cardiac pre and post conditioning

Transcription

1 cardiac pre and post conditioning i Stefan De Hert Department of Anesthesiology University Hospital Ghent University of Ghent 2010 Universitair Ziekenhuis Gent Belgium

2 = limited exposition to a small potential noxious stimulus that protects against the effects of a greater exposition to a noxious stimulus Mythridates king of Pontus BC

3 PRE conditioning limited exposition is applied BEFORE the longlasting l noxious stimulus POST conditioning limited exposition is applied AFTER the longlasting noxious stimulus

4 PRE conditioning ischemic pre conditioning Murry CE et al. Circulation 1986; 74: a rapid adaptive response to a brief ischemic insult, which slows the rate of cell death and extent of cell dysfunction during a subsequent, prolonged period of ischemia

5 ischemic pre conditioning CONTROL IPC short occlusion sustained ischemia short reperfusion // reperfusion //

6 ischemic pre conditioning

7 ischemic pre conditioning windows of protection degree of protec ction early phase late phase time elapsed from preconditioning stimulus (hours)

8 ischemic pre conditioning early and late preconditioning CONTROL ischemia reperfusion EARLY IPC IPC washout ischemia reperfusion LATE IPC IPC washout ischemia reperfusion

9 MPTP synthesis of cytoprotective proteins

10 mitochondrial permeability transition pore Zaugg M et al. Br J Anaesth 2003; 91: Honda Y et al. Ann N Y Acad Sci 2005; 1047:

11 by courtesy of Prof Dr Colin Royse, Melbourne, Australia

12 mitochondrial permeability transition pore inhibition i of MPTP opening, attenuates lethal lmyocardial injury that occurs at the time of reperfusion 58 patients withacute ST elevation MI immediately before PCI study group: 2.5 mg / kg cyclosporine control group: normal saline Piot C et al. N Engl J Med 2008; 359:

13 ischemic pre conditioning clinical implications?

14 prodromal angina preinfarction angina is associated with a lower infarct size and a greater infarct size limitation after thrombolysis group A: preinfarction angina n = 12 group B: NO preinfarction angina n = p < 0.01 p < 0.04 p < group A group B 0 group A group B 0 group A group B peak CKMB # infarcted segments % salvaged myocardium Ottani F et al. Circulation 1995; 91:

15 ischemic preconditioning and coronary surgery IPC reduces myocardial injury after coronary surgery n = 16 serum troponin T (µg/l) at 72 hours n = 17 2 p = control IPC Jenkins DP et al. Heart 1997; 77:

16 ischemic pre conditioning remote preconditioning Kharbanda RK et al. Lancet 2009; 374:

17 Hausenloy DJ et al. Cardiovasc Res 2008; 79:

18 elective CABG surgery with CPB study group: (n = 27) control group: (n = 30) RIPC: 3 x 5 min tourniquet inflation upper arm interspersed by 5 min release after anesthesia, before start of surgery normal saline Hausenloy DJ et al. Lancet 2007; 370:

19 POST conditioning Cour M et al. J Cardiovasc Pharmacol Ther 2010; in press

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21 30 patients with acute ST elevation MI after PCI study group: control group: postconditioning protocol no intervention Staat P et al. Circulation 2005; 112: Thibault H et al. Circulation 2008; 117:

22 A1 receptor agonists ischemic (pre )conditioning pharmacological modulation pharmacological (pre )conditioning hypotension, bradyarrhythmias, renal VC, pain, tachyphylaxis KATP channel openers hypotension, arrhythmias, hth renal VC, pain, protein kinase activators carcinogenic effects

23 pharmacological conditioning anesthetic agents

24 anesthetic PRE conditioning volatile anesthetics BEFORE myocardial ischemia reduce myocardial ischemic injury 60 min control 60 min LAD occlusion 3 hrs reperfusion 30 min control 30 min sevoflurane 60 min LAD occlusion 3 hrs reperfusion size k) 30 control sevoflurane dial infarct area at risk myocard (% of a * Toller W et al. Anesthesiology 1999; 91:

25 anesthetic POST conditioning volatile anesthetics AFTER myocardial ischemia (during early reperfusion) reduce myocardial ischemic injury 30 min ischemia 120 min reperfusion 15 min volatile anesthetic control desflurane sevoflurane t size sk) dial infarct f area at ris myocard (% of 60 * * 40 * 20 0 Preckel B et al. Br J Anaesth 1998; 81:

26 anesthetic PRE and POST conditioning 50 farct size at risk) ardial inf of area a myoca (% o control sevo PC sevo REP sevo PC + REP Obal D et al. Anesth Analg 2005; 101:

27 anesthetic PRE conditioning clinical implications?

28 anesthetic PRE conditioning anesthesia and surgery CPB preconditioning ischemia reperfusion Belhomme D et al. Circulation 1999; 100 (suppl II) Penta de Peppo A et al. Ann Thorac Surg 1999; 68: Tomai F et al. G Ital Cardiol 1999; 29: Haroun Bizri S et al. J Cardiothor Vasc Anesth 2001; 15: Pouzet B et al. Ann Thorac Surg 2002; 73: Julier K et al. Anesthesiology 2003; 98: Forlani S et al. J Cardiovasc Surg (Torino) 2004; 45: Fellahi JL et al. Eur J Anaesth 2004; 21: Lee MC et al. Eur J Anaesth 2006; 23: Murphy GS et al. J Cardiothor Vasc Anesth 2006; 20: Meco M et al. Eur J Cardiothor Surg 2007; 32: Piriou V et al. Br J Anaesth 2007; 99: isoflurane enflurane isoflurane isoflurane sevoflurane sevoflurane isoflurane isoflurane isoflurane morphine desflurane sevoflurane

29 cardiac function biochemical marker Belhomme et al. not reported lower 5 nucleotidase n = 20 Penta de Peppo et al. improved function no effect n = 16 Tomai et al. improved function (subgroup) lower Tn (subgroup) n = 40 Haroun Bazri et al. improvedfunction not reported td n = 49 Pouzet et al. not reported no effect n = 20 Julier et al. not reported lowerbnp n = 72 Forlani et al. no effect lower Tn n = 40 Fellahi et al. not reported no effect n = 359 Lee et a. al. improved poedfunction cto lower Tn n = 40 Murphy et al. improved function no effect n = 46 Meco et al. improved dfunction lower Tn and BNP n = 28 Piriou V et al. no effect no effect n = 72

30 n = 14 n = 14 n = 14 Bein B et al. Anaesthesia 2008; 63:

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32 anesthetic PRE and POST conditioning sternotomy ischemia CPB De Hert SG et al. Anesthesiology 2004; 101:

33 troponin I levels tropon in I (ng/m ml) tropon in I (ng/m ml) PROPOFOL SEVO pre 8 (n = 50) 8 (n = 50) baseline T0 T6 T12 T24 T48 baseline T0 T6 T12 T24 T SEVO all (n = 50) * * * * tropon in I (ng/m ml) tropon in I (ng/m ml) SEVO post (n = 50) 0 0 baseline T0 T6 T12 T24 T48 baseline T0 T6 T12 T24 T48

34 stroke volume propofol p sevo PRE sevo POST sevo ALL 80 * = p < * 50 * * * 40 base pre CPB post CPB ICU T6 ICU T12

35 conclusions ischemic pre and post conditioning protect the myocardium anesthetic agents confer pharmacological conditioning effects extent of protective effects of anesthetic «conditioning» in the clinical setting depends on the protocol used effects on outcome?

36 ... other types of cardioprotection??? The role of mitochondrial and sarcolemmal K ATP channels in canine ethanol-induced preconditioning in vivo Pagel PS, et al: Anesth Analg 2002;94: dogs 60 min coronary occlusion, 3 h reperfusion