Ischemic Preconditioning

Sandhu, Reena; Diaz, Roberto J.; Mao, Guo Dong; Wilson, Gregory J.

doi:10.1161/01.cir.96.3.984

Cited by 89 publications

(19 citation statements)

References 33 publications

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“…A previous study in rabbits had suggested that IP is a dose-dependent phenomenon (17). We have therefore tried to increase the protection of IP by increasing the number of preconditioning ischemia-reperfusion cycles from one to four with the aim to possibly attenuate this greater protection with TNF-␣ antibodies.…”

Section: Discussionmentioning

confidence: 99%

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

Belosjorow

Bolle

Duschin

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Pretreatment with tumor necrosis factor-α (TNF-α) antibodies abolishes myocardial infarct size reduction by late ischemic preconditioning (IP). Whether or not TNF-α is also important for myocardial infarct size reduction by classic IP is unknown. Anesthetized rabbits were untreated ( group 1, n = 7), classically preconditioned by 5 min left coronary artery occlusion/10 min reperfusion ( group 2, n = 6), or pretreated with TNF-α antibodies without ( group 3, n = 6) or with IP ( group 4, n = 6) before undergoing 30 min of occlusion and 180 min of reperfusion. Infarct size in group 1 was 44 ± 11 (means ± SD)% of the area at risk. With a comparable area at risk, infarct size was reduced to 13 ± 7%, 23 ± 8%, and 19 ± 12% (all P < 0.05) in groups 2, 3, and 4, respectively. The circulating TNF-α concentration was increased during ischemia in group 1 from 752 ± 403 to 1,542 ± 482 U/ml ( P < 0.05) but remained unchanged in all other groups. Circulating TNF-α concentration during ischemia and infarct size correlated in all groups ( r = 0.76). IP, TNF-α antibodies, and the combined approach reduced infarct size to a comparable extent. Therefore, the question of whether or not TNF-α is causally involved in the infarct size reduction by IP in rabbits could not be answered.

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Section: Discussionmentioning

confidence: 99%

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

Belosjorow

Bolle

Duschin

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Because hypoxia-reoxygenation transition is also part of the protocol of ischemic preconditioning, it may be supposed that the described mechanism of protection is contained within the complex protective mechanism of ischemic preconditioning. It is possibly responsible for the finding in some biological models that ischemic preconditioning can provide myocardial protection independent of PKC activation (20,21,23,27).…”

Section: Discussionmentioning

confidence: 99%

“…cellular calcium; heart function; ischemia; reperfusion SEVERAL STUDIES (18,25,32) have demonstrated that protection of the myocardium against ischemia-reperfusion injury caused by a brief preceding ischemia (ischemic preconditioning) is due to the release and accumulation of endogenous mediators, such as adenosine or noradrenaline, during ischemic preconditioning and a subsequent activation of protein kinase C (PKC). There are, however, data (20,23,27) indicating that protection by ischemic preconditioning can also be achieved independent of PKC activation. The mechanism of this PKC-independent protection could not be explained.…”

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confidence: 99%

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Role of protein phosphatases in hypoxic preconditioning

Ladilov

Maxeiner

Wolf

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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To find a protein kinase C (PKC)-independent preconditioning mechanism, hypoxic preconditioning (HP; i.e., 10-min anoxia and 10-min reoxygenation) was applied to isolated rat hearts before 60-min global ischemia. HP led to improved recovery of developed pressure and reduced end-diastolic pressure in the left ventricle during reperfusion. Protection was unaffected by the PKC inhibitor bisindolylmaleimide (BIM; 1 mol/l). It was abolished by the inhibitor of protein phosphatases 1 and 2A cantharidin (20 or 5 mol/l) and partially enhanced by the inhibitor of protein phosphatase 2A okadaic acid (5 nmol/l). In adult rat cardiomyocytes treated with BIM and exposed to 60-min simulated ischemia (anoxia, extracellular pH 6.4), HP led to attenuation of anoxic Na ϩ /Ca 2ϩ overload and of hypercontracture, which developed on reoxygenation. This protection was prevented by treatment with cantharidin but not with okadaic acid. In conclusion, HP exerts PKC-independent protection on ischemic-reperfused rat hearts and cardiomyocytes. Protein phosphatase 1 seems a mediator of this protective mechanism. cellular calcium; heart function; ischemia; reperfusion SEVERAL STUDIES (18,25,32) have demonstrated that protection of the myocardium against ischemia-reperfusion injury caused by a brief preceding ischemia (ischemic preconditioning) is due to the release and accumulation of endogenous mediators, such as adenosine or noradrenaline, during ischemic preconditioning and a subsequent activation of protein kinase C (PKC). There are, however, data (20,23,27) indicating that protection by ischemic preconditioning can also be achieved independent of PKC activation. The mechanism of this PKC-independent protection could not be explained. Brief periods of hypoxia, i.e., hypoxic preconditioning (HP), which do not allow accumulation of ischemic mediators, can also provide protection against ischemia-reperfusion injury (17,19,30,32). Previous studies (14, 26) of isolated hearts demonstrated that protection induced by HP does not involve the activation of adenosine receptors or G i proteins, suggesting a protective signaling different from well-known mechanisms of ischemic preconditioning. A protective role of PKC in HP was suggested for cultured embryonic cardiac myocytes (6, 29), but this was not demonstrated in adult cardiac myocytes or the adult whole heart. In general, the mechanisms of HP-induced protection are still not fully understood. For the present study, we hypothesized that HP leads to protection due to a PKC-independent mechanism. We (1) tested whether protection induced by HP is PKC independent and (3) which other type of signaling is responsible for HPinduced protection. Motivated by reports (2, 3) that inhibitors of these protein phosphatases (PP) can imitate ischemic preconditioning in some experimental models, we focused our study on the role of serine threonine PP1 and PP2A.We used the experimental model of isolated Langendorff-perfused rat hearts exposed to 60 min of global ischemia and 60 min of reperfusion. To test for im...

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“…1 for overview of protocols). The duration of this stabilization period has been shown to be sufficiently long to exclude an effect of the surgical procedures on the development of infarct size (28).…”

Section: Experimental Protocols/designmentioning

confidence: 99%

Cardiac effects of postconditioning depend critically on the duration of index ischemia

Manintveld

Hekkert²,

Bos³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

100

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Postconditioning (POC) is known as the phenomenon whereby brief intermittent ischemia applied at the onset of reperfusion following index ischemia limits myocardial infarct size. Whereas there is evidence that the algorithm of the POC stimulus is an important determinant of the protective efficacy, the importance of the duration of index ischemia on the outcome of the effects of POC has received little attention. Pentobarbital sodiumanesthetized Wistar rats were therefore subjected to index ischemia produced by coronary artery occlusions (CAO) of varying duration (15-120 min) followed by reperfusion, without or with postconditioning produced by three cycles of 30-s reperfusion and reocclusion (3POC30). 3POC30 limited infarct size produced by 45-min CAO (CAO45) from 45 Ϯ 3% to 31 Ϯ 5%, and CAO60 from 60 Ϯ 3% to 47 Ϯ 6% (both P Յ 0.05). In contrast, 3POC30 increased infarct size produced by CAO15 from 3 Ϯ 1% to 19 Ϯ 6% and CAO30 from 36 Ϯ 6 to 48 Ϯ 4% (both P Յ 0.05). This deleterious effect of 3POC30 was not stimulus sensitive because postconditioning with 3POC5 and 3POC15 after CAO30 also increased infarct size. The cardioprotection by 3POC30 after CAO60 was accompanied by an increased stimulation of Akt phosphorylation at 7 min of reperfusion and a 36% lower superoxide production, measured by dihydroethidium fluorescence, after 2 h of reperfusion. Consistent with these results, cardioprotection by 3POC30 was abolished by phosphatidylinositol-3-OH-kinase inhibition, as well as nitric oxide (NO) synthase inhibition. The deleterious effect of 3POC30 after CAO15 was accompanied by an increased superoxide production with no change in Akt phosphorylation and was not affected by NO synthase inhibition. In conclusion, the effect of cardiac POC depends critically on the duration of the index ischemia and can be either beneficial or detrimental. These paradoxical effects of POC may be related to the divergent effects on Akt phosphorylation and superoxide production.

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Ischemic Preconditioning

Cited by 89 publications

References 33 publications

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

TNF-α antibodies are as effective as ischemic preconditioning in reducing infarct size in rabbits

Role of protein phosphatases in hypoxic preconditioning

Cardiac effects of postconditioning depend critically on the duration of index ischemia

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