Compensatory mechanisms

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Compensatory mechanisms

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Case study
1971
1992
2002
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Drink and smoke MUCH MORE
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Drink and smoke
1988
1994
Hyperlipemia, obesity, Hepatic steatosis, Drink
and smoke
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Angina? hight HR ???MI ??? ??? ???
2005
2006
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SNS ?RAS??
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MI??
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CK-MB,cTnT,Myo??
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How can he survive for so long?
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Compensatory mechanisms

• Neurohormonal mechanisms
• Ventricular remodeling

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Compensatory mechanisms

• Neurohormonal mechanisms
• activation of SNS
• activation of RAS
• neurohormonal alterations of renal function
• neurohormonal alteratons in the periheral
  vasculature
• nitric oxide

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Compensatory mechanisms

• Ventricular remodeling
• alterations in myocyte biology
• myocardial changes
• alterations in ventricular chamber geometry

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SNS
PSNS?
Ach?
Damage and remodeling
heart
ß1-R?
HR?contractility ?
Too long and too much
BP?
CO?
RAS?
kidney
NE?
SNS?
Peripheral vascular resistance?
a-R?
ß-R?
CNS?
input?
Redistribution of blood flow
ß2-R?
release?
hypersensitization
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o
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RAS
AVP?
SNS?
angiotensinogen
RAS?
renin?
kidney?
CNS cardioregulatory centers?
Angiotensin I
Adrenal gland
ACE
heart
Baroceptors unload
Angiotensin II
Peripheral vasoconstriction
Adrenal gland
? Reabsorption of water and sodium, ?secretion of
potassium and hydrogen ions
Aldosterone?
?cardiac myocytes remodeling
Retention of water and sodium
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Nitric oxide

• NO synthase(NOS)--NOS1neuronal
  --NOS2inducible
• --NOS3endothelial-constitutive
• NO activates GC cGMP PKG
  signaling events vasodilationmodulat
  es the activity of several key Ca channels
  involved in excitation contraction coupling,
  mitochondrial respiratory complexs(normal)
• HFvasodilation blunted
• myocardiumcomplex(short-term alterations in
  function and energetics
• long-term on structure)
• subcellular location of NO becomes disrupted

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Ventricular remodeling

• Alterations in Myocyte Biology
• --hypertrophyß-R desenditization
• fetal gene expression
• Myocardial Changes
• --myocyte loss(necrosis,apoptosis,autophagy)
• --alterations in extracellular
  matrix(degradation,fibrosis)
• Alterations in Left Ventricular Chamber Geometry
• --dilation(sphericity)wall thinningmitral
  valve incompetence

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Pressure(hypertension or aortic stensis)?
Systolic wall stress?
? Sarcomeres parallel myocyte widening
Concentric cardiac hypertrophy
Ventricular volume?
Diastolic wall stress?
?Sarcomeres series myocyte lengthing
eccentric cardiac hypertrophy
preload?
Ventricular remodeling
hypertrophy
Hemodynamic overloading?
MMPs?
hypoxemia
afterload?
ECM degradation?
Energy utilization?
Growth factor?
Energy starvation
apoptosis?
Progressive dilation?
necrosis?
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Myocyte hypertrophy
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Cardiac hypertrophy
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Summary

• HF is a progressive disease, which has many
  compensatory mechanisms.
• Something new is needed to be found.

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• Thanks a lot

Thanks a lot !!!