Inhibition of hepatic damage and liver fibrosis by brain natriuretic peptide

Anti-fibrotic and organ protective effects of brain natriuretic peptide (BNP) have been reported. In this study, effects of BNP on liver fibrosis were examined in the carbon tetrachloride (CCl₄)-induced liver fibrosis model using BNP-transgenic (Tg) and wild-type (WT) mice. Twice-a-week intraperitoneal injections of CCl₄ for 8 weeks resulted in massive liver fibrosis, augmented transforming growth factor (TGF)-β₁ and type I procollagen α₁ chain (Col1a1) mRNA expression, and the hepatic stellate cell (HSC) activation in WT mice, all of which were significantly suppressed in Tg mice. These observations indicate that BNP inhibits liver fibrosis by attenuating the activation of HSCs.     

High prevalence of cerebral venous sinus thrombosis (CVST) as presentation of cystathionine beta-synthase deficiency in childhood: Molecular and clinical findings of Turkish probands

Classical homocystinuria is the most commonly inherited disorder of sulfur metabolism, caused by the genetic alterations in human cystathionine beta-synthase (CBS) gene. In this study, we present comprehensive clinical findings and the genetic basis of homocystinuria in a cohort of Turkish patients. Excluding some CBS mutations, detailed genotype–phenotype correlation for different CBS mutations has not been established in literature. We aimed to make clinical subgroups according to main clinical symptoms and discussed these data together with mutational analysis results from our patients. Totally, 16 different mutations were identified; twelve of which had already been reported, and four are novel (p.N93Y, p.L251P, p.D281V and c.829−2A>T). The probands were classified into three major groups according to the clinical symptoms caused by these mutations. A psychomotor delay was the most common diagnostic symptom (n = 12, 46.2% neurological presentation), followed by thromboembolic events (n = 6, 23.1% vascular presentation) and lens ectopia, myopia or marfanoid features (n = 5, 19.2% connective tissue presentation). Pyridoxine responsiveness was 7.7%; however, with partial responsive probands, the ratio was 53.9%.     

Isolating Primary Melanocyte-like Cells from the Mouse Heart

We identified a novel population of melanocyte-like cells (also known as cardiac melanocytes) in the hearts of mice and humans that contribute to atrial arrhythmia triggers in mice. To investigate the electrical and biological properties of cardiac melanocytes we developed a procedure to isolate them from mouse hearts that we derived from those designed to isolate neonatal murine cardiomyocytes. In order to obtain healthier cardiac melanocytes suitable for more extensive patch clamp or biochemical studies, we developed a refined procedure for isolating and plating cardiac melanocytes based on those originally designed to isolate cutaneous melanocytes. The refined procedure is demonstrated in this review and produces larger numbers of healthy melanocyte-like cells that can be plated as a pure population or with cardiomyocytes.     

Close Proximity of Left Anterior Descending Artery to the Right Ventricular Lead Apparently Implanted into the Mid-septum

Right ventricular (RV) mid-septal pacing should have fewer negative effects on left ventricular function compared to apical pacing. However, targeting the mid-septum may be technically challenging since it is usually done with two-dimensional fluoroscopy. The rotation of the heart and various shapes of the RV make it difficult to assess, whether the lead is really anchored in the septum. Many leads, apparently anchored in the septum, are in fact anchored in the anterior wall or anteroseptal groove, and some can get anchored in close proximity to the left anterior descending artery (LAD). We report three cases from our series of 51 patients, in whom the RV lead thought to be implanted in the mid-septum was in fact anchored in close proximity of LAD when assessed using computed tomography.     

消融右肺动脉神经节丛对肾上腺素能刺激和胆碱 能刺激诱发房颤的影响

目的:探讨右肺动脉神经节丛(RPVGP)消融对胆碱能及儿茶酚胺诱发房颤的影响。方法:20只犬麻醉开胸后,暴露RPVGP,分别在消融RPVGP前后,经股静脉静滴乙酰胆碱(ACh)及儿茶酚胺。测量房颤诱发率及两类递质诱发房颤的阈浓度。结果:RPVGP消融前,静滴Ach和异丙基肾上腺素(IPA)及肾上腺素(EPI)(1～100μmol/l)均可诱发AF,诱发率100%。Ach、IPA和EPI的诱发阈浓度分别为2.6±0.3μmol/l,3.3±0.2μmol/l,5.6±0.2μmol/l。RPVGP消融后,Ach及儿茶酚胺的AF诱发率分别降至10%及35%,且三种递质的诱发阈浓度分别提高至2.6±0.3μmol/l、22.5±2.4μmol/l和26.±2.6μmol/(lP<0.05)。结论:消融RPVGP使乙酰胆碱和儿茶酚胺诱发房颤的阈浓度增高,并降低此二类介质的房颤诱发率。     

Suppression of cardiac phosphatidate phosphohydrolase 1 activity and lipin mRNA expression in Zucker diabetic fatty rats and humans with type 2 diabetes mellitus

Lipin functions in mammalian phospholipid biosynthesis through its phosphatidate phosphohydrolase 1 (PAP₁) activity. Here, we studied cardiac PAP₁ activity and lipin expression ex vivo in 8-month-old Zucker diabetic fatty (ZDF) rats and humans with type 2 diabetes mellitus undergoing open heart surgery for coronary bypass grafting. Compared to non-diabetic littermates (ZDF-fa/+), left ventricular PAP₁ activity was 29% lower in diabetic ZDF-fa/fa rats. Left ventricular PAP₁ activities were 2.1-fold (ZDF-fa/fa) and 3.6-fold (ZDF-fa/+) higher than the respective atrial activities, indicating marked differences in cardiac distribution of PAP₁. PAP₁ activity was highly related with cardiac lipin-1 and lipin-3 mRNA expression in ZDF rats (r = 0.99 and 0.96). Consistent with the findings in experimental animals, human atrial tissue displayed PAP₁ activity that was 33% lower in those having diabetes than in non-diabetic controls. Accordingly, atrial lipin-1 and lipin-3 mRNA expression in diabetic patients was 50% and 59% lower as in non-diabetic patients, respectively. Insulin therapy increased both PAP₁ activity and lipin mRNA expression in diabetic patients. We conclude that suppression of cardiac PAP₁ activity/lipin expression may contribute to metabolic dysfunction of the diabetic heart.     

Post-natal heart adaptation in a knock-in mouse model of calsequestrin 2-linked recessive catecholaminergic polymorphic ventricular tachycardia

Cardiac calsequestrin (CASQ2) contributes to intracellular Ca²⁺ homeostasis by virtue of its low-affinity/high-capacity Ca²⁺ binding properties, maintains sarcoplasmic reticulum (SR) architecture and regulates excitation–contraction coupling, especially or exclusively upon β-adrenergic stimulation. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with cardiac arrest in children or young adults. Recessive CPVT variants are due to mutations in the CASQ2 gene. Molecular and ultra-structural properties were studied in hearts of CASQ2^R33Q/R33Q and of CASQ2^−/− mice from post-natal day 2 to week 8. The drastic reduction of CASQ2-R33Q is an early developmental event and is accompanied by down-regulation of triadin and junctin, and morphological changes of jSR and of SR-transverse-tubule junctions. Although endoplasmic reticulum stress is activated, no signs of either apoptosis or autophagy are detected. The other model of recessive CPVT, the CASQ2^−/− mouse, does not display the same adaptive pattern. Expression of CASQ2-R33Q influences molecular and ultra-structural heart development; post-natal, adaptive changes appear capable of ensuring until adulthood a new pathophysiological equilibrium.     

Response to atrial overdrive pacing during narrow QRS tachycardia. What is the mechanism?

A 35-year old lady with no pre-excitation on surface electrocardiogram underwent EP study for recurrent palpitation and documented adenosine responsive narrow QRS tachycardia. Regular narrow QRS tachycardia was induced with critical AH delay on programmed atrial stimulation. An atrial overdrive pacing (AOD) was performed during the tachycardia (Fig: 1 & 2). What is the response to AOD and what is the mechanism of tachycardia?     

Effect of c‐Ski on atrial remodelling in a rapid atrial pacing canine model

Atrial fibrosis is an important factor in the initiation and maintenance of atrial fibrillation (AF); therefore, understanding the pathogenesis of atrial fibrosis may reveal promising therapeutic targets for AF. In this study, we successfully established a rapid atrial pacing canine model and found that the inducibility and duration of AF were significantly reduced by the overexpression of c‐Ski, suggesting that this approach may have therapeutic effects. c‐Ski was found to be down‐regulated in the atrial tissues of the rapid atrial pacing canine model. We artificially up‐regulated c‐Ski expression with a c‐Ski–overexpressing adenovirus. Haematoxylin and eosin, Masson's trichrome and picrosirius red staining showed that c‐Ski overexpression alleviated atrial fibrosis. Furthermore, we found that the expression levels of collagen III and α‐SMA were higher in the groups of dogs subjected to right‐atrial pacing, and this increase was attenuated by c‐Ski overexpression. In addition, c‐Ski overexpression decreased the phosphorylation of smad2, smad3 and p38 MAPK (p38α and p38β) as well as the expression of TGF‐β1 in atrial tissues, as shown by a comparison of the right‐atrial pacing + c‐Ski‐overexpression group to the control group with right‐atrial pacing only. These results suggest that c‐Ski overexpression improves atrial remodelling in a rapid atrial pacing canine model by suppressing TGF‐β1–Smad signalling and p38 MAPK activation.     

血管钠肽、 C型钠尿肽和心房钠尿肽舒血管作用的对比

本实验采用离体血管灌流方法,观察和比较血管钠肽（ＶＮＰ）,Ｃ型钠尿肽（ＣＮＰ）和心房钠尿肽（ＡＮＰ）对大鼠肺动脉,腹主动脉和腹腔静脉的舒张作用。．结果表明,ＶＮＰ,ＣＮＰ和ＡＮＰ对离体大鼠的保留内皮与去内皮的肺动脉,腹主动脉和腹腔静脉均有浓度依赖性舒张作用。