The present study reports the development and characterization of a murine model of right ventricular dysfunction following graded constriction in the pulmonary artery via microsurgical approaches. To analyze in vivo ventricular function, a technique of x-ray contrast microangiography was developed to allow the quantitative analysis of ventricular volumes and of ejection fraction in normal and pressure-overloaded right ventricle. Severe, chronic pulmonary arterial banding for 14 days resulted in right ventricular dilatation and dysfunction, associated with right atrial enlargement, and angiographic evidence of tricuspid regurgitation. These effects were dependent on the extent of hemodynamic overload, since more moderate pulmonary arterial constriction resulted in hypertrophy with maintenance of right ventricular function. With severe pulmonary artery constriction, the murine right ventricle displays a failing heart phenotype including chamber dilation with reduced function that resembles right ventricular dysfunction in man during chronic pulmonary arterial hypertension. Northern and immunoblot analyses demonstrate a marked down-regulation of phospholamban mRNA and its corresponding protein with both levels of constriction, while a less pronounced but significant depression of sarcoplasmic reticulum Ca2+-ATPase protein was observed with severe overload, suggesting that this pattern is an early genetic marker of ventricular dysfunction. By coupling mouse genetics with this murine model and the ability to assess cardiac function in vivo, one should be able to test the role of the down-regulation of phospholamban and other defred alterations in the cardiac muscle gene program in the onset of the failing heart phenotype.Cardiac muscle failure is one of the most important problems in cardiovascular medicine. Although the physiology of the failing heart has been the subject of intense scientific inquiry, relatively little is known regarding the signaling pathways within cardiac muscle cells which mediate the progression from compensatory hypertrophy to cardiac muscle dysfunction. Although ventricular chamber dilation with reduced myocardial shortening and contractile velocity (1), as well as abnormal Ca2+ handling, appear to be hallmarks of the end-stage failing human heart (2), the molecular pathways which lead to these distinct phenotypes are unclear. One of the difficulties has been the paucity of animal model systems for analysis of the effects of the manipulation of a set of genes on cardiac function in the intact animal.Utilizing recent advances in microsurgical approaches to create a graded constriction in the pulmonary artery (PA), we have developed and characterized a murine model of right ventricle (RV) hypertrophy and failure. In addition, a technique for digitized microangiography was developed to allow the quantitative analysis of in vivo cardiac function, ventricular volumes, and ejection fraction in normal and pressureoverloaded murine myocardium. Severe, chronic pulmonary arterial banding for ...

ABSTRACT:A study was carried out on the effects of interactions between nitrile-butadiene rubber (NBR) and silica on the developments of agglomerates by silica particles and of bound rubber in NBR/silica composites. The mechanical properties of the composites were also investigated in relation to the structure development. Transmission infrared spectra revealed the existence of hydrogen bonding between nitrile groups in NBR and silanol groups on the silica surface. The number of hydrogen bonds increased with the increasing nitrile group content of NBR. Transmission electron microscopy observations and thermal analysis revealed that the averaged size of agglomerates in composites decreased, and simultaneously the amount of filler-gel in silica-filled NBR decreased with increasing nitrile group content of NBR. These results suggest that the hydrogen bonding between nitrile groups and silanol groups suppresses the development of agglomerates by silica particles, that is, the dispersion of silica is improved by the hydrogen bonding. At a given nitrile group content of NBR, the storage modulus and the initial slope of stress-strain curves for vulcanized composites increased with increasing the amount of filler-gel. Further, at a larger strain, the composites showed a clear pseudo-yielding point on the stressstrain curves, with this tendency more prominent in the larger agglomerate size. These results suggest that the mechanical properties for NBR/silica composites are affected by the content of filler-gel.

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