Myocardial Protection in Pediatric Cardiac

Surgery

No Disclosures

High KHigh K++ cardiac arrestMelrose 1955 –Potassium citrate ( 77m mol/L)

~~20 years(Mortality 20 years(Mortality ~~10-20%)10-20%)Hypothermia: systemic and/or topical Hypothermia: systemic and/or topical

Bigelow et al. 1950; Shumway et al. 1959; Swan 1973

Continuous or intermittent aortic occlusionCooley et al. 1962

Aortic root or intracoronary blood perfusion Kay et al. 1958

Ellectrically induced VF (fibrilator) Ellectrically induced VF (fibrilator) Senning 1952

History History

Pharmacological arrest was first Pharmacological arrest was first successfully used by successfully used by Bretschneider* in 1964 (HTK)Bretschneider* in 1964 (HTK)

St. Thomas in 1975 St. Thomas in 1975 Blood cardioplegia Blood cardioplegia

Buckberg et al, in 1978 Buckberg et al, in 1978

History History

*Bretschneider HJ (1964) U˝ berlebenszeit und Wiederbelebungszeit des Herzens bei Normo

undHypothermie. Verh Deutsch Ges Kreislaufforschung 30: 11 34.

Importance of MP

1.1. IIrreversible ischemic damage rreversible ischemic damage begins tobegins to occur in the occur in the normothermic normothermic heart after only 20 heart after only 20 minmin

2.2. However, However, when current techniques when current techniques of myocardial protection are used, of myocardial protection are used, arrest times of more than 4 or 5 arrest times of more than 4 or 5 hours may behours may be tolerated without tolerated without irreversible damageirreversible damage

1. Reimer KA,et al. Am J Cardiol 1983;52:72A2. Hosenpud JD, et al. J Heart Lung Transplant 2001;20;805

Morphological differences between pediatric/adult

myocardium In the newborn only 30% of the In the newborn only 30% of the

myocardial massmyocardial mass comprises comprises contractile tissue compared with contractile tissue compared with 60% in60% in the mature myocardium. the mature myocardium.

Pediatric myocardium has fewer Pediatric myocardium has fewer mitochondria andmitochondria and less oxidative less oxidative capacity.capacity.

Clinical differences between pediatric/adult

myocardium NNormal immature myocardiumormal immature myocardium has a has a

greater tolerance to ischemia when greater tolerance to ischemia when compared tocompared to mature myocardiummature myocardium11..

HHypoxicypoxic neonatal heart is more neonatal heart is more sensitive to ischemia than thesensitive to ischemia than the adultadult2. .

When cWhen compared with infants, ompared with infants, children children have have had significantly less had significantly less reperfusion injury and better reperfusion injury and better clinical outcomeclinical outcome 3..

1. Yano Y et al. J Thorac Cardiovasc Surg 1987;94:8872. Kempsfor RD, et al. J Thorac Cardiovasc Surg 1989;97:8563. Imura H, et al. Circulation 2001;103:1551

1. Physiological differences between

pediatric/adult myocardium Immature myocardium Immature myocardium 1-3

Decreased ventricular complianceDecreased ventricular compliance Less preload reserveLess preload reserve Decreased Decreased sensitivity to catecholamines sensitivity to catecholamines in in

immature heartsimmature hearts Less inotropic reserve (with maximum Less inotropic reserve (with maximum

adrenergic stimuli)adrenergic stimuli) More (-) inotropic response to anesthetic agentsMore (-) inotropic response to anesthetic agents Cardiac output in pediatric patients is more Cardiac output in pediatric patients is more

dependent on heart rate and sinus rhythm.dependent on heart rate and sinus rhythm. Increase oIncrease off afterload will produce significant afterload will produce significant

hemodynamic impairmenthemodynamic impairment

1. Teitel D, et al. J Am Coll Cardiol 1983;1:11832. Boudreaux JP, et al. Anesth Analg 1984;63:7313. Caspi J, et al. Circulation 1991;84(Suppl 3):394

2. Physiological differences between pediatric/adult

myocardium Immature myocardium is more sensitive to Immature myocardium is more sensitive to

extracellular Ca levels than mature extracellular Ca levels than mature myocardiummyocardium1,21,2..

The The sarcoplasmic reticulum is underdeveloped in sarcoplasmic reticulum is underdeveloped in the pediatricthe pediatric heart heart

reduced storage capacity for calcium reduced storage capacity for calcium 33

The activity of the SR Ca ATPase is lower than in The activity of the SR Ca ATPase is lower than in the adult heartthe adult heart

Antioxidant defense Antioxidant defense systemsystem is reduced in is reduced in cyanotic heart defectscyanotic heart defects4,54,5

Catalase ↓Catalase ↓ Superoxide dismutase ↓Superoxide dismutase ↓ Glutathione reductase ↓Glutathione reductase ↓

1. Gombosova I, et al. Am J Physiol 1998;274:H21232. Boucek RJ, et al. Pediatr Res 1984;18:9483. Boland R, et al. J Biol Chem 1974;249:6124. Teoh KH,et al. J Thorac Cardiovasc Surg 1992; 104:1595. del Nido PJ,et al. Circulation 1987;76:174

Differences between the immature and mature

myocardium on primary sourse of ATP

Myocardial protection in pediatric cardiac

surgery Cardioplegic arrest On-pump beating heart

The advantages of cardioplegia

Diastolic arrest of the contractive components and cessation of electrical activity

Reduction of metabolic activity (arrest and hypothermia)

Intermittent oxygen delivery (blood) Maintaining acid-base balance Maintaining high osmotic P counteracts

tissue edema Modifying reperfusion (prevention of

reperfusion injury) Reversible Low toxicity

TThehe type of type of cardioplegia cardioplegia

There is still no consensus on the type of cardioplegia

There are 167 different cardioplegic solutions used for only heart transplantation in USA 1.

1.Demmy TL, et al. Ann Thorac Surg 1997;63:262

Cardioplegia Composition and

additives K+

Mg++

Ca++

Buffering Systems (HCO3

-, THAM) Glutamate–aspartate Glucose

Insulin Oxygen-derived free

radical scavengers Superoxide dismutase,

catalase, Glutathione peroxidase, Glutathione, Vit E,A, ascorbate, Allopurunol Desferrioxamine

Procainamide

Beta blockers (esmolol)

Na+-H+ exchange inhibitor (Amiloride, Cariporide)

Na+blocker (lidocaine, tetrodotoxin)

L-Arginine

K+ channel openers Aprikalim, pinacidil,

nicorandilC

a++ channel blockers

Blood vs crystalloid cardioplegia

Crystalloid cardioplegia Delivery is simple and cheap One single shot is possible

Blood cardioplegiaHemoglobin is used for O2 transportationMetabolic substrates Physiological buffersPhysiological osmotic PLess hemodilution Endogeneous oxygen free radical scavengerBlood C is superior to crystalloid C over 1 h ischemia

* Corne AF. J Thorac Cardiovasc Surg 93:163:19872,*

Hypothermia

Hypothermia has been used since Hypothermia has been used since 1950 for myocardial protection 1950 for myocardial protection

The methods to cool the heart The methods to cool the heart Cold cardioplegia Cold cardioplegia Systemic coolingSystemic coolingTopical myocardial cooling » damage to Topical myocardial cooling » damage to

phrenic nerve !!phrenic nerve !!

Less OLess O2 2 consumption in arrested consumption in arrested heartheart

Warm cardioplegia

Hypothermia - Hypothermia - depletion of depletion of myocardialmyocardial energy suppliesenergy supplies

Lichtenstein * 1989 6.5 h CC (normothermic continuous blood cardioplegia)

*Lichtenstein SV et al, Lancet 1989.**Lichtenstein SV et al, Ann Thorac Surg 1991.

Warm and cold combined cardioplegia

Warm and cold combined blood Warm and cold combined blood cardioplegia cardioplegia Warm inductionWarm inductionCold cardioplegiaCold cardioplegiaHot shotHot shot

Delivery techniques Antegrade, retrograde, or

combined?A

nterograde delivery: a

dvantages and disadvantages Simple Uniform distribution

of cardioplegia AI: poor antegrade

coronary perfusion Aortic valve or root

surgery injury to the

coronary ostia

Delivery techniques Antegrade, retrograde, or

combined?R

etrograde delivery: a

dvantages and disadvantages Nonphysiological Nonhomogenous

distribution Decreased flow to the

right ventricle and septum

The advantage in AI and aortic root surgery

Risk of ruptere of the coronary sinus

Single-dose/multi-dose /multi-dose CardioplegiaCardioplegia

Single-doseSingle-doseContinuous (adult heart)Continuous (adult heart)Multi-dose cardioplegiaMulti-dose cardioplegia

Cold cardioplegia every 20-30 minCold cardioplegia every 20-30 minWarm cardioplegia every 15-20 minWarm cardioplegia every 15-20 min

Myocardial injury after surgery

Ventricular hypertrophyVentricular hypertrophy Pre-ischemic energy depletionPre-ischemic energy depletion Length of the ischemic intervalLength of the ischemic interval Incomplete myocardial protectionIncomplete myocardial protection

Ventricular distention (failure to vent the LA adequately)

Retraction and stretch injury to the myocardium

Ventriculotomy edema (hemodilution or low colloid oncotic P)

Reperfusion injury Reperfusion injury Coronary artery injury or embolism of air Coronary artery injury or embolism of air

bubbles bubbles

Low output after surgery

Hypocalcemia, acidosis, hypoxia

Residuel volume overload (VSD, PY,AY)

Residual pressure overload (LVOTO,RVOTO)

Cardiac compression (oedema, tamponade)

Decreased preload (hypovolemia, diastolic dysfunction)

Increased afterload (systemic HT, PHT)

Arrhythmia (AV block, AF, JET, VT )

Myocardial protection in our clinic

Miniplegia – Anterograde

On-pump beating BDCPS, FontanPS, PVR, TVR

The cystalloid composition for

Miniplegia Infusion pump composition

30 meq K+

10 meq Mg++

20 ml 30% dextrose Induction [[KK++]] 25 meq/L 25 meq/L Maintenance [[KK++]] 13 meq/L 13 meq/L

1. Result 1. Result

WhenWhen a medical a medical center decide center decidess onon the myocardial protection the myocardial protection method, the most important method, the most important determinants are the determinants are the clinical clinical results results and the surgeons’ and the surgeons’ experiences.experiences.

ThThisis method method shouldshould be effective, be effective, simple, cheap and simple, cheap and should should be be accepteacceptedd by by allall surgeonssurgeons..

2. Results2. Results

Myocardial protection is challengingMyocardial protection is challenging in in some casessome cases

LLongong operations operations CComplexomplex operations operations which recurrent which recurrent

cardioplegia delivery from the cardioplegia delivery from the open open aortic root aortic root isis requiredrequired

Newborn patientsNewborn patients Preoperatively damaged Preoperatively damaged

myocardiummyocardium

3. Results3. Results

The The medical medical center center shouldshould evaluate evaluate the protection method with respect to the protection method with respect to the outcome in different proceduresthe outcome in different proceduresIf the morbidity and mortality rate If the morbidity and mortality rate

is high in especially long and is high in especially long and complex procedures, complex procedures, the the myocardial myocardial protection methodprotection method must also be must also be considered as a risk factor. considered as a risk factor.

T

Thank You!