11 心衰 简化.ppt

Calcium channel Calcium Channel The density of β-adrenoceptor and generation of norepinephrine(NE) decreased. Acidosis blunted sensitivity of NE to β-adrenoceptor. Hyperkalemia inhibited the calcium influx. What happened to the channel in heart failure? ①肥大心肌β-R密度相对↓NE ↓ ②酸中毒时，H+降低β-R对NE的敏感 ③高钾血症 Re-uptake Storing Release M SR Handling of calcium by SR Dysfunction of calcium handling by SR In heart failure Expression of pump ATP supply β-adrenoceptor activation Re-uptake calcium of SR ATP-dependent pump Phospholamban Ca2+-induced Ca 2+ release (CICR) Ryanodine receptor (RyR) Protein and mRNA level of RyR are both found to reduce in heart failure. Ca2+ content of SR decrease in heart failure. Hydrogen (H) increases the affinity of calcium and its binding protein, so it is difficult to be released. In heart failure Release calcium from SR Concentration of cytosolic calcium Normal affinity of troponin to calcium (1) Damage of myocardial cells (2) Myocardial metabolic dysfunction (3) Dysfunction of EC coupling (4) Hypertrophy Weaken of cardiac contractility Weaken of contractility Abnormity of diastolic properties of ventricle Asynergia of ventricular contraction and relaxation Mechanisms for heart failure Myocardial relaxation is an active process, not merely an intermittent rest period between systolic periods. Up to 15% of myocardial energy may be expended for that relaxation. Diastolic stage is important to blood supply for heart itself and it is also necessary for the venous return. Diastolic properties of ventricle (1) Delayed calcium decrease (2) Impaired dissociation of the actin-myosin complex (3) Decreased diastolic potential energy of ventricles (4) Reduced compliance of myocardium Abnormity of diastolic properties of ventricle After each systole, the concentration of myoplasmic Ca2+ need to decrease from 10-5mol/L to 10-7mol/L, allowing separating of the actin-myosin cross-bridges. Without