Prezentace aplikace PowerPoint

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HEART FAILURE
ACUTE (cardiogenic shock) CHRONIC
(congestive) need for urgent therapy
CO (0) ischemia - CNS, myocard
heart rate
contractility contractility
tamponade compensatory mech.
CO valvular apparatus
(periferal resistance)
neurohumoral response
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CHRONIC HEART FAILURE
contractile
dysfunction ischemia load
hypertension Ca2
CO
ischemia valvular
energy EDP
edema
cardiomyopathy morphology

overload wall stress
cytoplasmic signaling cascades
mitochondriae
growth factors early genes
restricted transcription factors
(TGFß, bFGF,
IGF-1,TNFa) (myc, fos,
jun) (GATA4, SRF,
TEF-1) mRNA
transcription
restricted genes
hypertrofic growth
apoptosis
contractile dysfunction
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maximal load
CO
exercise
normal
failure compensated
rest
decompensated
edema EDP
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afferents
efferents chemoreceptors

heart rate baroreceptors
CNS contractility
volumoreceptors
vasoconstriction muscle
metaboreceptors
renin
Na
reabsorption Vasoconstriction noradrenaline
angiotenzin endothelial
dysfunction Reactivity of vessels prognostic
factor
flow (ml/min/100g) 30 20
10 0
Ach µg/min
0 4 8 16
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Endotelial dysfunction NO eNOS shear stress
ROS NAD(P)H oxidase angiotensin
II Endothelial progenitor cells
(EPC) prostacyclin endothelin
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SR Ca content

SERCA2 Phospholamban

Na/ Ca2 channel

leak

ic Ca2
t
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Ca 2 SERCA2 Phospholamban, Na/ Ca2
channel, leaking SR
Na Ca2
Ca2
K
Ca2
SR
Ca2
Ca2
Ca2
Calcium cycling
N
ryanodine rec. SERCA
inositol phosphate rec. Phospholamban
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glycolysis utilization of fatty acids failing
myocard restricted sources of
energy higher cost of contraction
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ANT adenine nucleotide translocator
Energy metabolism
Mitochondrial matrix ADP Pi
oxid.phosphorylation ATP ANT
mi-CK ADP
PCr intermembraneous space
myofibrils
Myosine ATPase ADP ATP
MM-CK Cr PCr
MM-CK Ca-ATPase
SR
Failure - Cr/ATP, ADP, MM-CK, mi-CK,
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Remodelling stimuli 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
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cessation of myocytes apoptosis (H2O2)

necrosis contractile apparatus No of
myofibriles in a cell
ATPase activity)
myosin isoforms (fetal)
regulatory
proteins troponin T2
titin
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alterations in the matrix collagen structure
depletion
MMP/TIMP
collagen degradation
collagen degradation
myocyte slippage
fibrosis
dilation
stiffness, difusion distance Diastolic Heart
Failure Heart Failure with Normal left
Ventricular Ejection Fraction