The effect of preconditioning (ischemic and pharmacological) on myocardial necrosis following coronary artery bypass graft surgery

Teoh, Lay Kheng; Grant, Ronald; Hulf, JA; Pugsley, W; Yellon, Derek M.

doi:10.1016/s0008-6363(01)00435-7

Cited by 76 publications

(48 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another study (170) acquired evidence of exaggeration of injury with ischemic Precon. Subsequent work by Teoh and colleagues (214,215) indicates a superior protection with ischemic Precon vs. intermittent cross-clamping, cold cardioplegia, or pharmacological Precon, with 50 -70% reductions in troponin T release compared with these interventions. Others present evidence that ischemic Precon is superior in limiting markers of cardiac cell damage vs. intermittent cross-clamp fibrillation (100,207).…”

Section: Clinical Application Of Precon and Postconmentioning

confidence: 99%

“…Indeed, one of the aims of ongoing research into the molecular bases of these responses is to identify candidates for pharmacological manipulation. While Teoh et al (214) acquired evidence of a superior effect of ischemic vs. pharmacological Precon, other support for benefit via conditioning pharmacomimetics has been acquired. Adenosine may play a key role in triggering cardioprotection with Precon and Postcon (77,231), although it provides other beneficial effects that may be independent of these responses (166).…”

Section: Clinical Application Of Precon and Postconmentioning

confidence: 99%

See 1 more Smart Citation

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

Section: Clinical Application Of Precon and Postconmentioning

confidence: 99%

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

show abstract

“…An elegant model of ischemic preconditioning is restricted to patients undergoing coronary artery bypass surgery. 37 This limitation hinders efficient screening of pharmacological or physiological interventions for their potential to interfere with ischemic preconditioning in conscious persons. In contrast to the limitations of these methods, ischemic forearm exercise followed by Annexin A5 scintigraphy is not biased by collateral circulation, detects membrane changes that directly result from ischemiareperfusion injury, and can easily be applied to volunteers with minimal risk of serious complications.…”

mentioning

confidence: 99%

Annexin A5 Scintigraphy of Forearm as a Novel In Vivo Model of Skeletal Muscle Preconditioning in Humans

et al. 2005

View full text Add to dashboard Cite

Background-Nonlethal ischemia and reperfusion reduce ischemia-reperfusion-induced cell death, a phenomenon called ischemic preconditioning. In animal models, this potent endogenous protection is mimicked in vivo by administration of adenosine. In humans, exploitation of ischemic preconditioning is hindered by the lack of an appropriate in vivo model to study this phenomenon. To solve this problem, we aimed to set up an easy-to-use human in vivo model to study ischemic or pharmacological preconditioning. Methods and Results-Healthy male volunteers performed unilateral ischemic handgrip. At reperfusion, we intravenously injected technetium-99m-labeled Annexin A5, a presumed marker of ischemic injury, and we imaged both forearms and hands simultaneously with a gamma camera. Region of interest analysis (counts per pixel) and subsequent calculation of the percentage difference in radioactivity between experimental and control hands (thenar muscle; meanϮSE) revealed significant uptake to the ischemically exercised tissue (26Ϯ3% at 4 hours after reperfusion; PϽ0.05). This selective localization of Annexin A5 was reduced by ischemic preconditioning (10 minutes of ischemia plus reperfusion before ischemic exercise) or by infusion of adenosine into the brachial artery to 6Ϯ1% and 10Ϯ3%, respectively (PϽ0.05 versus ischemic exercise alone), resembling observations in animal models with infarct size as an end point.Appropriate control experiments supported our conclusion. Conclusions-Annexin

show abstract

“…9 Possibly the most direct evidence for the occurrence of preconditioning in humans comes from studies in patients undergoing coronary artery surgery, where it has been shown that the introduction of two 3-minute periods of global ischemia early in the operation reduced the loss of high energy phosphates 10 and troponin T after the subsequent prolonged period of ischemia during the fashioning of the coronary graft anastomoses. 11,12 Thus, overall, the available evidence supports the notion that preconditioning not only occurs in humans but does so within context of clinical procedures and as such may be of potential benefit to patients.…”

Section: See P 3091mentioning

confidence: 62%

Preconditioning and Arrhythmias

Taggart

Yellon

2002

Circulation

View full text Add to dashboard Cite

A brief episode of myocardial ischemia confers endogenous cardioprotection during a subsequent prolonged period of ischemia. This phenomenon, known as preconditioning, 1 offers one of the most powerful mechanisms for reducing the speed and extent of myocardial cell damage resulting from an acute or sustained ischemic insult. This protection has been shown to occur in a wide variety of animal species, including man, and exists in two forms, namely an early or classic preconditioning 1 and delayed or second window of protection. 2 The "gold standard" used in these animal studies for assessing a preconditioning effect has been measurement of the extent of limitation of infarct size. 3 Studies in humans therefore necessarily rely on a less direct approach. 4 For example, clinical observation has shown that the occurrence of episodes of angina shortly before a myocardial infarction reduces mortality and morbidity. 4,5 In the setting of percutaneous transluminal coronary angiography, it has been shown that measures of ischemia, such as angina and ST elevation, in the ECG occurring during the period when the coronary artery is occluded by the inflated balloon are less during a second balloon inflation compared with the first. 6 -8 These studies are not always easy to interpret, however, because of confounding variables such as uncertainties about the recruitment of collaterals in response to the preconditioning ischemia, the adequacy of the very short See p 3091duration of ischemia sometimes used during the preconditioning phase, and the use of the amount of ST segment shift in the ECG as a quantitative measure of ischemia. 4 One study largely overcomes the uncertainties with regard to collateral flow in patients undergoing percutaneous transluminal coronary angiography and demonstrates an antiarrhythmic effect of preconditioning. 9 Possibly the most direct evidence for the occurrence of preconditioning in humans comes from studies in patients undergoing coronary artery surgery, where it has been shown that the introduction of two 3-minute periods of global ischemia early in the operation reduced the loss of high energy phosphates 10 and troponin T after the subsequent prolonged period of ischemia during the fashioning of the coronary graft anastomoses. 11,12 Thus, overall, the available evidence supports the notion that preconditioning not only occurs in humans but does so within context of clinical procedures and as such may be of potential benefit to patients.Whereas preconditioning has been shown to dramatically reduce infarct size in all species studied, the situation with regard to surrogate endpoints 13 such as ventricular arrhythmias is less clear. The majority of studies in animal models report a reduction in arrhythmias after preconditioning protocols. 14,15 Some studies, on the other hand, report a worsening of arrhythmias. For example, in the original study by Murray et al, 1 there was a trend to an increased susceptibility to ventricular fibrillation (VF) in preconditioned dogs. In another study, although ...

show abstract

The effect of preconditioning (ischemic and pharmacological) on myocardial necrosis following coronary artery bypass graft surgery

Abstract: Ischemic preconditioning is superior to the other techniques at limiting myocardial necrosis during CABG. Pharmacological preconditioning may confer some benefit but this was not statistically shown using a specific adenosine A1 agonist (GR79236X).

Cited by 76 publications

References 39 publications

Clinical cardioprotection and the value of conditioning responses

Clinical cardioprotection and the value of conditioning responses

Annexin A5 Scintigraphy of Forearm as a Novel In Vivo Model of Skeletal Muscle Preconditioning in Humans

Preconditioning and Arrhythmias

Contact Info

Product

Resources

About