Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial

Eitel, Ingo; Stiermaier, Thomas; Rommel, Karl Philipp; Fuernau, Georg; Sandri, Monica; Mangner, Norman; Linke, Axel; Erbs, Sandra; Lurz, Philipp; Boudriot, Enno; Mende, Meinhard; Desch, Steffen; Schuler, Gerhard; Thiele, Holger

doi:10.1093/eurheartj/ehv463

Cited by 194 publications

(190 citation statements)

References 36 publications

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“…A few studies revealed that a stronger stimulus or the combination of 2 conditioning phenomena 96 resulted in greater protection, as expected. However, a truly optimal stimulus has never been defined, and this is not a trivial issue.…”

Section: Lack Of Phase II Studiessupporting

confidence: 59%

“…[73][74][75][76][77][78][79][81][82][83]86,[91][92][93] In most of the studies, the patient cohorts were small; of note, the 3 studies with the largest patient cohorts were neutral with respect to infarct size. 90,94,96 All studies in adult 97,98 or pediatric [99][100][101][102][103] cardiac surgery reported a significant infarct size reduction, as reflected by biomarker (creatine kinase-muscle brain, and troponin) release. A consistent reduction of infarct size by biomarker release and by imaging was confirmed in recent meta-analyses.…”

Section: Ischemic Postconditioningmentioning

confidence: 99%

“…All studies that used an ischemic perconditioning protocol of repeated arm or leg ischemia/reperfusion in patients with acute STEMI found reduced infarct size, which was significant in most of them, no matter whether reperfusion was by primary PCI 96,[106][107][108][109][110][111] or thrombolysis 112 and no matter whether biomarker release or imaging was used to assess infarct size ( Figure 3). A retrospective analysis of the CONDI trial (Effect of Remote Ischemic Conditioning on Clinical Outcome in (Table 3).…”

Section: Remote Ischemic Conditioningmentioning

confidence: 99%

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Time to Give Up on Cardioprotection?

Heusch

Rassaf

2016

Circulation Research

170

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Abstract:The mortality from acute myocardial infarction (AMI) remains significant, and the prevalence of postmyocardial infarction heart failure is increasing. Therefore, cardioprotection beyond timely reperfusion is needed. Conditioning procedures are the most powerful cardioprotective interventions in animal experiments. However, ischemic preconditioning cannot be used to reduce infarct size in patients with AMI because its occurrence is not predictable; several studies in patients undergoing surgical coronary revascularization report reduced release of creatine kinase and troponin. Ischemic postconditioning reduces infarct size in most, but not all, studies in patients undergoing interventional reperfusion of AMI, but may require direct stenting and exclusion of patients with >6 hours of symptom onset to protect. Remote ischemic conditioning reduces infarct size in patients undergoing interventional reperfusion of AMI, elective percutaneous or surgical coronary revascularization, and other cardiovascular surgery in many, but not in all, studies. Adequate dose-finding phase II studies do not exist. There are only 2 phase III trials, both on remote ischemic conditioning in patients undergoing cardiovascular surgery, both with neutral results in terms of infarct size and clinical outcome, but also both with major problems in trial design. We discuss the difficulties in translation of cardioprotection from animal experiments and proof-ofconcept trials to clinical practice. Given that most studies on ischemic postconditioning and all studies on remote ischemic preconditioning in patients with AMI reported reduced infarct size, it would be premature to give up on cardioprotection. (Circ Res. 2016;119:676-695.

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Section: Lack Of Phase II Studiessupporting

confidence: 59%

Section: Ischemic Postconditioningmentioning

confidence: 99%

Section: Remote Ischemic Conditioningmentioning

confidence: 99%

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Time to Give Up on Cardioprotection?

Heusch

Rassaf

2016

Circulation Research

170

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“…Remote ischemic conditioning by repetitive limb ischemia/reperfusion also reduces myocardial damage in patients undergoing elective interventional2 or surgical coronary revascularization3, 4, 5, 6 and in those with reperfused acute myocardial infarction 7, 8, 9, 10, 11, 12, 13. Cardioprotection was confirmed by reduced release of cardiac biomarkers2, 3, 4, 5, 6, 10 or by increased salvage in cardiac imaging7, 8, 9, 11 but also resulted in improved short‐5, 8 and more long‐term2, 4, 13, 14, 15 clinical outcome in retrospective analyses. Recently, the first prospective, randomized trial on patients with reperfused acute myocardial infarction confirmed improved clinical outcome as a primary end point of remote ischemic conditioning during follow‐up for 3.6 years 13.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning

Kleinbongard

Gedik

Kirca

et al. 2018

JAHA

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BackgroundRemote ischemic preconditioning (RIPC) by repeated brief cycles of limb ischemia/reperfusion attenuates myocardial ischemia/reperfusion injury. We aimed to identify a functional parameter reflecting the RIPC‐induced protection in human. Therefore, we measured mitochondrial function in right atrial tissue and contractile function of isolated right atrial trabeculae before and during hypoxia/reoxygenation from patients undergoing coronary artery bypass grafting with RIPC or placebo, respectively.Methods and ResultsOne hundred thirty‐seven patients under isoflurane anesthesia underwent RIPC (3×5 minutes blood pressure cuff inflation on the left upper arm/5 minutes deflation, n=67) or placebo (cuff uninflated, n=70), and right atrial appendages were harvested before ischemic cardioplegic arrest. Myocardial protection by RIPC was assessed from serum troponin I/T concentrations over 72 hours after surgery. Atrial tissue was obtained for isolation of mitochondria (RIPC/placebo: n=10/10). Trabeculae were dissected for contractile function measurements at baseline and after hypoxia/reoxygenation (60 min/30 min) and for western blot analysis after hypoxia/reoxygenation (RIPC/placebo, n=57/60). Associated with cardioprotection by RIPC (26% decrease in the area under the curve of troponin I/T), mitochondrial adenosine diphosphate–stimulated complex I respiration (+10%), adenosine triphosphate production (+46%), and calcium retention capacity (+37%) were greater, whereas reactive oxygen species production (−24%) was less with RIPC than placebo. Contractile function was improved by RIPC (baseline, +7%; reoxygenation, +24%). Expression and phosphorylation of proteins, which have previously been associated with cardioprotection, were not different between RIPC and placebo.ConclusionsCardioprotection by RIPC goes along with improved mitochondrial and contractile function of human right atrial tissue.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01406678.

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“…Based on fact that perconditioning is performed in a distant tissue, is a non-invasive procedure and do not increase the surgical time, thus does not require direct access to the artery and could be easily applied during the surgery or endovascular surgery [15][16][17][18][19] ; this ischemic conditioning must be test in human IR syndromes 20,31 . However, new studies aim to understanding the mechanism are need 32 .…”

Section: ■ Discussionmentioning

confidence: 99%

Perconditioning combined with postconditioning on kidney ischemia and reperfusion

et al. 2017

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Purpose: To evaluate if combination of perconditioning and postconditioning provides improved renal protection compared to perconditioning alone in a model of renal reperfusion injury. Methods: Thirty rats were assigned into 6 groups: normality; sham; ischemia and reperfusion; postconditioning; perconditioning; perconditioning + postconditioning. Animals were subjected to right nephrectomy and left renal ischemia for 30 minutes. Postconditioning consisted of 3 cycles of 5 min renal perfusion followed by 5 min of renal ischemia after major ischemic period. Perconditioning consisted of 3 cycles of 5 min hindlimb ischemia followed by 5 min of hindlimb perfusion contemporaneously to renal major ischemic period. After 24 hours, kidney was harvested and blood collected to measure urea and creatinine. Results: Perconditioning obtained better values for creatinine and urea level than only postconditioning (p<0.01); performing both techniques contemporaneously had no increased results (p>0.05). Regarding tissue structure, perconditioning was the only technique to protect the glomerulus and tubules (p<0.05), while postconditioning protected only the glomerulus (p<0.05). Combination of both techniques shows no effect on glomerulus or tubules (p>0.05). Conclusions: Perconditioning had promising results on ischemia and reperfusion induced kidney injury, enhanced kidney function and protected glomerulus and tubules. There was no additive protection when postconditioning and perconditioning were combined.

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Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial

Abstract: NCT02158468.

Cited by 194 publications

References 36 publications

Time to Give Up on Cardioprotection?

Time to Give Up on Cardioprotection?

Mitochondrial and Contractile Function of Human Right Atrial Tissue in Response to Remote Ischemic Conditioning

Perconditioning combined with postconditioning on kidney ischemia and reperfusion

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