simplified version of cardioplegia

1. MYOCARDIAL
PROTECTION
DR.R.JAIGANESH

2. INTRODUCTION:
 Myocardial ischaemia exists whenever the energy
demand of the myocardium exceeds supply.
 If Ischaemia persists - ultimately energy-dependant
systems begin to ‘shut down’ – electromechanical coupling
and contractility declines,membrane pump functions cease with
changes to intracellular ionic concentrations, and damage
occurs to the Sarcoplasmic Reticulum and
Mitochondria.
 Finally, lipases and proteases are activated and cellular
necrosis occurs.

3.  Initially, ischaemic-induced cellular changes are
potentially reversible, but cell death eventually occurs if
allowed to progress
 By manipulating the ischaemic process, decreasing
metabolic demands,stabilizing membranes and
maintaining intracellular homeostasis, myocardial
tolerance to ischaemia can be significantly increased
and irreversible cell damage averted.

4. ISCHEMIA REPERFUSION
INJURY:
 Ischemia-reperfusion injury occurs as the result of
attenuation or cessation of coronary blood flow.
 2 theories: calcium hypothesis and free radical hypothesis
 The calcium hypothesis suggests that the inability of the
myocyte to modulate intracellular and intraorganellar calcium
homeostasis induces a cascade of events culminating in cell
injury and death

5.  As the sodium-calcium exchanger is activated,sodium is
transported to the extracellular space and calcium is taken up
into the cytosol, increasing cytosolic calcium concentration
([Ca2+]i).
 Increased [Ca2+]i accumulation is also augmented by
ischemia-induced depolarization of the membrane potential,
which allows the opening of the L-type calcium channels
and further calcium entry into the myocyte.
 Cellular and cytosolic calcium-dependent phospholipases
and proteases are in turn activated, inducing membrane injury
and the further entry of calcium into the cell.

6.  The free radical hypothesis- the accumulation of
partially reduced molecular oxygen known as reactive
oxygen species (ROS)during the early stages of
reperfusion causes myocardial cellular damage and
cell death.
 Major ROS - superoxide(•OH−), hydrogen peroxide
(H2O2), hydroxy radical (•OH), and lipid peroxides.
 They are highly reactive and cytotoxic.

7. MYOCARDIAL STUNNING
 The term “Myocardial Stunning” was coined by Braumwald
and Kloner in 1982
 “Myocardial dysfunction that persists after reperfusion
despite the absence of irreversible damage.”
 This transient contractile dysfunction is fully reversible with
time (may take hours to days), although inotropic or
mechanical circulatory support may be required.

8.  3 main mechanisms are involved in the establishment of the
stunned myocardium:
- Formation of O2-free radicals,
- Accumulation of intracellular Ca2+, and
- Degradation of contractile proteins – collectively termed
“Reperfusion Injury”.
 Ca2+ and ROS are both activators of MPT(Mitochondrial
Permeability Transition Pore -Opening of this channel leads to
loss of mitochondrial function and ATP, and eventually ion
homeostasis) during ischaemia and reperfusion.

9. MYOCARDIAL HIBERNATION:
 Coined by Rahimtoola in 1985
 “persistent myocardial dysfunction at rest associated
with cardiac ischaemia”
 The abolition of contractility of hibernating cardiac tissue is
attributable to chronic stunning caused by multiple episodes of
severe ischaemia followed by repetitive reperfusion
 Contraction improves after revascularisation.

11. PRINCIPLES OF CP:
 The basic principles for adequate myocardial
protection include :
(1) rapid induction of arrest,
(2) mild or moderate hypothermia,
(3) appropriate buffering of the
cardioplegic solution,
(4) avoidance of substrate depletion,
(5) attention to intracellular edema.

12. Rapid Cardiac Arrest:
 CP induces diastolic arrest by altering the resting
membrane potential (-90mV) and ionic
gradients(Na,K,Ca,Cl)in myocyte by two mechanisms:
 Extracellular solutions(St Thomas)- prevents cardiac
repolarisation (maintaining hyperpolarisation) by
increasing the K concentration in ECF
 Intracellular solutions( Bredtschneider) – block
depolarisation by lowering extracellular sodium
concentrations.

13.  Induction of immediate cardiac arrest after the aorta
clamped minimizes the depletion of high-energy
phosphate moieties by useless mechanical work
 The heart will remain arrested until the concentration
of extracellular potassium or other cardioplegic
ingredient is decreased by noncoronary collateral
mediastinal blood flow, re-infusions of cardioplegia
are necessary every 15 to 30 minutes

14. Hypothermia
 Hypothermia decreases the rate of the
metabolic degradation of energy stores and
reduces myocardial oxygen consumption
during surgically induced ischemia

17. Buffering of the Cardioplegic
Solution
 Necessary to combat the unremitting intracellular
acidosis associated with surgically induced aortic
cross clamping
 With the recent development of a myocardial tissue
pH probe, there is clinical evidence that
maintenance of the tissue pH of 6.8 or greater is
associated with adequate myocardial protection

18.  Thus, frequent infusions of cardioplegia, every 15 to 20
minutes, are necessary to prevent intracellular acidosis from
reaching irreversible metabolic levels.
 In addition,hypothermia assists in the neutralization of
acidosis because pH rises 0.0134 unit for each degree
decrease in degree centigrade.
 Bicarbonate, phosphate,aminosulfonic acid, tris-
hydroxymethylamino-methane(THAM), and histidine
buffers are used.

19. Avoidance of Myocardial
Edema
 Avoidance of myocardial edema by controlling
osmolarity is important to control volume regulation of
the fluid compartments of the heart
 Hypotonic cardioplegic solutions cause myocardial
edema
 Hyperosmotic cardioplegia with an osmolarity in excess
of 400 mOsm/L cause myocardial dehydration

20.  Isotonic solutions in the range of 290 to 330mOsm/L or
slightly hyperosmolar solutions appear to have the greatest
clinical use
 Inert sugars including mannitol and sorbitol as well as
metabolizable sugars such as glucose and dextrose have
been used to increase osmolarity
 Oncotic agents such as albumin and macromolecules,
including dextrans and hydroxyethyl starches, have been
used to prevent myocardial edema

21. THANK YOU