Basic principles of myocardial proctection

1. BASIC PRINCIPLES OF
MYOCARDIAL PROTECTION
Dr Chaina Paul

2. After the initiation of open heart surgery using extracorporeal
circulation by Gibbon it became obvious that aortic cross-
clamping was necessary to provide a bloodless field to
facilitate the precise repair of intracardiac defects, prevent air
embolism when the left side of the heart was opened, and
avoid a turgid myocardium resistant to retraction.
MELROSE TECHNIQUE- operating for rheumatic mitral valve in
a patient with AR, Melrose et al introduced the concept of
“elective cardiac arrest” by rapidly injecting into the aortic
root, after aortic cross-clamping, a 2.5% potassium citrate
solution in warm blood to arrest the heart.

3. During the 1960s two distinct technical pathways for
managing ischemic arrest evolved-
1.The “rapid operators” performing uncomplicated
cases with short ischemic times using c normothermi
ischemic arrest, =“stone heart” syndrome related to
ischemic contracture of the myocardium.
2.Intermittent aortic cross-clamping, involving
reperfusion of the coronary circulation for 5 min
following 15 min of ischemic arrest.
Later studies demonstrated that there was no
functional or metabolic advantage to intermittent
reperfusion for normothermic ischemic periods up to
60 min.

4. Reintroduction of Cardioplegia
While cardioplegia had been abandoned for alternative
techniques in the United States after the adverse
experience with the Melrose potassium solution,
Bretschneider, Germany, induced cardiac arrest using a
sodium-poor, calcium-free, procaine-containing
solution (Bretschneider solution). Hearse et al[93]
introduced the concept of using an extracellular rather
than an intracellular solution (St. Thomas’ solution).

5. PRINCIPLES:
The objective of any type of myocardial management
during CPB should be limiting injury during ischemia by
some combination of –
myocardial hypothermia
electromechanical arrest,
washout,
O2 and other substrate enhancement,
oncotic manipulation, and buffering.

6. A rational approach for protecting the heart during surgically
induced ischemia –
=Requirements for sustaining the ischemic cell.
=Compatible with the technical aspects of the operative
procedure to provide -
a flaccid arrested heart,
a bloodless operative field,
and sufficient time for the satisfactory repair of complex
cardiac defects
=The ability of the heart to assume normal electromechanical
function adequate to support the systemic circulation must
rapidly follow the ischemic interval

7. 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.

8. 1.RAPID CARDIAC ARREST
Rapid cardiac arrest remains the mainstay of adequate
myocardial protection.
“achieved by targeting various points in the excitation–
contraction coupling pathway”

10. Potassium is the most common agent used for
chemical cardioplegia and produces rapid diastolic
arrest
MECHANISM:As the extracellular potassium
concentration increases- the resting myocardial cell
membrane becomes depolarized- the voltage-
dependent fast sodium channel is inactivated arresting
the heart in diastole, and the slow calcium channel is
activated resulting in cytosolic calcium overload..
The optimum concentration of potassium is thought to
vary between 15 and 40 mmol/liter.

11. polarized arrest:
where the cell membrane potential remains close to
resting potential.
Agents includes-
1.Sodium channel blockade:
which arrests the heart by preventing the rapid
sodium-induced depolarization of the action potential,
includes procaine and tetrodotoxin.
2.Potassium channel openers:
(KCOs) induce arrest by membrane hyperpolarization.

12. potassium–adenosine triphosphate (KATP) channel subtypes-
two types are identified-
one subtype located in the sarcolemma (sarcKATP) membrane
and the other in the inner membrane of the mitochondria
(mitoKATP) .
KCOs have been used in conjunction with hyperkalemic and
magnesium–containing cardioplegic solutions.
mitochondrial-specific KCOs, such as diazoxide, have been
demonstrated to have potential benefits when used with
magnesium-supplemented potassium cardioplegia.

13. Hyperpolarized cardiac arrest by adenosine by antagonizing calcium
channels and inhibits both the SA and the AV nodes and atrial myocardial
contraction, results in sinus slowing and arrest.
Adenosine half life is 10s in blood-
it has been used as a pretreatment before the initiation of CPB as an arresting
agent by bolus infusion and
as an additive to potassium cardioplegia, where it reduces the time to arrest
and reduces potassium-induced cytosolic calcium overload.
It may also improve functional recovery when infused during the reperfusion
period.

14. 2.HYPOTHERMIA
Mild (tepid at the room temperature range of 28–32° C) or
moderate (22–25° C)- an indispensable adjunct for adequate
myocardial protection.
Hypothermia decreases the rate of the metabolic degradation of
energy stores during surgically induced ischemia.
Experimental evidence that there is a significant decrease of left
ventricular myocardial oxygen consumption of the heart in the
beating nonworking, fibrillating, and arrested states at 22° C as
compared to a myocardial temperature of 37° C

16. There is minimal advantage in reducing the myocardial
temperature below 22° C,in that the myocardial oxygen
consumption is decreased by only a minimal amount.
In the clinical setting, it is virtually impossible to maintain a
uniform myocardial temperature below 22° C solely by the use of
-cold (4° C) intracoronary cardioplegia infusate and regional
hypothermia-
in the presence of coronary obstructions, ventricular
hypertrophy, and variations in mediastinal noncoronary
collateral blood flow.

17. The lack of uniformity of myocardial temperatures in various
myocardial segments-
the atrial and ventricular septums are warmed by systemic and
pulmonary venous return,
heat sinks such as the liver warm the base of the heart,
and the anterior situated right ventricle is warmed by the
operative environmemt.
There is no correlation between myocardial tissue acidosis and
temperature.

18. 3.BUFFERING OF THE CARDIOPLEGIC SOLUTION
To combat the unremitting intracellular acidosis associated with
surgically induced myocardial ischemia.
Ischemia results in the rapid accumulation of hydrogen ions and
the reduction of intracellular Ph.
Maintenance of the tissue pH of 6.8 or greater is associated with
adequate myocardial protection.
Frequent infusions of cardioplegia, every 15–20 min, are
necessary to prevent intracellular acidosis from .

19. Hypothermia assists in the neutralization of acidosis, since pH
rises 0.0134 unit for 1degreeC decrease in temperature.
The infusion of hypothermic cardioplegia does not restore pHi to
prearrest levels, but rather prevents further deterioration of the
pH.
Repeated episodes of normothermic arrest increases
intracellular metabolic acidosis and associated with increased
injury during .
Bicarbonate, phosphate, aminosulfonic acid, tris-
hydroxymethylaminomethane (THAM), and histidine buffers
have all been utilized as cardioplegia additives to modulate pH.

20. 4. AVOIDANCE OF MYOCARDIAL EDEMA
causes-
Myocardial edema is a known consequence of ischemia .
Cardioplegic infusions.
Hemodilution from crystalloid priming of the extracorporeal circuit.
The activation of humoral and cellular mediators that increase
microvascular permeability.
Impairment of myocardial lymphatic function may play major roles in
the development of myocardial edema--Myocardial lymphatic function
is dependent upon the beating heart to transport fluid and is
significantly reduced or completely stopped during cardiac arrest.

21. osmolarity of cardioplegia-
Hypotonic cardioplegic solutions cause myocardial edema.
Hyperosmotic cardioplegia with an osmolarity in excess of 400
mOsm/liter has been shown to cause myocardial dehydration---
Isotonic solutions in the range of 290–330 mOsm/liter or slightly
hyperosmolar solutions appear to have the greatest clinical use.
To increase osmolarity-Inert sugars, including mannitol and sorbitol
metabolizable sugars- glucose and dextrose
Oncotic agents - albumin and macromolecules-dextrans and
hydroxyethyl starches, have been used to prevent myocardial edema.

22. DIFFERENT METHODS OF MYOCARDIAL
MANAGEMENT

23. CONTINUOUS NORMOKALEMIC CORONARY PERFUSION
Empty Beating Heart
The earliest intracardiac operations were performed on
normothermic, perfused, empty beating heart.
Current information indicates that the method is not ideal.
= Water tends to accumulate in the myocardium during
CPB; as a result, ventricular distensibility in dog models is
decreased by nearly 50% after 3 hours of CPB with the
heart perfused, empty, and beating.

24. =The distribution of coronary blood is abnormal. The change in
myocardial compressive forces and left ventricular wall geometry
impede intracoronary collateral flow supplying potentially
ischemic areas of myocardium.

25. perfusion of individual coronary arteries
Individual coronary artery cannulation is necessary when
perfusing the empty beating heart for surgery on the aortic
valve.
This technique is not ideal for the following reasons-
The tip of the cannula may extend beyond the bifurcation
of the left main coronary artery.
1% of patients, LAD & LCX - these two arteries arise separately
from the aortic sinus, making proper individual cannulation even
more difficult.
In left dominant systems, the left main
coronary artery is shorter than normal,making individual
coronary perfusion more difficult.

26. In about 50% of
patients, the conus artery supplying the infundibulum of
the right ventricle arises separately from the aortic sinus
and is not perfused by a cannula inserted into the right coronary
ostium.
Mechanical injury to the coronary ostia
can occur during direct coronary ostial cannulation -
intraoperative myocardial
infarction and late coronary ostial stenosis.

27. periods of global
myocardial ischemia- between aortic clamping
and initiation of right and left coronary artery perfusion.
This interval varies, but can seldom be reduced below 2 to 3
minutes.
When this method is used, the heart should be kept
beating and the perfusate should be warmer than
30°C.
Studies showed that when ventricular
fibrillation persisted throughout the period of coronary
perfusion, risk of perioperative infarction and death was higher
than if the heart were beating.

28. HYPOTHERMIC FIBRILLATING HEART
Continuous coronary perfusion AND
ventricular fibrillation induced electrically or spontaneously
and
maintained by
moderately hypothermic (25°C-30°C) coronary perfusion or
electrically.
Coronary perfusion can
be through the intact aortic root (as in CABG) or by individual
coronary perfusion cannulae during aortic root surgery.

29. MODERATELY HYPOTHERMIC INTERMITTENT GLOBAL
MYOCARDIAL ISCHEMIA
Requires conducting CPB with the perfusate
temperature at 25°C to 30°C.
The surgeon works on or in
the heart intermittently for periods of 10 to 15 minutes,
during which time the ascending aorta is clamped and the aortic
clamp is released (or individual coronary perfusion resumed) for
3 to 5 minutes.
When the technique is used optimally, the heart
is made to beat (not fibrillate) during this interval.

30. PROFOUNDLY HYPOTHERMIC GLOBAL MYOCARDIAL ISCHEMIA
The heart profoundly cooled - perfusate,
by filling the pericardium with very cold saline solution,
or by both, after which the aorta is clamped.
The cardiac
operation is done during a single period of aortic clamping.
Myocardial temperature is generally about 22°C with these
methods
most surgeons believe that this allows 45 to 60 minutes of
safe global myocardial ischemia.
Profoundly hypothermic cardiac ischemia without cardioplegia
may be preferred for infant cardiac surgery in which
hypothermic circulatory arrest is used..

31. DRUG-MEDIATED MYOCARDIAL PROTECTION
Both β-adrenergic receptor blocking and calcium channel
blocking drugs- in conjunction with one of the other
methods.
The calcium channel blocking agents verapamil and diltiazem -
advantageous because of their prevention of calcium influx
into cells and their coronary vasodilatory effects.
Disadvantages-
potent negative inotropes and produce prolonged
electromechanical quiescence, at least when used
clinically in cardioplegic solutions.

32. COLD CARDIOPLEGIA (MULTIDOSE)
Induce chemical arrest to conserve
energy during the period of myocardial ischemia
by two basic mechanisms-
1.Inhibition of the fast sodium current to prevent conduction
of the myocardial action potential .
2. Inhibition of calcium activation of myofilaments to
prevent myocyte contraction.

33. -Cardioplegic Solution
Mixed with blood (at a 2 : 1 or 4 : 1 blood-to-solution ratio),
and extracellular solutions and intracellular solutions as
distinguished
by their potassium concentrations.
Delivery can be intermittent (multidose) or continuous.

34. Technique of Antegrade Infusion
After CPB is established with the perfusate at 32°C (under
which conditions ventricular fibrillation should not develop),
an aortic root catheter is inserted
Cold cardioplegic infusion is begun promptly at a flow
of 150 mL · min−1 · m−2 for 3 minutes in adults; the average
adult is given a dose of about 750 mL.
In infants and children with a body surface area of
less than 1 m2, the infusion is given at the same flow rate
(150 mL · min−1 · m−2 body surface area), but for only
2 minutes.
External cooling of the heart started.

35. The slush is never placed in the pericardial space because left
phrenic nerve damage may result.
Left or right ventricle is not allowed to become
distended at any time and prevented by-
A left ventricular vent (introduced
through a right pulmonary vein)or
suction through an aortic root catheter for others, and simple
needle aspiration of the ventricle across the ventricular septum.

36. Cardioplegic solution is reinfused about every 25
minutes.
After the first infusion, the potassium concentration
of any subsequently infused cardioplegic solution is
reduced to about 10 mmol · L−1.
If serum potassium levels reach 7 to 8 mEq · L−1
(a rare occurrence), a bolus injection of 400 mg · kg−1
of glucose (as 50% glucose) and 0.2 unit · kg−1 of soluble
insulin may be given after the beginning of myocardial
reperfusion

37. Technique of Retrograde Infusion
Retrograde infusion of cardioplegic solutions directly into the
coronary sinus was suggested by Lillehei and colleagues in
1956.
The right ventricle (particularly its midportion) and right atrium
are less well perfused.
Retrograde coronary sinus
infusion is particularly advantageous in the presence of
acutely developing high-grade coronary artery stenoses or
obstruction.

38. Technique-a purse-string stitch is placed in the
right atrial wall, and a small stab wound is made in the
middle, through which the retrograde infusion catheter is
introduced and under digital control manipulated into the
coronary sinus.
The catheter is attached to one arm of the
cardioplegia infusion line and de-aired. The pressure measuring
arm of the catheter is connected to a manometer. Coronary
sinus pressure must not be allowed to rise above
50 mmHg during coronary sinus infusion.

39. Both the antegrade and retrograde
routes of cardioplegia routinely, delivered in either
an alternating sequential fashion or simultaneously-
allows rapid electromechanical quiescence,
protects against uneven cardioplegic distribution, and
may maximize the duration of ischemia while avoiding
cardioplegia overdose.

40. Single-Dose Cold Cardioplegia in
Neonates and Infants
single-dose, oxygenated St. Thomas solution Using a simple
pressure bag, it is infused into
the aortic root proximal to the aortic clamp. The dose is
20 mL · kg−1 and is not repeated.
The del Nido cardioplegic solution (Baxter) is combined
with blood in a ratio of four parts solution to one part
blood.
In neonates, infants, and children has been very
favorable, with most surgeons noting more rapid return
of sinus rhythm and excellent cardiac function despite
longer recommended periods .

41. CONTINUOUS CARDIOPLEGIA
Cold Perfusion
Continuous antegrade cold blood cardioplegia has been used
as an alternative to single-dose and multidose intermittent
cold cardioplegia.
Warm Perfusion
Continuous warm blood cardioplegia, administered by antegrade
infusion or by retrograde coronary sinus infusion after
an initial antegrade dose, has also been used for CABG and
other cardiac operations.

42. Cold Cardioplegia, Controlled Aortic Root
Reperfusion, and (When Needed) Warm
Cardioplegic Induction
Technique for Elective Surgery
After completion of operation,
controlled aortic root reperfusion is begun, initially using
warm, hyperkalemic, modified, and enriched blood cardioplegia.
The aortic root pressure is kept at 30 mmHg for the first 60 to 120 seconds of
the reperfusion .
The flow is then increased until the aortic root pressure is 50 to 75 mmHg in
adults (or to the normal systemic arterial diastolic pressure in infants and
children whose body surface area is <1 m2).
A total of 500 mL of the modified blood reperfusate is administered.
For patients with a body surface area of less than 1.5 m2, the reperfusate
volume = 500 × BSA ÷ 1.5.
Then continues with normothermic, normokalemic, unmodified blood.

43. Avoiding ventricular distention.
The heart remains flaccid and electromechanically quiescent
for 2 to 10 minutes after the onset of the controlled aortic
root reperfusion.
The interval between the beginning of the controlled
aortic root reperfusion and cardiac action begins is usually 10 to
25 minutes.

44. for Energy-Depleted Hearts
CPB at 35°C is established.
The aortic root catheter is inserted.
The aorta is clamped, and warm hyperkalemic, modified and enriched
blood infusion is begun at the usual flow rate for induction of
cardioplegia and continued for 8 minutes.
Subsequent cold infusions are given every 20 to 30 minutes
as usual, except with a potassium concentration of about
10 mmol ·
After completing the cardiac procedure,
warm reperfusion is performed in the standard manner.

45. THANK YOU