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Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion.

Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK - Basic Res. Cardiol. (2010)

Bottom Line: Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults.Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05).Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway. lars.breivik@biomed.uib.no

ABSTRACT
Short non-lethal ischemic episodes administered to hearts prior to (ischemic preconditioning, IPC) or directly after (ischemic postconditioning, IPost) ischemic events facilitate myocardial protection. Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults. We propose that coronary IPC effluent contains hydrophobic cytoprotective mediators acting via PI3K/Akt-dependent pro-survival signaling at ischemic reperfusion. Ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. IPC effluent administered for 10 min prior to index ischemia attenuated infarct size by ≥55% versus control hearts (P < 0.05). Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05). The IPC effluent significantly increased Akt phosphorylation in un-preconditioned hearts when administered before ischemia or at reperfusion, while pharmacological inhibition of PI3K/Akt-signaling at reperfusion completely abrogated the cardioprotection offered by effluent administration. Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05). The total hydrophobic effluent fraction significantly reduced infarct size independently of temporal administration (before ischemia, at reperfusion or as remote postconditioning). In conclusion, the IPC effluent retains strong cardioprotective properties, containing hydrophobic mediator(s) < 30 kDa offering cytoprotection via PI3K/Akt-dependent signaling at ischemic reperfusion.

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The temporal effect of treatment with IPC effluent on myocardial infarct size. Infarct size is expressed as percentage of the region at risk of infarction (area at risk). Effluent from preconditioned donor hearts (IPC) administered either 10 min prior to index ischemia (EffPre) or for 10 min at ischemic-reperfusion (EffRep) significantly reduced infarct size in non-preconditioned recipient hearts as compared to controls (Ctr). Bars represent mean ± SEM. N ≥ 7 in each group. *P < 0.05 versus Ctr group
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Fig2: The temporal effect of treatment with IPC effluent on myocardial infarct size. Infarct size is expressed as percentage of the region at risk of infarction (area at risk). Effluent from preconditioned donor hearts (IPC) administered either 10 min prior to index ischemia (EffPre) or for 10 min at ischemic-reperfusion (EffRep) significantly reduced infarct size in non-preconditioned recipient hearts as compared to controls (Ctr). Bars represent mean ± SEM. N ≥ 7 in each group. *P < 0.05 versus Ctr group

Mentions: Administration of IPC effluent from the onset of reperfusion significantly reduced infarct size in un-preconditioned recipient hearts compared to controls (EffRep: 25 ± 4% vs. Ctr: 54 ± 5%, P < 0.05; Fig. 2). Furthermore, the infarct size reduction was comparable to that of hearts subjected to ischemic preconditioning (IPC) or treated with IPC effluent prior to index ischemia (EffPre) (IPC: 21 ± 2%, EffPre: 24 ± 6% vs. EffRep: 25 ± 4%, ns; Fig. 2).Fig. 2


Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion.

Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK - Basic Res. Cardiol. (2010)

The temporal effect of treatment with IPC effluent on myocardial infarct size. Infarct size is expressed as percentage of the region at risk of infarction (area at risk). Effluent from preconditioned donor hearts (IPC) administered either 10 min prior to index ischemia (EffPre) or for 10 min at ischemic-reperfusion (EffRep) significantly reduced infarct size in non-preconditioned recipient hearts as compared to controls (Ctr). Bars represent mean ± SEM. N ≥ 7 in each group. *P < 0.05 versus Ctr group
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3012213&req=5

Fig2: The temporal effect of treatment with IPC effluent on myocardial infarct size. Infarct size is expressed as percentage of the region at risk of infarction (area at risk). Effluent from preconditioned donor hearts (IPC) administered either 10 min prior to index ischemia (EffPre) or for 10 min at ischemic-reperfusion (EffRep) significantly reduced infarct size in non-preconditioned recipient hearts as compared to controls (Ctr). Bars represent mean ± SEM. N ≥ 7 in each group. *P < 0.05 versus Ctr group
Mentions: Administration of IPC effluent from the onset of reperfusion significantly reduced infarct size in un-preconditioned recipient hearts compared to controls (EffRep: 25 ± 4% vs. Ctr: 54 ± 5%, P < 0.05; Fig. 2). Furthermore, the infarct size reduction was comparable to that of hearts subjected to ischemic preconditioning (IPC) or treated with IPC effluent prior to index ischemia (EffPre) (IPC: 21 ± 2%, EffPre: 24 ± 6% vs. EffRep: 25 ± 4%, ns; Fig. 2).Fig. 2

Bottom Line: Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults.Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05).Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway. lars.breivik@biomed.uib.no

ABSTRACT
Short non-lethal ischemic episodes administered to hearts prior to (ischemic preconditioning, IPC) or directly after (ischemic postconditioning, IPost) ischemic events facilitate myocardial protection. Transferring coronary effluent collected during IPC treatment to un-preconditioned recipient hearts protects from lethal ischemic insults. We propose that coronary IPC effluent contains hydrophobic cytoprotective mediators acting via PI3K/Akt-dependent pro-survival signaling at ischemic reperfusion. Ex vivo rat hearts were subjected to 30 min of regional ischemia and 120 min of reperfusion. IPC effluent administered for 10 min prior to index ischemia attenuated infarct size by ≥55% versus control hearts (P < 0.05). Effluent administration for 10 min at immediate reperfusion (reperfusion therapy) or as a mimetic of pharmacological postconditioning (remote postconditioning, RIPost) significantly reduced infarct size compared to control (P < 0.05). The IPC effluent significantly increased Akt phosphorylation in un-preconditioned hearts when administered before ischemia or at reperfusion, while pharmacological inhibition of PI3K/Akt-signaling at reperfusion completely abrogated the cardioprotection offered by effluent administration. Fractionation of coronary IPC effluent revealed that cytoprotective humoral mediator(s) released during the conditioning phase were of hydrophobic nature as all hydrophobic fractions with molecules under 30 kDa significantly reduced infarct size versus the control and hydrophilic fraction-treated hearts (P < 0.05). The total hydrophobic effluent fraction significantly reduced infarct size independently of temporal administration (before ischemia, at reperfusion or as remote postconditioning). In conclusion, the IPC effluent retains strong cardioprotective properties, containing hydrophobic mediator(s) < 30 kDa offering cytoprotection via PI3K/Akt-dependent signaling at ischemic reperfusion.

Show MeSH
Related in: MedlinePlus