Preconditioning Improves Myocardial Preservation in Patients Undergoing Open Heart Operations

Lu, Erxiong; Chen, Shengxi; Yuan, Ming-Dao; Hu, Tiehui; Zhou, Han-Cha; Luo, Wanjun; Li, Guo-Hu; Xu, Liao-Mei

doi:10.1016/s0003-4975(97)00838-2

Cited by 59 publications

(37 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, no study has ever truly shown that remote preconditioning of human myocardium is at all feasible. Indeed, there are many studies on human myocardium showing that ischaemic preconditioning can be elicited in experimental conditions, and protects against standardised ischaemic and reperfusion insult [22][23][24]. The same was shown with various forms of pharmacological preconditioning [25][26][27][28].…”

Section: Discussionmentioning

confidence: 86%

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

et al. 2018

View full text Add to dashboard Cite

A b s t r a c tBackground: Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. Aim:The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. Methods:The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. Results and conclusions:In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in a controlled experimental setting. The study might therefore indicate future directions in trials of clinical implementation of remote preconditioning. INTRODUCTIONNo experimental study showed that human myocardium can be remotely preconditioned against standardised ischaemic/hypoxic insult. We aim to remove this major knowledge gap by applying remote preconditioning to the patient and studying ex-vivo the myocardium obtained thereafter. We assume that we will be able to show that remote preconditioning by brief periods of ischaemia of the arm protects segments of human right atrial appendage myocardium subjected to simulated hypoxia and reoxygenation in-vitro.This proof of principle is crucial. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the e...

show abstract

Section: Discussionmentioning

confidence: 86%

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Others present evidence that ischemic Precon is superior in limiting markers of cardiac cell damage vs. intermittent cross-clamp fibrillation (100,207). Interestingly, trials of Precon stimuli in patients undergoing CABG with cold cardioplegia generally fail to alter enzyme markers of cardiac damage (37, 64, 233, 235, 236), although some detect reduced troponin I (101) or CK release (139).…”

Section: Clinical Application Of Precon and Postconmentioning

confidence: 99%

Clinical cardioprotection and the value of conditioning responses

Peart

Headrick²

2009

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Adjunctive cardioprotective strategies for ameliorating the reversible and irreversible injuries with ischemia-reperfusion (I/R) are highly desirable. However, after decades of research, the promise of clinical cardioprotection from I/R injury remains poorly realized. This may arise from the challenges of trialing and effectively translating experimental findings from laboratory models to patients. One can additionally consider whether features of the more heavily focused upon candidates could limit or preclude therapeutic utility and thus whether we might shift attention to alternate strategies. The phenomena of preconditioning and postconditioning have proven fertile in identification of experimental means of cardioprotection and are the most intensely interrogated responses in the field. However, there is evidence these processes, which share common molecular signaling elements and end effectors, may be poor choices for clinical exploitation. This includes evidence of age dependence, limiting efficacy in target aged or senescent hearts; refractoriness to conditioning stimuli in diseased myocardium; interference from a variety of relevant pharmaceuticals; inadvertent induction of these responses by prior ischemia or commonly used drugs, precluding further benefit; and sex dependence of protective signaling. This review focuses on these features, raising questions about current research strategies, and the suitability of these widely studied phenomena as rational candidates for clinical translation.

show abstract

“…Reactions were terminated by the addition of SDS Laemmli sample buffer at 90 • C. Samples were then heated for 5 min and subjected to SDS/PAGE. [8][9][10][11][12][13][14][15][16][17]] These peptides were then conjugated to the protein transducing domain of the HIV-Tat protein (amino acids 47-57) as described previously [37]. An HIV-Tat carrier-carrier peptide (YGRKKRRQRRR-YGRKKRRQRRR) was synthesized as a control.…”

Section: In Vitro Phosphorylation Assaysmentioning

confidence: 99%

“…Experimentally, it is the most powerful form of cardiac protection known and it has been demonstrated in cardiac myocytes [2][3][4][5], intact hearts [6,7] and many animal species [8][9][10][11], including humans [12][13][14]. Downstream signalling molecules reported to be involved in PC include ATPdependent potassium channels [4,12,15,16], PKC (protein kinase C) isoenzymes [2, 3,12,15,17,18], MAPK (mitogen-activated protein kinase) enzymes [19][20][21], tyrosine kinases [22][23][24], PI3K (phosphoinositide 3-kinase) [22,25], heat-shock proteins [5,16,26], nitric oxide [27][28][29], free radicals [21,25,30] etc.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning

Ogbi

Johnson

2005

Biochemical Journal

117

View full text Add to dashboard Cite

We have previously identified a phorbol ester-induced PKCϵ (protein kinase Cϵ) interaction with the (∼18 kDa) COIV [CO (cytochrome c oxidase) subunit IV] in NCMs (neonatal cardiac myocytes). Since PKCϵ has been implicated as a key mediator of cardiac PC (preconditioning), we examined whether hypoxic PC could induce PKCϵ–COIV interactions. Similar to our recent study with phorbol esters [Ogbi, Chew, Pohl, Stuchlik, Ogbi and Johnson (2004) Biochem. J. 382, 923–932], we observed a time-dependent increase in the in vitro phosphorylation of an approx. 18 kDa protein in particulate cell fractions isolated from NCMs subjected to 1–60 min of hypoxia. Introduction of a PKCϵ-selective translocation inhibitor into cells attenuated this in vitro phosphorylation. Furthermore, when mitochondria isolated from NCMs exposed to 30 min of hypoxia were subjected to immunoprecipitation analyses using PKCϵ-selective antisera, we observed an 11.1-fold increase in PKCϵ–COIV co-precipitation. In addition, we observed up to 4-fold increases in CO activity after brief NCM hypoxia exposures that were also attenuated by introducing a PKCϵ-selective translocation inhibitor into the cells. Finally, in Western-blot analyses, we observed a >2-fold PC-induced protection of COIV levels after 9 h index hypoxia. Our studies suggest that a PKCϵ–COIV interaction and an enhancement of CO activity occur in NCM hypoxic PC. We therefore propose novel mechanisms of PKCϵ-mediated PC involving enhanced energetics, decreased mitochondrial reactive oxygen species production and the preservation of COIV levels.

show abstract

Preconditioning Improves Myocardial Preservation in Patients Undergoing Open Heart Operations

Cited by 59 publications

References 22 publications

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

Clinical cardioprotection and the value of conditioning responses

Protein kinase Cϵ interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning

Contact Info

Product

Resources

About