Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit.

Iwamoto, Toshihiro; Miura, Tetsuji; Adachi, Takeo; Noto, T; Ogawa, Takashi; Tsuchida, Akihito; Ito, Osamu

doi:10.1161/01.cir.83.3.1015

Cited by 97 publications

(31 citation statements)

References 23 publications

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“…In keeping with these results, Tritto and coworkers (60) noted that a brief (5-min) exposure of isolated rabbit hearts to a free radical-generating solution resulted in subsequent reduction of infarct size. In contrast, Iwamoto et al (61) were unable to abolish the protective effects of ischemic preconditioning against infarction with either SOD alone or SOD and catalase in open-chest rabbits. Richard et al (62) were also unable to block preconditioning against infarction with MPG in openchest rats.…”

Section: Discussionmentioning

confidence: 87%

Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs.

Sun¹,

Tang²,

Park³

et al. 1996

J. Clin. Invest.

223

137

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Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3). On day 1, pigs received an i.v. infusion of a combination of antioxidants (superoxide dismutase, catalase, and N -2 mercaptopropionyl glycine; group II, n ϭ 9), nisoldipine (group III, n ϭ 6), or vehicle (group I [controls], n ϭ 9). In the control group, systolic wall thickening (WTh) in the ischemic-reperfused region on day 1 remained significantly depressed for 4 h after the 10th reperfusion, indicating myocardial "stunning." On days 2 and 3, however, the recovery of WTh improved markedly, so that the total deficit of WTh decreased by 53% on day 2 and 56% on day 3 compared with day 1 ( P Ͻ 0.01), indicating the development of a powerful cardioprotective response (late preconditioning against stunning). In the antioxidant-treated group, the total deficit of WTh on day 1 was 54% less than in the control group ( P Ͻ 0.01). On day 2, the total deficit of WTh was 85% greater than that observed on day 1 and similar to that observed on day 1 in the control group. On day 3, the total deficit of WTh was 58% less than that noted on day 2 ( P Ͻ 0.01). In the nisoldipine-treated group, the total deficit of WTh on day 1 was 53% less than that noted in controls ( P Ͻ 0.01). On days 2 and 3, the total deficit of WTh was similar to the corresponding values in the control group. These results demonstrate that: ( a ) in the conscious pig, antioxidant therapy completely blocks the development of late preconditioning against stunning, indicating that the production of reactive oxygen species (ROS) on day 1 is the mechanism whereby ischemia induces the protective response observed on day 2; ( b ) antioxidant therapy markedly attenuates myocardial stunning on day 1, indicating that ROS play an important pathogenetic role in postischemic dysfunction in the porcine heart despite the lack of xanthine oxidase; ( c ) although the administration of a calcium-channel antagonist (nisoldipine) is as effective as antioxidant therapy in attenuating myocardial stunning on day 1, it has no effect on late preconditioning on day 2, indicating that the ability of antioxidants to block late preconditioning is not a nonspecific result of the mitigation of postischemic dysfunction on day 1. Generation of ROS during reperfusion is generally viewed as a deleterious process. Our finding that ROS contribute to the genesis of myocardial stunning but, at the same time, trigger the development of late preconditioning against stunning supports a complex pathophysiological paradigm, in which ROS play an immediate injurious role (as mediators of stunning) followed by a useful function (as mediators of subsequent preconditioning). (

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Section: Discussionmentioning

confidence: 87%

Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs.

Sun¹,

Tang²,

Park³

et al. 1996

J. Clin. Invest.

223

137

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“…31 P NMR spectra were obtained at 109. 16 MHz using a JEOL GSX 270 wide-bore NMR spectrometer (6.35 tesla field strength; Nihon Denshi, Tokyo, Japan). The proton signal from the heart was used for shimming.…”

Section: P Nuclear Magnetic Resonance (Nmr) Spectroscopymentioning

confidence: 99%

“…However, in the present study neither 5-HD nor NAC inhibited the cardioprotection induced by IPC, suggesting that IPC is not mediated through the mitoKATP channel opening or ROS production during the preconditioning period. Several investigators have also documented that the administration of 5-HD [13][14][15] and ROS scavengers 16,17,26 could not cancel the cardioprotective effects of IPC. Lim et al have indicated that DZ and 5-HD have additional effects on mitochondrial function, independently of any effects on mitoKATP channels.…”

Section: Involvement Of Mitokatp Channels and Ros In Dz-and Ipc-inducmentioning

confidence: 99%

“…11,12 These findings support the hypothesis that IPC is mediated through the opening of mitoKATP channels and ROS production. Nevertheless, several investigators have argued against the contribution of mitoKATP channels [13][14][15] and ROS 16,17 to IPC. The protective effects of IPC and the mitoKATP channel opener diazoxide (DZ) in whole heart models have been generally evaluated as reduced infarct size and improved contractile function during reperfusion.…”

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confidence: 99%

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Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

Wakahara¹,

Katoh²,

Yaguchi³

et al. 2004

Circ J

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schemic preconditioning (IPC) is a phenomenon whereby brief intermittent periods of ischemia protect the myocardium against subsequent lethal ischemia. 1 Although the mechanisms responsible for IPC still remain elusive, several factors, such as adenosine, acetylcholine and opioids, which activate protein kinase C, have been implicated in the cardioprotective effect of IPC. 2 Recently, ATP-sensitive potassium (KATP) channels and reactive oxygen species (ROS), among the signaling pathways mediating IPC, have attracted considerable attention. Though the involvement of sarcolemmal KATP channels in IPC was first suggested, 3 subsequent studies have reported that mitochondrial KATP (mitoKATP) channels play a potential role for the cardioprotective effects of KATP channel openers. 4 More recent studies have indicated that the opening of mitoKATP channels induces cardioprotection by generating ROS, which may act as intracellular messengers. 5,6 It has been reported that pretreatment with mitoKATP channel openers 4 or exogenous H2O2 7,8 induces IPC-like protective effects, and that IPC-induced cardioprotection is antagonized by mitoKATP channel inhibitors 9,10 or ROS scavengers. 11,12 These findings support the hypothesis that IPC is mediated through the opening of mitoKATP channels and ROS production. Nevertheless, several investigators have argued against the contribution of mitoKATP channels [13][14][15]17 to IPC. The protective effects of IPC and the mitoKATP channel opener diazoxide (DZ) in whole heart models have been generally evaluated as reduced infarct size and improved contractile function during reperfusion. IPC also has beneficial effects on energy metabolism, such as reduced intracellular acidification during ischemia and postischemic preservation of high-energy phosphates. [18][19][20] Measurement of these parameters may reveal the difference in the cardioprotective mechanisms between IPC and DZ. Moreover, a comparison of IPC and DZ under the same experimental condition would minimize the discrepancy in the results caused by the experimental conditions and models used. However, few studies have compared the effects of IPC and DZ on energy metabolism under the same experimental conditions. Therefore, in the present study we investigated the involvement of the opening of mitoKATP channels and ROS production in IPC-and DZ-induced cardioprotection, using the mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) and the antioxidant N-acetylcysteine (NAC), in perfused Background Recent studies have implicated the opening of mitochondrial KATP (mitoKATP) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC). Methods and ResultsThe involvement of mitoKATP channels and ROS in the cardioprotective effects of both IPC and the mitoKATP channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pHi) were also examined using 31...

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“…as to whether the experiments are performed under in vitro or in vivo conditions, the dose and route of administration of the antioxidant applied, as well as the intensity of the preconditioning stimulus (i.e. the duration and number of the preconditioning occlusions) [57,58,59,60] which may substantially determine the signaling pathways which lead to cardioprotection [61]. In addition, the possible trigger or mediator role of ROS in PC and their relation to the mitoK ATP channels, is also not fully elucidated [62,63].…”

Section: The Role Of Reactive Oxygen Species In Preconditioningmentioning

confidence: 99%

The antiarrhythmic effect of exogenous peroxynitrite and preconditioning: the involvement of nitric oxide, superoxide and peroxynitrite

Kiss

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Full papersIWe showed, that compared to the controls, two 5 min periods of the 100 nM concentration of PN, similar to the same periods of preconditioning ischaemia, markedly reduced the severity of arrhythmias and attenuated the generation of NT that resulted from a 25 min occlusion and reperfusion of the left anterior descending coronary artery. Since these effects were not modified by the prior administration of 5-HD, we concluded that, in contrast to PC, the antiarrhythmic effect of PN does not involve the opening of mitoK ATP channels.However, the observed attenuation in I/R-induced NT formation following PC and PN has promted us to examine, whether this results from a reduced NO or from a reduced O 2 . production. Therefore, in another series of experiments we measured changes in plasma and tissue nitrate/nitrite (NOx, a biomarker of NO production), O 2 . and NT productions in control, in PC and in PN treated dogs. We have found that in contrast to the controls in which the plasma NOx levels were markedly decreased by the end of the occlusion, in dogs subjected to PC and PN infusion NOx levels were maintained over the entire ischaemic period.

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Myocardial infarct size-limiting effect of ischemic preconditioning was not attenuated by oxygen free-radical scavengers in the rabbit.

Abstract: Ischemic preconditioning delays ischemic myocardial necrosis regardless of myocardial xanthine oxidase content. Free radicals are unlikely to have a major role in the mechanism of the preconditioning in rabbits.

Cited by 97 publications

References 23 publications

Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs.

Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs.

Difference in the Cardioprotective Mechanisms Between Ischemic Preconditioning and Pharmacological Preconditioning by Diazoxide in Rat Hearts

The antiarrhythmic effect of exogenous peroxynitrite and preconditioning: the involvement of nitric oxide, superoxide and peroxynitrite

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