Cellular mechanisms of ischemia-reperfusion injury

Slides:

Advertisements

Similar presentations

Cardiomyocyte hypercontracture Gao Qin. Background The first minutes of reperfusion repre-sent a window of opportunity for cardioprotection Development.

Advertisements

General Principles of Cell Injury

Mitochondrial potassium transport: the role of the MitoK ATP WeiGuo

Hyperpolarized / Polarized arrest as an alternative to Depolarized arrest Guo Wei Zhejiang University School of Medicine.

Victor A. Maltsev, PhD, Edward G. Lakatta, MD Heart Rhythm

Volume 105, Issue 1, Pages (July 2013)

Prevention of ischemia-reperfusion injury in cardiac surgery: Therapeutic strategies targeting signaling pathways Kay Maeda, MD, PhD, Marc Ruel, MD,

C.Allyson Walker, BA, Francis G. Spinale, MD, PhD

Celsior versus custodiol: early postischemic recovery after cardioplegia and ischemia at 5°C Juergen Ackemann, MD, Wolfgang Gross, PhD, Martin Mory,

Gregory M. Faber, Yoram Rudy Biophysical Journal

Volume 104, Issue 8, Pages (April 2013)

Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury Albert J Chong, MD, Timothy H Pohlman, MD, Craig R Hampton, MD, Akira Shimamoto,

Salah Sabbagh, MD, Michele M. Henry Salzman, BS, Robert A

Heart preservation in HTK solution: role of coronary vasculature in recovery of cardiac function Yuhei Saitoh, MD, PhD, Michio Hashimoto, PhD, Kwansong.

C. Allyson Walker, BA, Fred A. Crawford, MD, Francis G

Immunology and failure of valved allografts in children

Philip J Wolfson, MD The Annals of Thoracic Surgery

The Annals of Thoracic Surgery

Mechanisms of myocardial reperfusion injury

Etienne Roux, Marko Marhl Biophysical Journal

Volume 23, Issue 2, Pages (February 2016)

Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac.

Impact of Reperfusion Calcium and pH on the Resuscitation of Hearts Donated After Circulatory Death Christopher White, MD, Emma Ambrose, BS, Alison Müller,

Triiodothyronine reverses depressed contractile performance after excessive catecholamine stimulation Tomasz Timek, MD, Christian-Friedrich Vahl, MD,

β-Agonists and metabolism

Hyperglycemia exaggerates ischemia-reperfusion–induced cardiomyocyte injury: Reversal with endothelin antagonism Subodh Verma, MD, PhD, Andrew Maitland,

Beneficial Effects of Fluosol–Polyethylene Glycol Cardioplegia on Cold, Preserved Rabbit Heart Joginder N Bhayana, MD, Zhong T Tan, MD, PhD, Jacob Bergsland,

Increased susceptibility of hypertrophied hearts to ischemic injury

Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis N. Hussain, C.J.L. McCartney, J.M. Neal, J.

Altered Myocardial Calcium Cycling and Energetics in Heart Failure—A Rational Approach for Disease Treatment Przemek A. Gorski, Delaine K. Ceholski,

Cardiac Muscle Physiology

Daniel R. Meldrum, MD, Brian D

Influence of Mechanical Cell Salvage on Red Blood Cell Aggregation, Deformability, and 2,3-Diphosphoglycerate in Patients Undergoing Cardiac Surgery With.

Volume 79, Issue 2, Pages (August 2000)

Intermittent aortic crossclamping prevents cumulative adenosine triphosphate depletion, ventricular fibrillation, and dysfunction (stunning): Is it preconditioning?

The Contribution of Na/H Exchange to Ischemia-Reperfusion Injury After Hypothermic Cardioplegic Arrest Takashi Yamauchi, MD, Hajime Ichikawa, MD, Yoshiki.

J. Darcy O'Brien, MS, Susan E. Howlett, PhD, Hayley J

Bradykinin pretreatment improves ischemia tolerance of the rabbit heart by tyrosine kinase mediated pathways Jun Feng, MD, PhD, Eliot R Rosenkranz, MD

Intracellular Ca2+ Release and Ischemic Axon Injury

Adenosine Prevents Hyperkalemia-Induced Calcium Loading in Cardiac Cells: Relevance for Cardioplegia Aleksander Jovanović, MD, Alexey E Alekseev, PhD,

Controlled hyperkalemic reperfusion with magnesium rescues ischemic juvenile hearts by reducing calcium loading Hajime Imura, MD, Hua Lin, MSc, Elinor.

Protecting the aged heart during cardiac surgery: The potential benefits of del Nido cardioplegia Stacy B. O’Blenes, MD, Camille Hancock Friesen, MD,

Dysfunction induced by ischemia versus edema: Does edema matter?

Ischemic preconditioning with opening of mitochondrial adenosine triphosphate– sensitive potassium channels or Na+/H+ exchange inhibition: Which is the.

Surgical Preparation Abolishes Endothelium-Derived Hyperpolarizing Factor-Mediated Hyperpolarization in the Human Saphenous Vein Jian-An Yang, MD, Guo-Wei.

Preconditioning and cardiac surgery

Daniel P. Mulloy, MD, Ashish K. Sharma, MBBS, PhD, Lucas G

Histopathologic consequences of hyperglycemic cerebral ischemia during hypothermic cardiopulmonary bypass in pigs Brendan P Conroy, MD, Marjorie R Grafe,

Histidine-Tryptophan-Ketoglutarate or Celsior: Which Is More Suitable for Cold Preservation for Cardiac Grafts From Older Donors? Sungsoo Lee, MD, Chien-Sheng.

The Annals of Thoracic Surgery

Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia Vivek Rao, MD, PhD, Frank Merante, PhD,

Eugene Braunwald JCHF 2013;1:1-20

Hans-Joachim Schäfers, MD, PhD, Diana Aicher, MD, Frank Langer, MD

Jun Feng, MD, PhD, Hongling Li, MD, MSc, Eliot R Rosenkranz, MD

Adenosine-enhanced ischemic preconditioning provides myocardial protection equal to that of cold blood cardioplegia James D McCully, PhD, Masahisa Uematsu,

Neal S Goldstein, MD The Annals of Thoracic Surgery

The End and After: How Dying Cells Impact the Living Organism

Integrated pharmacological preconditioning in combination with adenosine, a mitochondrial KATP channel opener and a nitric oxide donor Yuka Uchiyama,

Early effects of hypothyroidism on the contractile function of the rat heart and its tolerance to hypothermic ischemia Manuel Galiñanes, MD, PhD, Ryszard.

Commentary: A paradox of remote ischemic preconditioning: Remote understanding, remote relevance, and remote future? Tyson A. Fricke, MBBS, BMedSci,

Toll-like receptor 4 inhibition attenuates ischemia-reperfusion injury in rats: Will it work in human beings? Chadrick E. Denlinger, MD The Journal.

Salvatore Pepe, PhD, FCSANZ, FAHA

Managing Pulmonary Artery Catheter-Induced Pulmonary Hemorrhage by Bronchial Occlusion René Schramm, MD, PhD, Ahmad Abugameh, MD, Dietmar Tscholl, MD,

Assessment of Sarcoplasmic Reticulum Ca2+ Depletion During Spontaneous Ca2+ Waves in Isolated Permeabilized Rabbit Ventricular Cardiomyocytes N. MacQuaide,

ATP-Independent Luminal Oscillations and Release of Ca2+ and H+ from Mast Cell Secretory Granules: Implications for Signal Transduction Ivan Quesada,

Marc Liesa, Orian S. Shirihai Cell Metabolism

Randy M. Stevens, MD, M. Salik Jahania, MD, Robert M

Aortic Valve Function After Bicuspidization of the Unicuspid Aortic Valve Diana Aicher, MD, Moritz Bewarder, Michael Kindermann, MD, Hashim Abdul-Khalique,

Volume 112, Issue 9, Pages (May 2017)

Fig. 2. Potential mechanisms and effects of impaired Ca2+ handling in DC. Impairment in cardiomyocyte Ca2+ influx and efflux, impaired release and reuptake.

Presentation transcript:

Cellular mechanisms of ischemia-reperfusion injury H.Michael Piper, MD, PhD, Karsten Meuter, MD, Claudia Schäfer, PhD The Annals of Thoracic Surgery Volume 75, Issue 2, Pages S644-S648 (February 2003) DOI: 10.1016/S0003-4975(02)04686-6

Fig 1 Reversible changes in cytosolic cation control in ischemia-reperfusion. In ischemia, cardiomyocytes accumulate Na+ by means of (1) the Na+/H+ exchanger, (2) the Na+/HCO3− symporter, and (3) other routes. With reduction of the Na+ gradient and membrane depolarization, the Na+/Ca2+ exchanger is turned into its “reverse mode,” which leads to cytosolic accumulation of Ca2+. In reperfusion, energy recovery reactivates Na+-K+-ATPase (4) and restores the Na+ gradient and the membrane potential. The “forward mode” of the Na+/Ca2+ exchanger eventually extrudes excess cytosolic Ca2+. ATP = adenosine triphosphate; NCE = Na+/H+ exchanger. The Annals of Thoracic Surgery 2003 75, S644-S648DOI: (10.1016/S0003-4975(02)04686-6)

Fig 2 Cause of cytosolic Ca2+ oscillations and Ca2+-induced contracture in cardiomyocytes. After ischemia, cardiomyocytes contain an excessive cytosolic Ca2+ overload. In the early phase of reoxygenation, this may still be aggravated by a reverse mode action of the Na+/Ca2+ exchanger. Reoxygenation causes a reenergization of the sarcoplasmic reticulum (SR). This starts to accumulate Ca2+ and, once full, releases Ca2+. These Ca2+ movements lead to oscillatory cytosolic Ca2+ elevations, which provoke uncontrolled myofibrillar activation. ATP = adenosine triphosphate; NCE = Na+/H+ exchanger. The Annals of Thoracic Surgery 2003 75, S644-S648DOI: (10.1016/S0003-4975(02)04686-6)

Fig 3 Characteristic changes in cytosolic Ca2+ and cell length in a single cardiomyocyte under simulated ischemia-reperfusion conditions. (Left panel) Cells are elongated in normoxia, become rigor-shortened in ischemia, and become hypercontracted upon reperfusion. (Upper panel) Rise of cytosolic Ca2+ (monitored by fluorescence of the indicator Fura-2, continuous trace) and cell shortening (open circles). During simulated ischemia, Ca2+ rises and rigor contracture develops. Upon reoxygenation Ca2+ declines and the cell hypercontracts. (Lower panel) Early reperfusion, in higher time resolution. Ca2+ level declines but starts to oscillate. During oscillations, extensive contracture develops. The Annals of Thoracic Surgery 2003 75, S644-S648DOI: (10.1016/S0003-4975(02)04686-6)

Fig 4 Importance of the rapidity of adenosine triphosphate (ATP) recovery for reoxygenation-induced contracture. Cardiomyocytes with rapid ATP recovery quickly pass through the critical window of rigor contracture and may develop Ca2+ contracture if they have a cytosolic Ca2+ overload. Cardiomyocytes with slow ATP recovery creep slowly through the critical window and develop rigor contracture. The Annals of Thoracic Surgery 2003 75, S644-S648DOI: (10.1016/S0003-4975(02)04686-6)

Fig 5 Relationship between cytosolic Ca2+ overload and reoxygenation-induced contracture. In cells with very slow energy recovery (mitochondrial damage, long ischemic exposure), contracture develops by a rigor-type mechanism that is essentially Ca2+-independent. In cells with fast energy recovery (intact mitochondria, brief ischemic exposure), contracture develops only at high cytosolic Ca2+ overload. States between these extremes are possible. The Annals of Thoracic Surgery 2003 75, S644-S648DOI: (10.1016/S0003-4975(02)04686-6)