1. 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

2. cytoplasmic signaling cascades
CHRONIC HEART FAILURE
contractile dysfunction
ischemia
load: hypertension Ca 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

3. CO exercise normal failure compensated decompensated maximal load rest
edema EDP

4. 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

5. 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

6. 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

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

8. 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

9. 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