cardiac muscle metabolism amal ahmed

8/2/2019 Cardiac Muscle Metabolism Amal Ahmed

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Cardiac Muscle Metabolism

Sept. 2010KFMC-
http://www.indexedvisuals.com/scripts/ivstock/pic.asp?id=294-004


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Heart

Main Function: Pumping of blood

Major pathway: Aerobic pathways i.ebeta oxidation and citirc acid cycle

Main substrate: Free fatty acids,lactate, ketone bodies, triglycerides,some glucose

lipoprotein lipase and respiratorychain well developed


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Skeletal Muscle Metabolism

Muscle fuel needs are dependenton activity level.

Muscle can store glycogen. Ifglucose is not available, glycogen

stores are hydrolyzed by the activemuscle.Muscle cells lack the enzymeglucose-6-phosphatase, thus,

muscle glycogen cannot supplyglucose to the circulation and othertissues.

Muscle can use both glucose and

fatty acids and occasionally evenamino acids as fuel.


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Skeletal Muscle (continued)

The resting muscle prefers fatty acids as

fuel. The active muscle undergoingrapid contraction prefers glucose.

During high activity, anaerobicrespiration ensues and glucose

metabolism produces high levels oflactate which is transported to the liver(Cori cycle).

During high activity, a large amount ofalanine is formed by transamination ofpyruvate. This is also sent to the liver(alanine) for disposal of N as urea.


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Cardiac Muscle

Heart metabolism is different fromskeletal muscle in 3 ways.Heart muscle can function only underaerobic conditions.Heart muscle cells are rich inmitochondria facilitating aerobicrespiration.Heart muscle is not able to storeglycogen.

Fatty acids are the preferred fuel of theheart. Glucose is the least favored fuel.

Ketone bodies and lactate are usedunder stress when the energy demandis high.


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The major metabolic substrates of the normal

well-oxygenated myocardium are free fattyacids in the fasted state and glucose in thefed state.

In general, the normal myocardium uses

whichever fuel is available.

During ischemia, there is a swing towardglucose metabolism and it is proposed thatglycolysis provides beneficial glycolytic ATPwhich has many protective actions, including

preservation of sodium pump activity.


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Energy Yield

The highest yield of ATP per molecule is from

fattyacids such as palmitate. This is because many of

the

carbon atoms in carbohydrates are partiallyoxidized

due to the presence of the oxygen in themolecule,

whereas fatty acid molecules contain littleoxygen

and, therefore, can yield more ATP for eachcarbon

atom.


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The disadvantage of fatty acids as a fuelis that for each molecule of ATP

produced, they require relatively moreoxygen.

Increased rates of delivery of FFAs are

potentially harmful to the ischemicmyocardium.

FFAs have oxygen-wasting potential

in the myocardium, and provision ofglucose rather than FFAs promotesrecovery in the postischemicreperfusion


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Cardiac muscle metabolismHeart failure is associated with a switch from fattyacids metabolism to glucose metabolism.

95 % of energy goes to ATP production in themitochondria.

Under severe ischemic conditions ATP degradesas follows: ATP ADT AMP adenosine (blood flow regulator)

Cellular membrane is permeable to adenosine. As

a result it is lost from the myocardium withblood flow, depleting up to of adenine basereserves during hour of ischemia. Such losscan cause cell death.


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AdenosineThe decrease in oxygen concentration in the heartcauses vasodilator substances to be released fromthe muscle cells that in turn dilate the arterioles.One of the substances which have the greatestvasodilator propensity is adenosine.

In the presence of a very low concentration ofoxygen in heart muscle, a large proportion of cell'sATP degrades to adenosine monophosphate; then asmall portion of this are further degraded to releaseadenosine into the tissue fluids of the heart muscle.

After the adenosine causes vasodilatation, much ofit is reabsorbed into the cardiac cells to be reused.Adenosine is not the only vasodilator product thathas been identified, while others include adenosinephosphate compounds, potassium ions, hydrogenions, carbon dioxide, and possibly, prostaglandins


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METABOLISM OF

THE ISCHEMIC HEART

In myocardial ischemia, myocardial cells are

suffering from a lack of oxygen, caused by

inadequate coronary blood flow.

Ischemia may be temporary and reversible, or

permanent and irreversible, leading to

myocardial infarction.

On the other hand, ischemia may also lead to

postischemic stunning, hibernation,

and preconditioning.


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Mitochondrial O2 deficit

Central to ischemia is the lack of an adequate oxygen

supply to the mitochondria (anaerobiosis), with aconsequent fall in the energy available to the cytoplasm.

The breakdown of high-energy phosphate compounds

accelerates glycolysis, pyruvate and NADH2, can enter

the mitochondria for oxidation.

The further conversion of pyruvate and NADH2 to lactate

explains the production of lactate by the ischemic

myocardium.

Direct monitoring of enhanced glycolysis in the human

ischemic myocardium can be achieved.


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Metabolic aspects of

viability of ischemic myocytes

It is proposed that an increase in glucoseuptake reflects continuing cell viability. Incontrast, decreased uptake is associated

with loss of viability of the ischemic cells,with damage progressing from reversibleto irreversible.

Cells threatened by ischemia could be

divided, according to their patterns ofglucose uptake, into those with increasedvalues (viable) or decreased values(nonviable).


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Preconditioning

A brief period of reversible ischemia beforesustained ischemia and reperfusion causescardioprotection against subsequent ischemia

This tolerance to ischemia is termed ischemicpreconditioning. The mechanisms responsible

for ischemic preconditioning are still remainunclear.

Ischemic preconditioning is:Reversible

Slowed energy utilizationReduction in myocardial necrosis

Increase protective abilities ofmyocardium

Presented as a normal proper protectivereaction of the ischemic myocardium


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Chaperones

They areabundantintracellular

proteins.Their mainfunction is

proteinfolding andtransport.

ischemic preconditioning


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Up regulation of the synthesis occurs

upon environmental stress

establishes a unique defense system

to maintain cellular protein

homeostasis and to ensure survival of

the cell.

In the cardiovascular system thisenhanced protein synthesis leads a

powerful increase in tolerance to such

endangering situations as ischemia.

cardiac muscle metabolism amal ahmed

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