Myocardial Protection

1. Myocardial Protection www.anaesthesia.co.in anaesthesia.co.in@gmail.com

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 80-100 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 Oxygen Demandreduction • Normothermic Arrest (37oC) 1mL/100g/min 90% • Hypothermic Arrest (22oC) 0.30 mL/100g/min 97% • 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

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

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;19:289-293 • free radicals are generated within 10 seconds of reperfusion after ischaemia Zweier JL, Flaherty JT, Weisfeldt ML. Proc Natl Acad Sci USA 1987;84:1404-1408

38. Reduce reperfusion injury • Reduce ionic calcium conc. in reperfusate • 1.0 meq/L…chelate with CPD • pH of 7.6-7.8 • 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