GLOBAL MYOCARDIAL ISCHEMIA AND REPERFUSION

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GLOBAL MYOCARDIAL ISCHEMIA AND REPERFUSION

• M.KUDUVALLI

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DEFINITION

• GLOBAL MYOCARDIAL ISCHEMIA REFERS TO A REDUCTION
  IN OXYGEN SUPPLY TO THE WHOLE OF THE MYOCARDIUM
  DUE TO AN INADEQUATE CORONARY BLOOD FLOW, DESPITE
  ADEQUATE OXYGEN CONTENT OF THE PERFUSATE
• TO BE DIFFERENTIATED FROM MYOCARDIAL HYPOXIA

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PROTECTIVE MECHANISMS AGAINST MYOCARDIAL ISCHEMIA
IN THE NORMAL HEART

• BLOOD IS CONTINUOUSLY MODIFIED
• FOR CORRECT COMPOSTITION
• FOR REMOVAL OF PARTICULATE AND GASEOUS EMBOLI
• MYOCARDIAL OXYGEN SUPPLY IS KEPT IN BALANCE WITH
  DEMAND
• HIGH DEGREE OF AUTOREGULATION OF CORONARY BLOOD
  FLOW

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MYOCARDIAL VULNERABILITY TO ISCHEMIC DAMAGE
DURING CPB

• PREOPERATIVE FUNCTIONAL CLASS
• VENTRICULAR HYPERTROPHY
• CORONARY ARTERY DISEASE
• CYANOTIC CONG. HEART DISEASE
• ISCHEMIA PRIOR TO CPB
• PREOPERATIVELY IN CARDIOGENIC SHOCK
• ANAESTHESIA
• MANIPULATION OF THE HEART

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VENTRICULAR HYPERTROPHY

• TRANSMURAL GRADIENTS OF ENERGY SUBSTRATE
  UTILIZATION MARKEDLY INCREASED
• XANTHINE OXIDASE LEVELS MARKEDLY INCREASED
• SUPEROXIDE DISMUTASE LEVELS MARKEDLY DECREASED
• ADEQUATE REPERFUSION OF HYPERTROPHIED MYOCARDIUM
  MORE DIFFICULT

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CHRONIC HEART FAILURE

• CHRONICALLY DEPLETED OF ENERGY CHARGE
• ENERGY CHARGE IS THE ENERGY PRODUCING CAPACITY OF
  THE PARTICULAR COMBINATION OF ADENINE NUCLEOTIDES
  PRESENT IN THE MITOCHONDRIA AND CYTOPLASM OF THE
  MYOCARDIAL CELL.
• NORMALLY 0.85.
• WOULD BE 1.0 IF ALL THE NUCLEOTIDES WERE PRESENT
  ONLY AS ATP

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EVENTS DURING CPB WHICH CAUSE ISCHEMIA

• ABNORMAL PERFUSATE COMPOSITION
• PERSISTENT VENTRICULAR FIBRILLATION
• INADEQUATE MYOCARDIAL PERFUSION
• VENTRICULAR DISTENSION
• VENTRICULAR COLLAPSE
• CORONARY EMBOLISM
• CATECHOLAMINES
• AORTIC CROSS-CLAMP
• REPERFUSION

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ABNORMALITIES IN PERFUSATE

• DENATURED PLASMA PROTEINS
• HIGH LEVELS OF FREE FATTY ACIDS
• VASOACTIVE SUBSTANCES
• CAPILLARY SLUDGING (PREDISPOSED TO BY
  HEPARINIZATION BY INCREASING THE SEDIMENTATION
  RATE)
• GAS AND PARTICULATE MICRO-EMBOLI

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VENTRICULAR FIBRILLATION

• INCREASED MYOCARDIAL WALL TENSION
• INCREASED MVO2
• IMPAIRED SUBENDOCARDIAL BLOOD FLOW
• ABOVE EFFECTS POTENTIATED BY
• VENTRICULAR DISTENSION
• VENTRICULAR HYPERTROPHY
• CORONARY ARTERY DISEASE

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INADEQUATE MYOCARDIAL PERFUSION

• PERFUSION PRESSURE IS VARIABLE AND NONPULSATILE
• CVR INCREASED DUE TO
• ABNORMALITIES OF PERFUSATE COMPOSITION AND
  VISCOSITY
• MICROEMBOLI
• ALTERED LYMPH FLOW
• MYOCARDIAL OEDEMA AFTER LONG CPB
• LOSS OF AUTOREGULATION

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STRATEGIES TO IMPROVE MYOCARDIAL PERFUSION

• KEEP PERFUSION GRADIENT BETWEEN 50 70 mmHg
• HIGHER PERFUSION PRESSURE IN CAD, HYPERTROPHIC
  VENTRICLES, AND IF VF OCCURS
• ?? PULSATILE FLOW

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VENTRICULAR DISTENSION

• CAUSES INCREASED MYOCARDIAL WALL TENSION AND MVO2
• REDUCES SUBENDOCARDIAL PERFUSION DUE TO INCREASED
  INTRACAVITY PRESSURE
• POTENTIATED BY
• INADEQUATE VENOUS RETURN
• AORTIC INSUFFICIENCY
• VF
• INCREASED PV RETURN AND NONCORONARY COLLATERAL
  FLOW IN THE QUIESCENT HEART
• POST-REPAIR CARDIAC FAILURE

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STRATEGIES TO PREVENT VENTRICULAR DISTENSION

• OPTIMIZE VENOUS DRAINAGE
• OPTIMIZE CPB FLOW RATES
• VENT THE LEFT HEART
• EARLY DEFIBRILLATION
• EARLY CROSS CLAMPING IN AORTIC INCOMPETENCE
• VASODILATORS MAY HELP SOMETIMES

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VENTRICULAR COLLAPSE

• PREDISPOSES TO ISCHEMIA IN THE PERFUSED, EMPTY,
  BEATING HEART
• CHANGES IN MYOCARDIAL COMPRESSIVE FORCES AND
  VENTRICULAR GEOMETRY CAUSE SUBENDOCARDIAL
  ISCHEMIA, ESPECIALLY IN HYPERTROPHIC,
  SMALL-CHAMBERED VENTRICLES

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CORONARY EMBOLISM

• GAS OR PARTICULATE
• REDUCE INCIDENCE BY
• APPROPRIATE FILTERS IN THE CIRCUIT
• VENTING OF VEIN GRAFTS
• ADEQUATE DEAIRING OF CHAMBERS

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INOTROPES DURING WEANING FROM CPB

• ENDOGENOUS CATACHOLAMINES ALREADY HIGH AT THE END
  OF CPB
• PROLONGED USE OF HIGH DOSE EXOGENOUS INOTROPES
  DISPROPORTIONATELY INCREASES MVO2
• STRATEGY
• OPTIMIZE HR, PRELOAD, AFTERLOAD PRIOR TO USE OF
  INOTROPES
• MECHANICAL SUPPORT IN PLACE OF VERY HIGH
  INOTROPIC SUPPORT

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AORTIC CROSS CLAMP

• PROBLEMS WITH NORMOTHERMIC ISCHEMIC ARREST
• PERSISTENT ELECTRICAL AND MECHANICAL ACTIVITY
  DURING MUCH OF THE ISCHEMIC PERIOD DEPLETES HIGH
  ENERGY PHOSPHATE AND COMPROMISES POST-REPAIR
  VENTRICULAR PERFORMANCE
• SAFE ISCHEMIC TIME INSUFFICIENT TO COMPLETE MOST
  REPAIRS
• INTERMITTENT CROSS CLAMP WITH PERIODS OF
  REPERFUSION DOES LITTLE TO IMPROVE OPERATING
  CONDITIONS OR PREVENT MYOCARDIAL NECROSIS.
  ACTUALLY MAY BE DELETERIOUS COMPARED TO A LONGER
  SINGLE PERIOD OF ISCHEMIA

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AORTIC CROSS CLAMP

• RAPID CESSATION OF ELECTRO-MECHANICAL ACTIVITY
  FOLLOWING CROSS CLAMP DESIRABLE BOTH FOR EXPOSURE
  AND MYOCARDIAL PRESERVATION
• DIFFERENCES IN MYOCARDIAL VULNERABILITY MAKE IT
  IMPOSSIBLE TO PREDICT A SAFE PERIOD OF ISCHEMIA
• EXTENT OF NECROSIS IS DIRECTLY PROPORTIONAL TO
  THE DURATION OF AORTIC CROSS CLAMP

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• STRATEGIES FOR MINIMIZING DELETERIOUS EFFECTS OF
  AORTIC CROSS CLAMP
• MINIMIZE THE DURATION WITH A WELL THOUGHT OUT AND
  EFFICIENTLY EXECUTED REPAIR
• MANIPULATE MYOCARDIAL METABOLISM DURING THE
  PERIOD OF CROSS CLAMP MYOCARDIAL PROTECTION

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PATHOPHYSIOLOGY OF GLOBAL MYOCARDIAL ISCHEMIA
? HIGH ENERGY PHOSPHATE PRODUCTION
PERSITENT HIGH ENERGY PHOSPHATE UTILIZATION
DECREASED HIGH ENERGY PHOSPHATE AVAILABILITY
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DECREASED HIGH ENERGY PHOSPHATE AVAILABILITY
FAILURE OF CALCIUM REGULATION
FAILURE OF CELLULAR VOLUME REGULATION
INCREASED INTRACELLULAR SODIUM
INCREASED INTRACELLULAR CALCIUM
ACTIVATION OF CALCIUM ATPASES
ACTIVATION OF CALCIUM LIPASES
MITOCHONDRIAL CALCIUM OVERLOAD
INTRACELLULAR OEDEMA
HIGH ENERGY PHOSPHATE UTILIZATION
? HIGH ENERGY PHOSPHATE PRODUCTION
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• OXIDATIVE PHOSPHORYLATION CEASES WHEN PO2 FALL
  BELOW 5 10 mmHg
• DURING ISCHEMIA, THE MAIN SOURCES OF HIGH ENERGY
  PHOSPHATE ARE CREATINE PHOSPHATE AND ANAEROBIC
  PRODUCTION OF ATP
• ANAEROBIC PRODUCTION OF ATP IS SELF- LIMITED
  BECAUSE OF ACCUMULATION OF METABOLITES SUCH AS
  LACTATE, PYRUVATE AND PROTONS, WHICH EVENTUALLY
  INHIBIT ESSENTIAL ENZYME SYSTEMS

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• CP AND ATP LEVELS DECLINE RAPIDLY FOLLOWING
  GLOBAL ISCHEMIA BECAUSE OF PERSISTENT ENERGY
  UTILIZATION FOR ELECTROMECHANICAL AND BASAL
  METABOLIC ACTIVITY
• THERE IS AN INITIAL RAPID REDUCTION OF ACTIVE
  DEVELOPMENT OF MYOCARDIAL TENSION WITHOUT A RISE
  IN RESTING TENSION
• SUBSEQUENTLY, RESTING TENSION INCREASES UNTIL A
  PLATEAU IS REACHED
• PROLONGED ISCHEMIA RESULTS IN SEVERE MYOCARDIAL
  CONTRACTURE

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ENERGY UTILIZATION IS CLOSELY LINKED TO MOVEMENT
OF CALCIUM IONS
TRANSPORT OF CALCIUM INTO THE MYOCYTE (CONSUMES
LITTLE ENERGY)
RISE IN INTRACELLULAR CALCIUM TRIGGERS A SERIES
OF REGULATORY REACTIONS RESULTING IN MYOCARDIAL
CONTRACTION AND ENERGY UTILIZATION
ENERGY DEPENDENT TRANSPORT OF CALCIUM TO OUTSIDE
THE CELL FOR MYOCARDIAL RELAXATION
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INCREASED PRODUCTION AND ACCUMULATION OF H IONS
AND FREE FATTY ACIDS
LOW PRODUCTION OF ATP DUE TO ANAEROBIC METABOLISM
INCREASED CYTOSOLIC CONCENTRATION OF IONIZED
CALCIUM
RELEASE OF INTRACELLULAR LIPOPROTEIN LIPASE
FORMATION OF RIGOR BONDS BETWEEN CONTRACTILE
PROTEINS WITH PERSISTENT ENERGY UTILIZATION
LOSS OF CELL INTEGRITY AND FUNCTION
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DAMAGE FROM GLOBAL MYOCARDIAL ISCHEMIA

• INVOLVES
• MYOCYTES
• VASCULAR ENDOTHELIUM
• SPECIALIZED CONDUCTION CELLS

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(MYOCARDIAL STUNNING)
(MYOCARDIAL NECROSIS)
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MYOCARDIAL STUNNING

• DEFINED AS REVERSIBLE DEPRESSION OF SYSTOLIC AND
  DIASTOLIC MYOCARDIAL FUNCTION, WITHOUT MYOCARDIAL
  NECROSIS, THAT ACCOMPANIES, AND FOR A TIME
  FOLLOWS, MYOCARDIAL ISCHEMIA
• STUNNED MYOCARDIUM HAS BEEN SHOWN TO HAVE A HIGH,
  NOT LOW, OXYGEN CONSUMPTION

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HYPOTHETICAL CAUSES OF MYOCARDIAL STUNNING

• ISCHEMIA INDUCED INFLUX OF CALCIUM INTO THE
  MYOCARDIAL CELLS
• RELEASE OF OXYGEN-DERIVED FREE RADICALS,
  PRESUMABLY BY ACTIVATED NEUTROPHILS IN THE FIRST
  FEW MINUTES OF REPERFUSION
• PROLONGED POST-ISCHEMIC DEPLETION OF MYOCARDIAL
  CELL ENERGY CHARGE
• POST-ISCHEMIC IMPAIRMENT OF CORONARY BLOOD FLOW
  OR CORONARY RESERVE
• APOPTOSIS (PROGRAMMED CELL DEATH)

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MYOCARDIAL NECROSIS

• END STAGE OF A COMPLEX PROCESS
• INITIATED BY THE ONSET OF GLOBAL MYOCARDIAL
  ISCHEMIA
• MAINTAINED BY CONTINUING ISCHEMIA
• AGGRAVATED BY REPERFUSION
• COMMONER WHEN ISCHEMIC PERIOD IS EXCESSIVE
• HOWEVER, EXCESSIVE IS DIFFICULT TO DEFINE

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• INITIAL MICROSCOPIC CHANGES
• GROSS MICROSCOPY
• CELLULAR SWELLING
• ULTRASTRUCTURAL CHANGES
• LOSS OF GLYCOGEN GRANULES
• INTRACELLULAR AND ORGANELLE SWELLING
• LATE MICROSCOPIC CHANGES
• GROSS MICROSCOPY
• FURTHER CELLULAR SWELLING
• DISRUPTION OF REGULAR MYOFIBRILLAR PATTERN
• CONTRACTURE BANDS
• ULTRASTRUCTURAL CHANGES
• CELLULAR AUTOLYSIS
• STRUCTURAL DEGENERATION OF INTRACELLULAR
  ORGANELLES

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ENDOTHELIAL CELL DAMAGE

• ENDOTHELIAL CELL SWELLING DEVELOPS DURING
  ISCHEMIA AND BECOMES MORE PROMINENT DURING
  REPERFUSION
• AFFECTS THE SECRETION OF EDRF AS WELL AS
  ENDOTHELINS (CONSTRICTORS)
• CONTRIBUTE TO THE WHOLE BODY INFLAMMATORY
  RESPONSE TO CPB
• CAN CAUSE INCREASE IN CVR, AND OBSTRUCTION TO
  CAPILLARY PERFUSION DURING REPERFUSION THE NO
  REFLOW PHENOMENON

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SPECIALIZED CONDUCTION CELL DAMAGE

• BECOME NON-FUNCTIONAL EARLY IN THE COURSE OF
  GLOBAL MYOCARDIAL ISCHEMIA
• RECOVERY TAKES LONGER THAN RECOVERY OF MYOCYTES

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ALL THE PATHOLOGICAL CHANGES DESCRIBED OCCUR
PREFERENTIALLY IN THE SUBENDOCARDIAL LAYERS OF
THE MYOCARDIUM, WITH THE SUBEPICARDIAL LAYERS
BEING LEAST AFFECTED
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CAN GLOBAL MYOCARDIAL ISCHEMIA BE BENEFICIAL?

• THE CONCEPT OF ISCHEMIC PRECONDITIONING AND ITS
  POTENTIAL APPLICATION IN CARDIAC SURGERY

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• DEFINED AS THE CONCEPT OF ENDOGENOUS ADAPTATION
  TO SUBLETHAL GLOBAL ISCHEMIA RESULTING IN
  PROTECTION AGAINST A LONGER LETHAL ISCHAEMIC
  EPISODE
• HAS BEEN DEMONSTRATED EXPERIMENTALLY IN ANIMAL
  HEARTS, AND ALSO IN CLINICAL CIRCUMSTANCES IN
  HUMANS IN A FEW STUDIES

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POSSIBLE MECHANISMS OF PRECONDITIONING

• INITIALLY THOUGHT TO BE DUE MANIFESTATION OF
  INCREASED COLLATERAL FLOW
• PRESENT RESEARCH HYPOYHETISES THE EFFECTS TO BE
  MEDIATED BY ADENOSINE AND A SIGNAL TRANSDUCTION
  PATHWAY INVOLVING G-PROTEINS, A PHOSPHOLIPASE AND
  PROTEIN KINASE C (PKC)
• ANOTHER HYPOTHESIS INVOLVED ATP-DEPENDANT K
  CHANNELS

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• SHOWN TO HAVE MAXIMUM BENEFIT WHEN THE ISCHEMIC
  PERIOD IS A SINGLE EPISODE OF 3 - 5 MINS, ABOUT 3
  - 5 MINS PRIOR TO THE PROLONGED ISCHEMIC PERIOD
• THE BENEFITS WEAR OFF BEYOND ABOUT 2 HOURS OF
  PROLONGED ISCHEMIA
• BENEFITS SEEN MAXIMALLY WITH LIMITING INFARCT
  SIZE AND ARRHYTHIAS AFTER THE ISCHEMIC PERIOD
• HAS NOT BEEN SHOWN TO HAVE SIGNIFICANT BENEFITS
  IN DECREASING MYOCARDIAL STUNNING RELATED LOW
  CARDIAC OUTPUT

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REPERFUSION AFTER GLOBAL MYOCARDIAL ISCHEMIA

• POST ISCHEMIA, THE MYOCARDIUM IS COMPOSED OF A
  HETEROGENOUS POPULATION OF CELLS
• IRREVERSIBLE DAMAGED
• MINIMALLY DAMAGED
• STUNNED MYOCARDIAL CELLS

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• POOR MYOCARDIAL PROTECTION BEFORE AND DURING
  CROSS CLAMP
• LARGE MASS OF IRREVERSIBLY DAMAGED CELLS LEADING
  USUALLY TO PATIENT DEATH
• OPTIMAL PROTECTION
• VIABLE MYOCARDIUM AND SURVIVAL WITH MINIMUM
  INTERVENTIONS
• SUBOPTIMAL PROTECTION
• POPULATION OF STUNNED CELLS WHOSE FATE DEPENDS ON
  REPERFUSION MANAGEMENT

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ABNORMALITIES ENCOUNTERED DURING REPERFUSION
ELECTRICAL HETEROGENOUS ACTIVITY INCREASED
AUTOMATICITY
STRUCTURAL MYOCARDIAL OEDEMA PLATELET
DEPOSITION VASCULAR INJURY VASCULAR COMPRESSION
BIOCHEMICAL ACIDOSIS DECREASED OXYGEN
UTILIZATION DECREASED H-E-P PRODUCTION INCREASED
CATACHOLAMINES INCREASED CELLULAR
CALCIUM INCREASED FREE RADICALS
MECHANICAL IMPAIRED SYSTOLIC AND DIASTOLIC
FUNCTION
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• THE RESPONSE OF MYOCARDIAL CELLS TO UNCONTROLLED
  REPERFUSION DEPENDS IN LARGE PART ON THE
  TIME-RELATED POINT ALONG THE PATHWAY TO CELL
  DEATH THAT HAS BEEN REACHED DURING THE PERIOD OF
  ISCHEMIA
• THE CRITICAL POINT AT WHICH THE EXPLOSIVE
  CELLULAR RESPONSE TO UNCONTROLLED PERFUSION IS
  SEEN CANNOT BE DEFINED

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MYOCARDIAL RESPONSE TO REPERFUSION

• MYOCARDIAL STUNNING
• REPERFUSION ARRHYTHMIAS
• VENTRICULAR TACHYCARDIA
• VENTRICULAR FIBRILLATION
• STONE HEART
• HARD AND FIBRILLATING HEART
• MAY INVOLVE ONLY SOME REGIONS OF THE HEART,
  TYPICALLY THE BASILAR PORTION OF THE LEFT
  VENTRICLE AND THE SUBENDOCARDIUM
• INDICATES USUALLY THAT THE HEART HAS REACHED THE
  POINT OF NO-RETURN, THOUGH NOT NECESSARILY SO.

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ENDOTHELIAL CELL DAMAGE DUE TO REPERFUSION

• MINIMAL AFTER ISCHEMIA, ALMOST EXCLUSIVELY
  POTENTIATED BY REPERFUSION
• SWELLING OF ENDOTHELIAL CELLS, AGGREGATION OF
  NEUTROPHILS AND PLATELET PLUGS CAUSE
  MICROVASCULAR OBSTRUCTION
• ADDITIONALLY, MYOCARDIAL OEDEMA CAN ALSO COMPRESS
  THE MICROVASCULATURE LEADING TO INHOMOGENEOUS
  REPERFUSION, OR SOMETIMES, THE NO-REFLOW
  PHENOMENON

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MOLECULAR BASIS OF REPERFUSION RESPONSE

• INFLUX OF CALCIUM INTO MYOCYTES, ESPECIALLY
  ACCUMULATION IN MITOCHONDRIA
• RELEASE OF COMPLEMENT FRAGMENTS SUCH AS C5a FROM
  ISCHEMIC MYOCARDIUM
• CHEMOTACTIC FOR NEUTROPHILS, WHICH
• PLUG MYOCARDIAL CAPILLARIES
• RELEASE LARGE AMOUNT OF OXYGEN DERIVED FREE
  RADICALS
• RELEASE ARACHIDONIC ACID METABOLITES WHICH CAUSE
  ENDOTHELIAL INJURY, PLATELET AGGREGATION AND
  VASOCONSTRICTION

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MECHANISM OF OXYGEN DERIVED FREE RADICAL
PRODUCTION ON REPERFUSION
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CONTROLLED REPERFUSION

• MINIMIZES THE PERSISTENCE OF MYOCARDIAL STUNNING
  INTO THE POST-CPB PERIOD
• PROVIDES FOR OPTIMAL RECOVERY OF FUNCTION OF
  REVERSIBLY DAMAGED MYOCARDIUM
• RESUSCITATES MYOCYTES THAT WOULD OTHERWISE HAVE
  UNDERGONE NECROSIS

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CONTROLLED REPERFUSION CONSISTS OF THE FOLLOWING

• MAINTINING ELECTROMECHANICAL QUIESCENCE DURING
  THE FIRST 3 5 MINS. OF REPERFUSION
• PERMITS MORE RAPID REPLETION OF MYOCARDIAL ENERGY
  CHARGE
• MINIMIZES REGIONAL HETEROGENECITY OF FLOW
• MINIMIZES MYOCARDIAL ENERGY EXPENDITURE TILL
  RECOVERY HAS BEEN ESTABLISHED
• MINIMIZES INTRACELLULAR ACCUMULATION OF CALCIUM
• LARGE BUFFERING CAPACITY OF REPERFUSATE TO COMBAT
  ACCUMULATED ACIDOSIS

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• MINIMIZING DAMAGE BY OXYGEN-DERIVED FREE RADICALS
• MAINTAINING LOW CALCIUM IN THE INITIAL PERFUSATE
  TO PREVENT INTRACELLULAR ACCUMULATION OF CALCIUM
• SUBTRATE ENHANCEMENT OF THE REPERFUSATE FOR
  REPLETION OF ENERGY CHARGE
• MAINTAINING LOW PERFUSION PRESSURES AROUND 30
  40 mmHg DURING THE FIRST COUPLE OF MINUTES OF
  REPERFUSION TO MINIMIZE ENDOTHELIAL CELL DAMAGE
  AND SWELLING

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SUGGESTED STRATEGIES FOR CONTROLLED REPERFUSION

• USING BLOOD AS THE REPERFUSATE INSTEAD OF
  CRYSTALLOID
• RBCs CONTAIN ABUNDANT FREE RADICAL SCAVENGERS
• BUFFERING CAPACITY OF BLOOD PROTEINS
• SUBSTRATE ENHANCEMENT s/a GLUTAMATE OR
  L-ASPARTATE
• BUFFERING AGENTS SUCH AS HYDROXYMETHYAL
  AMINOMETHANE AND HISTIDINE
• LOW CALCIUM CONTENT

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• ENOUGH POTASSIUM CONTENT TO MAINTAIN
  ELECTROMECHANICAL QUIESCENCE, USUALLY 10 20
  mEq/L
• OPTIMUM PERFUSION PRESSURE OF THE REPERFUSATE
• MAINTAINING TEMPERATURE OF REPERFUSATE BETWEEN 35
  37 DEG. CENT.
• CONTINUING CONTROLLED REPERFUSION TILL THE HEART
  IS BEATING FORCEFULLY, PREFERABLY IN SINUS RHYTHM

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• RECENT RESEARCH SHOWS THAT SODIUM INFLUX INTO THE
  CELL ON REPERFUSION AND THE RESULTANT CELLULAR
  OEDEMA CONTRIBUTES SIGNIFICANTLY TO CELL INJURY
  AND DEATH
• ISCHEMIC PRECONDITONING HAS BEEN SHOWN TO REDUCE
  REPERFUSION INJURY BY COMPLEX MECHANISMS, BUT
  PRINICIPALLY BY PROTECTION OF MITOCHONDRIA.
• THIS IMPROVES ATP PRODUCTION AND ENHANCES THE
  FUNCTION OF ATP DEPENDENT Na/K EXCHANGE PUMPS

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CONCLUSION

• ADEQUATE INSIGHT OF PATHOPHYSIOLOGY OF GLOBAL
  MYOCARDIAL ISCHEMIA AND REPERFUSION IS ESSENTIAL
  FOR APPROPRIATE MYOCARDIAL MANAGEMENT DURING AND
  AFTER CPB
• SEVERAL DEFICIENCIES IN AVAILABLE INFORMATION,
  PRESENTLY THE SUBJECT OF RESEARCH
• PRESENT DAY STRATEGIES OF MYOCARDIAL PROTECTION
  WOULD PROBABLY BE BETTER DESCRIBED AS MYOCARDIAL
  DAMAGE LIMITATION !

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Thank you!