Cardiac metabolism & reperfusion injury

Dr.Nermeen BastawyPhysiology Department

Faculty of MedicineCairo University

Cardiac metabolism

Cardiac muscle is adapted to be highly resistant to fatigue: Large number of myoglobin & mitochondia continuous aerobic ATP production via oxidative phosphorylation.

The heart is so tuned to aerobic metabolism that it is unable to pump sufficiently in ischemic conditions.

Normally, about 1% of energy is derived from anaerobicmetabolism. This can increase to 10% under moderately hypoxia .

Dysregulation of cardiac metabolism common diseases that leads to heart failure.

Aerobic production of ATP

The heart requires ATP for Na+/K+-ATPase) & for contraction and relaxation.

Therefore, ++HR & contractility ++myocardial metabolism.

Heart has limited ability for anaerobic metabolism

Fuel sources

The heart can use a variety of substrates to oxidatively regenerate ATP depending upon availability.

In the postabsorptive state several hours after a meal, the heart utilizes mainly FFA (60-70%)

Following a CHO meal, the heart utilizes glucose. Lactate can be used during exercise. The heart can also utilize amino acids & ketones.

Ketone bodies are particularly important in diabetic acidosis.

During ischemia and hypoxia, the heart is able to utilize glycogen for anaerobic production of ATP & formation of lactic acid. However, the amount of ATP produce by this pathway is very small. Furthermore, the heart has a limited glycogen, which is rapidly depleted.

Myocardial O2 consumption (MVO2)

MVO2 is determines by mechanical activity of the myocardium which affected by: inotropic state, HR, SV & ventricular pressure.

Under basal conditions, MVO2 is 9.7ml/100 g/min.

During exercise, ++ MVO2 through ++ coronary blood flow.

Cardiac work

Cardiac efficiency Cardiac efficiency = cardiac work per

min / MVO2 External cardiac work = MAP x SV Cardiac efficiency is 20-25 % in

normal heart & 5-10% in failing heart.

Cardiac ischemia

During cardiothoracic surgery During myocardial infarction Cardiac arrest Shock (-- BP) or hypoxia Birth asphyxia

Cardiac metabolism during ischemia

During ischemia, substantial changes occur in cardiac energy metabolism.

Some of these metabolic changes are beneficial and may help the heart adapt to the ischemic condition.

However, accumulation of intermediates metabolites contribute to the severity of the ischemic injury stunned or hibernating myocardium, cell death and contractile disfunction.

Reperfusion injury Is the tissue damage caused when

blood supply returns to the tissue after a period of ischemia or hypoxia.

The restoration of circulation

oxidative stress inflammation & oxidative damage.

Reperfusion injury Dramatic changes in cardiac metabolism

and contractile function, also occur during myocardial reperfusion.

The reperfusion injury may cause in the death of cardiac myocytes that were still viable immediately before myocardial reperfusion.

This form of myocardial injury, by itself can induce cardiomyocyte death and increase infarct size.

Mechanism of RI The inflammatory process is partially

responsible for the damage of reperfusion injury.

WBCs carried by returning blood++ IL, TNF-α,NO & ROS damages cell membrane, ptns, DNA & apoptosis.

WBCs also bind to Bl.V endothelium obstructing them and leading to more ischemia.

RI also hyperkalemia