HEART FAILURE ACUTE (cardiogenic shock) CHRONIC (congestive)

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Presentation transcript:

HEART FAILURE ACUTE (cardiogenic shock) CHRONIC (congestive) heart rate contractility contractility tamponade compensatory mech. CO valvular apparatus (periferal resistance) neurohumoral response CO (0) ischemia - CNS, myocard

cytoplasmic signaling cascades CHRONIC HEART FAILURE contractile dysfunction ischemia load: hypertension Ca2+ CO ischemia valvular energy EDP edema cardiomyopathy morphology overload wall stress cytoplasmic signaling cascades growth factors early genes restricted transcription factors (TGFβ, bFGF, IGF-1,TNFα) (myc, fos, jun) (GATA4, SRF, TEF-1) mRNA transcription restricted genes hypertrofic growth apoptosis contractile dysfunction

CO exercise normal failure compensated decompensated maximal load rest edema EDP

Vasoconstriction afferents efferents chemoreceptors heart rate baroreceptors CNS contractility volumoreceptors vasoconstriction muscle metaboreceptors renin Na+ reabsorption Vasoconstriction noradrenaline angiotenzin endothelial dysfunction flow (ml/min/100g) 30 20 10 Ach μg/min 0 4 8 16 32

Remodelling stimuli cytokines neurohormonal oxidative stress wall stress cytokines neurohormonal oxidative stress myocyte hypertrofy ventricular enlargement altered intersticial matrix fetal gene expression altered Ca handling proteins systolic or diastolic dysfunction myocyte death

myocyte death apoptosis (H2O2) nekrosis alterations in excitation-contraction forth-frequency relationship SERCA2 + Phospholamban Na/ Ca2+ channel influx Na (afterdepolarisation) Ca2+ release channel (CRC) voltage-dependent Ca2+ channel ? calsequestrin alterations in contractile apparatus volume ccupied by myofibrils reduction of ATPase aktivity myosin isoforms changes altered regulatory proteins ic Ca2+ t

Calcium cycling N SR Na+ Ca2+ Ca2+ Ca2+ K+ Ca2+ Ca2+ Ca2+ ryanodine rec. SERCA inositol phosphate rec. Phospholamban

alterations in the matrix collagen strut depletion MMP/TIMP collagen degradation collagen degradation myocyte slippage fibrosis dilation stiffness, difusion distance myocardial energetics production O2 consumption by mitochondrias reserves phosphocreatin/ATP creatinkinase ATP/ADP NO

myofibrils Mitochondrial matrix ADP + Pi oxid.phosphorylation ATP ANT mi-CK ADP + PCr intermembraneous space Myosine ATPase ADP ATP MM-CK Cr PCr MM-CK Ca-ATPase SR Failure - Cr/ATP, ADP, MM-CK, mi-CK, SERCA