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Ischaemic Pre-conditioning in Myocardial Protection: Mechanisms and Clinical Implications

Explore the phenomenon of ischaemic pre-conditioning in myocardial protection, its history, endpoints, and types. Discover the time course, triggers, mediators, and end effectors involved in early and delayed preconditioning. Uncover the clinical implications, including the use of medication and anaesthetic-induced preconditioning. Delve into the effect of medication in an ICU setting at Nishtar Hospital.

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Ischaemic Pre-conditioning in Myocardial Protection: Mechanisms and Clinical Implications

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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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