Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-28T05:51:41.302Z Has data issue: false hasContentIssue false

The effect of anaesthetics on the myocardium – new insights into myocardial protection

Published online by Cambridge University Press:  26 August 2005

N. C. Weber
Affiliation:
University Hospital Düsseldorf, Department of Anaesthesiology, Düsseldorf, Germany
B. Preckel
Affiliation:
University Hospital Düsseldorf, Department of Anaesthesiology, Düsseldorf, Germany
W. Schlack
Affiliation:
University Hospital Düsseldorf, Department of Anaesthesiology, Düsseldorf, Germany
Get access

Extract

Summary

A variety of laboratory and clinical studies clearly indicate that exposure to anaesthetic agents can lead to a pronounced protection of the myocardium against ischaemia–reperfusion injury. Several changes in the protein structure of the myocardium that may mediate this cardioprotection have been identified. Ischaemia–reperfusion of the heart occurs in a variety of clinical situations including transplantations, coronary artery bypass grafting or vascular surgery. Ischaemia may also occur during a stressful anaesthetic induction. Early restoration of arterial blood flow and measures to improve the ischaemic tolerance of the tissue are the main therapeutic options (i.e. cardioplegia and betablockers). There exists increasing evidence that anaesthetic agents interact with the mechanisms of ischaemia–reperfusion injury and protect the myocardium by a ‘preconditioning’ and a ‘postconditioning’ mechanism. Hence, the anaesthesiologist may substantially influence the critical situation of ischaemia–reperfusion during surgery by choosing the appropriate anaesthetic agent. This review summarizes the current understanding of the mechanisms of anaesthetic-induced myocardial protection. In this context, three time windows of anaesthetic-induced cardioprotection are discussed: administration (1) during ischaemia, (2) after ischaemia–during reperfusion (postconditioning) and (3) before ischaemia (preconditioning). Possible clinical implications of these interventions will be reviewed.

Type
Review
Copyright
© 2005 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Spieckermann PG, Bruckner J, Kubler W, Lohr B, Bretschneider HJ. [Preischemic stress and resuscitation time of the heart.] Verh Dtsch Ges Kreislaufforsch 1969; 35: 358364.Google Scholar
Davis RF, DeBoer LW, Rude RE, Lowenstein E, Maroko PR. The effect of halothane anesthesia on myocardial necrosis, hemodynamic performance, and regional myocardial blood flow in dogs following coronary artery occlusion. Anesthesiology 1983; 59: 402411.Google Scholar
Buljubasic N, Stowe DF, Marijic J, Roerig DL, Kampine JP, Bosnjak ZJ. Halothane reduces release of adenosine, inosine, and lactate with ischemia and reperfusion in isolated hearts. Anesth Analg 1993; 76: 5462.Google Scholar
Buljubasic N, Marijic J, Stowe DF, Kampine JP, Bosnjak ZJ. Halothane reduces dysrhythmias and improves contractile function after global hypoperfusion in isolated hearts. Anesth Analg 1992; 74: 384394.Google Scholar
Tarnow J, Markschies-Hornung A, Schulte-Sasse U. Isoflurane improves the tolerance to pacing-induced myocardial ischemia. Anesthesiology 1986; 64: 147156.Google Scholar
Takahata O, Ichihara K, Ogawa H. Effects of sevoflurane on ischaemic myocardium in dogs. Acta Anaesthesiol Scand 1995; 39: 449456.Google Scholar
Oguchi T, Kashimoto S, Yamaguchi T, Nakamura T, Kumazawa T. Comparative effects of halothane, enflurane, isoflurane and sevoflurane on function and metabolism in the ischaemic rat heart. Br J Anaesth 1995; 74: 569575.Google Scholar
Pagel PS, Hettrick DA, Lowe D, Tessmer JP, Warltier DC. Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs. Anesthesiology 1995; 83: 10211035.Google Scholar
Rosenkranz ER, Buckberg GD. Myocardial protection during surgical coronary reperfusion. J Am Coll Cardiol 1983; 1: 12351246.Google Scholar
Schlack W, Hollmann M, Stunneck J, Thamer V. Effect of halothane on myocardial reoxygenation injury in the isolated rat heart. Br J Anaesth 1996; 76: 860867.Google Scholar
Preckel B, Schlack W. Effect of anesthetics on ischemia–reperfusion injury of the heart. In: Vincent JL, ed. Yearbook of Intensive Care and Emergency Medicine. Berlin: Springer, 2000: 165176.
Siegmund B, Schlack W, Ladilov YV, Balser C, Piper HM. Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture. Circulation 1997; 96: 43724379.Google Scholar
Kowalski C, Zahler S, Becker BF et al. Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system. Anesthesiology 1997; 86: 188195.Google Scholar
Chiari PC, Bienengraeber MW, Pagel PS, Krolikowski JG, Kersten JR, Warltier DC. Isoflurane protects against myocardial infarction during early reperfusion by activation of phosphatidylinositol-3-kinase signal transduction: evidence for anesthetic-induced postconditioning in rabbits. Anesthesiology 2005; 102: 102109.Google Scholar
Buhre W. Cardioprotective and anti-inflammatory action of isoflurane during coronary artery bypass surgery. Habilitationsschrift. RWTH, Aachen, 2001.
De Hert SG, Van der Linden PJ, Cromheecke S et al. Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration. Anesthesiology 2004; 101: 299310.Google Scholar
Ross S, Munoz H, Piriou V, Ryder WA, Foex P. A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning. Acta Anaesthesiol Scand 1998; 42: 2331.Google Scholar
Ebel D, Schlack W, Comfere T, Preckel B, Thamer V. Effect of propofol on reperfusion injury after regional ischaemia in the isolated rat heart. Br J Anaesth 1999; 83: 903908.Google Scholar
Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986; 74: 11241136.Google Scholar
Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: Part 1. Circulation 2001; 104: 29812989.Google Scholar
Kloner RA, Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: Part 2. Circulation 2001; 104: 31583167.Google Scholar
Marber MS, Latchman DS, Walker JM, Yellon DM. Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction. Circulation 1993; 88: 12641272.Google Scholar
Baxter GF, Marber MS, Patel VC, Yellon DM. Adenosine receptor involvement in a delayed phase of myocardial protection 24 hours after ischemic preconditioning. Circulation 1994; 90: 29933000.Google Scholar
Kirsch GE, Codina J, Birnbaumer L, Brown AM. Coupling of ATP-sensitive K+ channels to A1 receptors by G proteins in rat ventricular myocytes. Am J Physiol 1990; 259: H820H826.Google Scholar
Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+ channel? Studies of contractile function after simulated ischemia in an atrial in vitro model. Circ Res 1995; 77: 10301035.Google Scholar
Light PE, Sabir AA, Allen BG, Walsh MP, French RJ. Protein kinase C induced changes in the stoichiometry of ATP binding activate cardiac ATP-sensitive K+ channels: a possible mechanistic link to ischemic preconditioning. Circ Res 1996; 79: 399406.Google Scholar
Takahashi T, Ueno H, Shibuya M. VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells. Oncogene 1999; 18: 22212230.Google Scholar
Kuboki K, Jiang ZY, Takahara N, et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 2000; 101: 676681.Google Scholar
Yang XM, Sato H, Downey JM, Cohen MV. Protection of ischemic preconditioning is dependent upon a critical timing sequence of protein kinase C activation. J Mol Cell Cardiol 1997; 29: 991999.Google Scholar
Gopalakrishna R, Anderson WB. Ca2+-and phospholipid-independent activation of protein kinase C by selective oxidative modification of the regulatory domain. Proc Natl Acad Sci USA 1989; 86: 67586762.Google Scholar
Baines CP, Wang L, Cohen MV, Downey JM. Protein tyrosine kinase is downstream of protein kinase C for ischemic preconditioning's anti-infarct effect in the rabbit heart. J Mol Cell Cardiol 1998; 30: 383392.Google Scholar
Fryer RM, Schultz JE, Hsu AK, Gross GJ. Pretreatment with tyrosine kinase inhibitors partially attenuates ischemic preconditioning in rat hearts. Am J Physiol 1998; 275: H2009H2015.Google Scholar
Weinbrenner C, Liu GS, Cohen MV, Downey JM. Phosphorylation of tyrosine 182 of p38 mitogen-activated protein kinase correlates with the protection of preconditioning in the rabbit heart. J Mol Cell Cardiol 1997; 29: 23832391.Google Scholar
Hattori R, Otani H, Uchiyama T et al. Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning. Am J Physiol Heart Circul Physiol 2001; 281: H1066H1074.Google Scholar
Maulik N, Yoshida T, Zu YL, Sato M, Banerjee A, Das DK. Ischemic preconditioning triggers tyrosine kinase signaling: a potential role for MAPKAP kinase 2. Am J Physiol 1998; 275: H1857H1864.Google Scholar
Fryer RM, Schultz JE, Hsu AK, Gross GJ. Importance of PKC and tyrosine kinase in single or multiple cycles of preconditioning in rat hearts. Am J Physiol 1999; 276: H1229H1235.Google Scholar
da SR, Lucchinetti E, Pasch T, Schaub MC, Zaugg M. Ischemic but not pharmacological preconditioning elicits a gene expression profile similar to unprotected myocardium. Phys Genom 2004; 20: 117130.Google Scholar
Weber NC, Toma O, Wolter JI et al. The noble gas xenon induces pharmacological preconditioning in the rat heart in vivo via induction of PKC-epsilon and p38 MAPK. Br J Pharmacol 2005; 144: 123132.Google Scholar
Weber NC, Toma O, Awab S, Preckel B, Schlack W. Does nitrous oxide precondition the rat heart in vivo? Anesthesiology 2005; in press.Google Scholar
Schultz JE, Hsu AK, Gross GJ. Morphine mimics the cardioprotective effect of ischemic preconditioning via a glibenclamide-sensitive mechanism in the rat heart. Circ Res 1996; 78: 11001104.Google Scholar
Tsuchida A, Miura T, Tanno M, Nozawa Y, Kita H, Shimamoto K. Time window for the contribution of the delta-opioid receptor to cardioprotection by ischemic preconditioning in the rat heart. Cardiovasc Drugs Therap 1998; 12: 365373.Google Scholar
Kuzume K, Wolff RA, Chien GL, Van Winkle DM. Remifentanil limits infarct size but attenuates preconditioning-induced infarct limitation. Coron Artery Dis 2004; 15: 449455.Google Scholar
Zhang Y, Chen ZW, Girwin M, Wong TM. Remifentanil mimics cardioprotective effect of ischemic preconditioning via protein kinase C activation in open chest of rats. Acta Pharmacol Sin 2005; 26: 546550.Google Scholar
Mullenheim J, Frassdorf J, Preckel B, Thamer V, Schlack W. Ketamine, but not S(+)-ketamine, blocks ischemic preconditioning in rabbit hearts in vivo. Anesthesiology 2001; 94: 630636.Google Scholar
Cope DK, Impastato WK, Cohen MV, Downey JM. Volatile anesthetics protect the ischemic rabbit myocardium from infarction. Anesthesiology 1997; 86: 699709.Google Scholar
Novalija E, Fujita S, Kampine JP, Stowe DF. Sevoflurane mimics ischemic preconditioning effects on coronary flow and nitric oxide release in isolated hearts. Anesthesiology 1999; 91: 701712.Google Scholar
Coetzee JF, le Roux PJ, Genade S, Lochner A. Reduction of postischemic contractile dysfunction of the isolated rat heart by sevoflurane: comparison with halothane. Anesth Analg 2000; 90: 10891097.Google Scholar
Han J, Kim E, Ho WK, Earm YE. Effects of volatile anesthetic isoflurane on ATP-sensitive K+ channels in rabbit ventricular myocytes. Biochem Biophys Res Commun 1996; 229: 852856.Google Scholar
Turner LA, Fujimoto K, Suzuki A, Stadnicka A, Bosnjak ZJ, Kwok WM. The interaction of isoflurane and protein kinase C-activators on sarcolemmal KATP channels. Anesth Analg 2005; 100: 16801686.Google Scholar
Stadnicka A, Bosnjak ZJ. Adenine nucleotide sensitivity of the rat sarcolemmal KATP channel is differentially modulated by isoflurane. Anesthesiology 2004; 101: A-631.Google Scholar
Kohro S, Hogan QH, Nakae Y, Yamakage M, Bosnjak ZJ. Anesthetic effects on mitochondrial ATP-sensitive K channel. Anesthesiology 2001; 95: 14351440.Google Scholar
Zaugg M, Lucchinetti E, Spahn DR, Pasch T, Schaub MC. Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial K(ATP) channels via multiple signaling pathways. Anesthesiology 2002; 97: 414.Google Scholar
Fujimoto K, Bosnjak ZJ, Kwok WM. Isoflurane-induced facilitation of the cardiac sarcolemmal K(ATP) channel. Anesthesiology 2002; 97: 5765.Google Scholar
Kwok WM, Martinelli AT, Fujimoto K, Suzuki A, Stadnicka A, Bosnjak ZJ. Differential modulation of the cardiac adenosine triphosphate-sensitive potassium channel by isoflurane and halothane. Anesthesiology 2002; 97: 5056.Google Scholar
Zhong L, Su JY. Isoflurane activates PKC and Ca(2+)-calmodulin-dependent protein kinase II via MAP kinase signaling in cultured vascular smooth muscle cells. Anesthesiology 2002; 96: 148154.Google Scholar
Sugioka S, Miyamae M, Domae N, Figueredo VM, Kotani J. Blockade of p38 mitogene activated protein kinase before and during ischaemia does not abolish sevoflurane-induced cardiac preconditioning in giunea pigs. Anesthesiology 2004; 101: A-708.Google Scholar
Uecker M, Da Silva R, Grampp T, Pasch T, Schaub MC, Zaugg M. Translocation of protein kinase C isoforms to subcellular targets in ischemic and anesthetic preconditioning. Anesthesiology 2003; 99: 138147.Google Scholar
Toma O, Weber NC, Wolter JI, Obal D, Preckel B, Schlack W. Desflurane preconditioning induces time-dependent activation of protein kinase C epsilon and extracellular signal-regulated kinase 1 and 2 in the rat heart in vivo. Anesthesiology 2004; 101: 13721380.Google Scholar
Da Silva R, Grampp T, Pasch T, Schaub MC, Zaugg M. Differential activation of mitogen-activated protein kinases in ischemic and anesthetic preconditioning. Anesthesiology 2004; 100: 5969.Google Scholar
Ismaeil MS, Tkachenko I, Gamperl AK, Hickey RF, Cason BA. Mechanisms of isoflurane-induced myocardial preconditioning in rabbits. Anesthesiology 1999; 90: 812821.Google Scholar
Piriou V, Chiari P, Knezynski S et al. Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium: possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels. Anesthesiology 2000; 93: 756764.Google Scholar
Toller WG, Kersten JR, Gross ER, Pagel PS, Warltier DC. Isoflurane preconditions myocardium against infarction via activation of inhibitory guanine nucleotide binding proteins. Anesthesiology 2000; 92: 14001407.Google Scholar
Kehl F, Krolikowski JG, Mraovic B, Pagel PS, Warltier DC, Kersten JR. Is isoflurane-induced preconditioning dose related? Anesthesiology 2002; 96: 675680.Google Scholar
Obal D, Weber NC, Zacharowski K et al. Role of protein kinase C-ε (PKC-ε) in isoflurane induced cardioprotection. Low, but not high concentrations of isoflurane activate PKC-ε. Br J Anaesth 2005; 94: 166173.Google Scholar
Mullenheim J, Ebel D, Frassdorf J, Preckel B, Thamer V, Schlack W. Isoflurane preconditions myocardium against infarction via release of free radicals. Anesthesiology 2002; 96: 934940.Google Scholar
Kersten JR, Orth KG, Pagel PS, Mei DA, Gross GJ, Warltier DC. Role of adenosine in isoflurane-induced cardioprotection. Anesthesiology 1997; 86: 11281139.Google Scholar
Toller WG, Montgomery MW, Pagel PS, Hettrick DA, Warltier DC, Kersten JR. Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C? Anesthesiology 1999; 91: 713722.Google Scholar
Kersten JR, Schmeling T, Tessmer J, Hettrick DA, Pagel PS, Warltier DC. Sevoflurane selectively increases coronary collateral blood flow independent of KATP channels in vivo. Anesthesiology 1999; 90: 246256.Google Scholar
Kersten JR, Gross GJ, Pagel PS, Warltier DC. Activation of adenosine triphosphate-regulated potassium channels: mediation of cellular and organ protection. Anesthesiology 1998; 88: 495513.Google Scholar
Ismaeil MS, Tkachenko I, Hickey RF, Cason BA. Colchicine inhibits isoflurane-induced preconditioning. Anesthesiology 1999; 91: 18161822.Google Scholar
Weber NC, Toma O, Wolter JI, Schlack W, Preckel B. Mechanisms of xenon and isoflurane induced preconditioning – a potential link to the cytoskeleton via the MAPKAPK-2 HSP27 pathway. Br J Pharmacol 2005; in press.Google Scholar
Baumert JH, Hein M, Roissant R. Effects of xenon on myocardial infarct size. Anesthesiology 2004; 101: A-635.Google Scholar
Hein H, Hecker KE, Horn NA, Roissant R, Baumert JH. Xenon anesthesia has no influence on post-ischemia recovery of LV function. Anesthesiology 2004; 101: A-705.Google Scholar
Kehl F, Pagel PS, Krolikowski JG et al. Isoflurane does not produce a second window of preconditioning against myocardial infarction in vivo. Anesth Analg 2002; 95: 11621168.Google Scholar
Lutz MR, Liu H. Sevoflurane produces a delayed window of protection in young rat myocardium and fails to in aged rat myocardium. Anesthesiology 2004; 101: A-732.Google Scholar
Takahashi MW, Otani H, Nakao S, Imamura H, Shingu K. The optimal dose, the time window, and the mechanism of delayed cardioprotection by isoflurane. Anesthesiology 2004; 101: A-632.Google Scholar
Fraessdorf J, Weber NC, Obal D et al. Morphine induces late cardioprotection in rat hearts in vivo. Involvement of opioid receptors and NF-κB. Anesth Analg 2005; in press.Google Scholar
Roscoe AK, Christensen JD, Lynch III C. Isoflurane, but not halothane, induces protection of human myocardium via adenosine A1 receptors and adenosine triphosphate-sensitive potassium channels. Anesthesiology 2000; 92: 16921701.Google Scholar
Hanouz JL, Yvon A, Massetti M et al. Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro. Anesthesiology 2002; 97: 3341.Google Scholar
Julier K, Da Silva R, Garcia C et al. Preconditioning by sevoflurane decreases biochemical markers for myocardial and renal dysfunction in coronary artery bypass graft surgery: a double-blinded, placebo-controlled, multicenter study. Anesthesiology 2003; 98: 13151327.Google Scholar
Fraessdorf J, Weber NC, Borowski A, Feindt P, Schlack W. Sevoflurane induced preconditioning in men: 1 MAC for 5 min does not influence the phosphorylation of protein kinase C-e in right atrial myocardium. Anesthesiology 2005; in press.Google Scholar
Fraessdorf J, Weber NC, Hermes M et al. Sevoflurane induced preconditioning in men: 1 MAC for 5 min does not influence the phosphorylation of tyrosine kinase Src at Tyr 416. Eur J Anaesthesiol 2005; 22 (Suppl 34): A-170.Google Scholar
Mullenheim J, Molojavyi A, Preckel B, Thamer V, Schlack W. Thiopentone does not block ischemic preconditioning in the isolated rat heart. Can J Anaesth 2001; 48: 784789.Google Scholar
Zaugg M, Lucchinetti E, Garcia C, Pasch T, Spahn DR, Schaub MC. Anaesthetics and cardiac preconditioning: Part II. Clinical implications. Br J Anaesth 2003; 91: 566576.Google Scholar
Barthel H, Ebel D, Mullenheim J, Obal D, Preckel B, Schlack W. Effect of lidocaine on ischaemic preconditioning in isolated rat heart. Br J Anaesth 2004; 93: 698704.Google Scholar
Scognamiglio R, Avogaro A, Vigili de KS et al. Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes. Diabetes 2002; 51: 808812.Google Scholar
Ebel D, Mullenheim J, Frassdorf J et al. Effect of acute hyperglycaemia and diabetes mellitus with and without short-term insulin treatment on myocardial ischaemic late preconditioning in the rabbit heart in vivo. Pflugers Arch 2003; 446: 175182.Google Scholar
Ebel D, Toma O, Weber NC, Huhn R, Preckel B, Schlack W. Hyperglycaemia blocks anaesthetic-induced preconditioning by desflurane during the mediator phase. Eur J Anaesthesiol 2005; 22 (Suppl 34): A-165.Google Scholar
Tomai F, De PR, Penta de PA et al. Beneficial impact of isoflurane during coronary bypass surgery on troponin I release. G Ital Cardiol 1999; 29: 10071014.Google Scholar
Haroun-Bizri S, Khoury SS, Chehab IR, Kassas CM, Baraka A. Does isoflurane optimize myocardial protection during cardiopulmonary bypass? J Cardiothorac Vasc Anesth 2001; 15: 418421.Google Scholar
Belhomme D, Peynet J, Louzy M, Launay JM, Kitakaze M, Menasche P. Evidence for preconditioning by isoflurane in coronary artery bypass graft surgery. Circulation 1999; 100: II340II344.Google Scholar
Penta de PA, Polisca P, Tomai F et al. Recovery of LV contractility in man is enhanced by preischemic administration of enflurane. Ann Thorac Surg 1999; 68: 112118.Google Scholar
Garcia C, Julier K, Bestmann L et al. Preconditioning with sevoflurane decreases PECAM-1 expression and improves one-year cardiovascular outcome in coronary artery bypass graft surgery. Br J Anaesth 2005; 94: 159165.Google Scholar
De Hert SG, ten Broecke PW, Mertens E et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology 2002; 97: 4249.Google Scholar
De Hert SG, Cromheecke S, ten Broecke PW et al. Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients. Anesthesiology 2003; 99: 314323.Google Scholar
De Hert SG, Van der Linden PJ, Cromheecke S et al. Choice of primary anesthetic regimen can influence intensive care unit length of stay after coronary surgery with cardiopulmonary bypass. Anesthesiology 2004; 101: 920.Google Scholar