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"MYOCARDIAL PROTECTION""MYOCARDIAL PROTECTION"
Refers to strategies and Refers to strategies and
methodologies used either to methodologies used either to
attenuate or to prevent postischemic attenuate or to prevent postischemic
myocardial dysfunction that occurs myocardial dysfunction that occurs
during and after heart surgery. during and after heart surgery.
•Pre-CPB hemodynamic stabilityPre-CPB hemodynamic stability•Cardioplegic techniquesCardioplegic techniques•Success & adequacy of surgical repairSuccess & adequacy of surgical repair•Separation from CPBSeparation from CPB•Hemodynamic stability in early Hemodynamic stability in early postop. postop. •Preexisting systemic & myocardial Preexisting systemic & myocardial diseasedisease
Multiple factors:
PREOPERATIVE FACTORSPREOPERATIVE FACTORS
INTRAOPERATIVE FACTORSINTRAOPERATIVE FACTORS
POSTOPERATIVE FACTORSPOSTOPERATIVE FACTORS
Preoperative factorsPreoperative factors
Adult Vs Vs pediatric
CAD Vs Valv HDCAD Vs Valv HD
Preop hemodyn stabilityPreop hemodyn stability
Ischemia/ infarctionIschemia/ infarction
Arrhythmias, hypotensionArrhythmias, hypotension
Intraoperative factorsIntraoperative factors
AnaestheticAnaesthetic
HypovolemiaHypovolemia
LV dysfnLV dysfn
Arrhythmias, tachy, HTArrhythmias, tachy, HT
Inadeq ventilationInadeq ventilation
Direct manipulationDirect manipulation
MIDCAB, OPCABMIDCAB, OPCAB
Postoperative factors:Postoperative factors:
Adequate ventilationAdequate ventilation
Avoid vent distensionAvoid vent distension
Avoid vasospasmAvoid vasospasm
Maintain hemodynamicsMaintain hemodynamics
Control bleedingControl bleeding
Maintain CBFMaintain CBF
15-20 mins following 15-20 mins following normothermic ischemia:normothermic ischemia:
Total diastolic arrest from cell Total diastolic arrest from cell membrane depolarisationmembrane depolarisation
Myocardial contracture … ‘stone heart’Myocardial contracture … ‘stone heart’ Vacuolization of SR, mitochondriaVacuolization of SR, mitochondria Release of lysosomal enzymes Release of lysosomal enzymes Uncoupling of oxidation and respirationUncoupling of oxidation and respiration Sequester calcium/expel hydrogenSequester calcium/expel hydrogen
Depletion of ATP < 50% of Depletion of ATP < 50% of Normal Level-Normal Level-Depletion of ATP < 50% of Depletion of ATP < 50% of Normal Level-Normal Level-
irreversible lethal cell injuryirreversible lethal cell injury
glycolysis is blocked glycolysis is blocked
increasing cellular acidityincreasing cellular acidity
protein denaturationprotein denaturation
structural, enzymatic, nuclear structural, enzymatic, nuclear changeschanges
Hibernating Hibernating myocardiummyocardium Moderate and persistent reduction in Moderate and persistent reduction in
myocardial blood flow cause diminished myocardial blood flow cause diminished regional contraction regional contraction (non-contractile) (non-contractile)
Metabolic processes remain intact Metabolic processes remain intact (viable) (viable)
Decrease in the magnitude of the pulse of Decrease in the magnitude of the pulse of calcium involved in the excitation-calcium involved in the excitation-contraction processcontraction process(inadequate calcium levels in the cytsol (inadequate calcium levels in the cytsol during each heart beat) during each heart beat)
Stunned myocardiumStunned myocardium
Severe reduction in myocardial blood flow
Function of the myocardium remains impaired (stunned) for a certain period despite reestablishment of flow
But full recovery is expected Process occurs over a period of 1-2 weeks
Contractile proteins recover if the myocyte is reperfused before irreversible damage
Myocardial Myocardial injury..factorsinjury..factors IschemiaIschemia Ventricular distensionVentricular distension TachycardiaTachycardia Hypertension / hypotensionHypertension / hypotension Fall in DPTI:TTI Fall in DPTI:TTI ratio Ventricular hypertrophyVentricular hypertrophy Reperfusion Reperfusion
Pharmacological Pharmacological measuresmeasures
•HypothermiaHypothermia and and potassiumpotassium infusions the cornerstone of infusions the cornerstone of myocardial protection during on-pump myocardial protection during on-pump heart surgery, heart surgery,
•Many other cardioprotective Many other cardioprotective techniques and methodologies techniques and methodologies available. available.
•The ideal cardioprotective technique, The ideal cardioprotective technique, solution, and/or method of solution, and/or method of administration has yet to be found.administration has yet to be found.
Myocardial OMyocardial O22 demand: demand:
75%
50%
10%
Non cardioplegic Non cardioplegic techniquestechniques
INTERMITTENT AoXCl + VF + MODERATE HYPOTHERMIC PERFUSION (30°C TO 32°C)
Quiet field (during ventricular fibrillation) Quiet field (during ventricular fibrillation)
Avoids the profound metabolic changes that Avoids the profound metabolic changes that
occur with more prolonged periods of ischemia.occur with more prolonged periods of ischemia.
Duration of fibrillation till completion of distalsDuration of fibrillation till completion of distals
Heart defib, proximals using an aortic partial Heart defib, proximals using an aortic partial
clampclamp
In 1992, Bonchek et al- 3000 pts of CABGIn 1992, Bonchek et al- 3000 pts of CABG
Elective operative mortality of rate 0.5%, Elective operative mortality of rate 0.5%,
an urgent mortality rate of 1.7%, and an an urgent mortality rate of 1.7%, and an
emergency rate of 2.3%.emergency rate of 2.3%.
Inotropic support was needed in only 6.6%Inotropic support was needed in only 6.6%
1% required IABP. 1% required IABP.
In 2002, Raco et al-In 2002, Raco et al-
800 pts CABG800 pts CABG
Mortality- 0.6%, 3.1%, 5.6% in Mortality- 0.6%, 3.1%, 5.6% in
elective, urgent, emergent groups. elective, urgent, emergent groups.
Intermittent AoXCl is a safe technique Intermittent AoXCl is a safe technique
both in elective and nonelective pts both in elective and nonelective pts
when performed by an exp surgeon.when performed by an exp surgeon.
SYSTEMIC HYPOTHERMIA AND SYSTEMIC HYPOTHERMIA AND ELECTIVE FIBRILLATORY ELECTIVE FIBRILLATORY ARRESTARREST
Systemic hypothermia (25-28°C)Systemic hypothermia (25-28°C)
Elective fibrillatory arrestElective fibrillatory arrest
Maintenance of perf pres bet 80-100 Maintenance of perf pres bet 80-100
mmHgmmHg
Surgical field may be obscured by Surgical field may be obscured by
blood during revascularizationblood during revascularization
In 1984, Atkins et al reported a low In 1984, Atkins et al reported a low
incidence of perioperative infarction incidence of perioperative infarction
(1.8 %) and a low hospital mortality (1.8 %) and a low hospital mortality
rate (0.4%) in 500 consecutive rate (0.4%) in 500 consecutive
patients using this technique. patients using this technique.
CONTINOUS CORONARY CONTINOUS CORONARY PERFUSIONPERFUSION
Continous blood perfusion of empty beating Continous blood perfusion of empty beating
heartheart
Aortic root/ ostial infusionAortic root/ ostial infusion
Used in OPCABUsed in OPCAB
Unsafe for open heartUnsafe for open heart
Continous retro + AoXCl- open heartContinous retro + AoXCl- open heart
CARDIOPLEGICCARDIOPLEGIC TECHNIQUESTECHNIQUES
Cardioplegic solutionsCardioplegic solutions
Crystalloid cardioplegiaCrystalloid cardioplegia Blood cardioplegiaBlood cardioplegia
Cardioplegic principlesCardioplegic principles
Immediate arrest..rapid infusion for Immediate arrest..rapid infusion for 2mins2mins
HypothermiaHypothermia Substrates…glucose/aa/adenosineSubstrates…glucose/aa/adenosine Maintain pH..bicarb/ THAM/ bloodMaintain pH..bicarb/ THAM/ blood Free radical damage… Free radical damage…
mannitol/deferoxamine/LDBC/allopurinolmannitol/deferoxamine/LDBC/allopurinol Edema ..mannitol/glucose/albuminEdema ..mannitol/glucose/albumin
Cardioplegic deliveryCardioplegic delivery
Antegrade routeAntegrade route Advantage: immediate cardioplegiaAdvantage: immediate cardioplegia Problems:Problems: Impaired perfusion beyond Impaired perfusion beyond
obstructionobstruction AVI..also in mitral surgery as aortic AVI..also in mitral surgery as aortic
root distorted on atrial retractionroot distorted on atrial retraction Hypertrophied heartHypertrophied heart
Retrograde routeRetrograde route Advantage: Advantage: Better septal coolingBetter septal cooling Cardioplegic solution perfuse beyond Cardioplegic solution perfuse beyond
stenosisstenosis Problems:Problems: RV not adequately protectedRV not adequately protected Risk of coronary sinus perforation / Risk of coronary sinus perforation /
myocardial hemorrage / edemamyocardial hemorrage / edema Infusion pressure kept < 50mmHgInfusion pressure kept < 50mmHg
Antegrade + retrogradeAntegrade + retrograde More prompt arrestMore prompt arrest Better disribution of solutionBetter disribution of solution
Hypothermia Hypothermia
Basal metabolism Basal metabolism
in the absence of myocardial in the absence of myocardial contraction, the myocyte still requires contraction, the myocyte still requires oxygen for basic “house keeping” oxygen for basic “house keeping” functions functions
This basal cost can be further reduced This basal cost can be further reduced with hypothermiawith hypothermia
–
Hypothermia Hypothermia
Oxygen DemandOxygen Demand reductionreduction
Normothermic Arrest (37Normothermic Arrest (37ooC) 1mL/100g/minC) 1mL/100g/min 90%90%
Hypothermic Arrest (22Hypothermic Arrest (22ooC) 0.30 mL/100g/min C) 0.30 mL/100g/min 97%97%
Hypothermic Arrest (10Hypothermic Arrest (10ooC)C) 0.14 mL/100g/min0.14 mL/100g/min ~ ~ 97%97%
Hypothermia Hypothermia
Decreased metabolic rateDecreased metabolic rate Ischemia: intracellular pH ….. Ischemia: intracellular pH …..
nonionised : ionised substrate ratio… nonionised : ionised substrate ratio… NI substrate escapeout of cell. NI substrate escapeout of cell.
Hypothermia NI:I ratioHypothermia NI:I ratio Semiliquid to semisolid memebrane.. Semiliquid to semisolid memebrane..
calcium influx.calcium influx. glutamate release in brain… ca glutamate release in brain… ca
sequest.sequest.
Hypothermia Hypothermia Total extracorporeal circulationTotal extracorporeal circulation Surface coolingSurface cooling Surface cooling with partial CPBSurface cooling with partial CPB Deep hypothermic total circulatory Deep hypothermic total circulatory
arrestarrest Low-flow, profoundly hypothermic Low-flow, profoundly hypothermic
perfusionperfusion
All cooling for 30mins before starting CPBAll cooling for 30mins before starting CPB
Problems of Problems of hypothermiahypothermia
DHCA can cause seizures, stroke, DHCA can cause seizures, stroke, change in mental status and muscle change in mental status and muscle tone, post pump choreoathetosis.tone, post pump choreoathetosis.
Neocortex, hippocampus, striatumNeocortex, hippocampus, striatum Loss of cerebral autoregulation<15°CLoss of cerebral autoregulation<15°C Coagulopathy,acidosis,enzyme Coagulopathy,acidosis,enzyme
dysfunctiondysfunction Along with alkalosis, shift Bohr’s oxy-Along with alkalosis, shift Bohr’s oxy-
dissociation curve to left.dissociation curve to left.
In a multicenter trial- continuous In a multicenter trial- continuous
warm blood cardioplegia Vs warm blood cardioplegia Vs
intermittent cold blood cardioplegia.intermittent cold blood cardioplegia.
Similar myocardial preservation Similar myocardial preservation
(mortality, postoperative incidence of (mortality, postoperative incidence of
myocardial infarction, need for myocardial infarction, need for
intraaortic balloon counterpulsation). intraaortic balloon counterpulsation).
RewarmingRewarming <10-12°C gradient between venous blood <10-12°C gradient between venous blood
and water temperature….also between and water temperature….also between arterial blood entering and core arterial blood entering and core temperature.temperature.
CPB withdrawn when bladder temp is 37°CCPB withdrawn when bladder temp is 37°C Prevent hyperthermiaPrevent hyperthermia Esophageal/PAC temp not reliableEsophageal/PAC temp not reliable Alpha stat method to correct pH……. Alpha stat method to correct pH…….
probably better neuro. outcome in probably better neuro. outcome in profound hypothermia profound hypothermia
Reperfusion Reperfusion
Cell damage following Cell damage following ischaemia is biphasic;ischaemia is biphasic;– injury being initiated during injury being initiated during
ischaemiaischaemia– exacerbated during reperfusionexacerbated during reperfusion
Components: Components:
Intracell Ca2+ overload during isch & reperIntracell Ca2+ overload during isch & reper
Oxidative stress induced by reactive oxygen Oxidative stress induced by reactive oxygen
species (ROS)species (ROS)
Ischemia Ischemia ↓ ↓ endogenous antioxidant defenseendogenous antioxidant defense
Loss of cell memb integrityLoss of cell memb integrity
conjugated dienes are “chemical conjugated dienes are “chemical signatures” of oxygen free-radical signatures” of oxygen free-radical lipid peroxidation lipid peroxidation
Romaschin AD, Rebeyka I, Wilson GJ, Romaschin AD, Rebeyka I, Wilson GJ, et al.et al.
J Mol Cell Cardiol 1987;19:289-293J Mol Cell Cardiol 1987;19:289-293 free radicals are generated within 10 free radicals are generated within 10
seconds of reperfusion after seconds of reperfusion after ischaemiaischaemia
Zweier JL, Flaherty JT, Weisfeldt ML.Zweier JL, Flaherty JT, Weisfeldt ML.Proc Natl Acad Sci USA Proc Natl Acad Sci USA
1987;84:1404-14081987;84:1404-1408
Reduce reperfusion Reduce reperfusion injuryinjury Reduce ionic calcium conc. in Reduce ionic calcium conc. in
reperfusatereperfusate 1.0 meq/L…chelate with CPD1.0 meq/L…chelate with CPD pH of 7.6-7.8pH of 7.6-7.8 Reperfusate pressure 50 mm Hg & Reperfusate pressure 50 mm Hg &
osmolality of 350 mOsm..reduce edemaosmolality of 350 mOsm..reduce edema Maintaining potassium arrestMaintaining potassium arrest Infusing at 37°CInfusing at 37°C
Calcium regulationCalcium regulation
Hallmark of reperfusion is Ca uptakeHallmark of reperfusion is Ca uptake Post ischemic failure of normal Post ischemic failure of normal
sequestration by SR / contractile sequestration by SR / contractile app.app.
Calcium phosphate crystal Calcium phosphate crystal deposition in mitochondrial matrixdeposition in mitochondrial matrix
Damage to respiratory chain and Damage to respiratory chain and failure of ATP productionfailure of ATP production
Other measures:Other measures:
Antioxidants- Vit E, glutathioneAntioxidants- Vit E, glutathione
OFR scavengers-SOD, catalase, OFR scavengers-SOD, catalase,
peroxidase, allopurinol, mannitol, peroxidase, allopurinol, mannitol,
CoQ10, deferoxamine mesylateCoQ10, deferoxamine mesylate
WBC filtersWBC filters
BLOOD CP LEUCOCYTE BLOOD CP LEUCOCYTE FILTRATIONFILTRATIONMyocardial ischemia and reperfusion- Myocardial ischemia and reperfusion-
activation of neutrophils activation of neutrophils
Benefit of filtration in:Benefit of filtration in:
1.1. patients undergoing emergency CABGpatients undergoing emergency CABG
2.2. prolonged crossclamping,prolonged crossclamping,
3.3. depressed ejection fraction,depressed ejection fraction,
4.4. heart transplantation. heart transplantation.
At least 90% of leucocytes must be At least 90% of leucocytes must be
removed to attenuate reperfusion removed to attenuate reperfusion
injury markedly.injury markedly.
Leucocyte depletion should be Leucocyte depletion should be
maintained for 5–10 min after the start maintained for 5–10 min after the start
of initial reperfusion prior to aortic of initial reperfusion prior to aortic
clamp release.clamp release.
Filters remove more than 90% of WBCsFilters remove more than 90% of WBCs
CONTROLLED CONTROLLED REPERFUSIONREPERFUSION Reduce reperfusion inj after ac coro occlusion. Reduce reperfusion inj after ac coro occlusion.
AoXCl release- blood CP given at 50 ml/min per AoXCl release- blood CP given at 50 ml/min per
graft with a perfusion pressure ≤50 mmHg for graft with a perfusion pressure ≤50 mmHg for
20 min into the grafts only. 20 min into the grafts only.
Cannulation of a side branch of the vein graft. Cannulation of a side branch of the vein graft.
Multicenter trial, the results were evaluated in Multicenter trial, the results were evaluated in
156 pts with acute coronary occlusion- reduced 156 pts with acute coronary occlusion- reduced
overall mortality from 8.7% to 3.9%. overall mortality from 8.7% to 3.9%.
Complications of Complications of protective strategies protective strategies
RV dysfunction..rewarming / poor RV dysfunction..rewarming / poor distribution…topical coolingdistribution…topical cooling
Coronary ostial stenosis..soft tipped Coronary ostial stenosis..soft tipped cannula/leakage around cannulacannula/leakage around cannula
Endothelial damage to vein graft from Endothelial damage to vein graft from hyperkalemic crystalloid cardioplegichyperkalemic crystalloid cardioplegic
Coronary sinus injuryCoronary sinus injury Infusion pressure <50mmHg through Infusion pressure <50mmHg through
sinussinus
Energy depleted heartEnergy depleted heart
Cardiogenic shock/ unstable anginaCardiogenic shock/ unstable angina Preop stabilisation with IABP / Preop stabilisation with IABP /
pharmacological support / MechVentpharmacological support / MechVent Prompt amino acid enriched warm Prompt amino acid enriched warm
blood cardioplegiablood cardioplegia Followed by cold cardioplegiaFollowed by cold cardioplegia Both antegrade + retrograde flowBoth antegrade + retrograde flow
PROTECTION PROTECTION STRATEGIES UNDER STRATEGIES UNDER INVESTIGATIONINVESTIGATION
Ischemic Ischemic preconditioningpreconditioning
Brief episode of ischemia slows the rate of ATP depletion during subsequent ischemic episodes.
(1) slowing of ATP depletion, or (2) limitation of catabolite accumulation
during the terminal episode of ischemia. Depletion of ATP could be slowed by a
reduction in energy demand during ischemia, or by an increase in the net availability of high-energy phosphates.
Brief periods of ischemia are known to cause prolonged contractile dysfunction, the so called "stunned myocardium."‘
preconditioning could effectively stun the myocardium ….reduce ATP utilization during the early phase of ischemia.
Intermittent ischemia results in degradation of larger molecules… breakdown products, lactate, H', NH3, inorganic phosphate, etc., are then washed out upon reperfusion….limit catabolite accumulation during the occlusion.
Alternatively, a reduced energy demand might drive anaerobic glycolysis to a lesser extent.
Enzyme xanthine oxidase contributes to myocardial cell death by generating superoxide anions
Preconditioning: adenine nucleotide content of the myocardium…. limit hypoxanthine accumulation and superoxide production.
Myocardial lipid peroxidation, estimated as MDA formation, is common during intermittent ischemia-reperfusion.
Huizer et al measured urate production by human hearts with CAD…net production of urate increased in ischemia.
A reduction in catabolite accumulation could limit the osmotic load that occurs during ischemia.
Another possibility is that preconditioning could limit accumulation of chemotactic factors that attract neutrophils to ischemic/reperfused tissue.
Preconditioning can only delay cell death
ineff if sustained ischemic insult > 3 hrsineff if sustained ischemic insult > 3 hrs Preconditioning failed to protect the mid
and subepicardial myocardium
Second phase of protection req 24 hours to Second phase of protection req 24 hours to
appear & sustained for up to 72 hours.appear & sustained for up to 72 hours.
Second window of protection (SWOP), late Second window of protection (SWOP), late
phase preconditioning, or delayed precond. phase preconditioning, or delayed precond.
Unlike classical preconditioning, which Unlike classical preconditioning, which
protects only against infarction, the late protects only against infarction, the late
phase protects against both infarction and phase protects against both infarction and
myocardial stunningmyocardial stunning
adenosine subtype 1 (A1) receptor
ischemic stimulus
G protein and protein kinase C (PKC).
ATP–regulated potassium channel (KATP).
protective effect
IP involves a complex cascade of intracellular events
amplified
effector
?
Anesthetic Anesthetic preconditioningpreconditioning
A safer and simpler alternative to IP is pharmacologic intervention by inhalation anesthetics
APC shares the same mechanism of action as IP
The effect of inhalation anesthetics was present 30 minutes after discontinuation… window of protection;
During this time, which can last for 1 to 2 hours, there is an acute memory phase of preconditioning.
Anesthetic Anesthetic preconditioningpreconditioning Isoflurane was administered in the
pre–cardiopulmonary bypass (CPB) period The higher cardiac index in the isoflurane
group was associated with a lesser degree of ST segment changes than in the control group.
There was no significant difference between the 2 groups in the incidence of reperfusion arrhythmias
Dogs were randomly assigned to receive 2 ml drug vehicle (50% polyethylene glycol in ethyl alcohol; control experiments) or glyburide (0.05 mg/kg sup -1 administered intravenously) in the presence or absence of 1 MAC (end-tidal) isoflurane in four experimental groups
Sevoflurane decreases the inflammatory response after CPB, as measured by the release of IL-6, CD11b/CD18, and TNF-α.
Total intravenous anesthesia was provided for both study and control groups by infusion of propofol,fentanyl, and midazolam. Sevoflurane 2% was added to the cardioplegia solution in the experimental group.
Myocardial function after CPB, as assessed by RWMA and LVSVI, was also improved
1. Normothermic global ischemia lasting 15 min 1. Normothermic global ischemia lasting 15 min significantly augmented the adhesion of PMNs to significantly augmented the adhesion of PMNs to the coronary endothelium.the coronary endothelium.
2. This effect could be completely blocked by 2. This effect could be completely blocked by halothane, isoflurane, or sevoflurane halothane, isoflurane, or sevoflurane continuously administered before and during continuously administered before and during ischemia and reperfusion at 1 and 2 MAC each.ischemia and reperfusion at 1 and 2 MAC each.
3. Isoflurane given under control conditions without 3. Isoflurane given under control conditions without ischemia had no effect on basal PMN adhesion.ischemia had no effect on basal PMN adhesion.
4. Administration of sevoflurane just at the onset of 4. Administration of sevoflurane just at the onset of reperfusion was as effective as continuous reperfusion was as effective as continuous application.application.
5. Suppression of the postischemic-enhanced PMN 5. Suppression of the postischemic-enhanced PMN adhesion by the volatile anesthetics was adhesion by the volatile anesthetics was independent of their vasodilating potency.independent of their vasodilating potency.
6. The volatile anesthetics did not influence the 6. The volatile anesthetics did not influence the severity of ischemic challenge, as judged by severity of ischemic challenge, as judged by myocardial lactate release.myocardial lactate release.
Adenosine Adenosine Coronary vasodilatationCoronary vasodilatation
Immediate arrestImmediate arrest
Ischemic preconditioningIschemic preconditioning
Retards ischemia-induced ATP deple, delays Retards ischemia-induced ATP deple, delays
onset of ischemic contracture, atten myo stun, onset of ischemic contracture, atten myo stun,
↓↓infarct sizeinfarct size
↓↓ lipid peroxidation, lipid peroxidation, ↑↑SOD, catalase, SOD, catalase,
glutathione peroxidase, glutath reductase.glutathione peroxidase, glutath reductase.
Sodium/Hydrogen Sodium/Hydrogen Exchange InhibitionExchange Inhibition
Amiloride, cariporide, eniporide, Amiloride, cariporide, eniporide,
zoniporidezoniporide
Ejection fraction was greater, the Ejection fraction was greater, the
resolution of regional left ventricular resolution of regional left ventricular
wall motion abnormalities tended to wall motion abnormalities tended to
occur earlier, and the cumulative occur earlier, and the cumulative
release of CK-MB was less. release of CK-MB was less.
opioidsopioids Hibernating animals use only '10% of their
normal, active energy expenditure. Hibernation is a process mediated by cyclical
variation in endogenous opiate compounds. δ-opiate receptor in particular is responsible. Hibernation reversed by opiate antagonists. Biological mechanism duplicated in humans,
thereby inducing a profound state of energy conservation.
Drugs with δ -opiate activity confer myocardial protection, which is additive to cardioplegia.
MYOCARD PROTECTION- MYOCARD PROTECTION- OPCABOPCAB
Short-acting beta blocker esmololShort-acting beta blocker esmolol
Cariporide and aprotinin- and aprotinin-
associated with a marked associated with a marked
attenuation of stunning.attenuation of stunning.
Conclusion:Conclusion:
Ideal solution, technique, or delivery Ideal solution, technique, or delivery
method has yet to be identifiedmethod has yet to be identified
Complexity of ischemia/reperfusion injury,Complexity of ischemia/reperfusion injury,
Ideal protection is no longer limited to OTIdeal protection is no longer limited to OT
Need to develop new therapeutic Need to develop new therapeutic
strategies to protect the heartstrategies to protect the heart
Thank you
Dr. Narender to continue…….
THANK YOU!
Pediatric CPBPediatric CPB
Immature handling of calciumImmature handling of calcium Immature myocardium can use carbo/ Immature myocardium can use carbo/
aa/ketones/MCFA/LCFA.aa/ketones/MCFA/LCFA. Hypoglycemia / hemodilutionHypoglycemia / hemodilution Resistant to ischemia : Resistant to ischemia :
1.1. increased gycolytic cababilityincreased gycolytic cabability
2.2. decreased 5’nucleotidase..increased decreased 5’nucleotidase..increased ATPATP
SUPPLY…. DEMANDSUPPLY…. DEMAND
100
0
.. ……………………………………………….LA or PA wedge
Ao
TTI
DPTI
Buckberg 1972
DPTI: diastolic pressure time index
TTI: tension time index
Protection strategiesProtection strategies
Design of cardioplegic solutionDesign of cardioplegic solution TemperatureTemperature Electromechanical work stateElectromechanical work state pHpH Metabolic substrates/additivesMetabolic substrates/additives
Protection techniquesProtection techniques
Systemic hypothermia with VFSystemic hypothermia with VF Ischemic arrest with hypothermiaIschemic arrest with hypothermia Continuous coronary perfusionContinuous coronary perfusion Chemical cardioplegiaChemical cardioplegia
Coming off bypassComing off bypass
Problems:Problems: Systemic rewarming and aortic Systemic rewarming and aortic
unclamping…tachy/fever/ increased SVR / unclamping…tachy/fever/ increased SVR / rise in circulating catecholaminesrise in circulating catecholamines
More compliant heart..greater LVED More compliant heart..greater LVED Acute withdrawal of CCB/BBAcute withdrawal of CCB/BB Coronary vasospasmCoronary vasospasm Elevated OElevated O22 req. of recovering req. of recovering
myocardiummyocardium
Solutions:Solutions: Reinstitute bypass in ventricular Reinstitute bypass in ventricular
distensiondistension Optimise hemodynamic parametersOptimise hemodynamic parameters High dose ionotropes better avoidedHigh dose ionotropes better avoided Adequate preloadAdequate preload Afterload reduction or IABPAfterload reduction or IABP Bleeding correctedBleeding corrected Failure to achieve Failure to achieve
separation….IABP/LVADseparation….IABP/LVAD
Cessation of Cessation of Myocardial Blood FlowMyocardial Blood Flow Cessation of Cessation of Myocardial Blood FlowMyocardial Blood Flow
mitochondriamitochondria
cellular pOcellular pO22 < < 5mmHg within 5mmHg within secondsseconds
oxidative oxidative phosporilation phosporilation stopsstops
cytosolcytosol
anaerobic glycolysisanaerobic glycolysis
glycogenglycogen
glucose-6-glucose-6-phosphatephosphate
pyruvatepyruvate
lactatelactate
cellular acidosiscellular acidosis
depletion of ATPdepletion of ATP
