Presentation is loading. Please wait.

Presentation is loading. Please wait.

Myocardial Protection

Similar presentations


Presentation on theme: "Myocardial Protection"— Presentation transcript:

1 Myocardial Protection

2 "MYOCARDIAL PROTECTION"
Refers to strategies and methodologies used either to attenuate or to prevent postischemic myocardial dysfunction that occurs during and after heart surgery.

3 Multiple factors: Pre-CPB hemodynamic stability
Cardioplegic techniques Success & adequacy of surgical repair Separation from CPB Hemodynamic stability in early postop. Preexisting systemic & myocardial disease

4 PREOPERATIVE FACTORS INTRAOPERATIVE FACTORS POSTOPERATIVE FACTORS

5 Preoperative factors Adult Vs pediatric CAD Vs Valv HD
Preop hemodyn stability Ischemia/ infarction Arrhythmias, hypotension

6 Intraoperative factors
Anaesthetic Hypovolemia LV dysfn Arrhythmias, tachy, HT Inadeq ventilation Direct manipulation MIDCAB, OPCAB

7 Postoperative factors:
Adequate ventilation Avoid vent distension Avoid vasospasm Maintain hemodynamics Control bleeding Maintain CBF

8 15-20 mins following normothermic ischemia:
Total diastolic arrest from cell membrane depolarisation Myocardial contracture … ‘stone heart’ Vacuolization of SR, mitochondria Release of lysosomal enzymes Uncoupling of oxidation and respiration Sequester calcium/expel hydrogen

9 Depletion of ATP < 50% of Normal Level-
irreversible lethal cell injury glycolysis is blocked increasing cellular acidity protein denaturation structural, enzymatic, nuclear changes

10 Hibernating myocardium
Moderate and persistent reduction in myocardial blood flow cause diminished regional contraction (non-contractile) Metabolic processes remain intact (viable) Decrease in the magnitude of the pulse of calcium involved in the excitation-contraction process (inadequate calcium levels in the cytsol during each heart beat)

11 Stunned 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

12 Myocardial injury..factors
Ischemia Ventricular distension Tachycardia Hypertension / hypotension Fall in DPTI:TTI ratio Ventricular hypertrophy Reperfusion

13 Pharmacological measures

14 Hypothermia and potassium infusions the cornerstone of myocardial protection during on-pump heart surgery, Many other cardioprotective techniques and methodologies available. The ideal cardioprotective technique, solution, and/or method of administration has yet to be found.

15 Myocardial O2 demand: 75% 50% 10%

16 Non cardioplegic techniques

17 INTERMITTENT AoXCl + VF + MODERATE HYPOTHERMIC PERFUSION (30°C TO 32°C)
Quiet field (during ventricular fibrillation) Avoids the profound metabolic changes that occur with more prolonged periods of ischemia. Duration of fibrillation till completion of distals Heart defib, proximals using an aortic partial clamp

18 In 1992, Bonchek et al- 3000 pts of CABG
Elective operative mortality of rate 0.5%, an urgent mortality rate of 1.7%, and an emergency rate of 2.3%. Inotropic support was needed in only 6.6% 1% required IABP.

19 In 2002, Raco et al- 800 pts CABG Mortality- 0.6%, 3.1%, 5.6% in elective, urgent, emergent groups. Intermittent AoXCl is a safe technique both in elective and nonelective pts when performed by an exp surgeon.

20 SYSTEMIC HYPOTHERMIA AND ELECTIVE FIBRILLATORY ARREST
Systemic hypothermia (25-28°C) Elective fibrillatory arrest Maintenance of perf pres bet mmHg Surgical field may be obscured by blood during revascularization

21 In 1984, Atkins et al reported a low incidence of perioperative infarction (1.8 %) and a low hospital mortality rate (0.4%) in 500 consecutive patients using this technique.

22 CONTINOUS CORONARY PERFUSION
Continous blood perfusion of empty beating heart Aortic root/ ostial infusion Used in OPCAB Unsafe for open heart Continous retro + AoXCl- open heart

23 CARDIOPLEGIC TECHNIQUES

24 Cardioplegic solutions
Crystalloid cardioplegia Blood cardioplegia

25 Cardioplegic principles
Immediate arrest..rapid infusion for 2mins Hypothermia Substrates…glucose/aa/adenosine Maintain pH..bicarb/ THAM/ blood Free radical damage… mannitol/deferoxamine/LDBC/allopurinol Edema ..mannitol/glucose/albumin

26 Cardioplegic delivery
Antegrade route Advantage: immediate cardioplegia Problems: Impaired perfusion beyond obstruction AVI..also in mitral surgery as aortic root distorted on atrial retraction Hypertrophied heart

27 Retrograde route Advantage: Better septal cooling Cardioplegic solution perfuse beyond stenosis Problems: RV not adequately protected Risk of coronary sinus perforation / myocardial hemorrage / edema Infusion pressure kept < 50mmHg Antegrade + retrograde More prompt arrest Better disribution of solution

28 Hypothermia Basal metabolism
in the absence of myocardial contraction, the myocyte still requires oxygen for basic “house keeping” functions This basal cost can be further reduced with hypothermia

29 Hypothermia Normothermic Arrest (37oC) 1mL/100g/min 90%
Oxygen Demand reduction Normothermic Arrest (37oC) 1mL/100g/min % Hypothermic Arrest (22oC) mL/100g/min % Hypothermic Arrest (10oC) 0.14 mL/100g/min ~ 97%

30 Hypothermia Decreased metabolic rate
Ischemia: intracellular pH ….. nonionised : ionised substrate ratio… NI substrate escapeout of cell. Hypothermia NI:I ratio Semiliquid to semisolid memebrane.. calcium influx. glutamate release in brain… ca sequest.

31 Hypothermia Total extracorporeal circulation Surface cooling
Surface cooling with partial CPB Deep hypothermic total circulatory arrest Low-flow, profoundly hypothermic perfusion All cooling for 30mins before starting CPB surface: <2.5 kg; small ascending aorta . Temp drops to 20c

32 Problems of hypothermia
DHCA can cause seizures, stroke, change in mental status and muscle tone, post pump choreoathetosis. Neocortex, hippocampus, striatum Loss of cerebral autoregulation<15°C Coagulopathy,acidosis,enzyme dysfunction Along with alkalosis, shift Bohr’s oxy-dissociation curve to left.

33  In a multicenter trial- continuous warm blood cardioplegia Vs intermittent cold blood cardioplegia.
Similar myocardial preservation (mortality, postoperative incidence of myocardial infarction, need for intraaortic balloon counterpulsation).

34 Rewarming <10-12°C gradient between venous blood and water temperature….also between arterial blood entering and core temperature. CPB withdrawn when bladder temp is 37°C Prevent hyperthermia Esophageal/PAC temp not reliable Alpha stat method to correct pH……. probably better neuro. outcome in profound hypothermia Mediastinum flushed with cold saline

35 Reperfusion Cell damage following ischaemia is biphasic;
injury being initiated during ischaemia exacerbated during reperfusion

36 Components: Intracell Ca2+ overload during isch & reper
Oxidative stress induced by reactive oxygen species (ROS) Ischemia ↓ endogenous antioxidant defense Loss of cell memb integrity

37 conjugated dienes are “chemical signatures” of oxygen free-radical lipid peroxidation
Romaschin AD, Rebeyka I, Wilson GJ, et al. J Mol Cell Cardiol 1987;19: free radicals are generated within 10 seconds of reperfusion after ischaemia Zweier JL, Flaherty JT, Weisfeldt ML. Proc Natl Acad Sci USA 1987;84:

38 Reduce reperfusion injury
Reduce ionic calcium conc. in reperfusate 1.0 meq/L…chelate with CPD pH of Reperfusate pressure 50 mm Hg & osmolality of 350 mOsm..reduce edema Maintaining potassium arrest Infusing at 37°C

39 Calcium regulation Hallmark of reperfusion is Ca uptake
Post ischemic failure of normal sequestration by SR / contractile app. Calcium phosphate crystal deposition in mitochondrial matrix Damage to respiratory chain and failure of ATP production

40 Other measures: Antioxidants- Vit E, glutathione
OFR scavengers-SOD, catalase, peroxidase, allopurinol, mannitol, CoQ10, deferoxamine mesylate WBC filters

41 BLOOD CP LEUCOCYTE FILTRATION
Myocardial ischemia and reperfusion- activation of neutrophils Benefit of filtration in: patients undergoing emergency CABG prolonged crossclamping, depressed ejection fraction, heart transplantation.

42 At least 90% of leucocytes must be removed to attenuate reperfusion injury markedly.
Leucocyte depletion should be maintained for 5–10 min after the start of initial reperfusion prior to aortic clamp release. Filters remove more than 90% of WBCs

43 CONTROLLED REPERFUSION
Reduce reperfusion inj after ac coro occlusion. AoXCl release- blood CP given at 50 ml/min per graft with a perfusion pressure ≤50 mmHg for 20 min into the grafts only. Cannulation of a side branch of the vein graft. Multicenter trial, the results were evaluated in 156 pts with acute coronary occlusion- reduced overall mortality from 8.7% to 3.9%.

44 Complications of protective strategies
RV dysfunction..rewarming / poor distribution…topical cooling Coronary ostial stenosis..soft tipped cannula/leakage around cannula Endothelial damage to vein graft from hyperkalemic crystalloid cardioplegic Coronary sinus injury Infusion pressure <50mmHg through sinus

45 Energy depleted heart Cardiogenic shock/ unstable angina
Preop stabilisation with IABP / pharmacological support / MechVent Prompt amino acid enriched warm blood cardioplegia Followed by cold cardioplegia Both antegrade + retrograde flow

46 PROTECTION STRATEGIES UNDER INVESTIGATION

47 Ischemic preconditioning
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.

48 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.

49 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.

50 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 hrs Preconditioning failed to protect the mid and subepicardial myocardium

51 Second phase of protection req 24 hours to appear & sustained for up to 72 hours.
Second window of protection (SWOP), late phase preconditioning, or delayed precond. Unlike classical preconditioning, which protects only against infarction, the late phase protects against both infarction and myocardial stunning

52 IP involves a complex cascade of intracellular events
ischemic stimulus adenosine subtype 1 (A1) receptor amplified G protein and protein kinase C (PKC). effector ATP–regulated potassium channel (KATP). ? protective effect

53 Anesthetic preconditioning
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.

54 Anesthetic preconditioning
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

55 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

56 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

57 1. Normothermic global ischemia lasting 15 min significantly augmented the adhesion of PMNs to the coronary endothelium. 2. This effect could be completely blocked by halothane, isoflurane, or sevoflurane continuously administered before and during ischemia and reperfusion at 1 and 2 MAC each. 3. Isoflurane given under control conditions without ischemia had no effect on basal PMN adhesion. 4. Administration of sevoflurane just at the onset of reperfusion was as effective as continuous application. 5. Suppression of the postischemic-enhanced PMN adhesion by the volatile anesthetics was independent of their vasodilating potency. 6. The volatile anesthetics did not influence the severity of ischemic challenge, as judged by myocardial lactate release.

58

59 Adenosine Coronary vasodilatation Immediate arrest
Ischemic preconditioning Retards ischemia-induced ATP deple, delays onset of ischemic contracture, atten myo stun, ↓infarct size ↓ lipid peroxidation, ↑SOD, catalase, glutathione peroxidase, glutath reductase.

60 Sodium/Hydrogen Exchange Inhibition
Amiloride, cariporide, eniporide, zoniporide Ejection fraction was greater, the resolution of regional left ventricular wall motion abnormalities tended to occur earlier, and the cumulative release of CK-MB was less.

61 opioids 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.

62 MYOCARD PROTECTION- OPCAB
Short-acting beta blocker esmolol Cariporide and aprotinin- associated with a marked attenuation of stunning.

63 Conclusion: Ideal solution, technique, or delivery method has yet to be identified Complexity of ischemia/reperfusion injury, Ideal protection is no longer limited to OT Need to develop new therapeutic strategies to protect the heart

64 Thank you THANK YOU! Dr. Narender to continue…….

65

66 Pediatric CPB Immature handling of calcium
Immature myocardium can use carbo/ aa/ketones/MCFA/LCFA. Hypoglycemia / hemodilution Resistant to ischemia : increased gycolytic cabability decreased 5’nucleotidase..increased ATP

67 SUPPLY…. DEMAND 100 Ao DPTI: diastolic pressure time index
Ao DPTI: diastolic pressure time index TTI: tension time index DPTI ……………………………………………….LA or PA wedge TTI Buckberg 1972

68 Protection strategies
Design of cardioplegic solution Temperature Electromechanical work state pH Metabolic substrates/additives

69 Protection techniques
Systemic hypothermia with VF Ischemic arrest with hypothermia Continuous coronary perfusion Chemical cardioplegia

70 Coming off bypass Problems:
Systemic rewarming and aortic unclamping…tachy/fever/ increased SVR / rise in circulating catecholamines More compliant heart..greater LVED Acute withdrawal of CCB/BB Coronary vasospasm Elevated O2 req. of recovering myocardium

71 Solutions: Reinstitute bypass in ventricular distension Optimise hemodynamic parameters High dose ionotropes better avoided Adequate preload Afterload reduction or IABP Bleeding corrected Failure to achieve separation….IABP/LVAD

72 Cessation of Myocardial Blood Flow
mitochondria cellular pO2 < 5mmHg within seconds oxidative phosporilation stops cytosol anaerobic glycolysis glycogen glucose-6-phosphate pyruvate lactate cellular acidosis depletion of ATP

73

74

75

76

77


Download ppt "Myocardial Protection"

Similar presentations


Ads by Google