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