1 / 25

Cardiomyocyte hypercontracture

Cardiomyocyte hypercontracture. Gao Qin. Background. The first minutes of reperfusion repre-sent a window of opportunity for cardioprotection Development of cardiomyocyte hyper - contracture is a predominant feature of reperfusion injury. Background.

lana-burnett
Télécharger la présentation

Cardiomyocyte hypercontracture

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cardiomyocyte hypercontracture Gao Qin

  2. Background • The first minutes of reperfusion repre-sent a window of opportunity for cardioprotection • Development of cardiomyocyte hyper- contracture is a predominant feature of reperfusion injury

  3. Background • A pattern of contracture and necrotic cell injury “Contraction band necrosis” can be found during the early stage of the infarct • “Contraction band necrosis” reflects hypercontracture of myocytes

  4. Infarct size Contraction band necrosis

  5. Confocal image of adult ventricular myocyte loaded with TMRM

  6. What causes contracture ?

  7. Mechanisms of contracture • Ischemia-induced contracture Rigor-type mechanism • Reperfusion-induced hypercontracture Ca2+ overload-induced contracture Rigor-type contracture

  8. Ischemia-induced contracture • Rigor-type mechanism Low cytosolic ATP myofibrillar shortening cytoskeletal defects cardiomyocytes more fragile and susceptible to mechanical damage

  9. Reperfusion-induced hypercontracture • Much greater myofibrillar shortening and cytoskeletal damage • Aggravated form of contracture lead to a marked rise in end-diastolic pressure

  10. Two causes for reperfusion- induced hypercontracture • Ca2+ overload-induced contracture energy recovery rapid but cytosolic Ca2+ load high • Rigor-type contracture energy recovery very slow

  11. Two causes for reperfusion- induced hypercontracture

  12. NCE forward NCE reverse Ca2+overload-induced hypercontracture NHE NBS NHE:Na+/H+ exchanger NCE:Na+/Ca2+ exchanger NBS: Na+/HCO3- symporter

  13. Ca2+overload-induced hypercontracture • Cyclic uptake and release of Ca2+ by the sarcoplasmic reticulum (SR) in reoxygenated cardiomyocyte (reperfused heart) triggers a Ca2+ oscillations-induced hypercontracture Reperfusion

  14. Ca2+overload-induced hypercontracture

  15. Treatments • Initial ,time-limited inhibition of the contractile machinery • Phosphatase 2,3-butanedione monoxime • cGMP-mediated effectors (NO,ANP) • Cytosolic acidosis (-)NHE,(-)NBS reduce the Ca2+ sensitivity of myofibrils

  16. Treatments • Reducing SR-dependent Ca2+oscillations • Interfering with SR Ca2+ ATPase or SR Ca2+ release • Interfering with SR Ca2+ sequestration • Inhibiting Ca2+ influx

  17. Rigor hypercontracture • Prolonged ischemia mitochondria can not recover cardiomyocytes may contain very low concentrations of ATP at the early of re- oxygenation induce rigor-type contracture major contributor to reoxygenation-induced hypercontracture Ca2+ independent

  18. Treatments • Improving the conditions for energy recovery • application of mitochondrial energy substrates (succinate) Accelerating oxidative energy production • protecting mitochondria from compulsory Ca2+ uptake Resuming oxidative phosphorylation

  19. Spread of hypercontrature gap junctionspreads cell injury

  20. Protective signaling pathways • PKC-dependent signaling • PKG-dependent signaling • PI 3-kinase signaling

  21. PKC- dependent signaling • Not improve the cellular state of energy or the progressive loss of control of cation homeostasis • But attenuate the development of hypercontracture

  22. PKG-dependent signaling

  23. PI 3-kinase signaling • Insulin protects the cells against hypercontracture through a PI 3-kinase-mediated pathway

  24. References • H.M. Piper, Y. Abdallah, C. Schäfer. The first minutes of reperfusion: a window of opportunity for cardioprotection. Cardiovascular Research 61 (2004) 365– 371 • Y. Ladilov, Ö. Efe, C. Schäfer, H.M. Piper et al. Reoxygenation- induced rigor-type contracture.Journal of Molecular and Cellular Cardiology 35 (2003) 1481–1490 • H. Michael Piper, K. Meuter, C.Schäfer. Cellular mechanisms of ischemia-reperfusion injury.The Annals of Thoracic Surgery 75 (2003) 644–648 • H.M. Piper, D. Garcıa-Dorado, M. Ovize. A fresh look at reperfusion injury.Cardiovascular Research 38 (1998) 291–300

More Related