Biomedical subjects

S Simonsen

Publications and source records attributed to S Simonsen.

At least 19 recordsLinked to original sources

PubMed2005

Serial measurements of peripheral vascular reactivity and exercise capacity in congestive heart failure and after heart transplantation.

BACKGROUND: The regulation of nutritive blood flow to skeletal muscles during exercise seems to make an important contribution to exercise capacity. In congestive heart failure (CHF) this regulation seems to be impaired, with attenuated peripheral vasodilatory capacity. The results regarding improvement of peripheral vasoreactivity after heart transplantation (HTx) are conflicting, and the contribution of impaired peripheral vasoreactivity to the observed reduced exercise capacity among heart transplant recipients (HTR) has not been well elucidated. We therefore assessed the reversibility of impaired vasoreactivity in forearm and calf after HTx with relationship to exercise capacity. METHODS AND RESULTS: The vasoreactivity of both forearm and calf was studied with venous occlusion plethysmography and related to exercise capacity in 64 patients with CHF and in 22 controls. Of these patients, 29 patients underwent HTx, and the same measurements were performed 10 days, 6 months and 1 year after HTx, and in a group of 15 HTR who had undergone HTx several years ago. Our main findings were (1) impaired resting blood flow in patients with CHF improved after HTx and even surpassed levels of controls; (2) peak forearm blood flow remained attenuated early after HTx, but normalized during the first year postoperatively; (3) both forearm and calf minimal resistance remained elevated after HTx; (4) vascular reactivity displays regional variations in forearm and calf both during CHF and after HTx; and (5) peripheral vascular reactivity relate to exercise performance in both patients with CHF and HTR, but the relationship seemed more pronounced in CHF. CONCLUSION: With impaired vasoreactivity related to limited exercise capacity in CHF, improvement is evident after HTx, but both forearm and calf minimal resistance remains elevated. These findings suggest increased vasoconstrictor drive to both exercising and non-exercising muscles, possibly contributing to persistent physical limitation after HTx.

Adult↗

PubMed2001

Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment.

BACKGROUND: Increasing evidence implicates innate immunity in the pathogenesis of congestive heart failure (CHF). In the present study, we examined the possible role of complement, an important part of innate immunity, in CHF. METHODS AND RESULTS: Complement activation was analyzed in systemic and coronary circulation in 39 patients with CHF and 20 healthy control subjects. In a double-blind, placebo-controlled study, we have recently reported that high-dose intravenous immunoglobulin (IVIG) improves left ventricular ejection fraction (LVEF) in these patients. To examine if this improvement was related to IVIG-induced effects on complement, we also examined complement activation during induction (first week) and maintenance therapy (6 months) with IVIG or placebo. Our main findings were: (1) We found enhanced systemic complement activation involving classic, alternative, as well as terminal pathway in patients with CHF compared with healthy control subjects. (2) Particularly enhanced complement activation was found in coronary sinus, representing venous drainage from the heart. (3) The systemic complement activation was further enhanced during IVIG but not during placebo therapy, particularly during induction therapy. (4) Although IVIG improved LVEF in patients with CHF, the degree of IVIG-mediated complement activation was negatively correlated with this improvement of LVEF. CONCLUSIONS: This study further supports the involvement of innate immunity in the pathogenesis of CHF. Our findings suggest that complement may be added to the list of possible therapeutic targets in CHF and that future studies with specific complement inhibitors may be of interest in this disorder.

C-Reactive Protein↗

PubMed2001

Omega-3 fatty acids enhance tumor necrosis factor-alpha levels in heart transplant recipients.

BACKGROUND: Proinflammatory cytokines may contribute to clinical complications in heart transplant (HTx) recipients. Previous studies have shown immunomodulating effects of omega-3 fatty acids, but the results are somewhat conflicting. In this study, we examined plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 10, and their relations to antioxidant vitamins in 45 HTx recipients before and after treatment with omega-3 fatty acids or placebo. METHODS: The patients were long-time survivors of heart transplantation, randomized in a double-blind fashion to receive omega-3 fatty acids (3.4 g/day) or placebo for 1 year. Plasma levels of cytokines were measured by enzyme immunoassays and vitamin A, vitamin E, and beta-carotene by high-performance liquid chromatography. RESULTS: In the omega-3, but not in the placebo group, there was a rise in the proinflammatory cytokine TNF-alpha (P<0.05), a decrease in the anti-inflammatory cytokine IL-10 (P=0.07), and a rise in TNF/IL-10 ratio (P<0.05) after 12 months, suggesting a proinflammatory net effect. In the omega-3 group, the increase in TNF-alpha was associated with an increase in eicosapentaenoic acid in plasma (r=0.58, P<0.02). During omega-3 fatty-acid treatment, but not during placebo, there was a decrease in vitamin E (P<0.05) and beta-carotene (P<0.05) levels, and the decrease in vitamin E was inversely correlated with the increase in TNF-alpha (r= -0.56, P<0.01). The rise in TNF-alpha levels during omega-3 fatty acids treatment was most pronounced in those patients with transplant coronary artery disease (P<0.04). CONCLUSION: Our data suggest that omega-3 fatty acids in HTx recipients may change the balance between proinflammatory and anti-inflammatory cytokines in an inflammatory direction, possibly related to prooxidative effects of these fatty acids.

Double-Blind Method↗

PubMed2001

[Immunomodulating treatment in advanced heart failure--effect of intravenous immunoglobulin].

BACKGROUND: Congestive heart failure is characterised by enhanced immune activation. Immune-mediated mechanisms may play a pathogenic role, hence the growing interest in therapeutic regimens that could modulate the immune response in heart failure. MATERIAL AND METHODS: In the present report we discuss the pathogenic role of immunological and inflammatory mediators in the pathophysiology of heart failure and discuss different treatment modalities with focus on our recent study with intravenous immunoglobulin. In that study 40 patients with symptomatic chronic heart failure and left ventricular ejection fraction (LVEF) < 40% were randomised in a double-blind fashion to receive therapy with immunoglobulin or placebo for a total period of 26 weeks. RESULTS: We found that intravenous immunoglobulin, but not placebo, shifted the cytokine balance in an anti-inflammatory direction, and that such a shift was associated with improvement in LVEF by 5 EF units. Functional capacity and haemodynamic variables also improved. INTERPRETATION: Our study supports the hypothesis that immunological variables might be of significant importance in the pathogenesis of heart failure and it suggests a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in such patients. These issues are further discussed in the present article.

Adjuvants, Immunologic↗

PubMed2001

[Inhalation of a prostacyclin analog (iloprost) in primary and secondary pulmonary hypertension].

BACKGROUND: Vasodilative therapy in the form of calcium channel blockers and, recently, continuous intravenous prostacyclin has improved exercise capacity and reduced mortality in primary pulmonary hypertension. Their clinical value is limited by either low rate of response or serious side effects. These shortcomings could be overcome by the use of iloprost, a stable prostacyclin analogue. Administering it by inhalation, we assessed its short-term efficacy in patients with primary and secondary pulmonary hypertension. MATERIAL AND METHODS: We studied six patients with primary and six with secondary pulmonary hypertension, all with New York Heart Association functional class III or IV symptoms of congestive heart failure. Iloprost was nebulised with 8 l/min of oxygen and administered in increasing doses from 10 to 40 micrograms via a facemask. The haemodynamic effects of iloprost was assessed by right-heart catheterisation. RESULTS: Inhalation of iloprost was well tolerated, and produced a median reduction in mean pulmonary artery pressure from 52 (42-63) to 41 (35-56) mm Hg (p < 0.05). Cardiac output increased from 3.5 (2.8-4.3) to 4.1 (3.1-5.1) l/min (p < 0.05) and pulmonary vascular resistance decreased from 1036 (722-1526) to 753 (446-1107) dyn.sek.cm-5 (p < 0.01). No changes occurred in heart rate, systemic blood pressure or pulmonary wedge pressure. INTERPRETATION: Drug testing with inhalation of iloprost is safe and causes beneficial haemodynamic changes with selective pulmonary vasodilatation. Since the long-term effect of medical intervention is based on the degree of acute pulmonary vascular reactivity, inhalation of iloprost may be a new therapeutic option for severe pulmonary hypertension.

Administration, Inhalation↗

PubMed2001

Effect of pravastatin on plasma markers of inflammation and peripheral endothelial function in male heart transplant recipients.

Statins appear to have several biologic effects beyond those of lipid metabolism, and we hypothesized that immunomodulating effects of statins are important for the beneficial effects of these medications after heart transplantation. Our findings suggest that pravastatin treatment reduces plasma markers of inflammation and improves peripheral endothelial function in heart transplant recipients, possibly contributing to the observed clinical benefits of statin treatment in these patients.

Cell Adhesion Molecules↗

PubMed2001

Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure.

BACKGROUND: Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P:<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro-atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P:<0.001) but remained unchanged during placebo. CONCLUSIONS: We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients.

Adjuvants, Immunologic↗

PubMed2001

Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure--modulatory effect of intravenous immunoglobulin.

OBJECTIVES: We sought to study the gene expression of chemokines and their corresponding receptors in mononuclear blood cells (MNCs) from patients with chronic heart failure (CHF), both of which were cross-sectional and longitudinal studies during therapy with intravenous immunoglobulin (IVIg). BACKGROUND: We have recently demonstrated that IVIg improves left ventricular ejection fraction (LVEF) in patients with CHF. Based on the potential pathogenic role of chemokines in CHF, we hypothesized that the beneficial effect of IVIg may be related to a modulatory, effect on the expression of chemokines and their receptors in MNCs. METHODS: We examined: 1) the gene expression of C, CC and CXC chemokines and their receptors in MNCs from 20 patients with CHF and 10 healthy blood donors; and 2) the expression of these genes in MNCs from 20 patients with CHF randomized in a double-blind fashion to therapy with IVIg or placebo for 26 weeks. RESULTS: Our main findings in CHF were: 1) markedly raised gene expression of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and interleukin (IL)-8; 2) enhanced gene expression of their corresponding receptors; 3) modulation in a normal direction of this abnormal chemokine and chemokine receptor gene expression during IVIg, but not during placebo therapy; 4) down-regulation of MIP-1alpha, MIP-1beta and IL-8 during IVIg at the protein level in plasma; and 5) a correlation between down-regulation of MIP-1alpha gene expression and improved LVEF during IVIg therapy. CONCLUSIONS: Our results further support a pathogenic role for chemokines in CHF and suggest that IVIg may represent a novel therapeutic approach, with the potential to improve LVEF in patients with CHF, possibly by modulatory effects on the chemokine network.

Aged↗

PubMed2001

Plasma exchange and heart-liver transplantation in a patient with homozygous familial hypercholesterolemia.

A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. Plasma exchange reduced total cholesterol levels from 25-30 mmol/L (967-1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long-term treatment. Due to end-stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart-liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.

Cholesterol↗

PubMed2001

Regional cardiac expression and concentration of natriuretic peptides in patients with severe chronic heart failure.

The purpose of this study was to examine the regional cardiac mRNA expression and concentration of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in relation to the circulating peptide concentrations in patients with chronic heart failure (CHF). The myocardial mRNA levels and peptide concentrations of BNP and ANP were analysed in seven different regions of the heart from patients undergoing cardiac transplantation. Autopsy samples from individuals without known cardiovascular disease were used as controls. The plasma levels of natriuretic peptides and their N-terminal propeptides, Nt-proBNP and Nt-proANP, were measured in the CHF patients and healthy volunteers. In the autopsy specimens, the atrial regions appeared to contain the highest peptide levels for BNP as well as ANP, the atrioventricular ratio being 12-262 and 72-637-fold, respectively. In the CHF patients there was a relative shift towards the ventricle for BNP, reducing the atrioventricular ratio to 6-16-fold. The circulating concentrations of BNP/Nt-proBNP in the CHF patients correlated closely to the BNP mRNA expression in most myocardial regions including the left ventricle (r = 0.72, P < 0.001). For circulating concentrations of ANP/Nt-proANP, such correlation were limited to the left atrium free wall (r = .66, P < 0.002). Thus, of the two natriuretic peptides, BNP/Nt-proBNP may be a better reflector of left ventricular overload.

Atrial Natriuretic Factor↗

PubMed2001

Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure.

BACKGROUND: Studies in different animal models and plasma analyses in humans suggest that members of the interleukin-6 (IL-6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL-6-related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end-stage heart failure and donor hearts. METHODS: Gene expression of cytokines/receptors of the IL-6 family was documented in myocardial samples using cDNA array hybridization and RNase protection assays. Immunohistochemistry was used to detect leukaemia inhibitory factor (LIF), IL-6 and glycoprotein 130 (gp130) in myocardial tissues. RESULTS: Myocardial gene activity was documented for the majority of IL-6 family cytokines and their receptors. Immunohistochemical analysis localized IL-6, LIF and their common receptor subunit gp130 to myocytes and vascular smooth muscle cells. LIF mRNA levels were enhanced in the left ventricles of CHF patients relative to the left ventricles of donor hearts (patients 4.6 +/- 4.7 vs. donors 0.3 +/- 0.3, P < 0.005). Myocardial IL-6 and gp130 mRNA levels were not statistically different between patients and donors, but in contrast to LIF mRNA expression in heart explants, gp130 mRNA levels were significantly higher in left atrium compared with left ventricle in both patients and donors. CONCLUSIONS: Both mRNA and proteins of gp130 and its ligands IL-6 and LIF are expressed in both nonfailing and failing human myocardium. The elevated LIF mRNA levels in left ventricles from patients with end-stage heart failure suggest a role for LIF in the pathogenesis of CHF.

Adult↗

PubMed2001

Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients.

BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension.

Blood Pressure↗

PubMed2001

Effect of metoprolol on cytokine levels in chronic heart failure--a substudy in the Metoprolol Controlled-Release Randomised Intervention Trial in Heart Failure (MERIT-HF).

BACKGROUND: Enhanced immune activation has been suggested to be involved in the pathogenesis of congestive heart failure (CHF). There is evidence for interactions between the sympathetic nervous system and the immune system. We therefore examined the effect of the selective beta(1)-receptor blocker metoprolol on various immunologic variables in CHF. METHODS: Eighty-one patients with CHF were randomized to metoprolol or placebo in a double-blind trial. Plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, soluble IL-2 receptor (sIL-2R), monocyte chemoattractant peptide-1, and IL-8 were measured at baseline, after 3 months, and at the end of the study (11.4 +/- 0.4 months). RESULTS: Our main findings were (1) at baseline TNF-alpha, IL-6, IL-8, monocyte chemoattractant peptide-1, and sIL-2R but not IL-10 levels were markedly elevated in patients with CHF compared with controls; (2) during treatment with metoprolol, but not with placebo, there was a significant decrease in sIL-2R after 3 months, with a return to baseline at the end of the study; and (3) levels of all other immunologic variables remained unchanged throughout the study in both the metoprolol and the placebo groups. CONCLUSIONS: Our findings suggest that metoprolol treatment in CHF is associated with a significant but temporary decrease in sIL-2R, possibly reflecting down-modulation of T-cell activation. However, an enhanced immune activation also persisted in the metoprolol group, suggesting a potential for more specific immunomodulatory therapy in CHF.

Adrenergic beta-Antagonists↗

PubMed2001

Natriuretic peptides in patients with aortic stenosis.

BACKGROUND: Whereas atrial natriuretic peptide (ANP) is secreted mainly from cardiac atria, brain natriuretic peptide (BNP) is produced to a larger extent in ventricles. Their relative importance as markers of cardiac function and myocardial hypertrophy is not yet clarified. This study evaluated circulating BNP and ANP and the N-terminal part of their propeptides (NT-proBNP and NT-proANP) as markers of left ventricular hypertrophy and atrial pressure increase in patients with aortic stenosis. METHODS: The plasma concentrations of BNP, NT-proBNP, ANP, and NT-proANP were measured by radioimmunoassay in 67 patients with aortic stenosis. Peptide plasma concentrations were related to measurements obtained by cardiac catheterization and echocardiography. RESULTS: Receiver operating characteristic curves indicated that BNP and NT-proBNP performed best in the detection of increased left ventricular mass and NT-proANP in the detection of increased left atrial pressure. NT-proBNP was significantly increased in mild left ventricular hypertrophy (left ventricular mass index, 78 to 139 g/m(2)), whereas NT-proANP was not increased until left ventricular mass index was 141 to 180 g/m(2). CONCLUSIONS: Plasma BNP and NT-proBNP may serve as early markers of left ventricular hypertrophy, whereas ANP and NT-proANP reflect left atrial pressure increase. The repeated and combined measurements of natriuretic peptides might provide diagnostic information relevant to the evaluation of the stage of aortic stenosis.

Adult↗

PubMed2001

Plasma N-terminal proatrial natriuretic factor can predict normal pulmonary capillary wedge pressure in cardiac transplant recipients.

BACKGROUND: Plasma N-terminal proatrial natriuretic factor (proANP) is closely related to atrial filling pressure, but this may be distorted in heart transplant recipients. OBJECTIVE: The aim of this study was to examine the usefulness of proANP as a non-invasive marker of cardiac filling pressure in transplanted patients with normal to moderately elevated serum creatinine (s-creatinine). METHODS: Blood was sampled at rest for analysis of proANP from 220 patients 1-13 (median 4) years after orthotopic heart transplantation undergoing routine diagnostic catheterization. RESULTS: In multivariate analysis proANP was significantly positively related to s-creatinine, mean pulmonary capillary wedge pressure (PCWP) and time after transplantation and negatively related to haemoglobin and cardiac index. All the patients with proANP below 1140 pmol/l had normal PCWP (<13 mmHg). The area under the receiver-operating characteristic curve for proANP for the detection of PCWP > 13 mmHg was 0.81. The positive predictive value of proANP for detection of increased PCWP was very low. CONCLUSION: A low proANP had a 100% negative predictive value for increased atrial pressure but the low positive predictive value makes proANP unsuitable as an indicator of increased atrial pressures in heart transplanted patients.

Adolescent↗

PubMed2000

Postexercise ischemia is associated with increased neuropeptide Y in patients with coronary artery disease.

BACKGROUND: Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. METHODS AND RESULTS: Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE. CONCLUSIONS: The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Analysis of Variance↗

PubMed2000

Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).

OBJECTIVES: Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. METHODS: In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). RESULTS: Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). CONCLUSIONS: Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Amlodipine↗

PubMed2000

CXC-chemokines, a new group of cytokines in congestive heart failure--possible role of platelets and monocytes.

OBJECTIVES: The purpose of the present study was to examine the circulating levels of CXC-chemokines in patients with various degree of congestive heart failure (CHF). BACKGROUND: CXC-chemokines may be important mediators in the persistent immune activation observed in CHF patients by activation of circulating neutrophils, T-cells and monocytes and possibly by the recruitment of these cells into the failing myocardium. METHODS: Levels of interleukin (IL)-8, growth-regulated oncogene (GRO) alpha and epithelial neutrophil activating peptide (ENA)-78 were measured both in serum and in platelet-free plasma by enzyme immunoassay in 47 patients with CHF and in 20 healthy controls. RESULTS: (i) CHF patients had significantly elevated levels of all the three CXC-chemokines with IL-8 and GRO alpha showing a gradual increase along with increasing NYHA class. (ii) There was an inverse correlation between IL-8 and left ventricular ejection fraction (EF) and cardiac index (CI). (iii) Both unstimulated and lipopolysaccharide (LPS)-stimulated monocytes from CHF patients released markedly elevated amounts of all three CXC-chemokines. (iv) Platelets from patients with severe CHF were characterised by decreased content of GRO alpha and ENA-78 as well as decreased release of these chemokines upon thrombin receptor stimulation. (v) Activated platelets stimulated peripheral blood mononuclear cells in vitro to enhanced release of IL-8, and neutralising antibodies against ENA-78 inhibited this interaction. CONCLUSIONS: This study demonstrates for the first time elevated levels of CXC-chemokines in CHF, which may be of importance for progression of heart failure. Our findings further suggest that activated monocytes and platelets may contribute to enhanced CXC-chemokine levels in CHF.

Analysis of Variance↗