Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol – a clinical trial

Kottenberg, Eva; Thielmann, Matthias; Bergmann, Lars; Heine, T.; Jakob, Heinz; Heusch, Gerd

doi:10.1111/j.1399-6576.2011.02585.x

Cited by 319 publications

(239 citation statements)

References 39 publications

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“…We became aware in our initial studies that propofol interferes with RIPC25, 26 and have since performed all our studies with isoflurane anesthesia. The RIPC protocol consisted of 3 cycles of 5‐minute left upper arm ischemia (by inflation of a blood pressure cuff to 200 mm Hg)/5 min reperfusion (cuff deflated).…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…Omitting the 4 studies using another protocol than the mainly used 3×5-min remote conditioning protocol from analysis, barely affected the heterogeneity (I 2 =68%, P=0.0009), and changed the pooled SMD in favor of RIC (-0.46, 95% CI: -0.76 to -0.16) in the Characteristic a Kottenberg et al 24 Lucchinetti et al 25 Hong et al 26 Target Figure 4B). 6,7,17,20,21, 23 Sensitivity analysis showed that the omission of each study one at a time did not appreciably change the pooled SMD, and the estimates in each case were within the CI of the pooled estimate ( Figure 5).…”

Section: Cabgmentioning

confidence: 99%

“…a Kottenberg et al allocated patients into 4 groups receiving either isoflurane or propofol anesthesia with or without remote ischemic preconditioning and presented data separately. 24 The effect sizes of the CABG studies are plotted against their precision, which is the inverse of standard error. Black boxes, original studies relating remote ischemic conditioning to biomarkers of myocardial injury; black diamond, standardized mean difference (SMD) and 95% confidence interval (95% CI) for the metaanalysis.…”

Section: Cabgmentioning

confidence: 99%

Remote Ischemic Conditioning in Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting

Yetgin

Manintveld

Boersma

et al. 2012

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp oronary heart disease (CHD) is the leading cause of death and disability worldwide and one of its major pathophysiological manifestations is acute myocardial infarction (AMI). Although percutaneous coronary intervention (PCI) remains the most effective treatment strategy in patients presenting with AMI, high-risk patients with severe CHD are being referred for coronary artery bypass grafting (CABG). With both forms of treatment, patients are subjected to acute ischemia-reperfusion injury (IRI) and despite the merits of PCI and CABG, mortality and morbidity in these patients remain significant. Thus, cardioprotective strategies further limiting IRI are of major clinical interest in these settings.Remote ischemic conditioning (RIC) represents a novel treatment strategy for limiting myocardial IRI by applying intermittent, sublethal episodes of ischemia and reperfusion to an organ or tissue distant from the heart. Experiments in a canine model by Przyklenk et al first demonstrated that brief ischemic episodes (4 times for 5 min followed by 5 min of reperfusion) of the left circumflex coronary artery significantly reduced myocardial infarct size following sustained occlusion of the left anterior descending coronary artery, that is, remote intracardiac conditioning.

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“…34 This could disrupt pharmacologic recruitment of cardioprotective signal transduction. 35,36 Detoxification of ROS by phenolic antioxidants involves conversion to peroxide and a phenoxyl radical that stimulates DNA fragmentation. 12 Furthermore, propofol induced transcriptional changes in fatty acid metabolism and DNA damage signalling, correlating with release of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of cardiac dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

Ansley

Raedschelders

Choi

et al. 2015

Can J Anesth/J Can Anesth

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Purpose The efficacy of myocardial conditioning strategies is compromised in patients with advanced age, diabetes, or low ejection fraction. We conducted a singlecentre parallel-arm blinded randomized-controlled trial to determine whether propofol provides perioperative myocardial protection. Methods Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass (CPB) with blood cardioplegia. The participants were stratified by diabetic status and left ventricular ejection fraction and randomly assigned to receive either an elevated dose of propofolpreviously associated with experimental cardioprotectionor an isoflurane preconditioning regime. The primary endpoint was the coronary sinus (CS) concentration of 15-F 2t -isoprostane (isoP). Secondary endpoints included inhospital low cardiac output syndrome (LCOS) and major adverse cardiac events, 12-and 24-hr CS cardiac troponin I (cTnI) release, and myocardial B-cell lymphoma 2 (Bcl-2) protein expression. Results Data were analyzed from 125 of 137 randomized participants. Participants receiving propofol experienced a greater mean (SD) increase from baseline in CS 15-F 2t -isoP levels compared with those receiving isoflurane [26.9 (10.9) pgÁmL -1 vs 12.1 (10.4) pgÁmL -1 , respectively; mean difference, 14.8; 95% confidence interval (CI), 11.0 to 18.6; P \ 0.001] but a decreased incidence of LCOS (20.9% vs 57.1%, respectively; relative risk [RR],0.37; 95% CI, 0.22 to 0.62; P \ 0.001). The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus (DM2) (P = 0.382) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup (17.9% vs 70.3%, respectively; RR, 0.26; 95% CI, 0.13 to 0.52; P \ 0.001). Propofol was associated with an increase in myocardial Bcl-2 protein expression (P = 0.005), a lower incidence of a CS cTnI threshold for myocardial infarction (P = 0.014), and fewer heart failure events (P \ 0.001). Conclusion Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest. The study is registered at www.clinicaltrials.gov (NCT00734383) and www.controlled-trials.com (ISRCTN70879185). RésuméObjectif L'efficacité des stratégies de conditionnement myocardique est compromise chez les patients âgés ainsi que chez ceux atteints de diabète ou présentant une fraction d'éjection faible. Nous avons réalisé une étude randomisée contrô lée unicentrique à bras parallèles et en aveugle afin de déterminer si le propofol procurait une protection myocardique en période périopératoire. Méthode Les patients enrô lés dans cette étude devaient subir une chirurgie de pontage aorto-coronarien primaire avec circulation extracorporelle (CEC) normothermique et cardioplégie sanguine. Les participants ont été stratifiés par statut diabétique et fraction d'éjection ventriculaire gauche, puis aléatoirement répartis en deux groupes, dont l'un recevrait...

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Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol – a clinical trial

Cited by 319 publications

References 39 publications

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

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

Remote Ischemic Conditioning in Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

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