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ISCHAEMIC PRE-CONDITIONING

ISCHAEMIC PRE-CONDITIONING. Prof. Mehdi Hasan Mumtaz. MYOCARDIAL ISCHAEMIC PRE-CONDITIONING. “Phenomenon by which a brief episod (s) of myocardial ischaemia increases the ability of te heart to tolerate a sbsequent prolonged period of ischaemia” ‘Murry et al’. HISTORY.

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ISCHAEMIC PRE-CONDITIONING

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  1. ISCHAEMICPRE-CONDITIONING Prof. Mehdi Hasan Mumtaz

  2. MYOCARDIAL ISCHAEMIC PRE-CONDITIONING “Phenomenon by which a brief episod (s) of myocardial ischaemia increases the ability of te heart to tolerate a sbsequent prolonged period of ischaemia” ‘Murry et al’

  3. HISTORY • 1986 – Murry & colleagues. • 1993 – Marber & colleagues. • 1997 – Cason & colleagues. Kersten & colleagues. • 1983-89 – Davis & colleagues.

  4. ENDPOINTS • Reperfusion arrythmias. • Slow energy metabolism. • Improve post-ischaemic function. • Protect coronary endothelium. • Post-ischaemic tension in atrial trabeculae muscle. • Resistance to hypoxic injury.

  5. TIME COURSE OF ISCHAEMIC PRECONDITIONING • Important factors. • Duration of ischaemia. • Number of cycles. • Duration of reperfusion. • Types. • Eary, classic. • Lte, second window of protection. Delayed.

  6. EARLY Immediate Lasts 2-3h. LATE 12-24h. Lasts 72h. Dpendent on: Cardioprotective proteins. Protects against stunning TYPES

  7. ADDITIONAL STRESSFUL STIMULIIN ADDITION TO ISCHAEMIC • Oxidative (hyperoxia). • Mecanical (stretch). • Electrical (rapid pacing). • Thermal. • Chemical (harmonal). • Ionic (calcium). • Pharmacological.

  8. CLASSIC/EARLY PRECONDITIONINGPutative Mecanisms • Opening of coronary colleterals. • Induction of oxidants. • Synthesis of protective proteins. • Changes in mitochondrial ATPases. • Not supported.

  9. PRECONDITIONING “Protection is receptor mediated” • Objective  Identification. • Triggers. • Tranducers. • End effectors in myocytes.

  10. RECEPTOR DEPENDENT Adenosine. Opoid receptors. Bradykinin. Bristaglandins. Adrenergic, angiotension, endothelin receptors. Purine. Ach. RECEPTOR INDEPENDENT Nitric oxide. Free radicals. Calcium. A. TRIGGERS – ISCHAEMIC PRECONTITIONG

  11. B-1 ATP sensitive K+ channels (K+ ATPS) B-2 Protein Kinase C (PKC) ISCHAEMIC PRE-CONDITIONINGB. MEDIATORS

  12. Sarcolemal “Blocked by” Salfonylurea S-hydroxydecanoate Mitochondrial “Opened by” Diazoxide. “Blocked by” 5HD ISCHAEMIC PRECONTITIONGB. MdiatorsB-1 K+ ATP Channels

  13. ISCHAEMIC PRECONTITIONG B – Mediators. B-2 Protein Kinase C (PKC). 1.  “Activator” Phorbol esters. 2.  “Inhibitor” Polymyxin. Stanrosporin

  14. Sodium proton exchange. Cytoskeleton changes. TNF  down regulation  Energy demand. Catbolite acumulation.  Lactate accumulation.  Glycogen store.  Intrcellular acidification. ISCHAEMIC PRECONTITIONGC. END EFFECTORS

  15. DELAYED PRE-CONDITIONING Complex polygemic phenomenon involving activation of several genes necessary for the synthesis of severe proteins and channels (K+ATD).

  16. DELAYED PRECONDITIONING • Latent period 12-24h. • Duration 72h. • Cardioprotective proteins. • Protects MI. • Protects M. Stunning.

  17. Parmacological Endotoxins. Adenosine agonists Opioid agonists. TNF Non-Parmacological Ischaemia. Stress. Rapid ventricular pacing. Exercise STIMULI FOR DELAYED PRE-CONDITIONING •  Infarction. •  Stunning. •  Arrythmias. •  Endothelial dysfunction

  18. DELAYED PRE-CONDITIONING “MEDIATORS & END EFFECTORS”  Related to changes in protein activity Heat stress proteins. HSP – 72. Antioxidant enzymes. (MnSod) NOS (cox – 2) Cytokine.

  19. DELAYED PRE-CONDITIONING • Requires. • Myocardial protein synthesis. • Phosphorylation of transcription factors. • NOS. • SOD. • Heat shock protein. • Role of ROS. • Role of NO.

  20. CLINICAL IMPLICATIONSUse of Nicorandil • K+ATD. • No donors. • Sulfonylurea. • COX-2. • Cogeners of adenosine. • Adenosis agonists. • PKC agonists.

  21. ANAESTHETIC INDUCEDPRECONDITIONING

  22. ANAESTHETIC INDUCEDPRECONDITIONINGVolatile Anaesthetics • Characteristics of preconditioning similar to those of ischaemic preconditioning” • A1 adenosin receptor activation. • KATP chanel activation. • Reduce Ca++ loading. • Augment post ischaemic contrctile responsiveness to Ca++. • infarct size. • Delayed preconditioning.

  23. EFFECT OF MEDICATION

  24. EFFECT OF MEDICATION

  25. EFFECT OF MEDICATION

  26. ICU – NISHTAR HOSPITAL

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