Immature Myocardium & Fetal
Circulation
Seoul National University Hospital
Department of Thoracic & Cardiovascular Surgery
Fetal Circulation
• Is adapted to a special situation
• Depends on placenta for O2/nutrients
• Is rarely overloaded, but if overloaded
little reserve
Fetal Circulation
 Parallel circulation (combined output)
 Communications between R and L heart
 Pulmonary circulation is redundant
Flow Pathway and Distribution
•
% indicates the proportion of combined output
Oxygen Saturation of Fetal Flow
Normal Fetal Circulation
• Major fetal flow patterns and blood hemoglobin oxygen saturation
Normal Fetal Circulation
• Values for percentages of cardiac output returning to and
leaving the heart in normal fetal lamb
Normal Fetal Circulation
• Values for vascular pressure in normal fetal lamb
Normal Fetal Blood Gas
Transitional Circulation and CHD
• As circulation separates, TGA can not supply enough
oxygen to the body
• Obstructed pathway in either side hardly tolerate
right : PA or critical PS in any CHD
left : Aortic atresia or critical AS, IAA, COA
mitral atresia + small PFO; obstructed TAPVR
Transitional Circulation
• Dramatic changes in circulation at the moment of
birth and onwards :
Air breadth - lung expansion - Rp ↓ Qp ↑ - LA pressure ↑ - PFO ↓
P O2 ↑ - ductus arteriosus and venosus ↓
Obliteration of placental circulation - Rs ↑ IVC pressure ↓ - PFO ↓
Congenital Heart Disease in Fetus
• Often silent :
TGA : has little effect
HLHS : RV is slightly overloaded
PA + IVS : no effect at all
• When CHD causes volume overload,
heart fails and hydrops ensues
Neonatal Circulation and CHD
Neonatal circulation
Potential of increased Rp
Potential of atrial communication
Compliance of two ventricles is nearly equal
CHD and neonatal circulation
VSD, PDA : usually not symptomatic
ASD : usually not symptomatic
Neonatal Circulatory Physiology
1. Decreased compliance of fetal & neonatal right
& left ventricle
2. Decreased capacity for peripheral vasodilation
3. Decreased capacity for response to volume load
due to diminished preload reservoir
Characteristics of Immature Myocardium
1. Greater tolerance to hypoxia & normothermic ischemia
in experimental study
1) greater capacity for anaerobic glycolysis
2) greater buffering capacity
3) decreased ATP flux secondary to lower levels of 5nucleotidase
2. Less tolerant to ischemia based on the duration of ischemia
at the onset of contracture or intracellular accumulation of
sodium and calcium, but recovery of pump function was
not assessed by several reports.
3. Compromised secondary to cyanosis, volume or pressure
overload with associated ventricular hypertrophy &
subendocardial ischemia in clinical setting
Normal Neonatal Myocardium
 Characteristics of normal myocardium
• Myocardial structure
Myocytes are smaller cells with single nuclei than adult and
less contractile materials(30%) than adult(60%), more water,
less collagen, more noncontractile protein.
Small volume of mitochondria, rudimentary sarcoplasmic
reticulum, fewer myofibrils, absence of T-tubules,
organization of immature muscle cells in random
• Function
Velocity of shortening is less.
Less compliant myocardium due to increased amount of
noncontractile cellular element in immature myocardium
Normal Neonatal Myocardium
• Response to hypoxia
Increased ability to tolerate periods of anoxia due to increased
glycogen storage and glycolytic acitivity
• Response to ischemia
Increased resistance to ischemia , but first 3-8 days of life
Early onset of irreversibly injured myocardium than mature
myocardium.
More reperfusion injury, but rapid recovery without irreversible
injury than mature myocardium
• Decreased clear ability of lactate production and with stress
caused by underlying cardiac disease, which causes high morbidity
& mortality.
Structure of Neonatal Myocardium
1. Stiffer due to more water, less collagen, more contractile
protein
2. Smaller cells with single nuclei, poorly developed
intercalated disks, greater mitotic activity, fewer mature
mitochondria, and fewer myofibrils
3. Greater storage of glycogen, enhanced rate of anaerobic
glycolytic ATP production
4. Calcium homeostasis is different & more dependent on
external calcium
Metabolism of Neonatal Myocardium
• Preference for glucose & glycogen over free fatty acid as
energy substrates and greater concentration of glycogen
in the heart
• Enhanced anaerobic glycolytic ATP production capacity
that may represent adaptation to relative O2 deprivation
during fatal condition
• Significant difference in calcium metabolism
(1) Amount of calcium within cardiac cell of neonate is
significantly less than that of adult.
(2) Decreased ability of immature sarcoplasmic reticulum to
accumulate calcium ---- the strength of contraction can be
increased in neonate by increasing in extracellular calcium
Neonatal Myocardial Management
 Trend of management
In 1990
Equal split in the preference for crystalloid vs. blood
cardioplegic solutions
In 1995
Trend toward the use of blood based solutions, with only
20% using crystalloid solutions
Neonatal Cardiac Surgery
 Potential for damage duing surgery
1. Preischemic stage
Hypothermia
2. Ischemic stage
Calcium content
Magnesium
Single vs. multidose
3. Postischemic stage
Myocardial Protection vs. Injury
• The surgical treatment of complex congenital heart
defects in the neonate requires controlled conditions
with unimpaired exposure in a bloodless, immobile
operative field.
• The cost one pays to obtain such exposure, however,
is a period of ischemic insults to myocardium.
Effect of Hypothermia
The term, cooling contracture, rapid cooling
contracture refers to as marked increase in resting
in response to sudden decrease in temperature.
(activation of myofilaments by the release of
calcium from intracellular stores)
Damage at Ischemic Stage
1. Calcium content
o Optimal calcium concentration(?)
o Calcium paradox in acalcemic solutions
o PH, Na, duration of ischemia, effects(?)
-> Reduction in the ionized level of this cation in the cardioplegic solution
results in better myocardial recovery
2. Magnesium
o Magnesium help maintain a negative resting membrane potential and
competitively inhibits sarcolemmal calcium influx
o Superior functional recovery with solution containing magnesium in
blood perfused neonatal rabbit model
o Optimal concentration is 16 mmol/l
citrate
calcium level
temperature
3. Single-dose vs. multidose
o No advantage with multiple administration
o More evident detrimental effects at infusion temperatures below 20oC
and with increasing frequency of administration
Damage at Postischemic Stage
 After early reperfusion, the postischemic myocardial
functional alternation may ensue
 Intervention aimed at the reduction of reperfusionmediated injury
1. substrate enhancement & ionic modification
2. free radical scavenging
3. leucocyte depletion
4. reduction in perfusion pressure and temperature
Protocols for Neonatal Myocardial
Protection (I)
Preischemic phase
o
A. Moderate hypothermic (25~28 C) continuous CP bypass,
with intermittent periods of low flow (50ml/kg/min)
B. Ionized calcium level in the range of 0.5~0.6 mmol/l
* fresh frozen plasma (citrate)
C. Gas flows are adjusted to maintain PCO2 level at
40~45 mmHg during cooling phase
Protocols for Neonatal Myocardial
Protection (II)
Ischemic phase
A. 2:1 blood : crystalloid formulation (Hct 5%)
B. Alkalotic cardioplegic solutions may not be a as
effective in the neonatal heart
C. Initial infusion is at or above room temperature
o
but is cooled to 10 C
Protocols for Neonatal Myocardial
Protection (III)
Postischemic phase
A. Bypass flow rate is reduced to 50% & temperature
o
20~25 C for several minutes.
B. Ionized level of calcium are not normalized until
myocardial activity has returned.