups. ERK1/2 were activated during reperfusion in both IPC and MPC groups. CONCLUSIONS: The data provide further evidence that apoptosis and necrosis contribute independently to infarct size after ischemia and reperfusion. Inhibition of the myocardial apoptotic processes by IPC may involve modulation of the expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL. ERK1/2 may be involved in the inhibition of both apoptosis and necrosis.

Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning?

AIM: To investigate whether remote ischaemic preconditioning (RIPC) can attenuate the inflammatory response and enzyme leakage that can occur after uncomplicated routine percutaneous coronary intervention (PCI). METHODS: 41 consecutive normotensive patients with stable angina and single-vessel disease were assigned to be exposed to RIPC (n = 20) or not (control group; n = 21) before elective PCI with stent implantation. RIPC was induced by three cycles of 5-min ischaemia-reperfusion of both upper limbs (inflation/deflation of blood pressure cuff). C reactive protein (CRP), creatine phosphokinase (CK), CK cardiac isoenzyme (CK-MB) and troponin I (TNI) were serially measured for 48 h. RESULTS: No difference in baseline values was observed between the groups. The CRP rose significantly (p<0.001) and at 48 h was similarly increased (>fourfold) in both groups (15.7 (2.6) v 14.0 (3.3) mg/l, RIPC v control; p = NS). However, sub-group analysis on the basis of statin use showed that the highest rise was in the group of patients with RIPC not taking statins and was significantly greater than in patients with RIPC taking statins (23.8 (3.71) v 11.4 (3.0) mg/l, respectively, p<0.01). Both CK-MB and TNI leakage were raised (slightly but significantly) after PCI in controls at 24 h compared with baseline values. However, this small rise was significantly worse after RIPC (CK-MB, 1.33 (0.27) v 3.57 (0.97) ng/ml, p<0.01; TNI, 0.255 (0.059) v 0.804 (0.232) ng/ml, p<0.05, respectively at 24 h). The increase was more marked in the RIPC subgroup not taking statins. CONCLUSIONS: RIPC does not reduce, but exacerbates, the enzyme and TNI release from the heart after single-vessel angioplasty with stent. Furthermore, the increased circulating CRP remains raised. It seems that there is an enhanced inflammatory response after RIPC in the absence of statin treatment.

Type II diabetes does not prevent the recruitment of collateral vessels and the normal reduction of myocardial ischaemia on repeated balloon inflations during angioplasty.

OBJECTIVE: To test whether type II diabetes prevents the recruitment of collaterals and the normal reduction of myocardial ischaemia on repeated balloon inflations during coronary angioplasty. METHODS: Two groups of patients were studied. A collateral circulation group consisted of 56 patients, 18 diabetic and 38 non-diabetic. All underwent a minimum of three balloon inflations. A pressure guide wire was used for the measurement of coronary wedge pressure (mm Hg). The angioplasty protocol was repeated in another group of 57 patients (myocardial ischaemia group) using both surface and intracoronary ECGs to assess myocardial ischaemia. RESULTS: In diabetic patients, mean (SD) coronary wedge pressure was 35 (12) mm Hg during the first balloon inflation, 39 (15) mm Hg during the second (p < 0.05 v first inflation), and 42 (17) mm Hg during the third (p < 0.05 v first inflation); in non-diabetic patients the respective values were 36 (16), 37 (16), and 37 (16) mm Hg (F = 4.73, p = 0.01). The ratio of coronary wedge pressure to mean arterial pressure in diabetic patients in the three balloon inflations was 0.33 (0.11), 0.36 (0.13), and 0.39 (0.15), respectively (p < 0.05 v the first inflation); and in non-diabetic patients it was 0.33 (0.15), 0.34 (0.15), and 0.35 (0.15) (F = 1.92, p = 0.15). In the diabetic group the response was independent of the type of treatment. No difference between diabetic and non-diabetic patients was observed in the normal reduction of myocardial ischaemia on repeated balloon inflations. CONCLUSIONS: Type II diabetes does not prevent the recruitment of collateral vessels and the normal reduction of myocardial ischaemia on repeated balloon inflations during coronary angioplasty in single vessel disease, regardless of the type of antidiabetic treatment.

A glossary of circulating cytokines in chronic heart failure.

Recent studies have emphasized the importance of biologically active molecules, termed cytokines, in the development and progression of the syndrome of chronic heart failure. This article summarizes a glossary of major cytokines and other cytokine-related inflammatory factors implicated in the pathophysiology of chronic heart failure, describing the source of their synthesis and factors regulating their secretion and analyzing their biologic effects on the cardiovascular system.

Heart failure in beta thalassemia: a 5-year follow-up study.

PURPOSE: To evaluate the survival of patients with beta thalassemia and heart failure who were treated with iron chelation therapy. SUBJECTS AND METHODS: Fifty-two consecutive patients with beta thalassemia and heart failure were followed in a prospective 5-year study. All patients underwent a full clinical examination with chest radiograph, electrocardiogram, and echocardiographic investigation performed at 6-month intervals or when a new symptom developed. RESULTS: Of the 52 patients (mean [+/- SD] age, 24 +/- 5 years), 25 (48%) survived 5 years after the onset of heart failure. Forty-three patients had left-sided heart failure, and 9 had right-sided heart failure. Those with left-sided heart failure were younger at presentation with heart failure (22 +/- 4 years vs. 31 +/- 6 years; P <0.001), had lower ejection fractions (36% +/- 9% vs. 64% +/- 10%; P <0.001), and had a lower mean serum ferritin level (3355 +/- 1241 ng/mL vs. 6,397 +/- 1,613 ng/mL; P <0.001). CONCLUSION: The 5-year survival rate in patients with beta thalassemia with heart failure was greater than previously reported. There are clinical characteristics that may make patients more likely to develop left- or right-sided heart failure.

Synthesis and study of a cyclic angiotensin II antagonist analogue reveals the role of pi*--pi* interactions in the C-terminal aromatic residue for agonist activity and its structure resemblance with AT(1) non-peptide antagonists.

The novel amide linked Angiotensin II (ANG II) cyclic analogue cyclo(3, 5) -[Sar(1)-Lys(3)-Glu(5)-Ile(8)] ANG II (18) has been designed, synthesized and bioassayed in anesthetized rabbits. The constrained cyclic analogue with a lactam amide bridge linking a Lys-Glu pair at positions 3 and 5 and possessing Ile at position 8, was synthesized by solution procedure using the maximum protection strategy. This analogue was found to be inhibitor of Angiotensin II. NMR spectroscopy coupled with computational analysis showed clustering between the side chains of the key aminoacids Tyr(4)-His(6)-Ile(8) similar to that observed with ANG II. The obtained data show that only pi*--pi* interactions observed in ANG II or its superagonist Sar(1) [ANG II] are missing. Therefore, it can be concluded that these interactions are essential for agonist activity. Conformational analysis comparisons between AT(1) antagonists losartan, eprosartan and irbesartan with C-terminal segment of cyclic compound 18 revealed structural similarities.

Dobutamine echocardiographic study in patients with nonischemic dilated cardiomyopathy and prognostically borderline values of peak exercise oxygen consumption: 18-month follow-up study.

OBJECTIVES: We sought to study the prognostic value of dobutamine echocardiography in patients with nonischemic dilated cardiomyopathy (DCM) and prognostically borderline values of peak oxygen consumption (VO2max) during exercise. BACKGROUND: Changes in echocardiographic variables assessed by dobutamine echocardiography can be used to evaluate the functional status of patients with chronic heart failure (CHF) and DCM. METHODS: In 27 consecutive patients (mean age 55 +/- 15 years) with VO2max values between 10 and 14 ml/kg body weight per min, a low infusion rate (10 microg/kg per min) dobutamine echocardiographic test was performed. The induced changes in echocardiographic variables were measured, and an 18-month follow-up study was done. RESULTS: At the end of the protocol, 9 patients (group I) had died from cardiac reasons, whereas the remaining 18 patients (group II) survived. After dobutamine infusion, the left ventricular end-systolic diameter (LVESD) was smaller in group II (6.22 +/- 0.94 cm) than in group I (6.99 +/- 0.76 cm; p < 0.05), whereas end-systolic wall stress (ESWS) was higher in group I (1030.66 +/- 193.98 g/cm2) than in group II (691.57 +/- 297.06 g/cm2; p < 0.05). The changes in LVESD and ESWS were greater in group I (0.75 +/- 0.36 cm and 463.11 +/- 159.87 g/cm2, respectively) than in group II (-0.04 +/- 0.36 cm and 83.16 +/- 291.74 g/cm2, respectively; p < 0.01 for both). CONCLUSIONS: In the "gray" zone of VO2max, dobutamine echocardiography seems to be a valuable prognostic indicator in patients with CHF and DCM.

Physical training reduces peripheral markers of inflammation in patients with chronic heart failure.

AIMS: Previous studies have shown an abnormal expression of cellular adhesion molecules and cytokines in chronic heart failure, which may be related to endothelial dysfunction characterizing this syndrome. Our study investigates the effects of physical training on serum activity of some peripheral inflammatory markers associated with endothelial dysfunction, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with chronic heart failure. METHODS AND RESULTS: Serum levels of GM-CSF, MCP-1, sICAM-1 and sVCAM-1 were determined in 12 patients with stable chronic heart failure (ischaemic heart failure: 6/12, dilated cardiomyopathy: 6/12, New York Heart Association: II-III, ejection fraction: 24+/-2%) before and after a 12-week programme of physical training in a randomized crossover design. In addition, the functional status of chronic heart failure patients was evaluated by using a cardiorespiratory exercise stress test to measure peak oxygen consumption. Physical training produced a significant reduction in serum GM-CSF (28+/-2 vs 21+/-2 pg. ml(-1), P<0.001), MCP-1 (192+/-5 vs 174+/-6 pg. ml(-1), P<0.001), sICAM-1 (367+/-31 vs 314+/-29 ng. ml(-1), P<0.01) and sVCAM-1 (1247+/-103 vs 1095+/-100 ng. ml(-1), P<0.01) as well as a significant increase in peak oxygen consumption (14.6+/-0.5 vs 16.5+/-0.5 ml. kg(-1)min(-1), P<0.005). A significant correlation was found between the training-induced improvement in peak oxygen consumption and percentage reduction in soluble adhesion molecules sICAM-1 (r=-0.72, P<0.01) and sVCAM-1 (r=-0.67, P<0.02). CONCLUSION: Physical training affects beneficially peripheral inflammatory markers reflecting monocyte/macrophage-endothelial cell interaction. Training-induced improvement in exercise tolerance is correlated with the attenuation of the inflammatory process, indicating that inflammation may contribute significantly to the impaired exercise capacity seen in chronic heart failure.