729-1 Modulation of Cardiac Hypertrophy by Blockade of the Renin Angiotensin System: Effects on LVH Regression, Gene Expression, and Survival

The aim of the present study was to investigate the contribution of the renin angiotensin system to maintenance of pressure overload left ventricular hypertrophy (LVH). Rats with fixed ascending aortic stenosis were treated with either vehicle (VEH, n=36), hydralazine (HYD, 20mg/kg/d, n=35). ramipril (RAM, 10mg/kg/d, n=35), or losartan (LOS, 40mg/kg/d, n=16) during weeks 6–12 after banding. We have previously demonstrated that compared to sham (n=36), VEH and HYD rats were characterized by a 1.8–1.9-fold increase of left ventricular to body weight ratios (LV/BW). whereas those aortic stenosis rats treated with RAM or LOS displayed a blunted increase of LV/BW (14-fold; p<0.05, each vs. HYD). We now extend these observations demonstrating that myocyte cross sectional widths were increased by 150% in VEH and HYD rats (p<0.001, vs. sham), whereas ramipril and losartan treatment resulted in myocyte widths that were only mildly elevated (53% and 28%, respectively). Furthermore, VEH and HYD displayed a 14–15 fold increase of LV atrial natriuretic peptide (ANP) mRNA as well as a 44% decrease of sarcoplasmatic reticulum (SR) Ca2+-ATPase (p<0.001, vs. sham). In contrast, alterations of ANP and SR-Ca2+-ATPase mRNA levels were significantly blunted by both RAM and LOS. The attenuation of LVH by RAM or LOS was not explained by blood pressure reduction that was similar in the HYD group. Finally, RAM and LOS decreased mortality (6 out of 51 animals; 11%)as compared to 20% in HYD and 31% in VEH groups (p<0.05).In summary, blockade of the renin angiotensin system may promote regression of pressure overload LVH on the macro-, and microscopical, as well as the molecular level by mechanisms that are, in part, independent of hemodynamic drug effects. LVH regression may improve survival despite persisting pressure overload

Time course of eosinophilic myocarditis visualized by CMR

We report the diagnostic potential of cardiovascular magnetic resonance (CMR) to visualize the time course of eosinophilic myocarditis upon successful treatment. A 50-year-old man was admitted with a progressive heart failure. Endomyocardial biopsies were taken from the left ventricle because of a white blood cell count of 17000/mm3 with 41% eosinophils. Histological evaluation revealed endomyocardial eosinophilic infiltration and areas of myocyte necrosis. The patient was diagnosed with hypereosinophilic myocarditis due to idiopathic hypereosinophilic syndrome. CMR-studies at presentation and a follow-up study 3 weeks later showed diffuse subendocardial LGE in the whole left ventricle. Upon treatment with steroids, CMR-studies revealed marked reduction of subendocardial LGE after 3 months in parallel with further clinical improvement. This case therefore highlights the clinical importance of CMR to visualize the extent of endomyocardial involvement in the diagnosis and treatment of eosinophilic myocarditis

First application of a new portable, miniaturized system for extracorporeal membrane oxygenation

Extracorporeal assist systems for respiratory and circulatory failure are increasingly used in intensive care medicine. Important technical innovations over the past years have resulted in improved biocompatibility and, consequently, reduced complication rates. Extracorporeal membrane oxygenation (ECMO) technology experienced a surge of use during the influenza A (H1N1) pandemic, but transport of unstable patients with life-threatening ARDS is still hazardous. We describe the first successful application of a newly developed, compact and easily portable ECMO device in a patient with severe ARDS due to influenza A (H1N1). Support with the miniaturized ECMO resulted in immediate improvement of gas exchange and a highly protective ventilation. Inspiratory pressure was decreased from 40 to 29 cmH2O and tidal volume per kilogram of predicted bodyweight could be reduced from 6.5 to 3.3 mL. Small and efficient heart-lung assist systems will become a tool of growing importance in intensive care medicine, both for profound respiratory and cardiac failure in the future. The reduced weight and compact design of the device greatly facilitates transport and handling of unstable patients on ECMO

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content. Conclusion Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling

Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk

Influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of rats

The aim of this study was to examine the influence of dietary NaCl intake on renin gene expression in the kidneys and adrenal glands of adult rats. Rats were kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin activity (PRA) and the relative abundance of renin messenger ribonucleic acid (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA values in animals on the low-salt diet increased transiently (about threefold) and then declined again during the third week of treatment. Renal renin mRNA levels in these animals paralleled the changes of PRA. Conversely, in the animals kept on a high-salt diet PRA values decreased transiently and renal renin mRNA decreased continuously to about 50% of control values. Arterial blood pressure measured in conscious animals was not significantly influenced by the different salt diets. To establish whether the changes in renin mRNA levels are mediated by renal nerve input, animals on the different diets were also studied after unilateral renal denervation. Renal nerve section led to a 50% decrease of renin mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In the animals on the low-salt diet renin mRNA rose to similar levels in the denervated to those in the innervated kidney, while in animals receiving a high-salt diet renin mRNA was further decreased in the denervated kidneys.(ABSTRACT TRUNCATED AT 250 WORDS

Increased myocardial SERCA expression in early type 2 diabetes mellitus is insulin dependent: In vivo and in vitro data

Background Calcium (Ca2+) handling proteins are known to play a pivotal role in the pathophysiology of cardiomyopathy. However little is known about early changes in the diabetic heart and the impact of insulin treatment (Ins). Methods Zucker Diabetic Fatty rats treated with or without insulin (ZDF +/- Ins, n = 13) and lean littermates (controls, n = 7) were sacrificed at the age of 19 weeks. ZDF + Ins (n = 6) were treated with insulin for the last 6 weeks of life. Gene expression of Ca2+ ATPase in the cardiac sarcoplasmatic reticulum (SERCA2a, further abbreviated as SERCA) and phospholamban (PLB) were determined by northern blotting. Ca2+ transport of the sarcoplasmatic reticulum (SR) was assessed by oxalate-facilitated 45Ca-uptake in left ventricular homogenates. In addition, isolated neonatal cardiomyocytes were stimulated in cell culture with insulin, glucose or triiodthyronine (T3, positive control). mRNA expression of SERCA and PLB were measured by Taqman PCR. Furthermore, effects of insulin treatment on force of contraction and relaxation were evaluated by cardiomyocytes grown in a three-dimensional collagen matrix (engineered heart tissue, EHT) stimulated for 5 days by insulin. By western blot phosphorylations status of Akt was determed and the influence of wortmannin. Results SERCA levels increased in both ZDF and ZDF + Ins compared to control (control 100 +/- 6.2 vs. ZDF 152 +/- 26.6* vs. ZDF + Ins 212 +/- 18.5*# % of control, *p < 0.05 vs. control, #p < 0.05 vs. ZDF) whereas PLB was significantly decreased in ZDF and ZDF + Ins (control 100 +/- 2.8 vs. ZDF 76.3 +/- 13.5* vs. ZDF + Ins 79.4 +/- 12.9* % of control, *p < 0.05 vs control). The increase in the SERCA/PLB ratio in ZDF and ZDF +/- Ins was accompanied by enhanced Ca2+ uptake to the SR (control 1.58 +/- 0.1 vs. ZDF 1.85 +/- 0.06* vs. ZDF + Ins 2.03 +/- 0.1* mug/mg/min, *p < 0.05 vs. control). Interestingly, there was a significant correlation between Ca2+ uptake and SERCA2a expression. As shown by in-vitro experiments, the effect of insulin on SERCA2a mRNA expression seemed to have a direct effect on cardiomyocytes. Furthermore, long-term treatment of engineered heart tissue with insulin increased the SERCA/PLB ratio and accelerated relaxation time. Akt was significantly phosphorylated by insulin. This effect could be abolished by wortmannin. Conclusion The current data demonstrate that early type 2 diabetes is associated with an increase in the SERCA/PLB ratio and that insulin directly stimulates SERCA expression and relaxation velocity. These results underline the important role of insulin and calcium handling proteins in the cardiac adaptation process of type 2 diabetes mellitus contributing to cardiac remodeling and show the important role of PI3-kinase- kt-SERCA2a signaling cascade

Nano-MIP based sensor for penicillin G: Sensitive layer and analytical validation

We herein report the synthesis of novel Penicillin G (PenG) imprinted polymer nanoparticles (MIPs) via inverse miniemulsion polymerization. Nanoscaled co-polymer particles consisting of N-(2-aminoethyl) methacrylamide hydrochloride as functional monomer and N,N’-Ethylenebisacrylamide as crosslinker have been synthesized in the presence of PenG. These particles have been applied to form a sensitive layer for label-free direct optical sensing of Penicillin G. As reference material non-imprinted particles (NIPs) were used. The particles were characterized via scanning electron microscopy (SEM) and dynamic light scattering (DLS). Particles in the size of ≈400 nm (z-average) and a low polydispersity index (PDI < 0.05) were observed. Azide modified MIPs/NIPs were covalently immobilized on alkyne-modified glass transducers by Cu(I) catalyzed 1,3-dipolar cycloaddition. The resulting particle-modified transducers served as sensing layer in an optical sensor setup (Reflectomteric Interference Spectroscopy – RIfS). To prove its reliability and stability the transducer was tested in 78 reproducible PenG measurements over the course of 26 h. The response time of the sensor was ≈1 min. For sensor calibration 14 randomized triplicate concentration dependency measurements for MIP and NIP transducers were conducted with different PenG concentrations ranging from 0.0015–0.0195 mol/L. MIP binding signals were significantly higher compared to the NIP. Determined recovery rates of three different transducers were in the range of 70–120 % which indicates a good chip to chip reproducibility. Sensor cross sensitivities between PenG and its structural buildings blocks phenylacetic acid and 6-aminopenicillanic acid were evaluated indicating a high selectivity for the presented sensor system