Matrix Metalloproteinase-2 Inhibition in Acute Ischemia-Reperfusion Heart Injury-Cardioprotective Properties of Carvedilol.

Matrix metalloproteinase 2 (MMP-2) is activated in hearts upon ischemia-reperfusion (IR) injury and cleaves sarcomeric proteins. It was shown that carvedilol and nebivolol reduced the activity of different MMPs. Hence, we hypothesized that they could reduce MMPs activation in myocytes, and therefore, protect against cardiac contractile dysfunction related with IR injury. Isolated rat hearts were subjected to either control aerobic perfusion or IR injury: 25 min of aerobic perfusion, followed by 20 min global, no-flow ischemia, and reperfusion for 30 min. The effects of carvedilol, nebivolol, or metoprolol were evaluated in hearts subjected to IR injury. Cardiac mechanical function and MMP-2 activity in the heart homogenates and coronary effluent were assessed along with troponin I content in the former. Only carvedilol improved the recovery of mechanical function at the end of reperfusion compared to IR injury hearts. IR injury induced the activation and release of MMP-2 into the coronary effluent during reperfusion. MMP-2 activity in the coronary effluent increased in the IR injury group and this was prevented by carvedilol. Troponin I levels decreased by 73% in IR hearts and this was abolished by carvedilol. Conclusions: These data suggest that the cardioprotective effect of carvedilol in myocardial IR injury may be mediated by inhibiting MMP-2 activation.

Cardiac arrest during percutaneous coronary intervention in a patient 'resistant' to clopidogrel - successful 50-minute mechanical chest compression.

We report a case of 72-year-old female patient with end-stage chronic kidney disease, undergoing percutaneous coronary intervention (PCI) that resulted in a cardiac arrest caused by a thrombus mediated flow limitation in the left coronary artery. With mechanical cardiopulmonary resuscitation (CPR) PCI of the left main artery was performed successfully during 50 min cardiac arrest. The patient was discharged from the hospital without compromising cardiac function and neurological deficits.

Serum levels of interleukin-6, interleukin-10 and C-reactive protein in patients with myocardial infarction treated with primary angioplasty during a 6-month follow-up.

INTRODUCTION: Recent studies indicate that inflammatory and immune factors are involved in the post-infarction cardiac remodeling. OBJECTIVES: We evaluated serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and C-reactive protein (CRP) in patients with acute coronary syndrome with ST-segment elevation myocardial infarction (STEMI) in the acute phase of the disease and 6 months later. Moreover we sought to determine the effect of selected clinical parameters on the levels of the inflammatory factors. PATIENTS AND METHODS: The study involved 75 patients with STEMI, aged 36-82 years, treated with primary angioplasty. Blood samples for determination of IL-6, IL-10 and CRP levels were taken on the 3rd and 7th day of hospitalization and after 6 months. RESULTS: In the acute phase of myocardial infarction (MI) the levels of IL-6, IL-10 and CRP, as well as the IL-6/IL-10 and CRP/IL-10 indexes were higher than in the control group. Six months later the CRP level decreased significantly, and the levels of IL-6 and IL-10 and the studied indices normalized. In the acute phase of MI there were positive correlations between the studied factors. The independent predictors of IL-6, IL-10 and CRP levels were body mass index (BMI), troponin I, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and the baseline levels of inflammatory markers. CONCLUSIONS: In the acute phase of MI, inflammatory activation is enhanced with predominant proinflammatory response. In the course of the healing process within 6 months inflammation is suppressed and the balance between pro- and anti-inflammatory activation is restored. The size of MI, BMI, lipid levels and the baseline levels of inflammatory markers influence the levels of inflammatory factors.

Plasma levels of TNF-alpha, IL-6, and IL-10 and their relationship with left ventricular diastolic function in patients with stable angina pectoris and preserved left ventricular systolic performance.

AIMS: The role of inflammation--a key factor underlying coronary artery disease (CAD) and systolic heart failure--in promotion of left ventricular (LV) diastolic dysfunction has not been investigated extensively so far. The aim of this study was: (i) to evaluate plasma levels of TNF-alpha, IL-6, and IL-10 in patients with stable CAD and preserved LV systolic function and (ii) to assess their relationships with LV diastolic function. METHODS: The study population consisted of 126 patients with single vessel and 58 patients with multivessel stable CAD and LV ejection fraction >50%, and 39 healthy controls. Each participant underwent echocardiographic study including estimation of LV diastolic function indices: peak velocities of early (E) and late (A) transmitral flows, deceleration time of E wave, isovolumic relaxation time, E wave (ETT) and A wave (ATT) transit time to the LV outflow tract, and flow propagation velocity of E wave (Ep). Plasma TNF-alpha, IL-6, and IL-10 levels were evaluated by radioimmunometric method. RESULTS: Patients with CAD presented higher TNF-alpha and IL-6 levels and higher values of IL-6/IL-10 and TNF-alpha/IL-10 ratio than the controls. IL-6 levels were higher in patients with multivessel disease than in those with single vessel disease. Significant correlations (all P<0.001) were found for TNF-alpha and Ep (r=-0.41), E/Ep (r=0.45), and ETT (r=0.38). IL-6 correlated with Ep (r=-0.39) and E/A (r=-0.33), whereas IL-10 with ETT (r=0.37), Ep (r=-0.44), and E/Ep (r=0.46). CONCLUSION: In patients with stable CAD and preserved LV systolic performance, plasma levels of TNF-alpha and IL-6 are elevated and there is association between immunoinflammatory activation reflected by plasma levels of cytokines and LV diastolic dysfunction.

Plasma neuropeptides and perception of pruritus in psoriasis.

The aim of this study was to evaluate the influence of selected neuropeptides on itching in psoriatic individuals. Fifty-nine patients (43 pruritic and 16 non-pruritic) with psoriasis were included in the study. The severity of psoriasis, measured using the Psoriasis Area and Severity Index scale, ranged between 2 and 43.7 points. The intensity of pruritus was evaluated using a Visual Analogue Scale. The plasma levels of substance P, vasoactive intestinal peptide, calcitonin gene-related peptide and neuropeptide Y were measured radioimmunologically. The plasma level of neuropeptide Y was significantly decreased in patients with pruritus compared with those without pruritus (21.6 +/- 39.6 pg/ml and 144.3 +/- 385.7 pg/ml, respectively; p=0.03). Levels of other neuropeptides did not differ significantly between pruritic and non-pruritic patients; however, a tendency to lower plasma levels of substance P and vasoactive intestinal peptide in patients with itching was noted. Moreover, a significant negative correlation was observed between pruritus severity and levels of substance P (r = -0.36; p=0.02), as well as between pruritus severity and plasma levels of vasoactive intestinal peptide (r = -0.34; p=0.03). The imbalance of neuropeptide activity in the sera of pruritic subjects may suggest a role for neuropeptides in perception of itching in psoriatic individuals.

Chemokines and left ventricular function in patients with acute myocardial infarction.

BACKGROUND: Leukocytes are activated in the inflammatory process involving locally atherosclerotic lesions through adhesive molecules attaching to the surface of endothelial cells, especially during acute myocardial infarction. The aim of the study was to assess MCP-1, MIP-1alpha, and RANTES serum levels in patients with STEMI and to correlate them with the severity of left ventricle (LV) dysfunction. METHODS: Forty patients were initially divided into two groups, with group 1 having an ejection fraction (EF) above 40% and group 2 an EF of 40% or less. Next, the patients were divided on the basis of wall motion score index (WMSI): group 3 had a WMSI of 1.3 or lower and group 4 had a WMSI above 1.3. A control group of ten volunteers was also included in the study. Serum samples were taken at admission as well as 3, 24, 48, 72 h, and 7 days after. RESULTS: The baseline serum levels of MCP-1 and RANTES in group 1 were significantly higher than in the controls (p<0.05 and p<0.005, respectively). The highest concentrations of chemokines were observed 3 h after admission. The serum levels of MIP-1alpha on admission and 3 h later were significantly higher in group 1 than in group 2 (p<0.03 and p<0.01, respectively). Maximum MIP-1 concentrations were observed 3 h after admission in group 3 and 24 h after admission in group 4 (p<0.006). In group 1, MIP-1alpha 3 h after admission correlated positively with the EF (r=0.444, p<0.05). In group 1 there was a negative correlation between MIP-1alpha concentration 3 h after admission and LV end-diastolic dimension (r=-0.492, p<0.02). CONCLUSIONS: Patients with myocardial infarction with an elevated ST segment had a significant increase in MCP-1, MIP-1alpha, and RANTES serum levels.

Plasma concentration of selected neuropeptides in patients suffering from psoriasis.

UNLABELLED: The aim of this study was to evaluate plasma levels of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) during psoriasis course. METHODS: Seventy-three patients with psoriasis and 32 healthy volunteers were included. Detailed demographic and disease anamnesis was obtained from every patient. The disease severity was assessed using the Psoriasis Area and Severity Index score. Plasma levels of SP, CGRP, VIP and NPY were measured radioimmunologically. RESULTS: Plasma levels of SP and NPY did not significantly differ between patients with psoriasis and controls (median SP: 52.8 and 57.9 pg/ml, respectively; P = 0.32; median NPY: 8.5 and 8.2 pg/ml, respectively; P = 0.67). CGRP plasma concentration was significantly elevated in psoriatic individuals both before (median 43.1 pg/ml) and after treatment (median 45.4 pg/ml), in comparison with healthy donors (median 13.5 pg/ml; P < 0.01 and P = 0.03, respectively). Treatment did not significantly influence plasma CGRP levels (P = 0.3). Median VIP plasma concentration in psoriatics before treatment was significantly higher compared with healthy controls (medians 66.9 and 60.1 pg/ml, respectively; P = 0.04), but the therapy resulted in significant decrease in VIP plasma level (median 19.0 pg/ml; P < 0.001). In psoriatic patients significant correlations were noted between NPY and VIP (R = 0.34; P < 0.01), and VIP and CGRP plasma levels, both before (R = 0.28; P = 0.03) and after the treatment (R = 0.44; P < 0.01). CONCLUSIONS: Based on our results and previous literature data it could be suggested that neuropeptides may be involved in the development of psoriatic lesions.

Expression of vascular adhesion protein-1 in atopic eczema.

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule with an enzymatic activity which partakes in the migration process of lymphocytes. The aim of this study was to investigate VAP-1 expression in atopic eczema (AE) in comparison with healthy controls and psoriatic individuals. MATERIAL AND METHODS: Forty adult patients suffering from AE aged between 18 and 56 years were included in the study. The control group consisted of 35 healthy volunteers aged between 19 and 49 years and of 71 psoriatic patients aged between 23 and 89 years. The serum concentration of soluble VAP-1 (sVAP-1) was evaluated by ELISA and VAP-1 expression in the skin by immunohistochemistry. RESULTS: Serum level of sVAP-1 in AE patients before treatment was significantly higher compared with healthy volunteers. Similarly, a higher mean number of VAP-1-positive vessels was found in both lesional and nonlesional atopic skin compared with healthy skin. Treatment of AE resulted in a significant reduction in the serum level of sVAP-1. On the other hand, both the serum level of sVAP-1 and the number of dermal vessels with expression of VAP-1 were significantly lower in AE patients compared with psoriatic individuals. CONCLUSION: This study indicates the important role of VAP-1 in the pathogenesis of chronic inflammatory cutaneous disorders, including AE.

Kinetics of chemokines in acute myocardial infarction.

BACKGROUND: Chemokines are supposed to play an important role in the activation of monocytes and in the development of atherosclerosis. There are also suggestions that chemokine-mediated enhanced coagulability may be related to the pathogenesis of acute coronary syndromes.Aim. To assess the kinetics of 3 chemokines: Monocyte Chemoattractant Protein-1 (MCP-1), Macrophage Inflammatory Protein-1alfa (MIP-1alpha) and Regulated on Activation Normal T cell Expressed and Secreted (RANTES) in patients with ST-elevation myocardial infarction (STEMI). METHODS: The study group consisted of 40 patients (pts) with STEMI who were divided into 2 groups -- 16 pts with anterior MI (AMI) and 24 pts with inferior or lateral MI (IMI). According to the type of received therapy, the pts were divided into 2 other groups: group A -- 30 pts treated with thrombolytic agents or primary angioplasty and group B -- 10 pts without recanalisation therapy. The control group consisted of 10 healthy volunteers. Blood samples for MCP-1, MIP-1alpha and RANTES serum levels was taken on admission and 3 h, 24 h, 48 h, 72 h and 7 days afterwards. RESULTS: The baseline MCP-1 and RANTES levels were significantly higher in pts with STEMI than in controls (1068.9 vs 880.9 pg/ml, p<0.05; 50.8 vs 33.9 pg/ml, p<0.005). In pts with STEMI, peak levels of MCP-1 and MIP-1alpha were significantly higher 3h than 24h from admission (MCP-1 1274.4 vs 1097.4 pg/ml, p<0.02; MIP-1alpha 39.2 vs 22.0 pg/ml, p<0.01). In all STEMI pts there was a positive correlation between MIP-1alpha 3h and left ventricular ejection fraction (LVEF) (r=0.455, p<0.05) and a negative correlation between MIP-1alpha 3h and LV end-diastolic diameter (LVEED) (r=-0.453, p<0.05). A significant positive correlation between TnI level and chemokines in both AMI and IMI patients was detected, being the highest in AMI and IMI groups when MIP-1alpha 24 h and TnI were compared (R=0.852, p<0.003 and R=0.646, p<0.0001). In pts with IMI, a positive correlation between RANTES, MIP-1alpha 3h and LVEF was found (R=0.322, p<0.03 and R=0.399, p<0.008). In group A, all MIP-1alpha values were significantly higher than in group B. Also, peak MIP-1alpha levels significantly differed between groups A and B (44.8 vs 8.3 pg/ml, p<0.006). In pts from group B, a negative correlation between MCP-1 measured an admission and LVEF was found (R=-0.690, p<0.05). CONCLUSIONS: We found a significant elevation of chemokines in the early period of acute MI. The correlations between different parameters suggest, that chemokines may serve as new parameters of immune activation in STEMI and also may play the dominant role in the cardiac inflammatory response and subsequent repair processes.

[Plasma levels of brain natriuretic peptide, cyclic 3'5'-guanosine monophosphate, endothelin 1, and noradrenaline in patients with chronic congestive heart failure]. / Stezenie mózgowego peptydu natriuretycznego, cyklicznego 3,5-guanozyno-monofosforanu, endoteliny-1 i noradrenaliny u chorych na przewlekla niewydolnosc krazenia.

Chronic congestive heart failure (CHF) is a complex clinical syndrome characterized by marked neurohormonal activation which may lead to further decompensation of the circulatory system. This study was undertaken to establish the role of certain hormones in pathogenesis of congestive heart failure. Plasma levels of brain natriuretic peptide (BNP), cyclic 3'5'-guanosine monophosphate (c-GMP), endothelin 1 (ET-1), and noradrenaline (NA) were examined in patients in patients with CHF and with decompensation of circulatory system. The survey was made in 92 patients with CHF, among them there were 42 females aged 50-76 years (mean 66 years) and 50 males aged 53-76 years (mean 68 years). All patients were divided into 3 groups according to NYHA classification. On admission blood samples were taken from all patients to determine plasma levels of BNP, c-GMP, ET-1, and NA. Then patients received captopril and furosemide. Next blood samples were taken between 5 and 7 day of the treatment, after entire remission symptoms of decompensation. Plasma levels of BNP, c-GMP, ET-1, and NA were estimated with radioimmunoassay. Our study showed that plasma levels of ET-1, BNP, c-GMP, and NA were increased in patients with CHF. 5-7 days of the treatment with ACE inhibitor and diuretic caused significant decrease of ET-1, BNP, and c-GMP levels, but did not influence NA plasma levels. Determination of ET-1, BNP, c-GMP, and NA plasma levels may be a noninvasive method useful in estimation of degree of CHF and efficacy of the treatment.