normal cardiac metabolism & O2 consumption . changes following ischemia or hypoxia

1. Cardiac metabolism &
reperfusion injury
Dr.Nermeen Bastawy
Physiology Department
Faculty of Medicine
Cairo University

2. 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.

3. 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

4. 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.

6. 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.

7. Cardiac work

8. 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.

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

10. 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.

11. 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.

12. 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.

13. 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