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1、1Heart Failure心力衰竭心力衰竭2Learning ObjectivesLearning ObjectivesLearning Objectives review definition etiology classification main mechanisms body response to heart failure clinical manifestations treating principles3IntroductionIntroductionIntroduction4IntroductionIntroductionIntroductionPerfect condu
2、ctive system Heart rate Rhythm Coordination Valve, atrium, ventricle5Turkey red Dark redIntroductionIntroductionIntroductioninterventricular septum interatriale septumIntact compartment6contractilityafterloadpreloadStroke VolumeCardiac outputHeart rateDeterminants of cardiac functionDeterminants of
3、cardiac function=SV HRIntroductionIntroductionIntroductionRemember this?Can patient with cardiac shock maintain their BP in shock stage 1?7Heart failure is the inability of the heart to supply adequate blood flow and generate a cardiac output sufficient to meet the metabolic demands of the body .Def
4、initionDefinition8PrevalencePrevalence2 to 3 million 400,000 new cases 1996 WHO survey:Incidence rate 1.9% menwomen2-year mortality rate 37%6-year mortality rate 82% American:China: cerebral vascular diseases, tumor, heart disorderWHO prediction: cardiac and cerebral vascular diseases should be the
5、No. 1 killer in 20209EtiologyEtiologydirect impairment of myocardial contractility and diastolic functionischemic heart disease (infarction, shock) myocarditis, cardiomyopathy, Kawasaki disease,result in excess pressure, volume or high-output states hypertension, aortic stenosis, pulmonary embolism,
6、 pulmonary heart disease afterload aortic or mitral regurgitation preload hyperthyroidism, anemia, pregnancy or infection Mitral/tricuspid stenosis, constrictive pericarditisPrimary myocardial dysfunctionVentricular overloadRestriction of filling10Preload Ca, ATP, MgMechanisms for heart failure46Inc
7、reased expression and function of the exchanger in human heart failure as well as in animal models. This increase is the consequence of defective SR Ca2+ uptake and depends on Ca2+i in the failing heart.It may play a key role for altered contractile function and arrhythmogenesis in hypertrophy and h
8、eart failure.Cardiovascular Research Volume: 57, Issue: 4 March 15, 2003Mechanisms for heart failure47Question In heart failure, it is calcium overload or low calcium that contribute to decreased contractility? Both; Mechanisms for heart failure48Dysfunction of excitation-contraction couplingDysfunc
9、tion ofCalcium handling by SRCa2+ binding to TroponinCalcium influxMechanisms for heart failure49ATP-dependent pumpPhospholamban, PLBIn heart failureExpression of PLB (受磷蛋白受磷蛋白) Beta-adrenoceptor activation ATP supplyMechanisms for heart failurePhosphotization-active50Ca2+-induced Ca 2+releaseRyanod
10、inereceptorSR Ca2+ content decrease mRNA and protein level are both found to reduce in heart failure Hydrogen increases affinity of calcium and its binding protein higher, so the calcium is difficult to be released.Mechanisms for heart failure51 Dysfunction of excitation-contraction couplingDysfunct
11、ion ofHandling the calcium by SRCa2+ binding to troponinCalcium influxMechanisms for heart failure52Concentration of cytosolic calciumNormal affinity of troponin to calciumMechanisms for heart failurehypoxiaH+ , the affinity of troponin to Ca+In normal myocyte,In failing heart,53Weaken contractility
12、Abnormity of diastolic properties of ventricle Altered signal transductionMechanisms for heart failureMechanisms for heart failureExcessive cardiac hypertrophy54Myocardial relaxation is an active process, not merely an intermittent rest period between systolic periods. Up to 15% of myocardial energy
13、 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 ventricleDiastolic properties of ventricleMechanisms for heart failure55(1) Delayed calcium decrease(2) Impaired dissociation of
14、 the actin-myosin complex(3) Decreased diastolic potential energy of ventricles(4) Reduced compliance of myocardiumAbnormity Abnormity of diastolic properties of ventricleof diastolic properties of ventricleMechanisms for heart failure56After each systole, the concentration of myoplasmic Ca2+ need t
15、o decrease from 10-5mol/L to 10-7mol/L, allowing decoupling of the actin-myosin cross-bridges. Without adequate ATP seen in myocardial ischemia and severe anemia, Ca2+ is delayed uptaked by sarcoplasmic reticulum and delayed efflux from the myocyte. Thus, Ca 2+ still combines with troponin and myoca
16、rdium can not relax fully. Delayed calcium decreaseMechanisms for heart failure57Myocardial relaxation is not a passive, but rather an energy- requiring activity. ATP is needed for the actin-myosin complex to dissociate, so inadequate ATP supply may lead to impairment of actin- myosin decoupling. Obviously, any pathologic factor with disorders in energy metabolism may result
