Preconditioning
2006; Lippincott Williams & Wilkins; Volume: 113; Issue: 1 Linguagem: Inglês
10.1161/circulationaha.105.569863
ISSN1524-4539
Autores Tópico(s)Cardiac Arrest and Resuscitation
ResumoHomeCirculationVol. 113, No. 1Preconditioning Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBPreconditioningA New Concept About the Benefit of Exercise Raúl J. Domenech, MD Raúl J. DomenechRaúl J. Domenech From Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Santiago, Chile. Originally published3 Jan 2006https://doi.org/10.1161/CIRCULATIONAHA.105.569863Circulation. 2006;113:e1–e3Case presentation: A 45-year-old man with coronary artery disease is found to be in good condition after his annual medical checkup, and his doctor advises him to continue with the same drugs, a prudent diet, entertainment, and regular exercise; however, the patient is afraid that he will not have time to exercise regularly.Benefits of ExerciseClinicians have learned about the beneficial effects of several factors that may prevent a myocardial infarction (MI), including avoidance of smoking; treatment of high blood pressure, diabetes, dyslipidemia, and obesity; and regular performance of exercise. This last factor is based on epidemiological observations such as a decrease in the incidence of MI in men who perform heavy work1,2; however, it is only in the last few years that the beneficial effect of exercise has obtained plausible explanations of its own, that is, apart from its effect on other risk factors. There are at least 3 distinct mechanisms for this benefit: (1) Improvement of endothelial function, thereby preventing atherosclerosis and coronary occlusion3; (2) prevention of remodeling after MI through the expression of oxidative metabolism-related genes4; and (3) delaying acute ischemic injury after a coronary occlusion by preconditioning.Since the discovery of ischemic preconditioning by Murry et al5 in 1986, studies have appeared in the literature searching for its mechanisms and for alternative ways to trigger it. The concept that 1 or 2 episodes of brief ischemia (&5 minutes in duration each), induced a few minutes or a few hours (early preconditioning) or 24 to 72 hours (late preconditioning or second window) before a prolonged coronary occlusion, followed by reperfusion substantially decreases the speed of the ischemic injury and limits infarct size is firmly established in all animal species studied in the experimental laboratory.6 It is one of the most powerful means of protecting the myocardium with the exception of early reperfusion. Several lines of evidence in coronary patients suggest but do not prove that the human myocardium is also protected by ischemic preconditioning. For example, preinfarction angina is associated with a smaller infarct size; a lower incidence of congestive heart failure, shock, and ventricular arrhythmias; and decreased mortality.7–9 The ST-segment elevation observed during angioplasty decreases after subsequent occlusions,10 which suggests that each occlusion provides preconditioning for the ischemic effect of the next one. Protocols of ischemic preconditioning before coronary artery bypass grafting preserve ATP levels during the subsequent global ischemic period11 and decrease serum levels of troponin T, thereby suggesting a smaller infarct size.12 Finally, the progressive decrease in the magnitude of ischemia during several consecutive episodes of exercise in patients with demand angina (warm-up phenomenon) suggests the preconditioning effect of each episode.13The protective effect of ischemic preconditioning can be reproduced by several drugs, thus avoiding the necessity of ischemic periods to induce it. Pharmacological preconditioning is potentially a strong therapeutic tool. For example, the opening of mitochondrial ATP-sensitive potassium channels appears to be an important mediator of ischemic preconditioning. The administration of a mitochondrial ATP-sensitive potassium channel opener before planned procedures that involve a potentially ischemic insult (such as coronary artery surgery or angioplasty in the presence of a non-ST-elevation acute coronary syndrome that includes unstable angina) has been proposed to "buy time" before proceeding to reperfusion.6 Thus, pharmacological preconditioning may be considered "insurance" to protect the heart against ischemia.6Among the maneuvers that induce preconditioning is exercise. Experiments in pigs14 and dogs15 showed that brief episodes of tachycardia that do not induce ischemia before a prolonged coronary occlusion decrease the infarct size (Figure) by a mechanism similar to that of ischemic preconditioning and that is mediated through modifications of sarcoplasmic reticulum and mitochondrial ATP-sensitive potassium channels.16,17 Subsequent experiments in rats18 and in dogs19 showed, as expected, that brief episodes of exercise also induced preconditioning of the infarct size. Interestingly, exercise induces early as well as late preconditioning and the magnitude of reduction in infarct size observed in dogs is much larger than that obtained with ischemic and tachycardia preconditioning (Figure). As yet, there are no studies that show this effect of exercise in humans. In light of these findings, the need for well-designed studies in humans to search for evidence of myocardial preconditioning by exercise is clear. Regular moderate exercise activity may protect against the effect of myocardial ischemia if a plaque rupture in a coronary artery occurs in an individual with or without previous clinical and laboratory evidence of coronary artery disease, delaying the injury, providing more time for revascularization, and thus yielding a smaller infarct size. Regular exercise may constitute a physiological "insurance policy" against the progression of ischemia. From a physiological point of view, it may be speculated that the myocardium is being preconditioned regularly by common daily physical activity. If tachyphylaxis exists for this protective action, as described for ischemic and pharmacological preconditioning, then episodes of moderate or heavy exercise should be needed to promote the late preconditioning effect.Clinical RecommendationsAccordingly, the recommendation for the patient under discussion should be to perform exercise that is at least of moderate magnitude but that is performed regularly,20 not only to obtain the beneficial effects of exercise on cardiovascular risk factors but also to obtain the "insurance" it provides.Download figureDownload PowerPointEffect of tachycardia (A) and exercise (B) on myocardial infarct size in dogs. C indicates control; T, preconditioning with tachycardia; EP, early preconditioning with exercise; LP, late preconditioning with exercise; and NV/RV (%), infarct size expressed in terms of necrotic region volume as percent of the risk region volume. *P at least <0.05. Modified from Domenech et al15 (A) and Domenech et al19 (B).Some of the studies cited in this report were funded by FONDECYT, Santiago, Chile.DisclosuresNone.FootnotesCorrespondence to Raúl J. Domenech, Instituto de Ciencias Biomédicas, Facultad de Medicina Universidad de Chile, Casilla 16038, Avenida Salvador 486 (Providencia), Santiago 9, Chile. E-mail [email protected] References 1 Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE, for the Determinants of Myocardial Infarction Onset Study Investigators. Triggering of acute myocardial infarction by heavy exertion: protection against triggering by regular exertion. N Engl J Med. 1993; 329: 1677–1683.CrossrefMedlineGoogle Scholar2 Willich SN, Lewis M, Lowel H, Arntz HR, Schubert F, Schroder R, for the Triggers and Mechanism of Myocardial Infarction Study Group. Physical exertion as a trigger of acute myocardial infarction. N Engl J Med. 1993; 329: 1684–1690.CrossrefMedlineGoogle Scholar3 Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005; 111: 363–368.LinkGoogle Scholar4 Freiman S, Scheinowitz M, Yekutieli D, Feinberg MS, Eldar M, Kessler-Icekson G. Prior exercise training improves the outcome of acute myocardial infarction in the rat. J Am Coll Cardiol. 2005; 45: 931–938.CrossrefMedlineGoogle Scholar5 Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986; 74: 1124–1136.CrossrefMedlineGoogle Scholar6 Yellon DM, Downey JM. Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol. Rev. 2003; 83: 1113–1151.CrossrefMedlineGoogle Scholar7 Kloner RA, Shook T, Przyklenk K, Davis VS, Junio L, Matthews RV, Burstein S, Gibson CM, Poole WK, Cannon CP, McCabe CH, Braunwald E. Previous angina alters in-hospital outcome in TIMI 4: a clinical correlate to preconditioning? Circulation. 1995; 91: 37–45.CrossrefMedlineGoogle Scholar8 Tamura K, Tsuji H, Nishiue T Tokunaga S, Iwasaka T. Association of preceding angina with in hospital life threatening ventricular tachyarrhythmias and late potentials in patients with a first acute myocardial infarction. Am Heart J. 1997; 133: 297–301.CrossrefMedlineGoogle Scholar9 Kloner RA, Shook T, Antman EM, Cannon CP, Przyklenk K, Yoo K, McCabe CH, Braunwald E, and the TIMI-9B Investigators. Prospective temporal analysis of the onset of preinfarction angina versus outcome: an ancillary study in TIMI-9B. Circulation. 1998; 97: 1042–1045.CrossrefMedlineGoogle Scholar10 Tomai F, Crea F, Chiariello L, Gioffre PA. Ischemic preconditioning in humans: models, mediators, and clinical relevance. Circulation. 1999; 100: 559–563.CrossrefMedlineGoogle Scholar11 Yellon DM, Alkhulaifi AM, Pugsley WB. Preconditioning the human myocardium. Lancet. 1993; 342: 276–277.CrossrefMedlineGoogle Scholar12 Jenkins DP, Pugsley WB, Alkhulaifi AM, Kemp M, Hooper J, Yellon DM. Ischemic preconditioning reduces troponin T release in patients undergoing coronary artery by-pass surgery. Heart. 1997; 77: 314–318.CrossrefMedlineGoogle Scholar13 Marber MS, Joy MD, Yellon DM. Warm-up angina: is it ischemic preconditioning? Br Heart J. 1994; 72: 213–215.Editorial.CrossrefMedlineGoogle Scholar14 Koning MMG, Gho BCG, van Klaarwater E, Opstal RLJ, Duncker DJ, Verdouw PD. Rapid ventricular pacing produces myocardial protection by nonischemic activation of ATP potassium channels. Circulation. 1996; 93: 178–186.CrossrefMedlineGoogle Scholar15 Domenech RJ, Macho P, Velez D, Sanchez G, Liu X, Dhalla L. Tachycardia preconditions infarct size in dogs: role of adenosine and protein kinase C. Circulation. 1998; 97: 786–794.CrossrefMedlineGoogle Scholar16 Domenech RJ, Sanchez G, Donoso P, Parra V, Macho P. Effect of tachycardia on myocardial sarcoplasmic reticulum and calcium dynamics: a mechanism for preconditioning? J Mol Cell Cardiol. 2003; 35: 1429–1437.CrossrefMedlineGoogle Scholar17 Macho P, Solis E, Sanchez G, Schwarze H, Domenech R. Mitochondrial ATP-dependent potassium channels mediate nonischemic preconditioning by tachycardia in dogs. Mol Cell Biochem. 2001; 216: 129–136.CrossrefMedlineGoogle Scholar18 Yamashita N, Hoshida S, Otsu K, Asahi M, Kuzuya T, Hori M. Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation. J Exp Med. 1999; 189: 1699–1706.CrossrefMedlineGoogle Scholar19 Domenech RJ, Macho P, Schwarze H, Sanchez G. Exercise induces early and late myocardial preconditioning in dogs. Cardiovasc Res. 2002; 55: 561–566.CrossrefMedlineGoogle Scholar20 Myers J. Exercise and cardiovascular health. Circulation. 2003; 107: e2–e5.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ahn N (2020) Effects of Combine Exercise on HSP70 and SOD1 Expression of Aorta, Skeletal Muscle and Myocardium in High Fat Diet induced Obese Aging Rats, Exercise Science, 10.15857/ksep.2020.29.3.248, 29:3, (248-255) Li J, Pan S, Wang J and Lu J (2019) Changes in Autophagy Levels in Rat Myocardium During Exercise Preconditioning-Initiated Cardioprotective Effects, International Heart Journal, 10.1536/ihj.18-310, 60:2, (419-428), Online publication date: 30-Mar-2019. Vicencio F, Jiménez P, Huerta F, Cofré-Bolados C, Gutiérrez Zamorano S, Garcia-Diaz D, Rodrigo R and Poblete-Aro C (2019) Effects of physical exercise on oxidative stress biomarkers in hypertensive animals and non-diabetic subjects with prehypertension/hypertension: a review, Sport Sciences for Health, 10.1007/s11332-019-00561-1, 15:3, (481-495), Online publication date: 1-Dec-2019. Domenech R, Macho P and Parra V (2016) Conditioning the Heart: Thirty Years of Research and Still Far from Humans, Current Treatment Options in Cardiovascular Medicine, 10.1007/s11936-016-0492-4, 18:12, Online publication date: 1-Dec-2016. Parra V, Macho P, Sánchez G, Donoso P and Domenech R (2015) Exercise Preconditioning of Myocardial Infarct Size in Dogs Is Triggered by Calcium, Journal of Cardiovascular Pharmacology, 10.1097/FJC.0000000000000191, 65:3, (276-281), Online publication date: 1-Mar-2015. Uryash A, Wu H, Bassuk J, Kurlansky P and Adams J (2012) Preconditioning with periodic acceleration (pGz) provides second window of cardioprotection, Life Sciences, 10.1016/j.lfs.2012.06.031, 91:5-6, (178-185), Online publication date: 1-Sep-2012. Guiraud T, Nigam A, Gremeaux V, Meyer P, Juneau M and Bosquet L (2012) High-Intensity Interval Training in Cardiac Rehabilitation, Sports Medicine, 10.2165/11631910-000000000-00000, 42:7, (587-605), Online publication date: 1-Jul-2012. Galvão T, Matos K, Brum P, Negrão C, da Luz P and Chagas A (2011) Cardioprotection conferred by exercise training is blunted by blockade of the opioid system, Clinics, 10.1590/S1807-59322011000100026, 66:1, (151-157), Online publication date: 1-Jan-2011. Álvarez-Gómez J and Hernández-García S (2011) Cardioprotección endógena en la rehabilitación cardiovascular, Revista Española de Cardiología Suplementos, 10.1016/S1131-3587(11)15008-6, 11, (45-49), Online publication date: 1-Dec-2011. Nigam A and Juneau M (2011) Exercise Training After an Acute Coronary Syndrome Acute Coronary Syndromes: A Companion to Braunwald's Heart Disease, 10.1016/B978-1-4160-4927-2.00032-3, (361-368), . Adams J, Wu H, Bassuk J, Arias J, Uryash A, Jorapur V, Lamas G and Kurlansky P (2010) Periodic acceleration (pGz) prior to whole body Ischemia reperfusion injury provides early cardioprotective preconditioning, Life Sciences, 10.1016/j.lfs.2010.02.022, 86:19-20, (707-715), Online publication date: 1-May-2010. Lee J and Kim W (2010) Pre-Exercise Protective Effects Against Renal Ischemic Reperfusion Injury in Hsp 70.1 Knockout Mice, Journal of Life Science, 10.5352/JLS.2010.20.4.555, 20:4, (555-560), Online publication date: 30-Apr-2010. Adams J, Wu H, Bassuk J, Arias J, Uryash A and Kurlansky P (2009) Periodic acceleration (pGz) acutely increases endothelial and neuronal nitric oxide synthase expression in endomyocardium of normal swine, Peptides, 10.1016/j.peptides.2008.10.014, 30:2, (373-377), Online publication date: 1-Feb-2009. Scrutinio D, Temporelli P, Passantino A and Giannuzzi P (2009) Long-term secondary prevention programs after cardiac rehabilitation for the reduction of future cardiovascular events: focus on regular physical activity, Future Cardiology, 10.2217/fca.09.12, 5:3, (297-314), Online publication date: 1-May-2009. Romero-Farina G, Candell-Riera J, Aguadé-Bruix S, de León G and Castell-Conesa J (2008) Influence of chronic angina prior to infarction in the diagnosis of viability and left ventricular remodelling in myocardial perfusion gated-SPECT, Revista Española de Medicina Nuclear (English Edition), 10.1016/S1578-200X(08)70037-8, 27:4, (245-252), Online publication date: 1-Jul-2008. Romero-Farina G, Candell-Riera J, Aguadé-Bruix S, de León G and Castell-Conesa J (2008) Influencia de la angina crónica previa al infarto en el diagnóstico de viabilidad y remodelado ventricular izquierdo en la gated-SPECT de perfusión miocárdica, Revista Española de Medicina Nuclear, 10.1157/13124633, 27:4, (245-252), Online publication date: 1-Aug-2008. Lee Jin , Chang Sup Shim and Wonkyu Kim (2008) Effects of Exercise on Hsp70 Knock-out Mice Fetuses Exposed to Maternal Hyperthermia, Korean Journal of Sport Science, 10.24985/kjss.2008.19.4.34, 19:4, (34-43), Online publication date: 1-Dec-2008. January 3, 2006Vol 113, Issue 1 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.105.569863PMID: 16391158 Originally publishedJanuary 3, 2006 PDF download Advertisement SubjectsAcute Coronary SyndromesMetabolismPrimary PreventionRehabilitationSecondary Prevention
Referência(s)