Ischemia-reperfusion injury following cardiac arrest and protective effects of hypothermia
Authors:
P. Ošťádal
Authors‘ workplace:
Kardiocentrum, kardiologické oddělení Nemocnice Na Homolce, Praha
Published in:
Kardiol Rev Int Med 2009, 11(1): 11-15
Overview
Ischemia-reperfusion injury following cardiac arrest and protective effects of hypothermia. Early restoration of spontaneous circulation after successful cardiopulmonary resuscitation is an essential lifesaving step. However, within minutes of global ischemia, several pathways are triggered that progress even after reperfusion and may cause further damage to ischemic but viable cells (ischemia-reperfusion (IR) injury). It is desirable, therefore, besides general resuscitation care and treatment of the cause of cardiac arrest to prevent also the harmful effects of IR injury. Several pathogenic mechanisms participate in IR injury: reactive oxygen species, ion imbalance, proteases activation, induction of apoptosis, and activation of inflammation. The majority of these processes are not tissue specific and may be detectable in different organs. In ischemia very sensitive brain tissue, IR injury is enhanced by accumulation and excitotoxicity of some neurotransmiters, disruptions of bloodbrain barrier, or oedema. Together with increasing knowledge of IR mechanism, substantial efforts have been made to develop protective methods against IR injury. Many therapeutic interventions targeted against “key” mechanisms of IR injury showed very promising results in experimental studies but failed completely in clinical settings. Recently, however, one therapeutic approach has been proved to be very effective also in clinical trials: mild hypothermia. Experimental studies have shown that hypothermia exerts beneficial effects simultaneously on various parallel pathways participating in IR injury and leads to significant neuroprotection. Therapeutic hypothermia, therefore, became one of the crucial methods in the current management of patients after cardiac arrest.
Keywords:
cardiac arrest – cardiopulmonary resuscitation – ischemia-reperfusion injury – hypothermia
Sources
1. Negovsky VA, Gurvitch AM. Post‑resuscitation disease – a new nosological entity. Its reality and significance. Resuscitation 1995; 30: 23–27.
2. Neumar RW, Nolan JP, Adrie C et al. Post‑cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 2008; 118: 2452–2483.
3. Nolan JP, Neumar RW, Adrie C et al. Post‑cardiac arrest syndrome: epidemiology, pathophysiology, treatment, and prognostication. A Scientific Statement from the International Liaison Committee on Resuscitation; the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; the Council on Stroke. Resuscitation 2008; 79: 350–379.
4. Laver S, Farrow C, Turner D et al. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med 2004; 30: 2126–2128.
5. Martin LJ, Al-Abdulla NA, Brambrink AM et al. Neurodegeneration in excitotoxicity, global cerebral ischemia, and target deprivation: A perspective on the contributions of apoptosis and necrosis. Brain Res Bull 1998; 46: 281–309.
6. Wolfson SK Jr, Safar P, Reich H et al. Dynamic heterogeneity of cerebral hypoperfusion after prolonged cardiac arrest in dogs measured by the stable xenon/CT technique: a preliminary study. Resuscitation 1992; 23: 1–20.
7. Fischer M, Böttiger BW, Popov-Cenic S et al. Thrombolysis using plasminogen activator and heparin reduces cerebral no-reflow after resuscitation from cardiac arrest: an experimental study in the cat. Intensive Care Med 1996; 22: 1214–1223.
8. Morimoto Y, Kemmotsu O, Kitami K et al. Acute brain swelling after out-of-hospital cardiac arrest: pathogenesis and outcome. Crit Care Med 1993; 21: 104–110.
9. Zeiner A, Holzer M, Sterz F et al. Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome. Arch Intern Med 2001; 161: 2007–2012.
10. Langhelle A, Tyvold SS, Lexow K et al. In-hospital factors associated with improved outcome after out-of-hospital cardiac arrest. A comparison between four regions in Norway. Resuscitation 2003; 56: 247–263.
11. Liu L, Yenari MA. Therapeutic hypothermia: neuroprotective mechanisms. Front Biosci 2007; 12: 816–825.
12. Ostadal P, Zdobnicka I, Dhalla NS. Does Reperfusion Cause Any Injury to the Myocardium? In: Dhalla NS, Chockalingam A, Berkowitz HI et al (eds). Frontiers in Cardiovascular Health. Boston, Dordrecht, London: Kluwer Academic Publishers 2003: 145–159.
13. Danton GH, Dietrich WD. Inflammatory mechanisms after ischemia and stroke. J Neuropathol Exp Neurol 2003; 62: 127–136.
14. Chi OZ, Liu X, Weiss HR. Effects of mild hypothermia on blood-brain barrier disruption during isoflurane or pentobarbital anesthesia. Anesthesiology 2001; 95: 933–938.
15. Jurkovich GJ, Pitt RM, Curreri PW et al. Hypothermia prevents increased capillary permeability following ischemia-reperfusion injury. J Surg Res 1988; 44: 514–521.
16. Laurent I, Monchi M, Chiche JD et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol 2002; 40: 2110–2116.
17. Ostadal P. What is ‚reperfusion injury‘? Eur Heart J 2005; 26: 99; author reply 99–100.
18. Kern KB, Hilwig RW, Berg RA et al. Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine. Circulation 1997; 95: 2610–2613.
19. Karimova A, Pinsky DJ. The endothelial response to oxygen deprivation: biology and clinical implications. Intensive Care Med 2001; 27: 19–31.
20. Gando S, Nanzaki S, Morimoto Y et al. Out-of-hospital cardiac arrest increases soluble vascular endothelial adhesion molecules and neutrophil elastase associated with endothelial injury. Intensive Care Med 2000; 26: 38–44.
21. Geppert A, Zorn G, Karth GD et al. Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation. Crit Care Med 2000; 28: 2360–2365.
22. Adrie C, Monchi M, Laurent I et al. Coagulopathy after successful cardiopulmonary resuscitation following cardiac arrest: implication of the protein C anticoagulant pathway. J Am Coll Cardiol 2005; 46: 21–28.
23. Hékimian G, Baugnon T, Thuong M et al. Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation. Shock 2004; 22: 116–119.
24. Spaulding CM, Joly LM, Rosenberg A et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. N Engl J Med 1997; 336: 1629–1633.
25. Lai CS, Hostler D, D‘Cruz BJ et al. Prevalence of troponin‑T elevation during out-of-hospital cardiac arrest. Am J Cardiol 2004; 93: 754–756.
26. Müllner M, Hirschl MM, Herkner H et al. Creatine kinase-mb fraction and cardiac troponin T to diagnose acute myocardial infarction after cardiopulmonary resuscitation. J Am Coll Cardiol 1996; 28: 1220–1225.
27. Nadkarni VM, Larkin GL, Peberdy MA et al. First documented rhythm and clinical outcome from in‑hospital cardiac arrest among children and adults. Jama 2006; 295: 50–57.
28. Škulec R, Bělohlávek J, Dytrych V et al. Protokol pro použití terapeutické mírné hypotermie u nemocných po srdeční zástavě. Cor Vasa 2007; 49: 61–65.
29. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346: 549–556.
30. Bernard SA, Gray TW, Buist MD et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346: 557–563.
31. Holzer M, Bernard SA, Hachimi-Idrissi S et al. Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data meta‑analysis. Crit Care Med 2005; 33: 414–418.
32. Lanier WL. Cerebral metabolic rate and hypothermia: their relationship with ischemic neurologic injury. J Neurosurg Anesthesiol 1995; 7: 216–221.
33. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in Mammalian central nervous system. J Cereb Blood Flow Metab 2003; 23: 513–530.
34. Mori K, Maeda M, Miyazaki M et al. Effects of mild and moderate hypothermia on cerebral metabolism and glutamate in an experimental head injury. Acta Neurochir Suppl 1998; 71: 222–224.
35. Graham SH, Shiraishi K, Panter SS et al. Changes in extracellular amino acid neurotransmitters produced by focal cerebral ischemia. Neurosci Lett 1990; 110: 124–130.
36. Busto R, Globus MY, Dietrich WD et al. Effect of mild hypothermia on ischemia‑induced release of neurotransmitters and free fatty acids in rat brain. Stroke 1989; 20: 904–910.
37. Kataoka K, Yanase H. Mild hypothermia – a revived countermeasure against ischemic neuronal damages. Neurosci Res 1998; 32: 103–117.
38. Globus MY, Busto R, Lin B et al. Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J Neurochem 1995; 65: 1250–1256.
39. Lei B, Tan X, Cai H et al. Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation. Stroke 1994; 25: 147–152.
40. Edwards AD, Yue X, Squier MV et al. Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate post‑insult hypothermia. Biochem Biophys Res Commun 1995; 217: 1193–1199.
41. Kumar K, Evans AT. Effect of hypothermia on microglial reaction in ischemic brain. Neuroreport 1997; 8: 947–950.
42. Wang GJ, Deng HY, Maier CM et al. Mild hypothermia reduces ICAM‑1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke. Neuroscience 2002; 114: 1081–1090.
43. Deng H, Han HS, Cheng D et al. Mild hypothermia inhibits inflammation after experimental stroke and brain inflammation. Stroke 2003; 34: 2495–2501.
44. Lee JE, Yoon YJ, Moseley ME et al. Reduction in levels of matrix metalloproteinases and increased expression of tissue inhibitor of metalloproteinase-2 in response to mild hypothermia therapy in experimental stroke. J Neurosurg 2005; 103: 289–297.
Labels
Paediatric cardiology Internal medicine Cardiac surgery CardiologyArticle was published in
Cardiology Review
2009 Issue 1
Most read in this issue
- Ischemia-reperfusion injury following cardiac arrest and protective effects of hypothermia
- Surgical treatment of atrial fibrillation
- Current issues in resynchronization therapy of patients with heart failure
- Do we have sufficient evidence in 2009 to decide whether to implant biventricular pacemaker or cardioverter-defibrillator to cardiac resynchronization therapy patients?