Immature Myocardium & Fetal Circulation

1. Immature Myocardium & Fetal Circulation Seoul National University Hospital Department of Thoracic & Cardiovascular Surgery

2. Fetal Circulation • Is adapted to a special situation • Depends on placenta for O2/nutrients • Is rarely overloaded, but if overloaded little reserve

3. Fetal Circulation • Parallel circulation (combined output) • Communications between R and L heart • Pulmonary circulation is redundant

4. Flow Pathway and Distribution • % indicates the proportion of combined output

5. Oxygen Saturation of Fetal Flow

6. Normal Fetal Circulation • Major fetal flow patterns and blood hemoglobin oxygen saturation

7. Normal Fetal Circulation • Values for percentages of cardiac output returning to and • leaving the heart in normal fetal lamb

8. Normal Fetal Circulation • Values for vascular pressure in normal fetal lamb

9. Normal Fetal Blood Gas

10. 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

11. 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 ↓

12. 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

13. 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

14. 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

15. 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 5- • nucleotidase • 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

16. 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

17. 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.

18. 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

19. 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

20. 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

21. Neonatal Cardiac Surgery • Potential for damage duing surgery • 1. Preischemic stage • Hypothermia • 2. Ischemic stage • Calcium content • Magnesium • Single vs. multidose • 3. Postischemic stage

22. 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.

23. 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)

24. 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

25. Damage at Postischemic Stage • After early reperfusion, the postischemic myocardial functional alternation may ensue • Intervention aimed at the reduction of reperfusion-mediated injury • 1. substrate enhancement & ionic modification • 2. free radical scavenging • 3. leucocyte depletion • 4. reduction in perfusion pressure and temperature

26. Protocols for Neonatal Myocardial Protection (I) • Preischemic phase • A. Moderate hypothermic (25~28oC) 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

27. Protocols for Neonatal Myocardial Protection (II) • Ischemic phase • 2:1 blood : crystalloid formulation (Hct 5%) • Alkalotic cardioplegic solutions may not be a as effective in the neonatal heart • C. Initial infusion is at or above room temperature but is cooled to 10oC

28. Protocols for Neonatal Myocardial Protection (III) Postischemic phase A. Bypass flow rate is reduced to 50% & temperature 20~25oC for several minutes. B. Ionized level of calcium are not normalized until myocardial activity has returned.