The document summarizes key differences between adult and pediatric myocardium that are important for myocardial protection in children undergoing cardiac surgery. The pediatric myocardium has poorer contractility, calcium handling, and antioxidant enzyme activity. It is also less sensitive to catecholamines. Effective myocardial protection strategies for children include hypothermia, venting, and blood or crystalloid cardioplegia delivered via antegrade routes. Components of cardioplegia like potassium, calcium, substrates and osmotic agents are tailored to the metabolic needs and sensitivities of the developing myocardium.
3. Structural differences
ā¢ Interstitial tissue contains more water and collagen when compared
to the adult heart
ā¢ Cellular level have a larger mass of non contractile elements
ā¢ Results in
ā¢ poor contractile response to inotropes
ā¢ poor preload reserve
ā¢ poor tolerance to afterload
4. ā¢ Poorly developed sarcoplasmic reticulum
ā¢ Mitochondria are fewer in number
ā¢ Has normal coronary arteries and healthy myocardium without
myocardial scarring and dysfunction.
ā¢ As a result there is uniform distribution of cardioplegia by antegrade
routes
5. Metabolic differences
ā¢ Immature myocardium metabolizes fatty acids, ketones and amino
acids, and glucose as its principal substrate
ā¢ Very efficient energy handler
ā¢ Greater dependence on anaerobic metabolism and hence greater
dependence on glycolysis with glucose as substrate
6. Calcium handling
ā¢ Has poorly developed sarcoplasmic reticulum which is the main
sources of intracellular calcium required for myocardial contraction.
ā¢ They have poor release of calcium from and reuptake into the
sarcoplasmic reticulum which translates into poor excitation
contraction coupling.
ā¢ Thus more dependent on the extracellular calcium for proper
functioning
7. Enzymatic activity
ā¢ Enzymes of free radical scavenging system namely
ā¢ superoxide dismutase,
ā¢ catalase and
ā¢ glutathione reductase
are deficient in particularly in those with cyanotic congenital heart
disease
ā¢ In the immature particularly cyanotic heart there is also an
overproduction of oxygen free radical upon re-oxygenation.
ā¢ The implication of these differences is that a cyanotic heart is more
prone to reperfusion injury after the release of aortic cross clamp
8. ā¢ Another enzyme which is less active in immature myocardium is 5-
nucleotidase (5NT). This enzyme catalyzes the conversion of ATP to
adenosine.
ā¢ Although AMP cannot readily pass out of the cell to the extracellular space,
adenosine is easily lost in the extracellular space through the plasma
membrane where 5NT resides.
ā¢ Loss of adenosine from the mature myocardium itself during ischemia to a
level of greater than 50% will inhibit full recovery of contractile function.
ā¢ Immature heart is less able to convert AMP to adenosine reduces the risk
of excessive depletion of the adenine nucleotide pool and immature
myocardium is more tolerant to ischemia
9. Catecholamine sensitivity
ā¢ Although the c-AMP functions normally, there is reduced coupling of
myocardial beta-receptors to the adenyl cyclase.
ā¢ The catecholamines thus have a poorer effect on the immature
myocardium as compared to adults, whereas, response to PDE III
inhibitors like milrinone is normal.
ā¢ Adrenaline and nor adrenaline as inotropes are thus less effective in
the children as compared to adults and milrinone has a better
response
10.
11. FUNCTIONAL CONSEQUENCE
ā¢ Immature myocardium has a poor diastolic reserve, tolerates after
load poorly and has a poor inotropic reserve but has an equivalent
ventricular mass
ā¢ More interventricular interdependence and more rate dependent for
cardiac output than the adult
ā¢ Immature myocardium is more dependent on the extracellular
calcium for proper functioning which forms the basis for maintaining
low levels of calcium in the cardioplegia and also accounts for
enhanced susceptibility of pediatric heart to calcium channel blockers
12. ā¢ Lack of free radical scavenging emzyme makes it more susceptible to
reperfusion injury
ā¢ Can use any use substrate as fuel and increased AMP pool in cells
makes it more tolerant to ischemia
ā¢ Catecholamines have a poorer effect on the immature myocardium
as compared to adults, whereas, response to PDE III inhibitors like
milrinone is normal
14. ā¢ The components to the myocardial protection are
ā¢ cardioplegia
ā¢ hypothermia
ā¢ adequate venting of heart to prevent distension
ā¢ adequate venous drainage
ā¢ precise surgical correction.
15. HYPOTHERMIA
ā¢ Hypothermia was the first cardio protection strategy to be applied in
the field of cardiac surgery.
ā¢ The proposed mechanism by which hypothermia affords myocardial
protection are
ā¢ suppression of cardiac metabolism and blunting of the effects of
cardiopulmonary bypass
ā¢ prevention of calcium accumulation in the mitochondria decrease
in sarcolemmal membrane permeability with reperfusion
16. ā¢ Experimental studies have shown that the benefit of adding
cardioplegia solution to hypothermia over hypothermia alone is
minor at low temperatures (below 15Ā°C), but becomes substantial
when the temperature increases (above 15C)
ā¢ In current practice used as an adjunct to chemical cardioplegia
17. techniques of empty beating heart and
fibrillatory arrest are not as popular
because the energy requirement of empty
beating heart and fibrillating heart is
considerably higher than the cardioplegic
heart
18. Points to remember
ā¢ Atrial and ventricular septa are warmed by systemic and pulmonary
venous return
ā¢ 2-stage cannulation contributes to rewarming as warmed systemic
venous blood comes back to the atrium before being drained
ā¢ Thus adequate venting and bicaval cannulation helps in maintaining
hypothermia
ā¢ Heat sinks such as the liver warm the base of the heart
ā¢ Anterior-situated right ventricle is warmed by the operative
environment
19. Advantages
ā¢ Decreased inflammatory response to cardiopulmonary bypass
ā¢ Decrease in dose of potassium in cardioplegia
ā¢ Prolongation of periods of cardiac arrest attained with any
cardioplegia solution
20. Disadvantages
ā¢ With hypothermia there is shift of pH towards alkalinity which impairs
enzyme function. In the cardiac myocytes there is enzyme disruption
and impaired ischemic anerobiasis that results in poor glucose
utilization.
ā¢ Impaired osmotic homeostasis results in myocardial & tissue edema.
ā¢ There is roleaux formation in coronary microcirculation leading to
uneven distribution of cardioplegia and uneven myocardial
protection.
21. ā¢ With fall in temperature, the hemoglobin- dissociation curve shifts to
left decreasing the release of oxygen to tissues
ā¢ The tissue uptake of oxygen decreases and there is decreased
function of membrane enzyme, resulting in poor oxygen utilization by
the tissues.
ā¢ Hypothermia is associated with coagulopathy, bleeding and increased
infections.
22. ā¢ Because of the lack of uniformity of myocardial temperatures in
various myocardial segments, there is no correlation between
myocardial tissue acidosis and temperature, leading to the recent
abandonment by many surgeons of routine myocardial temperature
monitoring during operative procedures
23. VENTING
ā¢ Immature myocardium is considerably more sensitive to stretch injury
ā¢ The common causes of stretch injury in the operating room are
ventricular distention and retraction.
ā¢ Exposure to the full perfusion pressure for even a few seconds
appears to have an extremely important impact on subsequent
myocardial performance
ā¢ Distention of LV results in distention of the left atrium and pulmonary
veins and a high transcapillary pressure within the lungs will result in
a situation called āpump lungā
24. ā¢ Causes of distention includes
ā¢ Return from lungs due to AP collaterals
ā¢ Small thebesian veins which directly open in left heart
ā¢ AR
ā¢ Potential sites for cardiac venting include the
ā¢ pulmonary artery
ā¢ superior pulmonary vein
ā¢ left atrium
ā¢ left ventricle
ā¢ Ascending aorta
25. cardioplegia
ā¢ Requirement of still and bloodless field during open heart surgery
requires that the aorta is to be cross clamped
ā¢ Role of cardioplegia is to prevent detrimental effects of short periods
of ischemia on myocardium during this time
26. ā¢ Essential characteristics of ideal cardioplegia must be
ā¢ rapid onset of cardiac arrest
ā¢ cessation of electromechanical activity
ā¢ suppression of myocardial energy demands
ā¢ maintenance of the intracellular elements during the arrest period and rapid
reversal of effect without any residual detrimental effect.
ā¢ be able to replenish the energy stores of the myocardium
ā¢ Wash away the products of metabolism from the myocardium
ā¢ prevent the adverse effect of reperfusion upon release of the aortic cross
clamp.
27. chief constituents of cardioplegia solution
ā¢ Membrane stabilizers:
ā¢ Lidocaine and procaine are the membrane stabilizers used most commonly.
ā¢ They prevent dysrhythmias in the post clamp period.
ā¢ Lidocaine also acts by blocking the sodium channels thus preventing influx of
detrimental amounts of sodium across the cell membrane damaged by the
potassium in cardioplegia solution.
28. ā¢ Buffers:
ā¢ There is some amount of metabolism still occurring in the cell even at very
low temperature.
ā¢ Buffers provide adequate pH for this metabolism to continue and maintain
the pH.
ā¢ Bicarbonates are the most commonly used buffers.
ā¢ Other widely used buffers in cardioplegic solutions include tromethamine
(THAM) and histidine.
29. ā¢ Substrates:
ā¢ Substrates are used in the cardioplegia solution to support the basal metabolism that
occurs in the myocytes even at very low temperatures.
ā¢ The most preferred substrate for the myocytes is glucose.
ā¢ The use of glucose in cardioplegia solutions results in increased oncotic pressure and
increased levels of lactate which is the metabolic end product of glucose in anaerobic
conditions.
ā¢ To wash away the lactate the cardioplegia infusions are required to be repeated at
small intervals.
ā¢ Newer concepts in cardioplegia have explored the non-glycolytic pathways of
generation of ATPs.
ā¢ Amino acids aspartate and glutamate enter the tri carboxylic acid cycle and have
been shown to be promising substrates
30. ā¢ Osmolar agents:
ā¢ Myocardial ischemia during the cross clamp damages the cell membranes that is
further aggravated by high content of potassium in the cardioplegia solutions. This
membrane injury results in cellular edema. Repeated doses of cardioplegia aggravate
the cellular edema.
ā¢ To counteract this, oncotic substances are required in the cardioplegia solutions.
ā¢ Too high an oncotic pressure may result in cellular dehydration. Therefore, an
optimal osmolality of 370 mOsm/L considered adequate bymost of investigators.
ā¢ Mannitol is the most commonly used oncotic substance in cardioplegia solutions.
ā¢ An advantage of adding mannitol is that it also has free radical scavenging action
which is useful during the reperfusion period
31. ā¢ Potassium
ā¢ Potassium is the main constituent of many of the cardioplegia solutions. It
brings about diastolic arrest by depolarizing the myocytes membrane.
ā¢ High levels of potassium have been associated with many detrimental effects
like
ā¢ Myocardial ionic and metabolic imbalances
ā¢ myocardial stunning
ā¢ Tissue edema
ā¢ Endothelial damage
ā¢ Free radical production
ā¢ Functional loss during reperfusion
ā¢ Hyperkalemia is also associated with direct endothelial toxicity and may be responsible
for āstone heartā contracture seen during reperfusion due to sudden calcium influx.
32. Calcium
ā¢ The calcium handling capacity of immature heart is relatively less well
developed.
ā¢ In acyanotic hearts calcium concentration does not make much
difference in outcome.
ā¢ In cyanotic and stressed heart even normocalcemic solution causes
ā¢ increased cellular injury
ā¢ manifested by depression in post bypass myocardial and endothelial cell
function
33. Magnessium
ā¢ Advantages are optimal when it is included with high potassium cardioplegia
ā¢ It prevents cytosolic, nuclear, and mitochondrial calcium accumulation
ā¢ Preserves high-energy phosphate moieties
ā¢ Enhance post ischemic functional recovery
34. Crystalloid cardioplegia
Most of them act by depolarizing the cell membrane due to high
content of potassium (10-20 mmol/L), thus providing
electromechanical arrest.
ā¢ They are of two types
a. Extracellular: These have higher levels of sodium, calcium and
magnesium.
Examples include Saint Thomas I and Saint Thomas II (PlegisolĀ®).
St. Thomas II is more common in use. It contains lower amount of potassium,
calcium and sodium and has more physiological pH (7.8) as compared to acidic
pH (5.5 - 7.0) of St. Thomas I.
35. b. Intracellular: They have no or low calcium and sodium.
ā¢ Bretschneider āHTK (CustodiolĀ®). CustodialĀ® cardioplegia is commonly used
intracellular cardioplegia solution.
ā¢ Contains reduced amounts of sodium, potassium and calcium.
ā¢ Magnesium as membrane stabilizing agent and is
ā¢ Enriched with histidine, tryptophan and ketoglutarate.
ā¢ pH of 7.02 ā 7.20.
ā¢ Single dose of CustodialĀ® cardioplegia delivered through the antegrade route
give good protection for up to 2 hours duration
36. Advantages of crystalloid cardioplegia include
ā¢ rapidity of induction
ā¢ uniform distribution
ā¢ rapidity of reversal of effects of cardioplegia
37. Blood Cardioplega
ā¢ Globally, blood cardioplegia is the most commonly used cardioplegia
Composition of blood
cardioplegia
(Buckberg/Beyersdorf)
38. ā¢ Blood cardioplegia is associated with multiple advantages.
ā¢ Owing to the presence of formed cellular elements in the solution, blood cardioplegia has
higher oxygen carrying capacity and higher concentration of natural substrates. Thus, in the
immediate post clamp period when the coronary blood supply is cut off but the heart is still
beating, blood cardioplegia ensures that the heart is arrested in an oxygen rich environment
with minimal loss of high energy phosphate bonds.
ā¢ Due to presence of naturally occurring buffers in the blood, a less acidotic environment is
available for cellular function.
ā¢ Presence of natural free radical scavengers in the blood helps in preventing reperfusion
injury, to which the immature heart is particularly sensitive..
ā¢ Disadvantage of blood cardioplegia is
ā¢ capillary plugging due to formed elements like neutrophils and platelets present in the blood
that may result in damage in small areas.
39. Institutional Practice
ā¢ St Thomas II ā¢ Prepared by adding 2 ampoules
to 500 ml of Ringer Lactate
ā¢ This crystalloid solution is mixed
with blood from the patient at a
ratio of 4:1 blood : crystalloid
ā¢ Delivery temperature 4-8 c
ā¢ Dose 20 ml/kg, ideally repeated
at intervals of 20 mins
40. DelNido
ā¢ The ratio of blood to crystalloid is 1:4.
ā¢ Cardioplegia uses
ā¢ potassium as arresting agent
ā¢ glucose as substrate
ā¢ bicarbonate as buffer
ā¢ mannitol as oncotic agent and free radical scavenger
ā¢ magnesium and lidocaine as membrane stabilizers
ā¢ It contains only traces of calcium.
42. ā¢ It is usually delivered in a dose of 20 ml/kg for induction which is
effective for a period up to 90- 120 minutes.
ā¢ Repeat dosage is given as 10 ml/kg for subsequent maintenance only
if procedure duration lasts for more than 90- 120 minutes