Haptoglobin genotype determines myocardial infarct size in diabetic mice.

OBJECTIVES: We sought to understand the importance of oxidative stress in explaining why the haptoglobin (Hp) genotype determines myocardial infarction (MI) size in diabetes mellitus (DM). BACKGROUND: Two common alleles (1 and 2) exist at the Hp locus in humans. The Hp 2 allele is associated with increased MI size in individuals with DM. In vitro, the Hp 2 protein is associated with increased generation of oxidatively active iron, whereas the Hp 1 protein is associated with increased production of the antioxidant cytokine interleukin (IL)-10. METHODS: Myocardial infarction was produced by myocardial ischemia-reperfusion (IR) in DM C57BL/6 mice carrying the Hp 1 or Hp 2 allele. Myocardial oxidative stress after IR was assessed using electrospray ionization mass spectrometry. Redox active iron and IL-10 were measured in the serum after IR. RESULTS: Myocardial infarction size was significantly larger in Hp 2 mice as compared with Hp 1 mice (44.3 +/- 9.3% vs. 21.0 +/- 4.0%, p = 0.03), and these larger infarctions were associated with a significant increase in a panel of hydroxyl-eicosatetraenoic acids. Redox active iron was greater in Hp 2 mice (0.45 +/- 0.11 micromol/l vs. 0.14 +/- 0.05 micromol/l, p = 0.02), whereas IL-10 was greater in Hp 1 mice (85.8 +/- 12.9 pg/microl vs. 46.7 +/- 10.8 pg/microl, p = 0.04) after IR. Administration of an antioxidant (BXT-51072) to Hp 2 mice reduced myocardial injury after IR by more than 80% (p = 0.003), but no myocardial protection was provided by the antioxidant to Hp 1 mice. CONCLUSIONS: The increased MI size in DM Hp 2 mice occurring after IR may be due to increased oxidative stress.     

Percutaneous approach to a stent-based ventricle to coronary vein bypass (venous VPASS): comparison to catheter-based selective pressure-regulated retro-infusion of the coronary vein.

AIMS: Percutaneous stent-based ventricle-to-coronary vein bypass (venous VPASS) is a new approach to chronic venous arterialization as a treatment modality in an otherwise no option patient with coronary artery disease. In this study, the efficacy of venous VPASS was compared with catheter-based selective pressure-regulated retro-infusion of arterial blood during acute ischaemia. METHODS AND RESULTS: In seven pigs, venous VPASS was established using a percutaneous ultrasound-guided puncture from the anterior cardiac vein to the left ventricle, with subsequent implantation of an ePTFE-covered stent graft. During left anterior descending artery (LAD) occlusion, coronary venous pressure in the distal anterior cardiac vein increased to 55+/-4 mmHg under conditions of venous VPASS compared with 78+/-5 mmHg during selective pressure-regulated retro-infusion. Significant preservation of regional myocardial function was observed during venous VPASS (67+/-6% baseline) and during selective retro-infusion (83+/-4%) compared with control LAD occlusion (0.4+/-2%). CONCLUSION: Percutaneous implantation of a PTFE covered stent (venous VPASS) was feasible and associated with significant preservation of regional myocardial function during acute ischaemia in pigs at reasonable levels of mean coronary venous pressure to avoid tissue damage during chronic application.     

Left ventricular assist devices as destination therapy in stage D heart failure

None     

Array‐based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non‐CNS diffuse large B‐cell lymphomas

Primary lymphomas of the central nervous system (PCNSL) are diffuse large B‐cell lymphomas (DLBCLs) confined to the central nervous system (CNS). We here performed array‐based DNA methylation analyses of 26 PCNSL and 78 DLBCL and validated our findings in an independent dataset. We identified 2847 CpGs differentially methylated between PCNSL and non‐CNS‐DLBCL. Neither a supervised analysis using these CpGs nor application of 3 CpG classifiers selected for class separation unambiguously separated PCNSL from non‐CNS‐DLBCL. Remarkably, 6/78 non‐CNS‐DLBCL consistently segregated with PCNSL, which displayed molecular features typical for PCNSL. Our findings suggest that a subset of non‐CNS‐DLBCL exists which molecularly resembles PCNSL.     

Differential effects of potassium channel blockers on the activity of the locomotor network in neonatal rat

The role played by various K+ channels during locomotor activity was studied using an in vitro neonatal rat spinal cord preparation. Locomotor-like activity was elicited by bath-applying serotonin (5-HT) and N-methyl-d-l-aspartate (NMA). Four different K+ channel blockers were tested by adding them to the superfusing saline. Each of the K+ channel blockers elicited a characteristic motor pattern with specific temporal parameters. Cs+ and tetraethyl ammonium both decreased the motor period, but had opposite effects on the burst amplitude. Apamin increased both the motor period and the burst amplitude. A dose-response relationship was established for the K+ channel blockers. The blockers elicited an unstable rhythmic activity, contrary to what occurred under control conditions. We also found that due to the specific changes that they elicit, the various blockers produce selective changes in the burst ratio. These results suggest that the various K+ channels contribute differently to the generation of locomotor activity.     

Label-free imaging of age-related cardiac structural changes in non-human primates using multiphoton nonlinear microscopy

Heart failure is one of the most common causes of morbidity and mortality. Both maturational abnormalities and age-associated cardiac pathologies contribute to heart failure. Imaging-based assessment to discern detailed cardiac structure at various maturational stages is imperative for understanding mechanisms behind cardiac growth and aging. Using multiphoton nonlinear optical microscopy (NLOM) based label-free imaging, we investigated cardiac structural composition in a human-relevant aging model, the common marmoset monkey (Callithrix jacchus). Animals were divided into three different age groups including neonatal, young adult and old. By devising a unique strategy for segregating collagen and myosin emitted second harmonic generation (SHG) signals, we performed a volumetric assessment of collagen and total scattering tissue (collagen + myosin). Aged marmoset hearts exhibited an increase in collagen and total scattering tissue volume at the sites of severe tissue remodelling indicating age-related cardiac fibrosis. Significantly low scattering tissue volume in neonatal marmoset hearts was attributed to a lack of binding between the myofibrils in maturing cardiac tissue. Comprehensive quantitative assessment of structural composition during maturation and aging of marmoset hearts revealed significant differences in myofibril length, alignment, curvature and angular distribution. In conclusion, label-free high-resolution NLOM facilitates visualization and quantification of subcellular structural features for understanding vital age-related morphological alterations in the marmoset heart.     

Noninvasive estimation of impaired hemodynamics for patients with acute myocardial infarction by Tei index.

BACKGROUND: Tei index, defined as the sum of isovolumic contraction and relaxation times divided by ejection time, has been proposed to express global left ventricular function. For patients with acute myocardial infarction (AMI), left ventricular function can potentially be a major determinant of hemodynamics with limited time for compensation, such as increased brain natriuretic peptide to attenuate congestion, and usually without any intervention to modify cardiac loading on arrival at the hospital during the acute phase. We, therefore, hypothesized that left ventricular function, expressed by the Tei index, allows noninvasive estimation of impaired hemodynamics for patients with AMI. METHODS: We studied 86 consecutive patients with first AMI (34 inferoposterior and 52 anteroseptal). Tei index was obtained as: (a - b)/b, where a is the interval between the cessation and onset of mitral flow and b is the ejection time by aortic flow by pulsed Doppler echocardiography. By using pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg or <18 mm Hg and cardiac index (CI) < or = 2.2 L/min/m(2) or > 2.2 L/min/m(2) by consecutive catheterization, patients were classified into 4 subsets: subset I with normal hemodynamics; subset II with elevated PCWP; subset III with reduced CI; and subset IV with both elevated PCWP and reduced CI. RESULTS: For patients with inferoposterior AMI, there was no significant correlation between the Tei index and PCWP or CI. For patients with anteroseptal AMI, however, the Tei index showed significant correlation both with PCWP (r = 0.59, P <.0001) and CI (r = -0.42, P <.01). Diagnosis of impaired hemodynamics (subset II-IV) by a Tei index > or = 0.60 showed a sensitivity, specificity, and accuracy of 86%, 82%, and 83%, respectively. CONCLUSIONS: Although the Tei index has limitations to evaluate hemodynamics in patients with inferoposterior AMI, the index allows approximate but quick and practical noninvasive estimation of impaired hemodynamics in patients with anteroseptal AMI.     

Pregnancy and lupus nephritis: report of 20 cases

AimPregnancies in women with lupus nephritis (LN) are a high-risk situation. The aim of this study is to evaluate the impact of pregnancy on LN on either maternal and fetal prognosis.Patients and methodsIt is a retrospective study of 20 pregnancies in 12 women with lupus nephritis.ResultsThere were 19 live births and five fetal losses. LN flares were observed in 50 % of the cases during pregnancy and 25 % after delivery.ConclusionPregnancies in women with LN require a multidisciplinary monitoring and intense maternal and fetal care.