Oxygen free radicals in volume overload heart failure

It has been suggested that oxygen free radicals (OFR) depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the cardiac contractility in the failing heart may be due to an increased OFR producing activity of polymorphonuclear (PMN) leukocytes. We studied the OFR producing activity (chemiluminescence) of PMN leukocytes from blood in dogs with heart failure due to chronic volume overload. The animals were divided into two groups: I) normal, (n = 10): II) dogs with mitral insufficiency (MI) of 6 to 9 months duration, (n = 10). Hemodynamic studies were done to establish the presence of heart failure. Blood samples were collected to measure PMN leukocyte chemiluminescence. There was a decrease in the cardiac index and index of myocardial contractility (dp/dt/IIP) and an increase in the left ventricular end-diastolic pressure in dogs with MI indicating left ventricular failure. The peak chemiluminescent activity of the PMN leukocytes in blood of dogs with failure was about four folds greater than that in the blood from normal dogs. These results suggest that there may be an increased OFR generation in dogs with volume overload heart failure. The decrease in the myocardial contractility in the failing heart might be due to an increase in the OFR produced by the PMN leukocytes.     

Neuroethology of olfactory preference development

Young mammals come to approach the odor of their mother, a response that facilitates their survival during early life. Young rats induce a cascade of events in their mother to induce the emission of her odor. The pups increase circulating prolactin levels, which increases food intake and the emission of large quantities of cecotrophe containing the maternal odor. This odor is synthesized by the action of cecal microorganisms and changes with maternal diet. The diet-dependence of the odor requires the pups to acquire their attraction to the odor postnatally. The acquisition of this preference occurs when an odor is paired with the tactile stimulation that pups receive during maternal care. The action of the tactile stimulation appears to be mediated by noradrenaline. The development of this type of olfactory attraction is accompanied by changes in the regions of the olfactory bulb that are responsive to the attractive odor. Metabolic, anatomical, and neurophysiological changes in response to the attractive odor emerge in such regions of the bulb after early olfactory preference training. © 1992 John Wiley & Sons, Inc.     

Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development

Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis. Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to explore the impact of lowered dosage of these BMP ligands. Genotyping pups bred between Bmp2 and Bmp4 heterozygous mice revealed that the ratio of adult compound heterozygous mice for Bmp2 and Bmp4 is much lower than expected. During embryogenesis, the compound heterozygous embryos showed several abnormalities, including defects in eye formation, body wall closure defects, and ventricular septal defects (VSD) in the heart. However, the ratio of the compound heterozygous embryos was the same as expected. Caesarean sections at E18.5 revealed that half of the compound heterozygotes died soon after birth, and the majority of the dead individuals exhibited VSD. Survivors were able to grow to adults, but their body weight was significantly lower than control littermates. They demonstrated progressive abnormalities in the heart, eventually showing a branched leaflet in atrioventricular valves. These results suggest that the dosage of both BMP2 and 4 is critical for functional heart formation during embryogenesis and after birth. genesis 47:374–384, 2009. © 2009 Wiley‐Liss, Inc.     

Heart valve macro- and microstructure

Each heart valve is composed of different structures of which each one has its own histological profile. Although the aortic and the pulmonary valves as well as the mitral and the tricuspid valves show similarities in their architecture, they are individually designed to ensure optimal function with regard to their role in the cardiac cycle.In this article, we systematically describe the structural elements of the four heart valves by different anatomical, light- and electron-microscopic techniques that have been presented. Without the demand of completeness, we describe main structural features that are in our opinion of importance in understanding heart valve performance. These features will also have important implications in the treatment of heart valve disease. They will increase the knowledge in the design of valve substitutes or partial substitutes and may participate to improve reconstructive techniques. In addition, understanding heart valve macro- and microstructure may also be of benefit in heart valve engineering techniques.     

Cortex-specific distribution of membrane-bound factors that promote neurite outgrowth of mitral cells in culture

To analyze regional differences in the embryonic mouse brain with respect to environmental influence on mitral cell neurites, olfactory bulb fragments were cultured on layers of brain cells which had been dissociated from various regions. Long mitral cell neurites elongated on paleocortex and neocortex cell layers, but not on the septum, mesencephalon, or diencephalon cell layers. Cell membranes prepared from the paleocortex and neocortex also supported outgrowth of long mitral cell neurites, but cell membranes prepared from the septum, mesencephalon, or diencephalon did not. The supportability of mitral cell neurites in the paleocortex and neocortex membranes was completely abolished by trypsin treatment. Neurite outgrowth of the mitral cells on poly-L -lysine was not inhibited by the mesencephalon or diencephalon membranes, but was promoted by the paleocortex and neocortex membranes. These results indicate that the paleocortex and neocortex regions selectively express membrane-bound factors which promote neurite outgrowth of mitral cells. © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 415–425, 1997.     

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%.     

Can isolated annular dilatation cause significant ischemic mitral regurgitation? Another look at the causative mechanisms

This study was to investigate the mechanisms of ischemic mitral regurgitation (IMR) by using a finite element (FE) approach. IMR is a common complication of coronary artery disease; and it usually occurs due to myocardial infarction. The pathophysiological mechanisms of IMR have not been fully understood, much debate remains about the exact contribution of each mechanism to IMR. Two patient-specific FE models of normal mitral valves (MV) were reconstructed from multi-slice computed tomography scans. Different grades of IMR during its pathogenesis were created by perturbation of the normal MV geometry. Effects of annular dilatation and papillary muscle (PM) displacement (both isolated and combined) on the severity of IMR were examined. We observed greater increase in IMR (in terms of regurgitant area and coaptation length) in response to isolated annular dilatation than that caused by isolated PM displacement, while a larger PM displacement resulted in higher PM forces. Annular dilation, combined with PM displacement, was able to significantly increase the severity of IMR and PM forces. Our simulations demonstrated that isolated annular dilatation might be a more important determinant of IMR than isolated PM displacement, which could help explain the clinical observation that annular size reduction by restrictive annuloplasty is generally effective in treating IMR.     

Tension to passively cinch the mitral annulus through coronary sinus access: An ex vivo study in ovine model

Introduction

The transcatheter mitral valve repair (TMVR) technique utilizes a stent to cinch a segment of the mitral annulus (MA) and reduces mitral regurgitation. The cinching mechanism results in reduction of the septal–lateral distance. However, the mechanism has not been characterized completely. In this study, a method was developed to quantify the relation between cinching tension and MA area in an ex vivo ovine model.

Method

The cinching tension was measured from a suture inserted within the coronary sinus (CS) vessel with one end tied to the distal end of the vessel and the other end exited to the CS ostium where it was attached to a force transducer on a linear stage. The cinching tension, MA area, septal–lateral (S–L) and commissure–commissure (C–C) diameters and leakage was simultaneously measured in normal and dilated condition, under a hydrostatic left ventricular pressure of 90 mmHg.

Results

The MA area was increased up to 22.8% after MA dilation. A mean tension of 2.1±0.5 N reduced the MA area by 21.3±5.6% and S–L diameter by 24.2±5.3%. Thus, leakage was improved by 51.7±16.2% following restoration of normal MA geometry.

Conclusion

The cinching tension generated by the suture acts as a compensation force in MA reduction, implying the maximum tension needed to be generated by annuloplasty device to restore normal annular size. The relationship between cinching tension and the corresponding MA geometry will contribute to the development of future TMVR devices and understanding of myocardial contraction function.     

Activity-dependent local protection and lateral inhibition control synaptic competition in developing mitral cells in mice

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