Eugene Yevstratov, MDInstitute of Cardiology and

Cardiovascular Surgery, Favaloro Foundation

Buenos Aires, Argentina

October/2002

1.Protect against ischemic injury2.Provide a motionless, bloodless field

3.Allow effective post-ischemic myocardial resuscitation

Goals of Myocardial protection

Spectrum of myocardial ischemic injury

Acute ischemic disfunction

Preconditioning

Stunning

Hibernation

Necrosis vs. Apoptosis

Acute ischemic disfunction

Reversible contractile failure

Perfusion pressure

O2 supply

Inmediate recovery

Preconditioning

ReversibleSlowed energy utilizationReduction in myocardial necrosisIncrease protective abilities of myocardiumPresented as a normal proper protective reaction of the ischemic myocardiumRecovery Hs,Ds

Stunning

Parcialy ReversibleMay be accompained by endothelial disfunction (NO) causing reduced coronary blood flowResult of ischemia-reperfusion insultMediated by increased intracellular Ca accumulationRecovery in Hs,Wks

Hibernation

Parcialy Reversible

Related to poor myocardial blood flow

Chronic

Recovery Wks,Mo

Necrosis

Irreversible

Hyper contracture - “contracture band necrosis”, “stone heart”

Osmotic/ionic dysregulation, membrane injury

Cell swelling&disruption

Lysis

Apoptosis

Irreversible

Death signal

Cell shrinkage

Cytoplasmic and nuclear condensation

Phagocytosis

Systems involved into membrane injury

MAC( membrane attack complex)

Adenosine dependent receptors

K+ATP dependent chanels

NHE(sodium hydrogen exchanger)

Cellular effects of ischemia

Altered membrane potentialAltered ion distribution(increase intracellularCa++/Na++)Cellular swellingCytoskeletal DisorganisationIncreased hypoxantineDecreased ATPDecreased phosphocreatineDecreased GlutationeCellular Acidosis

Straqtegies for Heart protection

Increase the O2 offer

Decreae oxygen demand

Methabolical intervention

Prevention of demand increased

Substrate disponsability

Myocardial O2 consumptions at 37C

Beating (full,perfused)

10ml/100gr/min

Beating (empty,perfused)

5,5ml/100gr/min

Fibrilating(empty,perfused)

6,5ml/100gr/min

K+ Cardioplegia(empty,crossclamp)

1,0ml/100gr/min

Myocardial O2 consumptionml/100gr/min

Temperatura C 37 32 28 22

Beating (empty) 5,5 5,0 4,0 2,9

Fibrilating (empty) 6,5 3,8 3,0 2,0

K+ cardioplegia 1,0 0,8 0,6 0,3

Cardioplegia - Options

No cardioplegia

Cardioplegia

Type ( blood vs crystalloid, cont vs intermittent )

Route ( antegrade vs retrograde )

Temperature ( warm vs cold )

Additives

Special consideration ( Acute infarction, Neonate)

Rivero Cardioplegia solutions

1 2

Mechanism of Cardioplegic Protection

Mechanical arrest ( K – induced, 80% reduction in O2 consumption)Hypotermia (10-15% furter reduction in O2 consumption)Aerobic metabolism – oxygenated cardioplegiaMaintain hypotermic arrest with readministration every 15-20 minRetrograde delivery LV RV protection

Other consideration

Protect from rewarming

Systemic hypotermia

Aortic/ventricular vents

Total bypass (caval oclusion)

Acute Ischemia

Waqrm induction

Substrate enhancement

Controlled reperfusion

Warm,hypocalcemic,alkaline cardioplegia

Retrograde or low flow-pressure antegrade perfusion

Energy replacement while arrested

Uniform warming

Cardioplegic Composition

Blood vs Crystalloid

Buffers

Calcium

Potassium

Free radical scavengers

Others

Blood vs Crystalloid

O2 carrying capacity ( Hematocrit 15 – 20 %)

Buffers –histidine

Free radical scavengers in RBCs

Improved rheologic / oncotic properties

Metabolic substrate

Buffers

THAM

Histidine

NaHCO3

Slightly alkaline reperfusion

Calcium, Potassium

Small amounts of calcium ( 0.1 – 0.5 mM/L )

Ca chelated in blood with citrate

10 – mM/L of potassium ( first dose highest )

> 30 mM/L – endothelial dysfunction

Free radical scavengers.Others

Allopurinol

Propofol

Deferoxamine

Metabolic substrates ( adenosine, nucleotid transport inhibitors...)

K- channel openers ( Nicorandil )

The ways of pharmacological therapy        Addition of metabolites or cofactors

Activation of enzymes or complexes involving in generation of reduced equivalents, and their utilisation Control of synthesis of mitochondrial factors, or genesis of mitochondria, and protection of mitochondria  Improving Ph balance in the ischemic heart

 

The End

Eugene Yevstratov E-mail

Fax 001775 679 2870

Institute of Cardiology and Cardiovascular Surgery, Favaloro Foundation

Buenos Aires, Argentina