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Rainer Dietz

Publications and source records attributed to Rainer Dietz.

At least 55 records · Page 3Linked to original sources

MR coronary angiography using 3D-SSFP with and without contrast application.

We compared the performance of a contrast-enhanced with a non-contrast breath-hold 3D-SSFP-sequence for Magnetic Resonance Coronary Angiography in seven healthy subjects and 14 patients. Visibility of coronary segments, vessel length, image quality and the influence of an extracellular contrast agent (Gadolinium-DTPA) were assessed. Overall, the performance of the sequence was better in healthy subjects than in patients. Although the application of Gadolinium-DTPA increased the contrast-to-noise-ratio of the right coronary artery, the overall performance was not significantly improved. We conclude that a 3D-SSFP-technique depicts extensive parts of the coronary arteries and does not require contrast application.

Adult↗

Mortality and morbidity reduction with Candesartan in patients with chronic heart failure and left ventricular systolic dysfunction: results of the CHARM low-left ventricular ejection fraction trials.

BACKGROUND: Patients with symptomatic chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) have a high risk of death and hospitalization for CHF deterioration despite therapies with angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and even an aldosterone antagonist. To determine whether the angiotensin-receptor blocker (ARB) candesartan decreases cardiovascular mortality, morbidity, and all-cause mortality in patients with CHF and depressed LVEF, a prespecified analysis of the combined Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) low LVEF trials was performed. CHARM is a randomized, double-blind, placebo-controlled, multicenter, international trial program. METHODS AND RESULTS: New York Heart Association (NYHA) class II through IV CHF patients with an LVEF of < or =40% were randomized to candesartan or placebo in 2 complementary parallel trials (CHARM-Alternative, for patients who cannot tolerate ACE inhibitors, and CHARM-Added, for patients who were receiving ACE inhibitors). Mortality and morbidity were determined in 4576 low LVEF patients (2289 candesartan and 2287 placebo), titrated as tolerated to a target dose of 32 mg once daily, and observed for 2 to 4 years (median, 40 months). The primary outcome (time to first event by intention to treat) was cardiovascular death or CHF hospitalization for each trial, with all-cause mortality a secondary end point in the pooled analysis of the low LVEF trials. Of the patients in the candesartan group, 817 (35.7%) experienced cardiovascular death or a CHF hospitalization as compared with 944 (41.3%) in the placebo group (HR 0.82; 95% CI 0.74 to 0.90; P<0.001) with reduced risk for both cardiovascular deaths (521 [22.8%] versus 599 [26.2%]; HR 0.84 [95% CI 0.75 to 0.95]; P=0.005) and CHF hospitalizations (516 [22.5%] versus 642 [28.1%]; HR 0.76 [95% CI 0.68 to 0.85]; P<0.001). It is important to note that all-cause mortality also was significantly reduced by candesartan (642 [28.0%] versus 708 [31.0%]; HR 0.88 [95% CI 0.79 to 0.98]; P=0.018). No significant heterogeneity for the beneficial effects of candesartan was found across prespecified and subsequently identified subgroups including treatment with ACE inhibitors, beta-blockers, an aldosterone antagonist, or their combinations. The study drug was discontinued because of adverse effects by 23.1% of patients in the candesartan group and 18.8% in the placebo group; the reasons included increased creatinine (7.1% versus 3.5%), hypotension (4.2% versus 2.1%), and hyperkalemia (2.8% versus 0.5%), respectively (all P<0.001). CONCLUSIONS: Candesartan significantly reduces all-cause mortality, cardiovascular death, and heart failure hospitalizations in patients with CHF and LVEF < or =40% when added to standard therapies including ACE inhibitors, beta-blockers, and an aldosterone antagonist. Routine monitoring of blood pressure, serum creatinine, and serum potassium is warranted.

Aged↗

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.

Adolescent↗

Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro: activation of CREB downstream of GSK3beta.

In vivo, left ventricular remodeling after myocardial infarction involves hypertrophy generally attributed to increased cardiac workload. We hypothesized that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied several participating kinases and transcription factors in isolated cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced cardiomyocyte hypertrophy assessed by 3H leucine incorporation and immunohistochemistry. Inhibition of reactive oxygen species (ROS), serine/threonine kinase AKT, and ERK abolished reoxygenation-induced hypertrophy. In addition, a beta2-adrenergic receptor (beta2-AR) antagonist, as well as Gi inhibitor pertussis toxin, blocked reoxygenation-induced hypertrophy. Hypoxia for 6 h increased transcription factors CREB, NF-kappaB, and GATA DNA binding activities. However, only CREB DNA-binding was sustained during reoxygenation. Inhibition of PI3-kinase, ERK, and PKA abrogated reoxygenation-induced CREB DNA-binding without affecting CREB serine-133 phosphorylation. These same pathways were found to regulate hypoxia/reoxygenation-induced GSK3beta kinase activity and CREB serine-129 de-phosphorylation. GSK3beta mutants resistant to phosphorylation blocked the stimulation of CRE-dependent transcription induced by hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant-negative mutant of CREB abrogated hypoxia/reoxygenation-induced hypertrophy. We suggest that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB activation. Inactivation of GSK3beta by hypoxia/reoxygenation, possibly integrating PI3-kinase and ERK pathways downstream of beta2-AR and ROS, is a prerequisite for CRE-dependent transcription. Transient hypoxia may contribute to cardiac hypertrophy in ischemic heart disease independent of cardiac workload.

Adrenergic beta-Antagonists↗

Rat corin gene: molecular cloning and reduced expression in experimental heart failure.

Stored cardiac pro-atrial natriuretic peptide (pro-ANP) is converted to ANP and released upon stretch from the atria into the circulation. Corin is a serin protease with pro-ANP-converting properties and may be the rate-limiting enzyme in ANP release. This study was aimed to clone and sequence corin in the rat and to analyze corin mRNA expression in heart failure when ANP release upon stretch is blunted. Full-length cDNA of rat corin was obtained from atrial RNA by RT-PCR and sequenced. Tissue distribution as well as regulation of corin mRNA expression in the atria were determined by RT-PCR and RNase protection assay. Heart failure was induced by an infrarenal aortocaval shunt. Stretch was applied to the left atrium in a working heart modus, and ANP was measured in the perfusates. The sequence of rat corin cDNA was found to be 93.6% homologous to mouse corin cDNA. Corin mRNA was expressed almost exclusively in the heart with highest concentrations in both atria. The aortocaval shunt led to cardiac hypertrophy and heart failure. Stretch-induced ANP release was blunted in shunt animals (control 1,195 +/- 197 fmol.min(-1).g(-1); shunt: 639 +/- 99 fmol.min(-1).g(-1), P < 0.05). Corin mRNA expression was decreased in both atria in shunt animals [right atrium: control 0.638 +/- 0.004 arbitrary units (AU), shunt 0.566 +/- 0.014 AU, P < 0.001; left atrium: control 0.564 +/- 0.009 AU, shunt 0.464 +/- 0.009 AU, P < 0.001]. Downregulation of atrial corin mRNA expression may be a novel mechanism for the blunted ANP release in heart failure.

Amino Acid Sequence↗

Delayed enhancement and T2-weighted cardiovascular magnetic resonance imaging differentiate acute from chronic myocardial infarction.

BACKGROUND: Delayed enhancement (DE) cardiovascular magnetic resonance (CMR) detects acute and chronic myocardial infarction (MI) by visualizing contrast media accumulation in infarcted segments. T2-weighted CMR depicts infarct-related myocardial edema as a marker of acute but not chronic myocardial injury. We investigated the clinical utility of an approach combining both techniques to differentiate acute from chronic MI. METHODS AND RESULTS: Seventy-three MI patients were studied in 2 groups. Group A consisted of 15 acute MI patients who were studied twice, on day 1 and 3 months after MI. In group B, 58 patients with acute or chronic MI underwent 1 CMR scan. T2-weighted and DE images of matched slices were acquired on a 1.5-T system. In group A, quantitative segmental and region of interest-based analyses were performed to observe signal changes between the acute and chronic phases. In group B, T2-weighted and DE images were examined visually by 2 blinded observers for the presence or absence of hyperintense areas in corresponding segments. For infarct localization, coronary angiography and/or ECG changes served as the reference standard. In group A, the contrast-to-noise ratio on T2-weighted images dropped in the infarcted segments from 2.7+/-1.1 on day 1 to 0.1+/-1.2 after 3 months (P<0.0001). There was no significant change in contrast-to-noise ratio in DE images (1.9+/-1.5 versus 1.3+/-1.0; P=NS). The qualitative assessment of T2-weighted and DE images in group B yielded a specificity of 96% to differentiate acute from chronic lesions. CONCLUSIONS: An imaging approach combining DE and T2-weighted CMR accurately differentiates acute from chronic MI.

Acute Disease↗

Regenerative capacity of the myocardium: implications for treatment of heart failure.

Research into myocardial regeneration has an exciting future, shown by the results of experimental and clinical work challenging the dogma that the heart is a postmitotic non-regenerating organ. Such studies have initiated a lively debate about the feasibility of novel treatment approaches leading to the recovery of damaged myocardial tissue. The possibility of reconstituting dead myocardium by endogenous cardiomyocyte replication, transplantation, or activation of stem cells--or even cloning of an artificial heart--is being advanced, and will be a major subject of future research. Although health expenditure for heart failure in the industrial world is high, we are still a long way from being able to treat the cause of reduced myocardial contractility. Despite the hopes of some people, conventional treatment for heart failure does not achieve myocardial regeneration. We present a virtual case report of a patient with acute myocardial infarction; we discuss treatment options, including strategies aimed at organ regeneration.

Animals↗

The intron 6 G/T polymorphism of c-myb oncogene and the risk for coronary in-stent restenosis.

BACKGROUND: The principle mechanisms leading to the development of atherosclerosis are long-term accumulation of lipids and cell proliferation. We have recently shown that a single nucleotide polymorphism in the c-myb gene is associated with the development of coronary artery disease in humans and intracellular lipid accumulation. C-myb expression has been further shown to be up-regulated during cell proliferation. The development of in-stent restenosis is predominantly driven by smooth muscle cell proliferation. METHODS: To study a possible association of c-myb with neointima formation in humans we genotyped 485 consecutive patients undergoing coronary stenting for a G/T-single nucleotide polymorphism in intron 6 of the cmyb gene. Restenosis was assessed by quantitative coronary angiography and angiographic follow-up after 6 months. To study the effect of c-myb on smooth muscle cell proliferation primary human smooth muscle cells were infected with recombinant adenovirus expressing c-myb, a dominant negative myb-engrailed fusion protein or control virus. RESULTS AND CONCLUSION: Restenosis > 50% occurred in 27.6% of patients with at least one G-allele and in 20.8% of those without (p = 0.10). Even after adjustment for the independent risk factors diabetes mellitus, reference lumen diameter, smoking, dyslipidemia and number of diseased vessels, the observed difference in the distribution of the c-myb alleles did not reach statistical significance (p = 0.08). Adenoviral gene transfer of c-myb did not increase proliferation of cultured smooth muscle compared to control virus or untransfected cells, while the expression of the dominant negative mutant reduced proliferation of VSMC as previously shown. Our results indicate that expression of c-myb, while being important for cell cycle is not sufficient to induce smooth muscle cell proliferation. The G/T-nucleotide transversion polymorphism in intron 6 of the c-myb oncogene that has been associated with atherosclerosis and lipid accumulation is not a risk factor for human in-stent restenosis.

Coronary Angiography↗

[OCTAVE and OPERA: discordance in hypertension therapy?].

While ACE-inhibitors have proven their prognostic benefit in many hypertension studies, a new approach has been proposed by inhibiting neutral endopeptidase, which degrades natriuretic peptides. The combined inhibition of ACE and endopeptidase was named "vasopeptidase-inhibition" and tested in several trial. Though effective in lowering blood pressure, a superiority to ACE-inhibitors alone could not be shown. A potentially serious side effect was the increased incidence of angioneurotic edema, which led to a complete stop in the development of this pharmaceutical strategy.

Angioedema↗

Regulation of caspase 3 and Fas in pressure overload-induced left ventricular dysfunction.

BACKGROUND: The presence of apoptotic cell death in cardiac myocytes is now well established and the contribution of apoptosis for the development of heart failure has been suggested. However, the mechanism responsible for the induction of apoptosis remains unclear. The present study was designed to investigate the involvement of Fas and caspase 3 in the transition from pressure overload-induced left ventricular hypertrophy (LVH) to left ventricular dysfunction (LVD). METHODS: Pressure overload induced LVH (10 days) and LVD (30 days) were induced by thoracic aortic banding. Changes in apoptosis-related genes were studied in rats with thoracic aortic banding. After 10 and 30 days, cardiac Fas mRNA expression was measured by RT-PCR. The mRNA expression of caspase 3 was detected by RNase protection assay. The activity of caspase 3 was measured by fluorometric assay. Protein levels of caspase 3 were measured by Western blot. RESULTS: Rats with aortic banding had increased heart/body weight ratios after 10 and 30 days, compared to controls. Central venous pressure and lung weights were increased, left ventricular contractility was significantly impaired only in rats after 30 days of aortic banding, indicating LVD. Caspase 3 mRNA expression (7.1+/-0.1 vs. 2.8+/-0.4, P<0.05), caspase 3 activity (1418+/-181 vs. 849+/-154 AU, P<0.05) as well as caspase 3 protein levels were increased in rats with LVD but not with LVH. Similarly, Fas mRNA was increased in rats with LVD. CONCLUSIONS: The activation of Fas and caspase 3 only after 30 days of aortic banding suggests that induction of these pathways may be involved in pressure overload-induced LVD.

Animals↗

Statins inhibit reoxygenation-induced cardiomyocyte apoptosis: role for glycogen synthase kinase 3beta and transcription factor beta-catenin.

BACKGROUND: Statins may improve left ventricular remodeling after myocardial infarction. We tested whether statins inhibit cardiomyocyte apoptosis through glycogen synthase kinase 3beta (GSK3beta) inactivation and evaluated activation of downstream transcription factors. METHODS/RESULTS: Mevastatin and pravastatin activated serine/threonine kinase Akt in neonatal cardiomyocytes dose and time dependently with maximal activation at 15 min/10 microM. Caspase-3 activity was induced 2.73 +/- 0.29-fold by 6 h of hypoxia followed by 18 h of reoxygenation. Pravastatin added at the beginning of the reoxygenation period reduced caspase-3 activation to 1.26 +/- 0.06-fold compared to control cells (P < 0.001). Similar results were obtained for mevastatin (decreased to 1.98 +/- 0.45-fold, P < 0.05). TUNEL staining of neonatal cardiomyocytes after 24 h reoxygenation and 4',6'-diamidino-2-phenylindole staining of adult rat cardiomyocytes after 6 h H(2)O(2) showed reduced cardiomyocyte apoptosis in the presence of statin. Analysis of signaling pathways downstream of Akt revealed phosphorylation of GSK3beta. Transcription factor cAMP-responsive element binding (CREB) protein showed weak phosphorylation at serine 133; transcription factor NF-kappaB was not significantly activated after statin treatment as evaluated by EMSA. The GSK3beta target protein beta-catenin was stabilized at 3 h after statin treatment both in neonatal as well as adult rat cardiomyocytes. Transfection with constitutive active GSK3betaS9A sensitized neonatal cardiomyocytes to hypoxia/reoxygenation-induced apoptosis as measured by annexin V/propidium iodide staining. Furthermore, myocardial protein extracts of mice revealed GSK3beta inactivation after administration of pravastatin intraperitoneally. CONCLUSIONS: Statins inhibit cardiomyocyte apoptosis in association with GSK3beta inactivation. Inactivation of GSK3beta leads to stabilization of beta-catenin in cardiomyocytes.

Animals↗

Increasing awareness and perception of heart failure in Europe and improving care--rationale and design of the SHAPE Study.

UNLABELLED: In the last decennia heart failure has become one of the most important diseases worldwide in terms of prevalence, morbidity, life expectancy, and in health care management and costs. Despite significant improvements in prevention and treatment, heart failure remains a frequently occurring disorder with increasing incidence and a high hospitalisation and death rate. As major health care problem it deserves full attention of health care authorities. Unfortunately, the seriousness of heart failure and the therapeutic possibilities are often not recognised by those directly involved, i.e. the doctor, the patient or his relatives, let alone that they are known to the general public and health care authorities. The SHAPE study aims at improving heart failure care by increasing awareness and perception of the disease in Europe. Firstly, awareness and perception of heart failure will be documented in the general public, primary care physicians and specialists (cardiologists, internists and geriatricians) in 9 European countries: France, Germany, Italy, the Netherlands, Poland, Romania, Spain, Sweden and the UK. Subsequently, the results will be used to design and carry out suitable awareness and educational programmes in these groups, aimed at improving heart failure care and research. Finally, the results of these programmes will be tested in a second documentation phase and adaptations made where needed. This manuscript describes the rationale and design of the first phase, the Documentation Phase.During the first documentation phase, 800 participants per country selected based on sex, two age groups and urban vs. rural location (100/cell) will be surveyed using a 32-question interview. Questions for the general public focus on recognition, incidence and prevalence, severity and prognosis of the disease in comparison to other disease areas, like cancer, on quality of life, therapeutic possibilities and availability of care. The primary care physician (PCP) survey aims at receiving a minimum of 300 responses. A questionnaire with 33 closed questions will be used covering the PCP's knowledge of heart failure, including prevalence, aetiology, new diagnostic and therapeutic developments and health care costs. Questions concerning diagnostic procedures and various treatments carried out by the PCP in his own practice, as well as referral patterns for diagnostic procedures and for specialist care. Questions relating to the type of practice and number of patients in each PCP's clinical practice. A minimum of 150 cardiologists and 150 internists + geriatricians will be surveyed per country. The specialist's questionnaire contains 31 questions focusing on identification of heart failure patients, patients at risk, use and availability of diagnostic tools, importance of therapies and order of treatment, perceived risks of treatment, relevance of counselling and advice, use of paramedical personnel, and questions concerning practice size, type of practice and number of patients with heart failure. CONCLUSION: This first part of the SHAPE study will provide important information about the level of knowledge and understanding of heart failure of the general public, as well as the perception of the relevance of heart failure and appropriate diagnostic and therapeutic approaches by both the primary care physician and the medical specialist. This knowledge will be extremely valuable when it comes to defining optimal educational programmes in the different target groups studied in SHAPE necessary to implement appropriate heart failure care in Europe and to obtain the means to do so.

Adult↗

Percutaneous transluminal septal artery ablation using polyvinyl alcohol foam particles for septal hypertrophy in patients with hypertrophic obstructive cardiomyopathy: acute and 3-year outcomes.

PURPOSE: To investigate the effect of septal artery occlusion with transluminally delivered polyvinyl alcohol (PVA) foam particles for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). METHODS: Percutaneous septal artery ablation was performed in 18 symptomatic patients (13 men; mean age 60+/-17 years, range 28-89) with drug-resistant HOCM. PVA foam particles were mixed with contrast medium and injected through an angiographic catheter under fluoroscopic control until complete stasis in the septal branch was achieved. Patients were monitored with echocardiography and cardiovascular magnetic resonance imaging. RESULTS: The septal artery was successfully occluded in all patients; no embolization of other coronary branches occurred after infusion of 3 to 8 mL (5.2+/-0.8) of PVA foam particles. The resting pressure gradient was diminished from 83+/-32 to 31+/-35 mmHg (p<0.05). Over a mean follow-up of 44+/-4 months, all patients had symptomatic improvement of their dyspnea and workload without the need for intensified drug therapy. The average NYHA functional class decreased from 3.3+/-0.5 to 1.3+/-0.7 (p<0.0001), with a significant increase in the area of the left ventricular outflow tract (1.3+/-0.2 to 2.6+/-0.2 cm2, p<0.0001). Three instances of transient atrioventricular block occurred, but no complete heart block was produced by the embolization procedure. CONCLUSIONS: Embolization of the septal artery with PVA foam particles appears effective and safe in this series of patients with hypertrophic obstructive cardiomyopathy. The pure ischemic infarction produced by PVA ablation might be the responsible for the lack of complete heart block and the need for permanent pacing.

Adult↗

Forced homodimerization by site-directed mutagenesis alters guanylyl cyclase activity of natriuretic peptide receptor B.

Natriuretic peptides mediate their physiologic effects through activation of membrane-bound, guanylyl cyclase-coupled receptors (NPRs). Receptor dimerization is an important feature of signal transduction. This study was aimed at characterizing structurally important residues of the extracellular ligand-binding domain of NPR-B for receptor dimerization and cGMP generation. Deletion mutagenesis was used to replace cysteine residues at positions 53 (C53S), 417 (C417S), and 426 (C426S) by serine. Receptor expression, dimerization, whole-cell cGMP response, and guanylyl cyclase activity of membrane fractions were determined in stably transfected COS-7 cells. C53S, C417S, and C426S mutants were expressed and found to form disulfide-bridged covalent dimers. In contrast to NPR-B and C53S, C417S and C426S mutants displayed constitutive activity in whole cells (C417S, 146+/-12%, P<0.01; C426S, 153+/-7% of ligand-independent NPR-B cGMP generation, P<0.01). The cGMP response of C417S and C426S mutants in whole cells was dose dependent and approximately 4 times lower than that in NPR-B, whereas it was blunted in C53S-transfected cells (1 micromol/L CNP, NPR-B 2868+/-436%; C53S, 206+/-16% of control, P<0.001 vs NPR-B, C417S, and C426S). Guanylyl cyclase assay in transfected cells confirmed the constitutive activity of C417S and C426S mutants. These data suggest that receptor dimerization by covalent disulfide bridges alters ligand-independent as well as ligand-dependent receptor activity. Localization of the crosslink in relation to the cell membrane is important for configuration of the extracellular domain and the consecutive signal transduction.

Animals↗

Blood oxygen level-dependent magnetic resonance imaging in patients with stress-induced angina.

BACKGROUND: Blood oxygen level-dependent (BOLD) MRI reflects tissue oxygenation and may be useful for the detection of myocardial ischemia in patients with suspected coronary artery disease. METHODS AND RESULTS: We studied 25 patients with stress-induced angina using a T2*-sensitive echo planar imaging sequence before and during adenosine in a single-slice approach. BOLD-MRI results were compared with quantitative angiography and adenosine thallium single-photon emission computed tomography (SPECT). Although image quality was variable because of artifacts, no data were excluded from the analysis. During adenosine, a mean signal intensity decrease was observed for myocardial segments related to coronary stenoses >75%. On average, a nonsignificant increase was observed in the other segments. The angiographically determined stenosis was correlated with BOLD-MRI results. Including all segments and using BOLD-MRI signal intensity increase cutoff value of 1.2%, BOLD-MRI had a sensitivity of 88% and a specificity of 47% to correctly classify severe stenoses. Adenosine thallium SPECT data from distal segments of the same coronary territory were also correlated with BOLD-MRI. However, variability was substantial. CONCLUSIONS: In patients with stress-induced angina, adenosine BOLD-MRI detects myocardial ischemia in myocardial segments related to severe coronary stenoses. Its potential will increase with additional improvement of spatial coverage and image quality.

Adenosine↗

Cardiovascular magnetic resonance of acute myocardial infarction at a very early stage.

OBJECTIVES: Very early changes in myocardial tissue composition during acute myocardial infarction (AMI) are difficult to assess in vivo. Cardiovascular magnetic resonance (CMR) imaging provides techniques for visualizing tissue pathology. BACKGROUND: The diagnostic role of CMR in very acute stages of myocardial infarction is uncertain. We investigated signal intensity changes beginning within 60 min after acute coronary occlusion in patients undergoing therapeutic septal artery embolization. METHODS: We investigated eight patients with hypertrophic obstructive cardiomyopathy undergoing interventional septal artery embolization by applying microparticles to reduce left ventricular outflow tract obstruction. In a clinical 1.5-tesla (T) CMR system, we visualized infarct-related myocardial signal by T(1)-weighted sequences before and 20 min after administration of contrast media (delayed enhancement) and edema-related signal by T(2)-weighted spin-echo sequences before and 58 +/- 14 min after the intervention as well as on days 1, 3, 7, 14, 28, 90, and 180 during follow-up. RESULTS: Infarct-related changes as defined by contrast enhancement were observed as early as 1 h after the intervention and during six months of follow-up. In contrast, infarct-related myocardial edema, as visualized by high signal intensity in T(2)-weighted spin-echo sequences, was not consistently detectable 1 h after acute arterial occlusion; this was possible in all subsequent studies until day 28. CONCLUSIONS: Contrast-enhanced magnetic resonance imaging detected infarct-related signal changes as early as 1 h after AMI in humans, whereas the sensitivity of edema-related signal changes was not sufficient during this very early stage.

Adult↗

Hydroxymethylglutaryl coenzyme A reductase inhibition reduces Chlamydia pneumoniae-induced cell interaction and activation.

BACKGROUND: Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms. METHODS AND RESULTS: We infected human macrophages that in coculture spread infection to vascular smooth muscle cells (VSMCs). Cerivastatin (250 nmol/L) reduced VSMC infection by 33%. Western blotting made it apparent that VSMC infection resulted in increased cell membrane-associated RhoA and Rac1, implying increased prenylation of these proteins. This effect was blocked by statin but circumvented by mevalonate. Cytochrome C assays showed that infected VSMCs produced increased reactive oxygen species that was blocked by statin. Infection increased nuclear transcription factor-kappaB expression in VSMCs that was dose-dependently suppressed by statin. Infected VSMCs produced and released RANTES and MCP-1. Statin dose-dependently blocked this production both at the mRNA and protein levels. Mevalonate and M geranylgeranylpyrophosphate circumvented these effects. CONCLUSIONS: C pneumoniae can be transmitted from macrophages to VSMCs. VSMCs showed an activation profile typical of atherosclerosis, namely Rac1 and RhoA prenylation, nuclear transcription factor-kappaB activation, reactive oxygen species production, and chemokine production. Statin reduces macrophage-mediated C pneumoniae-induced signaling and transmission.

Animals↗