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Eosinophils are circulating and tissue-resident leukocytes that have potent proinflammatory effects in a number of diseases. Recently, eosinophils have been shown to have various other functions, including immunoregulation and antiviral activity. Eosinophil levels vary dramatically in a number of clinical settings, especially following eosinophil-targeted therapy, which is now available to selectively deplete these cells. There are key coronavirus disease 2019 (COVID-19)-related questions concerning eosinophils whose answers affect recommended prevention and care. First, do patients with eosinophilia-associated diseases have an altered course of COVID-19? Second, do patients with eosinopenia (now intentionally induced by biological drugs) have unique COVID-19 susceptibility and/or disease course? This is a particularly relevant question because eosinopenia is associated with acute respiratory deterioration during infection with the severe acute respiratory syndrome coronavirus 2, the causative agent of COVID-19. Third, do eosinophils contribute to the lung pathology induced during COVID-19 and will they contribute to immunopotentiation potentially associated with emerging COVID-19 vaccines? Herein, we address these timely questions and project considerations during the emerging COVID-19 pandemic.

Aims To assess the impact of the lockdown due to coronavirus disease 2019 (COVID-19) on key quality indicators for the treatment of ST-segment elevation myocardial infarction (STEMI) patients. Methods Data were obtained from 41 hospitals participating in the prospective Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) study, including 15,800 patients treated for acute STEMI from January 2017 to the end of March 2020. Results There was a 12.6% decrease in the total number of STEMI patients treated at the peak of the pandemic in March 2020 as compared to the mean number treated in the March months of the preceding years. This was accompanied by a significant difference among the modes of admission to hospitals (p = 0.017) with a particular decline in intra-hospital infarctions and transfer patients from other hospitals, while the proportion of patients transported by emergency medical service (EMS) remained stable. In EMS-transported patients, predefined quality indicators, such as percentages of pre-hospital ECGs (both 97%, 95% CI = − 2.2–2.7, p = 0.846), direct transports from the scene to the catheterization laboratory bypassing the emergency department (68% vs. 66%, 95% CI = − 4.9–7.9, p = 0.641), and contact-to-balloon-times of less than or equal to 90 min (58.3% vs. 57.8%, 95%CI = − 6.2–7.2, p = 0.879) were not significantly altered during the COVID-19 crisis, as was in-hospital mortality (9.2% vs. 8.5%, 95% CI = − 3.2–4.5, p = 0.739). Conclusions Clinically important indicators for STEMI management were unaffected at the peak of COVID-19, suggesting that the pre-existing logistic structure in the regional STEMI networks preserved high-quality standards even when challenged by a threatening pandemic. Clinical trial registration NCT00794001

Hemodialysis (HD) patients exhibit chronic inflammation and leukocyte activation. We investigated the surface-marker profile of monocytes by flow cytometry to assess the chronic effect of uremia and the acute effect of dialysis on their phenotypical and functional features in 16 healthy controls (CON) and 15 HD patients before and after a polysulfone-based dialysis session. Median fluorescence intensities were analyzed indicating expression of CD14, CD16, integrins (CD11b, CD18), chemokine receptors (CCR2, CX3CR1), scavenger receptors (CD36, CD163) and Toll-like receptor-2 (TLR2). Before and after dialysis, HD patients harbour 0.9-fold less CD14++CD16− (Mo1), 1.8-fold more CD14++CD16+ (Mo2) and CD14+CD16++ (Mo3) monocytes than CON. HD patients’ Mo1 showed elevated expression of CD11b (1.7-fold), CD18 (1.2-fold) and CD36 (2.1-fold), whereas CD163 expression was reduced in Mo1 and Mo2 (0.6-fold) compared to CON. These markers remained unaffected by dialysis. CX3CR1 expression on Mo2 and Mo3 was lower in HD patients before (0.8-fold) and further diminished after dialysis (0.6-fold). Stimulation of monocytes resulted in diminished responses in HD patients compared to CON. In conclusion, a systematic analysis of the expression of particular surface markers on distinct monocyte subsets may help to distinguish between uremia and/or dialysis induced effects and to evaluate the functionality of monocytes and biocompatibility of HD.

Heart failure causes electrophysiological changes in the heart. Downregulation of repolarizing K+-currents leads to a prolongation of the cardiac action potential. Nevertheless, little is known about the differential expression of atrial and ventricular K+-channels in the failing heart. Ten rabbits underwent progressive rapid right ventricular pacing for 30 days. Digitized ECGs and echocardiograms were obtained. Left ventricular and left atrial tissue was harvested and mRNA levels of BNP, Kv4.3, rERG, Kv1.5, and KvLQT1 were measured by real time PCR. Experimental heart failure was characterized by left ventricular dilatation (13 ± 1 mm vs. 9 ± 1, p

Background The combination of high-frequency oscillatory ventilation (HFOV) and extracorporeal carbon dioxide removal with the interventional lung assist (iLA) in severe acute respiratory distress syndrome (ARDS) represents a novel treatment option. Methods The study used a retrospective single-center analysis of 21 consecutive adult patients with severe ARDS, ventilated with HFOV/iLA. Efficiency, side effects, and outcome of combined treatment are presented as median (interquartile range). Measurements and Main Results The following were used to determine patient characteristics: sequential organ failure assessment score, 14; simplified acute physiology score II, 41; and Murray score, 4. The duration of combined treatment was 6 days. The blood flow through the iLA was 1.9 L/min. The Pao 2 /inspired fraction of oxygen ratio increased from 61 (47-86) to 98 (67-116) within 2 hours and to 106 (70-135) mm Hg at 24 hours. Paco 2 decreased from 58 (50-76) to 37 (29-47) mm Hg at 2 hours with normalization of pH 7.28 (7.16-7.36) to 7.43 (7.33-7.49) after 2 hours associated with hemodynamic stabilization. In 6 patients, complications due to iLA treatment were observed, and in 3 patients, complications associated with HFOV were seen. Weaning from HFOV/iLA was successful in 10 patients. The 30-day mortality rate was 43%, and hospital mortality rate was 57%. Conclusion The combination of HFOV/iLA is an option in severe pulmonary failure if conventional ventilation fails and pumpdriven extracorporeal membrane oxygenation therapy is not available.

Background: Whereas N-terminal pro-brain natriuretic peptide (NT-proBNP) is approved for risk stratification of patients with acute coronary syndromes (ACS), short-term temporal changes in NT-proBNP concentrations and the optimal time points for sampling are not clear. The purpose of this study was to better define the short-term changes in NT-proBNP in relation to clinical presentation, reperfusion and prognostic value in patients with ACS, as well as to identify the optimum time points for sampling. Methods: We studied daily plasma concentrations of NT-proBNP in 133 unselected patients with myocardial infarction (n=65), stable coronary artery disease (CAD, n=46) and no CAD (n=22) who underwent coronary angiography. Results: Patients with non-ST-elevation myocardial infarction (NSTEMI) presented with markedly higher NT-proBNP than patients with ST-elevation myocardial infarction (STEMI) [1305 (741–3208) ng/L vs. 170 (70–424) ng/L, p48 h vs. Conclusions: In patients with NSTEMI, NT-proBNP may be increased as high as concentrations usually associated with acute congestive heart failure despite the absence of clinical signs. In contrast, patients with STEMI and short time to presentation may present with completely normal NT-proBNP, but dramatic short-term increases following reperfusion. NT-proBNP reflects ischemic burden, reperfusion success and prognosis, and the current data support repetitive sampling in patients with ACS. Clin Chem Lab Med 2010;48:875–81.

CD4(+)CD25(high) regulatory T cells (T(reg)) have the potent ability to suppress host immune responses, thus preventing autoimmune diseases. However, increased T(reg) frequencies have also been found in cancer patients implicating their involvement in tumor escape from immunological control. We investigated the frequency, functional effects and gene expression pattern of T(reg) in patients with renal cell carcinoma (RCC). Therefore, T(reg) were isolated from the peripheral blood of 11 treatment-naïve RCC patients and 11 healthy donors applying a magnetic cell separation system. Frequency, purity after isolation and function were evaluated using FACS and suppression assays, respectively. Gene expression patterns were compared applying a self-developed customized oligonucleotide microarray and by quantitative RT-PCR. T(reg) frequencies were significantly increased in RCC patients; suppression assays proved that the isolated CD4(+)CD25(high) cells had the functional characteristics of T(reg) cells. Comparing gene expression profiles between T(reg )of RCC patients and healthy controls revealed significant differences in the expression levels of 49 genes. Gene ontology identified an association of significantly up-/downregulated genes to six functional classes, particularly genes involved in apoptosis control such as LGALS1, LGALS3, BAX, IL7R and TNFRSF25. In RCC patients, frequencies of functionally active T(reg) cells were elevated; the T(reg) gene expression pattern differed significantly between patients and controls. As several anti-apoptotic genes were upregulated and pro-apoptotic genes were downregulated in RCC patients, we conclude that T(reg) cells derived from RCC patients might be less responsive to apoptotic stimuli, possibly promoting their accumulation in tumor patients.

Background— Spatial and timely variations in QT interval, even within its normal range, may underlie susceptibility to cardiac arrhythmias and sudden cardiac death. Given its important role in cardiac electrophysiology, we hypothesized that common genetic variation in ankyrin-B gene ( ANK2 ) might modify QT interval length. Methods and Results— The study population consisted of 1188 participants of the World Health Organizational Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO MONICA) general population survey Cooperative Health Research in the Region of Augsburg (KORA S3). Corrected QT interval was calculated using population specific linear regression formulas. A total of 22 single-nucleotide polymorphisms in the genomic region of ANK2 gene were genotyped using TaqMan technology. In a replication study, 6 single nucleotide polymorphisms were genotyped in 3890 individuals from a second population study (KORA S4). The rare variant of the single-nucleotide polymorphism rs6850768 (allele frequency, 0.28) significantly influenced duration of the QT interval, both in KORA S3 and KORA S4 populations. In homozygotes, the shortening of the QT interval was 3.79 ms (95% CI, 1.48 to 5.58; P =0.001 and P =0.0008 for log-additive and dominant model, respectively) in KORA S3 and 2.94 ms (95% CI, 1.11 to 4.77; P =0.001 and P =0.006 for log-additive and dominant genetic model, respectively) in KORA S4. A common 2-locus haplotype (rs11098171-rs6850768; population frequency, 28%) was associated with a QT interval difference of 2.85 ms (permutation; P =0.006) in KORA S3 and 1.23 ms (permutation; P =0.009) in KORA S4. Reverse transcription–polymerase chain reaction expression analysis of the human ANK2 5′ genomic region in the human left ventricular tissue revealed 2 previously unidentified ANK2 5′ exons in the proximity of the identified variants. Conclusions— Common genetic variants juxtaposed with novel exons in the distant 5′ genomic region of ANK2 influence the QT interval length in the general population. These findings support the role of ankyrin-B in normal cardiac electric activity.

PPARalpha (peroxisome-proliferator-activated receptor alpha) regulates the expression of genes that are involved in lipid metabolism, tissue homoeostasis and inflammation. Consistent rodent and human studies suggest a link between PPARalpha function and cardiovascular disease, qualifying PPARalpha [PPARA in HUGO (Human Genome Organisation) gene nomenclature] as a candidate gene for coronary artery disease. In the present study, we comprehensively evaluated common genetic variations within the PPARalpha gene and assessed their association with myocardial infarction. First, we characterized the linkage disequilibrium within the PPARalpha gene in an initial case-control sample of 806 individuals from the Regensburg Myocardial Infarction Family Study using a panel of densely spaced SNPs (single nucleotide polymorphisms) across the gene. Single SNP analysis showed significant association with the disease phenotype [OR (odds ratio)=0.74, P=0.012, 95% CI (confidence interval)=0.61-0.94 for rs135551]. Moreover, we identified a protective three-marker haplotype with an association trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.02). Subsequently, we were able to confirm the single SNP and haplotype association results in an independent second case-control cohort with 667 cases from the Regensburg Myocardial Infarction Family Study and 862 control individuals from the WHO (World Health Organization) MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99 for rs135551 and OR=0.80, P=0.034, 95% CI=0.65-0.98 for the three-marker haplotype respectively). From these cross-sectional association results, we provide evidence that common variations in the PPARalpha gene may influence the risk of myocardial infarction in a European population.

Recently, the genetic variant Y402H in the CFH (complement factor H) gene was associated with an increased risk for MI (myocardial infarction) in a prospective Caucasian cohort. In another nested case-control study, however, the CFH -Y402H variant did not carry susceptibility to MI. The aim of the present study was to test for an association between the CFH -Y402H variant and MI in a large case-control sample with a familial background for CAD (coronary artery disease). A total of 2161 individuals from the German MI family study were studied by questionnaire, physical examination and biochemical analyses. MI patients ( n =1188; 51.4±8.6 years at first MI) were recruited from families with at least two members affected by MI and/or severe CAD. Spouses, sisters-in-law and brothers-in-law respectively, without MI/CAD were included as unaffected controls ( n =973; 56.9±9.8 years). Genotyping was performed using a TaqMan assay. The common Y402H variant in the CFH gene was not associated with classical cardiovascular risk factors (diabetes, hypercholesterolaemia, hypertension, obesity, smoking and C-reactive protein serum levels). No association was found between the CFH -Y402H variant and susceptibility to MI. Separate analyses in both men and women revealed no gender-specific influence of the gene variant on cardiovascular risk factors or MI. This investigation was unable to replicate the association between the common CFH -Y402H variant and susceptibility to MI in our large Caucasian population which is enriched for genetic factors. We conclude that the CFH -Y402H variant has no relevant risk-modifying effect in our population.

Purpose. – Patients with an acute myocardial infarction (AMI) are of high risk to develop ischemia-induced ventricular arrhythmias, leading to sudden cardiac death (SCD) in about one third of all AMI patients. The individual susceptibility to ischemia-induced arrhythmias may be modified by polymorphisms in genes encoding ion channels. The cardiac ATP-dependent potassium channel (K ATP ) current is generated by ion channels encoded by the KCNJ11 gene and the SUR2a gene. Opening of the K ATP channel during ischemia results in action potential shortening in various studies and may therefore influence the outcome of AMI patients. Methods. – Using a three-primer strategy, we sequenced the complete coding and adjacent 5′ and 3′ sequences of the intronless KCNJ11 gene (1.3 kb) prospectively in two groups. Patients of group 1 ( n = 84) survived three or more transmyocardial infarctions without developing any ventricular arrhythmias. Patients of group 2 died suddenly from their first myocardial infarction ( n = 86), most of them witnessed SCDs. Results. – We identified a total of six known polymorphisms (K23E, A190A, L267V, L270V, I337V, and K281K) and two new polymorphisms (L267L, 3′UTR +62 G/A). The allele, genotype, and haplotype frequencies did not differ between the two groups. All polymorphisms were found to be in Hardy–Weinberg equilibrium. In addition, we identified two novel missense mutations in a highly conserved region of the gene in two patients of group 2 (P266T and R371H) with yet unknown functional consequences. Conclusion. – In this study of AMI patients, SCD was not related to polymorphisms in the KCNJ11 gene.

The heart rate turbulence (HRT) parameters were introduced for risk stratification of ventricular arrhythmias in postmyocardial infarction patients. However, the relationship of these parameters with other risk stratificators such as heart rate variability (HRV), repolarization parameters or left ventricular function is unknown. Furthermore, the influence of age and medication on HRT remains to be evaluated. Holter ECG's of 509 post‐MI patients (1–10 years after MI) were screened for single ventricular extrasystole. In 196 patients the parameters' turbulence onset (TO) and turbulence slope (TS) could be computed. A pathological TO (>0%) and TS ( 45%. In contrast, the percentage of pathological HRT was not different between patients with left ventricular hypertrophy (16 out of 59, 27%) compared to patients without LVH (38 out of 133, 28%). The HRT was pathological in 14 out of 24 patients with diabetes mellitus (58%) compared to 40 out of 172 (23%) normoglycemic patients (TO: −0.6 ± 3.1 vs. −2.5 ± 5.5, P < 0.02). HRT was similar in patients with ß‐blockers (n = 96) as in patients without ß‐blockers (n = 100). In stable post‐MI patients, HRT is influenced by age and left ventricular function and correlates with heart rate variability. Therapy with ß‐blockers has no influence on HRT, while diabetic patients may have an increased likelihood of pathological HRT.

Activation of cytokines such as interleukin-6 (IL-6) has been implicated in the pathogenesis of left ventricular dysfunction and hypertrophy since they have been shown to mediate cell proliferation, negative inotropic effects and myocardial hypertrophy. However, the effects of immunosuppressive therapy on cytokines in the treatment of heart failure and hypertrophy are unclear.To test the hypothesis that systemic immunosuppresion may influence serum and myocardial IL-6 and, thereby, may affect progression of myocardial hypertrophy. We studied the effects of chronic treatment with methotrexate (MTx) and with the ACE inhibitor ramipril on IL-6 in rats with pressure overload left ventricular hypertrophy (LVH) due to aortic banding.Animals were treated with either vehicle (n = 6) or methotrexate (MTx 1: 0.3 mg/kg BW/week; MTx 2: 0.9 mg/kg BW/week; i.p.; n = 6 each group) once a week during weeks 4-12 after aortic banding; sham-operated rats served as controls (CTRL; n = 8). During the development of LVH, serum IL-6 was determined by rat-specific ELISA and 12 weeks after aortic banding myocardial IL-6 was measured using a tissue superfusion technique or determining of protein concentration.Aortic banding significantly lowered blood pressure, increased left ventricular weight and resulted in elevated serum IL-6 levels (27.6 +/- 5.1 vs 19.1 +/- 2.3 pg/ml, p0.05) compared to CTRL. MTx treatment normalised the initially elevated serum IL-6 levels after 8 weeks of treatment. The significant increase in IL-6 concentration in the superfusate of all aortic banding groups compared to CTRL (30%, p0.05) was not altered by prior MTx therapy. Accordingly, both doses of MTx failed to prevent LVH progression (1.67 +/- 0.23 g vs. 2.32 +/- 0.31 g, p0.05). In contrast, chronic inhibition of the RAAS not only prevents LVH but also reduces myocardial IL-6 concentration (6898 +/- 355 vs. 3073 +/- 366 pg/mg protein, p0.05).Pressure overload LVH in rats is characterized by an increase in serum levels of IL-6 as well as myocardial IL-6. Chronic immunosuppressive therapy normalized systemic IL-6 levels, but failed to reduce cardiac IL-6 expression and the progression of LVH, while ACE inhibition is sufficient to modify LVH and thereby normalises myocardial IL-6 expression.

We created a mouse model with a prolonged Q-T interval and spontaneous arrhythmias by overexpressing the NH2terminus and first transmembrane segment ( Kv1.1N206Tag) of a delayed rectifier potassium channel (LQT+/ − mouse). Analyses were performed using whole cell recordings of cardiac myocytes, surface electrocardiography, and programmed electrical stimulation. Action potential duration (APD) was prolonged to the same extent and was more highly variable in myocytes derived from LQT+/ − and LQT+/+ mice than in myocytes derived from wild-type (WT) FVB mice. Under ketamine anesthesia, the Q-T interval of both LQT+/+ and LQT+/ − mice was comparably prolonged versus that of WT mice. Stimulation of the right ventricle using an intracardiac catheter induced polymorphic ventricular tachyarrhythmias in 50% of the LQT+/ − mice and 36% of the LQT+/+ mice, whereas polymorphic ventricular tachyarrhythmias were not inducible in WT mice. The analyses of LQT+/ − and LQT+/+ mice indicate that prolongation of the Q-T interval in LQT mice is associated with prolonged APD, increased dispersion of APD among cardiocytes, and inducibility of polymorphic ventricular tachycardia, providing the substrate for spontaneous arrhythmias in these animals.

The safety and efficacy of adding oral carvedilol (25 mg twice daily) to standardized treatment of unstable angina was assessed in a multicenter, randomized, double-blind, placebo- controlled trial on 116 patients with acute unstable angina. Patients were monitored in an intensive care unit and underwent 48-hour Holter monitoring to assess transient ischemia. Carvedilol as adjunctive therapy resulted in a significant reduction of median heart rate (65 vs 75 beats/min, p

After the gastrointestinal tract, the lung is the second largest surface for interaction between the vertebrate body and the environment. Here, an effective gas exchange must be maintained, while at the same time avoiding infection by the multiple pathogens that are inhaled during normal breathing. To achieve this, a superb set of defense strategies combining humoral and cellular immune mechanisms exists. One of the most effective measures for acute defense of the lung is the recruitment of neutrophils, which either phagocytose the inhaled pathogens or kill them by releasing cytotoxic chemicals. A recent addition to the arsenal of neutrophils is their explosive release of extracellular DNA-NETs by which bacteria or fungi can be caught or inactivated even after the NET releasing cells have died. We present here a method that allows one to directly observe neutrophils, migrating within a recently infected lung, phagocytosing fungal pathogens as well as visualize the extensive NETs that they have produced throughout the infected tissue. The method describes the preparation of thick viable lung slices 7 hours after intratracheal infection of mice with conidia of the mold Aspergillus fumigatus and their examination by multicolor time-lapse 2-photon microscopy. This approach allows one to directly investigate antifungal defense in native lung tissue and thus opens a new avenue for the detailed investigation of pulmonary immunity.

Seventy-seven diabetics with a duration of the disease ranging from 2 to 55 years (average 18.5 years) were studied with infrared videopupillometry. The prevalence of diabetic autonomic neuropathy at the pupillary control system (pANP) was studied comparatively using several pupillary tests. The average prevalence using age-dependent parameters was 30.2% [maximal pupillary area: 22.1%, maximal contraction velocity: 24.7%, contraction velocity at 1 s (CV1): 28.6%, and dilation velocity at 6 s (DV6): 45.5%]. Comparing these percentages to prevalences of other diabetic late complications, e.g. retinopathy (49.4%), DV6 seems to be good for the diagnosis of pANP. If CV1 and DV6 are expressed in percent of the maximal pupillary area (CV1% and DV6%), they become age-independent. The average CV1% and DV6% of diabetics differ highly significantly from those of normals (CV1%: 58.6 +/- 14.5 vs. 64.1 +/- 6.4%, 2 p less than 0.005, and DV6%: 6.0 +/- 2.9 vs. 7.3 +/- 1.1%, 2 p less than 0.001). The average prevalence of pANP using these age-independent parameters was 25.4%. These data suggest that the prevalence of pANP, especially disorders of pupillary dilation (DV6), is high in long-standing diabetes. Furthermore, CV1% and DV6% have proved to be valid parameters in finding differences in the light reflex in non-age-matched study groups.

BACKGROUND: Ablation of atrial fibrillation (AF) has been one of the most difficult and time-consuming electrophysiological procedures. Due to the rapidly increasing demand for ablation procedures, technical advances would be helpful to reduce complexity and procedure time in AF ablation. Therefore, we investigated the feasibility of a single-catheter technique for pulmonary vein (PV) isolation utilizing a decapolar catheter combined with a duty-cycled, unipolar-bipolar radiofrequency (RF) generator. METHODS: AF mapping and ablation was performed in 21 consecutive patients (mean age 59 +/- 12 years, 9 males) with paroxysmal AF (n = 17) and persistent AF (n = 4). The ablation catheter was forwarded to the LA via single-transseptal puncture. All electrodes were energized in 2 to 5 applications per vein, followed by segmental RF applications, as needed, to achieve electrical isolation. To assess left atrial anatomy for purposes of catheter manipulation, and later evaluate the possibility of asymptomatic PV-stenosis, CT or MR imaging was performed both prior to ablation and at 6-month follow-up. RESULTS: Isolation could be achieved in 85/86 veins (99%). Procedure time for ablation was 81 +/- 13 minutes, and fluoroscopy time was 30 +/- 11 minutes. There were no procedural complications. Success rate at 6 months was 86% (18/21). MR or CT imaging excluded asymptomatic PV-stenosis. CONCLUSION: Mapping and ablation of PVs can be performed in a safe and efficient manner using a single-catheter technique, with short procedure times and minimal learning curve. Thus, this system may be of high interest not only for high volume but all centers performing AF ablation.

Myocardial infarction (MI) is a complex disease. Multiple genes and their interaction with various environmental factors influence the pathogenesis of MI that is thought to be tightly regulated by inflammatory pathways. Recent progress in genetic analysis includes the use of large-scale genome-wide association studies that have proven to be powerful tools even in the analysis of multifactorial phenotypes. However, certain genes are only sparsely represented on the available gene chips and additional candidate gene approaches are necessary. One such example is the CNR2 gene, encoding the cannabinoid receptor 2 (CB2), which has been implicated in mediating anti-inflammatory and anti-atherosclerotic effects in vivo. We therefore hypothesized that genetic variations within the CNR2 gene are associated with the development of MI or classic cardiovascular risk factors. In a large case-control study, 1,968 individuals from the German MI family study were examined with 13 single nucleotide polymorphisms (SNPs) covering CNR2 and the adjacent genes. The association of these SNPs with MI or cardiovascular risk factors, such as arterial hypertension, obesity, hypercholesterolemia and diabetes mellitus, was determined. In allelic and genotypic models, none of the SNPs showed a significant association with MI. Separate analyses for men and women revealed no gender-specific relationship between common genetic variations within the CNR2 gene and MI. Moreover, no significant association between CNR2 gene variants and common cardiovascular risk factors was observed. We therefore provide evidence in a large German population that common polymorphisms within the CNR2 gene confer no susceptibility to MI or to cardiovascular risk factors.

Congestive heart failure (CHF) is often associated with atrial fibrillation. The safety of many antiarrhythmic drugs in CHF is limited by proarrhythmic effects. We aimed to assess the safety of a novel atrial-selective K(+)-channel blocker AVE0118 in CHF compared to a selective (dofetilide) and a non-selective IKr blocker (terfenadine). For the induction of CHF, rabbits (n = 12) underwent rapid right ventricular pacing (330-380 bpm for 30 days). AVE0118 (1 mg/kg) dofetilide (0.02 mg/kg) and terfenadine (2 mg/kg) were administered in baseline (BL) and CHF. A six-lead ECG was continuously recorded digitally for 30 min after each drug administration. At BL, dofetilide and terfenadine significantly prolonged QTc interval (218 +/- 30 ms vs 155 +/- 8 ms, p = 0.001 and 178 +/- 23 ms vs. 153 +/- 12 ms, p = 0.01, respectively) while QTc intervals were constant after administration of AVE0118 (p = n.s.). In CHF, dofetilide and terfenadine caused torsades de pointes and symptomatic bradycardia, respectively, and prolonged QTc interval (178 +/- 30 ms vs. 153 +/- 14 ms, p = 0.02 and 157 +/- 7 ms vs. 147 +/- 10 ms, p = 0.02, respectively) even at reduced dosages, whereas no QTc-prolongation or arrhythmia was observed after full-dose administration of AVE0118. In conclusion, atrial-selective K(+)-channel blockade by AVE0118 appears safe in experimental CHF.

Aims Prolongation of QT dispersion can be observed in some patients with myocardial infarction and serves as a possible independent risk factor for sudden cardiac death. Angiotensin-converting enzyme (ACE) inhibition has been shown to reduce QT dispersion in myocardial infarction patients. We hypothesized that ACE gene I/D polymorphism, which is known to modulate ACE activity, may also affect QT dispersion after myocardial infarction. Methods and Results We studied 609 myocardial infarction patients (532 men, aged 56·1±0·3; mean 5·5 years after myocardial infarction) from a population-based myocardial infarction register by standardized questionnaire, anthropometry, ECG, echocardiography, and genotyping of ACE I/D polymorphism. In addition, 540 unaffected siblings (251 men, age 54·6±0·4 years) of these patients were studied by the same protocol. As compared with their healthy siblings, mean QT dispersion was prolonged in myocardial infarction patients (65·9±1·4ms vs 91·2±2·3ms, respectively, P

1. Adenosine is an endogenous nucleoside which causes a brief blockade of the AV nodal conduction pathway following intravenous administration. 2. Such a brief AV block can be used therapeutically for reliable termination of AV nodal re-entry tachycardia and WPW re-entry tachycardia. It can also be used for demasking atrial activity in rapid suspected supraventricular tachycardia with a broad QRS complex or a Delta wave, not present during sinus rhythm with normal AV node conduction, indicating the presence of a hidden WPW syndrome. 3. Side effects after adenosine application are frequent, but very transient rarely serious (1-3% of cases, e.g. status asthmaticus, ventricular fibrillation) and therefore require a certain degree of experience with this drug on the part of the treating physician.

Transmyocardial laser-revascularisation (TMLR) is a new and promising method for the treatment of angina pectoris in patients with no other therapeutic options. We investigated the incidence of ventricular arrhythmias (VA) before, immediately after and 4 months after TMLR.