Does Cardiopulmonary Bypass Alone Elicit Myoprotective Preconditioning?

Burns, Paul; Krukenkamp, Irvin B.; Caldarone, Christopher A.; Gaudette, Glenn R.; Bukhari, Emad; Levitsky, Sidney

doi:10.1161/01.cir.92.9.447

Cited by 52 publications

(14 citation statements)

References 23 publications

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“…33 This finding is consistent with the previously mentioned observation that interventions that cause PKC activation (as expected to have occurred in this study after isoflurane treatment in view of the elevated levels of ecto-5Ј-nucleotidase) improve the recovery of function after cardioplegic arrest. 24,25 Despite these caveats, the present data demonstrate that even if cardiopulmonary bypass, by itself, 34 and opioid-based anesthesia 35 have a preconditioning effect, there is still some room left for additional compounds like isoflurane to act as preconditioning mimetics in the human heart. As such, these results support additional studies to determine how this drug or others can be optimally used to "turn on" the signaling pathway responsible for the cardioprotective effects of preconditioning.…”

Section: Ii-342mentioning

confidence: 71%

Evidence for Preconditioning by Isoflurane in Coronary Artery Bypass Graft Surgery

Belhomme¹,

Peynet²,

Louzy³

et al. 1999

Circulation

207

106

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Background-Experimentally, isoflurane, a commonly used volatile anesthetic agent, mimics the cardioprotective effects of ischemic preconditioning via a mechanism that could involve the activation of protein kinase C. The present study was designed to assess the clinical relevance of this observation in patients undergoing elective CABG. Methods and Results-Twenty patients were included in the study. In 10 of them, preconditioning was elicited after the onset of cardiopulmonary bypass via a 5-minute exposure to isoflurane (2.5 minimum alveolar concentration), followed by a 10-minute washout before aortic cross-clamping and cardioplegic arrest. Ten case-matched control patients underwent an equivalent period (15 minutes) of prearrest isoflurane-free bypass. Outcome measurements included troponin I and creatine kinase-MB isoenzyme (until the third postoperative day) levels and the activity of ecto-5Ј-nucleotidase, which contributes to adenosine production and is considered to be a reporter of protein kinase C activation, as assessed in right atrial biopsy samples taken before bypass and at the end of the preconditioning protocol (or after 15 minutes of bypass in control patients Key Words: ischemia Ⅲ bypass Ⅲ anesthesia I schemic preconditioning is recognized as one of the most effective means of reducing cellular necrosis. As such, its implementation during cardiac surgery might be clinically relevant, particularly in high-risk patients in whom any additional myocardial ischemic injury induced with cardiopulmonary bypass and superimposed cardioplegic arrest can adversely affect postoperative outcome. Because in this setting it is particularly desirable to avoid an ischemic-type preconditioning stimulus, 1-3 extensive research is targeted toward identifying the pharmacological mediators of the preconditioning phenomenon in an attempt to exploit them therapeutically.There is compelling evidence that the preconditioning signal activates various membrane receptors, which triggers a signaling pathway leading to the activation of several kinases, 4 in particular, protein kinase C (PKC), 5 and the subsequent opening of ATP-dependent potassium channels, possibly at the mitochondrial level. 6,7 How opening of these channels elicits cardioprotection is not yet established but might involve the limitation of calcium influx, better control of cellular volume, or both. This scheme provides a framework for rationalizing interventions targeted at mimicking preconditioning and, in this perspective, makes logical the use, among other drugs, of potassium channel openers.Within this class of drugs, only nicorandil is currently available for human use. However, aside from the fact that nicorandil cannot be administered intravenously, this compound has marked nitrovasodilatory properties, which can be Circulation is available at http://www.circulationaha.org II-340by guest on May 10, 2018http://circ.ahajournals.org/ Downloaded from of concern. Alternatively, isoflurane is a volatile anesthetic agent that has been reported in animal mo...

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Section: Ii-342mentioning

confidence: 71%

Evidence for Preconditioning by Isoflurane in Coronary Artery Bypass Graft Surgery

Belhomme¹,

Peynet²,

Louzy³

et al. 1999

Circulation

207

106

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“…Preconditioning is initiated by brief, nonlethal periods of ischemia, and provides local tissue protection from the effects of further prolonged episodes of ischemia. In the heart, IPC reduces experimental infarct size by up to 75% in many different species (2)(3)(4)(5)(6). The effects of IPC are immediate, triggered by release of several mediators (including adenosine and bradykinin) (7,8), and dependent on the activation of complex second messenger systems (1).…”

mentioning

confidence: 99%

Remote Ischemic Preconditioning Provides Early and Late Protection Against Endothelial Ischemia-Reperfusion Injury in Humans

Loukogeorgakis

Panagiotidou

Broadhead

et al. 2005

Journal of the American College of Cardiology

367

333

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“…There are some data to suggest that perconditioning might reduce infarct size in humans 8 ; however, further research is certainly needed. Although preconditioning consistently reduces infarct size in all animal models, [13][14][15][16][17][18] it cannot be utilized in clinical practice because of the unknown timing of AMI. Additionally, preconditioning and postconditioning appear to preserve left ventricular function and reduce arrhythmias in the cardiac surgery and myocardial infarct settings, respectively (Table 2).…”

Section: Protective Actions Of Ischemic Conditioning In the Clinical mentioning

confidence: 99%

Protecting the Heart From Ischemia: An Update on Ischemic and Pharmacologic Conditioning

Gerczuk¹,

Kloner²

2011

Hosp Pract

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The attempt to fi nd treatments that will reduce myocardial cell death during periods of ischemia and subsequent reperfusion has spanned nearly 40 years. Although many therapies have shown promise in animal models, relatively few have been successful in clinical trials. Some of the most effective clinical therapies involve techniques designed to elicit the heart's own innate capacity to protect itself. The ability of the heart to render itself more resistant to ischemia/reperfusion injury was not appreciated until the description of ischemic preconditioning in 1986. Following the discovery that brief, nonlethal episodes of ischemia conditioned the heart to better tolerate a subsequent prolonged episode of ischemia, alternative ways of evoking this endogenous cardioprotection were described. Ischemic postconditioning and remote conditioning are potentially useful tools for protecting ischemic myocardium, and have been shown to be benefi cial in small clinical trials. Several pharmacologic agents have the ability to mimic the effects of ischemic conditioning and can also reduce the amount of cell death during ischemia/reperfusion. This article provides the clinician with an overview of the different techniques of ischemic conditioning and how they can protect the myocardium from ischemia/ reperfusion injury. Additionally, several pharmacologic agents that can protect the heart in a similar manner are discussed.

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Does Cardiopulmonary Bypass Alone Elicit Myoprotective Preconditioning?

Abstract: CPB alone appears sufficient to elicit the PC response important for myocardial protection during cardiac surgery. These data suggest that myocardial alpha-adrenergic receptor and adenosine receptor stimulation are involve in initiating CPB-induced PC.

Cited by 52 publications

References 23 publications

Evidence for Preconditioning by Isoflurane in Coronary Artery Bypass Graft Surgery

Evidence for Preconditioning by Isoflurane in Coronary Artery Bypass Graft Surgery

Remote Ischemic Preconditioning Provides Early and Late Protection Against Endothelial Ischemia-Reperfusion Injury in Humans

Protecting the Heart From Ischemia: An Update on Ischemic and Pharmacologic Conditioning

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