An Introduction to Cardioprotection

2011 ◽  
Keyword(s):  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Myocardial Damage ◽  
Myocardial Salvage ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Ischaemia Reperfusion ◽  
Considerable Morbidity

• In its broadest sense, the term ‘cardioprotection’ encompasses ‘all mechanisms and means that contribute to the preservation of the heart by reducing or even preventing myocardial damage’• However, for the purposes of this book, the term ‘cardioprotection’ will refer to the endogenous mechanisms and therapeutic strategies that reduce or prevent myocardial damage induced by acute ischaemia-reperfusion injury• In this context, cardioprotection begins with the primary prevention of coronary heart disease and includes the reduction of myocardial injury sustained during coronary artery bypass graft surgery, and an acute myocardial infarction, conditions with considerable morbidity and mortality• An understanding of the pathophysiology of acute myocardial ischaemia-reperfusion injury is essential when designing new cardioprotective strategies• Several methods exist for both quantifying myocardial damage induced by acute ischaemia-reperfusion injury and for assessing myocardial salvage following the application of cardioprotective strategies• Importantly, novel cardioprotective strategies must be capable of preventing and reducing myocardial damage over and above that provided by current optimal therapy.

scholarly journals Effects of mycophenolate mofetil on acute ischaemia-reperfusion injury in rats and its consequences in the long term

2009 ◽  
Vol 25 (5) ◽  
pp. 1443-1450 ◽  
Author(s):  
M. Sabbatini ◽  
F. Uccello ◽  
V. Serio ◽  
G. Troncone ◽  
V. Varone ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Reperfusion Injury ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Ischaemia Reperfusion

scholarly journals e0141 The effects and mechanisms between DIDS and EDRV on acute ischaemia-reperfusion injury myocardium

Heart ◽  
2010 ◽  
Vol 96 (Suppl 3) ◽  
pp. A45-A45
Author(s):  
L. Yan-xia ◽  
L. Jia-ni ◽  
S. Ming-zhi ◽  
Z. Meng ◽  
Z. Ya-li ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Ischaemia Reperfusion

scholarly journals Comet Assay in Evaluating DNA Damage Associated With Ischaemia-Reperfusion Injury in Patients Undergoing Coronary Surgery

2009 ◽  
Vol 60 (3) ◽  
pp. 307-315
Author(s):  
Bensu Karahalil ◽  
Tulin Gumus ◽  
Esra Emerce ◽  
Seval Izdes ◽  
Orhan Kanbak ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Bypass Graft ◽  
Coronary Surgery ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Significant Difference ◽  
Lactate Levels

Comet Assay in Evaluating DNA Damage Associated With Ischaemia-Reperfusion Injury in Patients Undergoing Coronary SurgeryIschaemia-reperfusion (I/R) injury is responsible for a number of conditions such as coronary bypass and myocardial infarction, and deaths. Oxygen-free radicals formed during I/R have been proposed as the leading causes of tissue injury, and they play an important role in I/R injury. I/R induces oxidative DNA damage (such as purinic and pyrimidinic base lesions). Comet assay is a suitable and sensitive method for early detection of low-level DNA damage. We used modified alkaline comet assay in peripheral blood lymphocytes and evaluated I/R-induced DNA damage in patients undergoing coronary artery bypass graft (CABG) operation (in vivo model for I/R). No statistically significant difference in DNA damage levels was found before surgery, after anaesthesia, ischemia, reperfusion, and surgery. However, blood lactate levels (assessed in parallel with the comet assay) increased after I/R and did not return to the baseline level. Our findings showed that I/R injury did not induce DNA damage, but increased the lactate levels. This finding suggests that there might be reversible and uncommon necrosis that did not reflect on overall DNA base damage. Further studies are needed using this approach.

Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology

2015 ◽  
Vol 113 (03) ◽  
pp. 513-521 ◽  
Author(s):  
Sang-Bing Ong ◽  
Andrew Hall ◽  
Rachel Dongworth ◽  
Siavash Kalkhoran ◽  
Aswin Pyakurel ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition ◽  
Cardiac Cells ◽  
Mitochondrial Morphology ◽  
Myocardial Infarct Size ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Mptp Opening ◽  
Ischaemia Reperfusion ◽  
Mitochondrial Elongation

SummaryThe mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; p< 0.05). This effect was associated with delayed time taken to induce mitochondrial permeability transition pore (MPTP) opening (by 2.4 ± 0.5 fold; N=80 cells/group: p< 0.05); and reduced cell death following simulated IRI (32.8 ± 1.2 % caAkt vs 63.8 ± 5.6 % control: N=320 cells/group: p< 0.05). Similar effects on mitochondrial morphology, MPTP opening, and cell survival post-IRI, were demonstrated with pharmacological activation of Akt using the known cardioprotective cytokine, erythropoietin (EPO). The effect of Akt on inducing mitochondrial elongation was found to be dependent on the mitochondrial fusion protein, Mitofusin-1 (Mfn1), as ablation of Mfn1 in mouse embryonic fibroblasts (MEFs) abrogated Akt-mediated mitochondrial elongation. Finally, in vivo pre-treatment with EPO reduced myocardial infarct size (as a % of the area at risk) in adult mice subjected to IRI (26.2 ± 2.6 % with EPO vs 46.1 ± 6.5 % in control; N=7/group: p< 0.05), and reduced the proportion of cells displaying myofibrillar disarray and mitochondrial fragmentation observed by electron microscopy in adult murine hearts subjected to ischaemia from 5.8 ± 1.0 % to 2.2 ± 1.0 % (N=5 hearts/group; p< 0.05). In conclusion, we found that either genetic or pharmacological activation of Akt protected the heart against acute ischaemia-reperfusion injury by modulating mitochondrial morphology.

scholarly journals The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction

2017 ◽  
Vol 8 (8) ◽  
pp. 695-702 ◽  
Author(s):  
Marcus Hortmann ◽  
Samuel Robinson ◽  
Moritz Mohr ◽  
Maximillian Mauler ◽  
Daniela Stallmann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Serum Level ◽  
Reperfusion Injury ◽  
Myocardial Damage ◽  
Artery Occlusion ◽  
Ischaemia Reperfusion Injury ◽  
St Segment Elevation ◽  
Ischaemia Reperfusion ◽  
Targeting Peptide ◽  
Mitochondria Targeting

Background: The extent of myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) depends on both the time to reperfusion as well as injury induced by ischaemia–reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia–reperfusion in the heart, the high-temperature requirement serine peptidase 2 (HtrA2) is translocated from the mitochondria to the cytosol, whereupon it induces protease activity-dependent apoptosis mediated via caspases. Myocardial damage induced by reperfusion cannot be monitored due to a current lack in specific biomarkers. We examined the serum level of HtrA2 as a potentially novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Methods: After informed consent, peripheral blood was obtained from patients ( n=19) with first-time acute anterior STEMI after percutaneous coronary intervention. Within this group, 10 of the patients received the mitochondria-targeting peptide elamipretide (phase 2a clinical study EMBRACE (NCT01572909)). Blood was also obtained from a control group of healthy donors ( n=16). The serum level of HtrA2 was measured by an enzyme-linked immunosorbent assay (ELISA). In a murine model of myocardial ischaemia–reperfusion injury, HtrA2 was determined in plasma by ELISA after left anterior descending artery occlusion. Results: HtrA2 median was significantly increased in patients with STEMI compared to healthy controls 392.4 (240.7–502.8) pg/mL vs. 1805.5 (981.3–2220.1) pg/mL ( P⩽0.05). Elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction 1805.5 (981.3–2220.1) pg/mL vs. 496.5 (379.4–703.8) pg/mL ( P⩽0.05). Left anterior descending artery occlusion in mice significantly increased HtrA2 mean in plasma (117.4 fg/ml±SEM 28.1 vs. 525.2 fg/ml±SEM 96; P⩽0.05). Conclusion: Compared to healthy controls, we found significantly increased serum levels of HtrA2 in patients with STEMI. The result was validated in a murine model of myocardial ischaemia–reperfusion injury. In humans the increased serum level was significantly reduced by the mitochondria-targeting peptide elamipretide. In conclusion, HtrA2 is detectable in serum of patients with STEMI and might present a novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Consequently, HtrA2 may also show promise as a biomarker for the identification of ischaemia–reperfusion injury. However, this must be validated in a lager clinical trial.

D-dimer Level is an Early Marker of Ischaemia/ reperfusion Injury After Coronary Artery Bypass Surgery

2019 ◽  
Vol 22 (3) ◽  
pp. 198-204
Author(s):  
Hasan Erdem ◽  
Kamil Cantürk Çakalağaoğlu ◽  
Emre Selçuk ◽  
Gökhan Keskin ◽  
Özge Altaş Yerlikhan ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Reperfusion Injury ◽  
Coronary Artery Bypass ◽  
Coronary Artery Bypass Surgery ◽  
Bypass Surgery ◽  
Artery Bypass ◽  
Ischaemia Reperfusion Injury ◽  
Early Marker ◽  
Ischaemia Reperfusion ◽  
D Dimer

scholarly journals Sustained Isoprostane E2 Elevation, Inflammation and Fibrosis after Acute Ischaemia-Reperfusion Injury Are Reduced by Pregnane X Receptor Activation

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0136173 ◽  
Author(s):  
Aimen O. Amer ◽  
Philip M. Probert ◽  
Michael Dunn ◽  
Margaret Knight ◽  
Abigail E. Vallance ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Pregnane X Receptor ◽  
Receptor Activation ◽  
Ischaemia Reperfusion Injury ◽  
Acute Ischaemia ◽  
Ischaemia Reperfusion
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