7.7.1 Protection strategies

 In addition to the cellular lesions caused by ischaemia (ATP depletion, disturbance of calcium homeostasis, acidosis, apoptosis, etc.), coexist those induced by reperfusion (massive supply of O₂ , production of free radicals, mitochondrial lesions, endothelial and myocardial dysfunction, "no-reflow" phenomenon, arrhythmias) [8]. These phenomena are complex and multifactorial; moreover, they are modified by the various myocardial pathologies. It is therefore not surprising that it is so difficult to prove univocally the effect of different measures used to reduce the impact of ischaemia-reperfusion.

A range of different strategies can be considered to mitigate these injuries and improve myocardial recovery [4].

• Cardioplegia: is the principal measure (see below);
• Hemodynamic regulation before and after bypass surgery: normocardia, normotension, DO₂ /VO₂ , etc;
• Decreased myocardial O demand₂ : decreased contractility and wall tension, beta-blockade;
• Reducing the inflammatory reaction: biocompatible material, mini-ECC, haemofiltration;

The latter is the subject of much research. Conditioning is an improvement in tolerance to ischaemia by brief episodes of arterial flow occlusion followed by periods of reperfusion (see Chapter 5 Conditioning). It is effective if applied before the ischaemic injury (preconditioning), but also after the event (postconditioning). It can even act at  distance by ischaemia of another organ or muscle group. An identical protective effect has been demonstrated experimentally with four anaesthetic agents (halogen, morphine, xenon, helium) and certain drugs (nicorandil, cyclosporine A, natriuretic peptide), but only halogens have a proven clinical effectivity. In coronary revascularisation and valve surgery, halogens improve recovery of myocardial function, reduce the risk of infarction and reduce tissue damage (troponin decrease) compared to intravenous anaesthesia [3,11]. The effect is maximal if halogen is used throughout the operation, including ECC [5]. Infarction rate and mortality tend to decrease (OR 0.51 and 0.31 respectively) in some but not all meta-analyses [1,9,13]. The literature of recent years shows that there is sufficient clinical and experimental evidence to recommend the routine use of halogenated agents during anaesthesia for coronary artery bypass grafting, as recommended in the US guidelines [7]. The anti-inflammatory effect of propofol, which is certainly of interest in the context of bypass surgery, is only apparent at very high concentrations [2].

Ischaemic preconditioning by iterative clamping and unclamping of the aorta prior to cardioplegia or reperfusion is difficult to achieve and performs poorly; moreover, it is highly emboligenic. In contrast, remote preconditioning prior to bypass surgery by iterative 5-minute episodes of ischaemia of the arm by inflation and deflation of a pressure cuff yields surprising results: after coronary artery bypass grafting, troponins are reduced (OR 0.83) and mortality is lowered (OR 0.27) [12]. Further work is required to determine whether this perfectly benign technique actually improves long-term outcomes. For the time being, it appears to only affect myocardial preservation but not patient morbidity and mortality [6,10].

However, care must be taken when translating results obtained in animal experiments or in randomised series of pre-selected patients into everyday practice. While the benefit of preconditioning is fairly clear in these circumstances, it is less clear in studies involving large classes of patients, because of the many confounding factors that occur in real life. However, if all the evidence suggests that halogens have some cardioprotective effect, it makes sense to choose them for anaesthesia when the risk of myocardial injury is high, as in coronary patients. This is largely a Pascal's wager: if the halogens are effective, the result is beneficial, and if they are not, nothing is lost since the patient must be put to sleep anyway. For more information on this subject, see Chapter 24 (see Myocardial Protection) where organ protection is discussed in detail. In clinical practice, myocardial protection focuses on two areas.

• Cardioplegia infusion: absolutely essential for myocardial survival during exclusion of the heart from circulation, it is an integral part of bypass surgery;
• Conditioning: sevoflurane, isoflurane, desflurane.

 © CHASSOT PG, GRONCHI F, April 2008, last update, December 2019

References

1. BIGNAMI E, BIONDI-ZOCCAI G, LANDONI G, et al. Volatile anesthetics reduce mortality in cardiac surgery. J Cardiothorac Vasc Anesth 2009; 23:594-9
2. CORCORAN TB, ENGEL A, SAKAMOTO H, et al. The effects of propofol on neutrophil function, lipid peroxidation and inflammatory response during elective coronary artery bypass grafting in patients with impaired ventricular function. Br J Anaesth 2006; 97:825-31
3. CROMHEECKE S, PEPERMANS V, HENDRICKX E, et al. Cardioprotective properties of sevoflurane in patients undergoing aortic valve replacement with cardiopulmonary bypass. Anesth Analg 2006; 103:289-96
4. DE HERT S, MOERMAN A. Myocardial injury and protection related to cardiopulmonary bypass. Best Pract Res Clin Anaesthesiol 2015; 29:137-49
5. FRÄSSDORF J, DE HERT S, SCHLACK W. Anaesthesia and myocardial ischaemia/reperfusion injury. Br J Anaesth 2009; 103:89-98
6. HAUSENLOY  DJ, CANDILIO L, EVANS R, et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med 2015; 373: 1408-17
7. HILLIS LD, SMITH PK, ANDERSON JL, et al. 2011 ACCF/AHA Guideline for coronary artery bypass graft surgery: Executive summary. Anesth Analg 2012; 114:11-45
8. KLONER RA, BROWN DA, CSETE M, et al. New and revisited approaches to preserving the reperfused myocardium. Nat Rev Cardiol 2017; 14:679-93
9. LANDONI G, GRECO T, BIONDI-ZOCCAI G, et al. Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery. Br J Anaesth 2013; 886-96
10. MEYBOHM P, BEIN B, BROSTEANU O, et al. A multicenter trial of remote ischemic precondioning for heart surgery. N Engl J Med 2015; 373:1397-407
11. PAC-SOO CK, MATHEW H, MA D. Ischaemic conditioning strategies reduce ischaemia/reperfusion-induced organ injury. Br J Anaesth 2015; 114:204-16
12. THIELMANN  M, KOTTENBERG E, KLEINBONGARD P, et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013; 382:597-604
13. UHLIG C, BLUTH T, SCHWARZ K, et al. Effects of volatile anesthetics on mortality and postoperative pulmonary and other complications in patients undergoing surgery: a systematic review and meta-analysis. Anesthesiology 2016; 124:1230-45