METABOLIC ERA IN

ISCHEMIC HEART DISEASE

Pintoko Tedjokusumo FIHA FSCAI FAsCC

Department of Cardiology and Vascular Medicine
Medical Faculty Pajajaran University/Hasan Sadikin Hospital

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MYOCARDIAL
CELLS
Normal state

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TYPES OF MEMBRANE ION TRANSPORT

1- Na+-K+ pump
2- Potassium-sodium leak channel
3- Voltage-gated sodium channel
4- Voltage-gated potassium channel
5- Calcium pump
6- Voltage-gated calcium channel
7- Na+-Ca2+ exchanger
8- ATP-sensitive potassium channel.

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 TYPES OF MEMBRANE ION TRANSPORT
In brief
1- Na+-K+ pump
2- Potassium-sodium leak 3 Na+
channel
ATP
3- Voltage-gated sodium 5
1
channel 2 K+
Ca2+ Ca2+
4- Voltage-gated potassium 6
channel Na+ 3 Na+ Na+
Na+
5- Calcium pump
6- Voltage-gated calcium 2 7 Ca2+
channel
8 4 Na+
7- Na+-Ca2+ exchanger
8- ATP-sensitive potassium
channel.

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 MYOCARDIAL ENERGY METABOLISM

CARBOHYDRATE supplies 20-40% of the total energy

for the healthy heart
(2 ATP)
Less oxygen consumption
Glucose- 6
LACTATE Phosphate LDH= lactate dehydrogenase
PDH= pyruvate dehydrogenase
PYRUVATE
LDH

PDH

Acetyl CoA

KREBS CYCLE ATP (38 ATP)

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MYOCARDIAL ENERGY METABOLISM

supplies 60-80% of the total energy FATTY ACID

for the healthy heart
More oxygen consumption

Acyl CoA

Beta oxidation
Acetyl CoA

KREBS CYCLE ATP

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 MYOCARDIAL ENERGY METABOLISM

CARBOHYDRATE FATTY ACID

With the same amount
of ATP produced, the
(2 ATP) fatty acid oxidation
Glucose- 6 consumes 15% more
LACTATE Phosphate oxygen than glucose
oxidation.

PYRUVATE Acyl CoA

LDH

PDH
Beta oxidation
Acetyl CoA

KREBS CYCLE ATP

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MYOCARDIAL ENERGY METABOLISM
IN TERMS OF PRODUCTIVITY

GLUCOSE OXIDATION:

ATP/ O2 = 6.4 / 1

FATTY ACID OXIDATION:

ATP/ O2 = 5.6 / 1

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 MYOCARDIAL ENERGY METABOLISM
Normal state

- In myocardial cells, the entrance to mitochondria are

partially regulated by malonyl-CoA

- This molecule results from acetyl-CoA with the catalysis

of acetyl-CoA carboxylase (ACC)

- Malonyl-CoA inhibits carnitine palmitoyl transferase

(CPT1), resulting in fatty acids prevented to move inside
mitochondria .

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 MYOCARDIAL ENERGY METABOLISM
CPT1= carnitine palmitoyl
Normal state
transferase 1 FATTY ACID
ACC= acetyl-CoA
carboxylase Acyl CoA
MCD= malonyl CoA
decarboxylase Malonyl
AMPK= AMP kinase CoA CPT1

BETA OXIDATION
ACC MCD
Acyl CoA dehydrogenase
Enoyl CoA hydratase
L-3 hydroxyacyl CoA
dehydrogenase
Acetyl CoA 3-ketoacyl CoA thiolase

Acetyl CoA
ATP KREBS CYCLE
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MYOCARDIAL
CELLS
Ischemic state

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 MYOCARDIAL ENERGY METABOLISM
Ischemic state (1)

- During ischemia, fatty acid oxidation and glucose

oxidation both decrease

- The phosphorylation of AMP and ADP to become ATP is

no longer occured

- AMP accumulation activates AMP kinase (AMPK)

- AMP kinase inhibits acetyl-CoA-carboxylase (ACC)

- These reactions result in the significant reduction of

malonyl-CoA fatty acids move unconditionally inside
mitochondria relatively increased -oxidation.
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 MYOCARDIAL ENERGY METABOLISM
Ischemic state (1)
AMP FATTY ACID

Acyl CoA

AMPK
Malonyl CPT1
CoA

ACC MCD
Beta
oxidation

Pyruvate Acetyl
dehydrogenase
CoA Acetyl
CoA

ATP KREBS CYCLE

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 MYOCARDIAL ENERGY METABOLISM
Ischemic state (2)

- Increased -oxidation inhibits pyruvate dehydrogenase

(PDH) anaerobic glycolysis is activated excess
production of H+

- During a much more severe ischemic insult, only ATP

production from anaerobic glycolysis still remains.

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 MYOCARDIAL ENERGY METABOLISM
Ischemic state (2)
CARBOHYDRATE FATTY ACID

(2 ATP)
Glucose- 6
LACTATE Phosphate

PYRUVATE
Acyl CoA
LDH

PDH

Acetyl
CoA
Beta oxidation

KREBS CYCLE ATP

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 MYOCARDIAL ENERGY METABOLISM
Ischemic state (3)

- H+ accumulation results in intracellular acidosis

- H+ is exhanged for Na+ (Na+/ H+ exchanger), then Na+ is

exchanged for Ca2+ (Na+/Ca2+ exchanger)
intracellular calcium overload

- The need to use ATP to re-establish homeostasis of H+,

Na+ and Ca2+ can lead to a decrease in cardiac
efficiency.

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MYOCARDIAL ENERGY METABOLISM
Ischemic state (3)

H+
Na+/ H+ H+ H+
exchanger
Na+ Na+

Na+/Ca2+ Na+ Na+

exchanger Ca2+ Ca2+

Ca2+
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 MYOCARDIAL
CELLS
Postischemic state

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 MYOCARDIAL CELLS
Postischemic state (1)

- It is time for myocardial reperfusion to occur

- Reperfusion is followed by the generation of

oxygen-derived free radical
Ex: superoxide anion [.O2-], hydrogen peroxide [H2O2] ,
hydroxyl radical [.OH]

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 MYOCARDIAL CELLS
Postischemic state (2)

TOXIC EFFECTS OF FREE RADICALS ON THE CELL:

1. blocking the mitochondrial respiratory chain ATP
2. damaging membrane structure by phospholipid
peroxidation membrane permeability to K+
(potassium leakage)
3. interfering with the calcium transport cellular calcium
overload
4. activating the production of thromboxane A2 from
arachidonic acid (a vasoconstrictor) worsened local
ischemia.
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 SUMMARY
MYOCARDIAL CONSEQUENCES
During Ischemic and Postischemic period

1. ATP

2. Intracellular acidosis

3. oxygen-derived free radical

4. Cellular calcium overload, potassium leakage

repolarization disorder

5. thromboxane A2.

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TREATMENT
OF
Ischemic heart disease

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TREATMENT OF ISCHEMIC HEART DISEASE
PRINCIPLES

1. Management of risk factors

2. Drug therapy
3. Revascularization:
PTCA: percutaneous transluminal coronary
angioplasty
CABG: coronary artery bypass grafting.

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 THANK YOU
FOR YOUR KIND
ATTENTION

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