Cyclosporine Protects the Heart during Aortic Valve Surgery

Chiari, Pascal; Angoulvant, Denis; Mewton, Nathan; Desebbe, Olivier; Obadia, Jean-François; Robin, Jacques; Farhat, Fadi; Jegaden, Olivier; Bastien, Olivier; Lehot, Jean‐Jacques; Ovize, Michel

doi:10.1097/aln.0000000000000331

Cited by 54 publications

(32 citation statements)

References 21 publications

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“…A study done on patients undergoing coronary artery bypass grafting surgery found no significant difference between the peak troponin T in CsA and placebo groups, except for the high-risk group with prolonged surgery -it showed that the extent of perioperative myocardial infarction was reduced in high-risk CsA patients [26]. Another RCT done in patients undergoing surgery for aortic stenosis showed a significant difference in the area under the curves for troponin I that favored the CsA group [27]. A few studies included in our meta-analysis used ST segment resolution as a surrogate marker of the successful coronary intervention [20,23].…”

Section: Discussionmentioning

confidence: 99%

“…However, the authors did not report adverse events and mortality data. It included three of the RCTs included in our analysis, along with one RCT in patient undergoing coronary artery bypass surgery and one RCT in patient undergoing surgery for aortic stenosis [19,23,24,26,27]. Additionally, two of the larger trials comparing the effect of cyclosporine in acute myocardial infarction have been published recently and were not included in this study.…”

Section: Discussionmentioning

confidence: 99%

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Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis

et al. 2017

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Background: Reperfusion injury is an important limiting factor associated with revascularization in acute myocardial infarction (AMI (OR 1.05,. Similarly, we did not find any significant differences in terms of cardiogenic shock, recurrent ischemia and myocardial infarction, heart failure and echocardiographic outcomes. Conclusions: Cyclosporine A is not helpful in preventing reperfusion injury in AMI. (Cardiol J 2017; 24, 1: 43-50)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis

et al. 2017

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“…In line with these findings, many antioxidants were studied, although clinical trials reported some controversial results, especially with mitochondria-targeted antioxidants (coenzyme Q10, mitoQ, and MTP-131) ( Table 1; Argaud et al, 2005;Karlsson et al, 2010;Skyschally et al, 2010;Chiari et al, 2014;Hausenloy et al, 2014;Cung et al, 2015;Dare et al, 2015;Eleawa et al, 2015;Hernandez-Resendiz et al, 2015;Gibson et al, 2016;Ottani et al, 2016). Coenzyme Q10 was shown to decrease the infarcted area, the inflammatory burden, and the oxidative stress and to normalize left ventricle function following AMI (Eleawa et al, 2015).…”

Section: Neutrophil Oxidants and Myocardial Remodelingmentioning

confidence: 97%

Neutrophil-Related Oxidants Drive Heart and Brain Remodeling After Ischemia/Reperfusion Injury

2020

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The inflammatory response associated with myocardial and brain ischemia/reperfusion injury (IRI) is a critical determinant of tissue necrosis, functional organ recovery, and long-term clinical outcomes. In the post-ischemic period, reactive oxygen species (ROS) are involved in tissue repair through the clearance of dead cells and cellular debris. Neutrophils play a critical role in redox signaling due to their early recruitment and the large variety of released ROS. Noteworthy, ROS generated during IRI have a relevant role in both myocardial healing and activation of neuroprotective pathways. Anatomical and functional differences contribute to the responses in the myocardial and brain tissue despite a significant gene overlap. The exaggerated activation of this signaling system can result in adverse consequences, such as cell apoptosis and extracellular matrix degradation. In light of that, blocking the ROS cascade might have a therapeutic implication for cardiomyocyte and neuronal loss after acute ischemic events. The translation of these findings from preclinical models to clinical trials has so far failed because of differences between humans and animals, difficulty of agents to penetrate into specific cellular organs, and specifically unravel oxidant and antioxidant pathways. Here, we update knowledge on ROS cascade in IRI, focusing on the role of neutrophils. We discuss evidence of ROS blockade as a therapeutic approach for myocardial infarction and ischemic stroke.

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“…Initial translational studies on human atrial tissue harvested from patients undergoing cardiac surgery revealed protective effects CsA (0.2 μM) against in vitro simulated IR [179] or lethal hypoxia/reoxygenation [180] injury and improved cell survival and recovery of baseline contractile function. Clinical studies that were initiated in 2008 on small groups of patients with MI demonstrated that administration of an intravenous bolus of CsA (2.5 mg/kg, IV) prior to PCI [181], sternotomy [182], and aortic clamping [183] significantly reduced MI size and improved post-operative recovery. On the other hand, administration of CsA before thrombolysis with streptokinase did not reduce myocardial injury or arrhythmias in patients with acute STEMI [184].…”

Section: Cypd As a Target For Cardioprotection Against Ir Injurymentioning

confidence: 99%

Mitochondrial permeability transition in cardiac ischemia–reperfusion: whether cyclophilin D is a viable target for cardioprotection?

Javadov

Jang

Parodi‐Rullán

et al. 2017

Cell. Mol. Life Sci.

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Growing number of studies provide strong evidence that the mitochondrial permeability transition pore (PTP), a non-selective channel in the inner mitochondrial membrane, is involved in the pathogenesis of cardiac ischemia–reperfusion and can be targeted to attenuate reperfusion-induced damage to the myocardium. The molecular identity of the PTP remains unknown and cyclophilin D is the only protein commonly accepted as a major regulator of the PTP opening. Therefore, cyclophilin D is an attractive target for pharmacological or genetic therapies to reduce ischemia–reperfusion injury in various animal models and humans. Most animal studies demonstrated cardioprotective effects of PTP inhibition; however, a recent large clinical trial conducted by international groups demonstrated that cyclosporine A, a cyclophilin D inhibitor, failed to protect the heart in patients with myocardial infarction. These studies, among others, raise the question of whether cyclophilin D, which plays an important physiological role in the regulation of cell metabolism and mitochondrial bioenergetics, is a viable target for cardioprotection. This review discusses previous studies to provide comprehensive information on the physiological role of cyclophilin D as well as PTP opening in the cell that can be taken into consideration for the development of new PTP inhibitors.

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Cyclosporine Protects the Heart during Aortic Valve Surgery

Abstract: Cyclosporine administration at the time of reperfusion protects against reperfusion injury in patients undergoing aortic valve surgery. The clinical benefit of this protection requires confirmation in a larger clinical trial.

Cited by 54 publications

References 21 publications

Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis

Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis

Neutrophil-Related Oxidants Drive Heart and Brain Remodeling After Ischemia/Reperfusion Injury

Mitochondrial permeability transition in cardiac ischemia–reperfusion: whether cyclophilin D is a viable target for cardioprotection?

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