ABSTRACT
Circumferential and noncircumferential myofiber contraction may have varying impact on systolic and diastolic function. The purpose of this study was to determine the relation of circumferential, longitudinal, and oblique fiber shortening to early diastolic filling in children. Twenty-five patients (8.1 +/- 5.6 years of age; 12 boys and 13 girls) with normal echocardiograms and no heart disease had prospective echocardiographic evaluation of circumferential (shortening fraction, fractional area change), longitudinal (left ventricular axial shortening), combined circumferential and longitudinal (left ventricular ejection fraction), oblique (left ventricular systolic twist [LVST]) shortening, and early diastolic filling. Mean LVST was 16 +/- 8 degrees. There was no relation between early diastolic filling indexes and indexes of circumferential or longitudinal shortening. However, there was a significant inverse relation between heart rate-corrected E-wave acceleration time and LVST (r = 0.63, P <.001). Oblique fiber shortening affects early diastolic filling in children. Describing the functional role of noncircumferential left ventricular myofibers may improve our understanding of global left ventricular function.
Subject(s)
Muscle Fibers, Skeletal/physiology , Myocardial Contraction , Ventricular Function , Adolescent , Child , Child, Preschool , Diastole , Echocardiography , Female , Heart Ventricles/diagnostic imaging , Humans , Infant , Infant, Newborn , Male , Observer Variation , Regression Analysis , Reproducibility of ResultsABSTRACT
The Ca(2+)-calmodulin-activated Ser/Thr protein phosphatase calcineurin and the downstream transcriptional effectors of calcineurin, nuclear factor of activated T cells, have been implicated in the hypertrophic response of the myocardium. Recently, the calcineurin inhibitory agents cyclosporine A and FK506 have been extensively used to evaluate the importance of this signaling pathway in rodent models of cardiac hypertrophy. However, pharmacologic approaches have rendered equivocal results necessitating more specific or genetic-based inhibitory strategies. In this regard, we have generated Tg mice expressing the calcineurin inhibitory domains of Cain/Cabin-1 and A-kinase anchoring protein 79 specifically in the heart. DeltaCain and DeltaA-kinase-anchoring protein Tg mice demonstrated reduced cardiac calcineurin activity and reduced hypertrophy in response to catecholamine infusion or pressure overload. In a second approach, adenoviral-mediated gene transfer of DeltaCain was performed in the adult rat myocardium to evaluate the effectiveness of an acute intervention and any potential species dependency. DeltaCain adenoviral gene transfer inhibited cardiac calcineurin activity and reduced hypertrophy in response to pressure overload without reducing aortic pressure. These results provide genetic evidence implicating calcineurin as an important mediator of the cardiac hypertrophic response in vivo.
