Alterations of Myocardial Contraction Associated with a Structural Heart Defect in Embryonic Chicks

Abstract

Ablation of cardiac neural crest at stages 8–10 produces a structural heart defect (persistent truncus arteriosus, PTA) in embryonic chicks. PTA is associated with decreased myocardial contractility, as indicated by decreased left ventricular ejection fraction. We compared the force of small ventricular strips from normal and defective chick hearts. In intact muscle, ablation of the neural crest leads to a 30–50% decrease in twitch force at any level of extracellular Ca²⁺ (0.45–20 mM) at embryonic days (ED) 7 and 15, relative to sham-operated controls. These differences could reflect defects at the level of the contractile apparatus and/or in the excitation-contraction coupling process. To distinguish changes of the contractile apparatus, we used detergent skinned preparations. The maximal Ca²⁺-activated force (Fmax) at ED 15 was not significantly different between control and experimental embryos. At ED 7, however, Fmax was reduced by 36% in experimental preparations. Electron-micrographs showed that the organization and orientation of the myofibrils was similar in experimental and control ventricles. At ED 14, however, the average myofibrillar diameter was significantly increased in experimental ventricles. The content of the major myofibrillar proteins (myosin heavy chain, actin, and tropomyosin), determined from Polyacrylamide gel electrophoresis and Coomassie Blue staining, normalized to total protein, was not statistically different in experimental and control ventricles at ED7. At ED 15, however, content of these proteins was doubled in experimental ventricles. These data suggest a possible defect of the contractile apparatus at both ED 7 and 15, since the ratio of Fmax/myosin is reduced in the experimental hearts.