This document discusses strategies for myocardial protection during cardiac surgery. It describes how ischemia leads to energy depletion and cell damage in the heart. The goals of myocardial protection techniques are to rapidly induce cardiac arrest, use mild hypothermia, properly buffer cardioplegic solutions, avoid substrate depletion, and prevent intracellular edema. This maintains intracellular homeostasis and maximizes the heart's tolerance to ischemia, preventing irreversible damage. The document outlines various cardioplegia solutions and approaches that achieve these protective goals.

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