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.Assiut University

QUIESCENT HEART


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HIDDEN DANGER CARDIAC CONDITIONING Remote Ischemic conditioning CONCLUSION

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THE HIDDEN DANGER (CPB) and cardioplegic arrest remain the most popular techniques in clinical intervention during open heart surgery. However, both can directly or indirectly result in cardiac morbidity following surgery. Cardioplegic arrest can render the heart quiescent but globally ischaemic and, upon reperfusion, triggers myocardial injury (reperfusion injury ).

Suleiman MS, Halestrap AP, Griffiths EJ. Mitochondria: a target for myocardial protection..Pharmacol Ther. Jan; 2001 89(1):29–46.

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THE HIDDEN DANGER For further reduction in morbidity and mortality, strategies to increase tissue tolerance to ischemia or reduce damage that occurs on reperfusion to be considered. One of the strategies that tries to protect the heart is the CARDIAC CONDITIONING

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if these tissues have already been exposed to several minor adverse or ,ischaemic events, medication,stress.. etc i.e. (conditioned ).

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 Halogenated anesthetics  Noble gas e. g. Xenon  Opioids  Potassium channel openers  Nitric oxide donors  Bradykinin receptor agonists  phosphodiesterase inhibitors  AMP-activated protein kinase activators  muscarinic agents  Angiotensin AT1 agonists  Endothelin

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A number of noxious stimuli when applied sparingly can trigger myocardial preconditioning. e.g.

 heat  stress,  rapid pacing,

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Gene therapy to induce a more permanent and long-last preconditioning phenotype

e.g. Gene therapy for eNOS and iNOS

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ischemic

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Injury  Lack of energy substrates  Lost cell wall pump activity  Lost antioxidant defense  Lost pH and calcium homeostasis  Lost mitochondrial integrity

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RIPC (inter organ) preconditioning is a recent observation in which , brief ischemia of one organ protection on distant organs without direct stress to the organ

Tapuria N, Kumar Y, Habib MM, Abu Amara M, Seifalian AM, Davidson BR. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review. J Surg Res. 2008 Dec;150(2):304-30.

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 Skeletal muscle  Kidney  intestine EMAD ZARIEF 2012


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ischemic protection

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Brief ischemic episodes

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ischemic protection

 cGMP-dependent protein kinase (cGMP/PKG) pathway ,  reperfusion injury salvage kinase (RISK) pathway ,  survivor activating factor enhancement (SAFE) pathway

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The effects of the ‘first window’ or early preconditioning, last 1–2 h, after which the protection wanes. The ‘second window’ or late preconditioning occurs 24 h following the initial preconditioning ischaemia and lasts for 48–72 h.20

YELLON D M , DOWNEY J M Physiol Rev 2003;83:1113-1151 EMAD ZARIEF 2012


EARLY PHASE

where cellular signaling, cascades +amplification immediate cardioprotection, (SWOP) later phase  genetic re-programming + de novo synthesis of proteins sustained cardioprotection.

YELLON D M , DOWNEY J M Physiol Rev 2003;83:1113-1151

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Tapuria N, Kumar Y, Habib MM, Abu Amara M, Seifalian AM, Davidson BR. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review. J Surg Res. 2008 Dec;150(2):304-30. EMAD ZARIEF 2012


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RIPC CLASSIC

Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 2007;370:575–9.

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EARLY AND LATE PRECONDITIONING

Zhou WW, Zeng DB, Chen RW, Liu J, Yang GX, Liu PB et al. Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants.

.

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RI PRE AND POST CONDITIONING

Luo W, Zhu M, Huang R, Zhang Y. A comparison of cardiac postconditioning and remote preconditioning in paediatric cardiac surgery. Cardiol Young 2011;21:266–70.

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CONCLUSION Endogenous ‘conditioning’ strategies can be applied prior to or during ischaemia or at the onset of reperfusion. RIPC beneficial in cardiac surgery, AAA surgery, elective PCI, PPCI. Potential benefit in cardiac arrest, cardiac transplantation, stroke and other surgical settings.

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REFERENCES Asger Granfeldt1, David J. Lefer2, and Jakob Vinten-Johansen. Protective ischaemia in patients: preconditioning and Postconditioning. Cardiovascular Research (2009) 83, 234–246

Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial. Lancet 2007;370:575–9. XIONG Jun, LIAO Xu, XUE Fu-shan, YUAN Yu-jing, WANG Qiang and LIU Jian-hua . Remote ischemia conditioning—an endogenous cardioprotective strategy from outside the heart . Chinese Medical Journal 2011;124(14):2209-2215 Robert Loveridge MA and Frank Schroeder MD DEAA. Anaesthetic preconditioning. Continuing Education in Anaesthesia, Critical Care & Pain | Volume 10 Number 2 ;2010

Jakub Marczaka,*, Rafał Nowickia, Julita Kulbackab and Jolanta Saczkob. Is remote ischaemic preconditioning of benefit to patients undergoing cardiac surgery?. Interactive CardioVascular and Thoracic Surgery 14 (2012) 634– 639

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