KATP channel blocker does not abolish the protective effect of Na +/H+ exchange 1 inhibition against ischaemia/reperfusion in aged myocardium

Hong Liu, Peter G Moore

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1 Citation (Scopus)

Abstract

Background and objective Ageing is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na +/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate whether NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium. Methods Hearts from 24-month-old rats were assigned to four groups: control group; APC group perfused with 2.5% sevoflurane before ischaemia; HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; and HOER5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury. Results Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134±12 mEqkg -1 dry weight in control group and 55±7 in HOE group (P<0.05). Intracellular Ca++ was 1764±142 nmol l -1 in control group and 694±213 in HOE group (P<0.05). Infarct size was measured at 28±4% in control group vs. 17±2% in HOE group (P<0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared with control (P<0.05). The beneficial effect of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups. Conclusion NHE inhibition was effective in protecting myocardium from I/R injury in aged rats, whereas APC was not. 5HD failed to block the protective effect of NHE inhibition.

Original languageEnglish (US)
Pages (from-to)740-746
Number of pages7
JournalEuropean Journal of Anaesthesiology
Volume27
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

KATP Channels
Reperfusion
Myocardium
Reperfusion Injury
Ischemia
Anesthetics
Control Groups
Phosphates
Weights and Measures
Wounds and Injuries

Keywords

  • Aged
  • Anaesthetic preconditioning
  • Ischaemic/reperfusion injury
  • Myocardium
  • Na/H exchange inhibition

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

@article{94506b07520a4c95b5cd8ce5aa593db2,
title = "KATP channel blocker does not abolish the protective effect of Na +/H+ exchange 1 inhibition against ischaemia/reperfusion in aged myocardium",
abstract = "Background and objective Ageing is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na +/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate whether NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium. Methods Hearts from 24-month-old rats were assigned to four groups: control group; APC group perfused with 2.5{\%} sevoflurane before ischaemia; HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; and HOER5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury. Results Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134±12 mEqkg -1 dry weight in control group and 55±7 in HOE group (P<0.05). Intracellular Ca++ was 1764±142 nmol l -1 in control group and 694±213 in HOE group (P<0.05). Infarct size was measured at 28±4{\%} in control group vs. 17±2{\%} in HOE group (P<0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared with control (P<0.05). The beneficial effect of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups. Conclusion NHE inhibition was effective in protecting myocardium from I/R injury in aged rats, whereas APC was not. 5HD failed to block the protective effect of NHE inhibition.",
keywords = "Aged, Anaesthetic preconditioning, Ischaemic/reperfusion injury, Myocardium, Na/H exchange inhibition",
author = "Hong Liu and Moore, {Peter G}",
year = "2010",
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doi = "10.1097/EJA.0b013e328337bb56",
language = "English (US)",
volume = "27",
pages = "740--746",
journal = "European Journal of Anaesthesiology",
issn = "0265-0215",
publisher = "Lippincott Williams and Wilkins",
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TY - JOUR

T1 - KATP channel blocker does not abolish the protective effect of Na +/H+ exchange 1 inhibition against ischaemia/reperfusion in aged myocardium

AU - Liu, Hong

AU - Moore, Peter G

PY - 2010/8

Y1 - 2010/8

N2 - Background and objective Ageing is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na +/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate whether NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium. Methods Hearts from 24-month-old rats were assigned to four groups: control group; APC group perfused with 2.5% sevoflurane before ischaemia; HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; and HOER5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury. Results Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134±12 mEqkg -1 dry weight in control group and 55±7 in HOE group (P<0.05). Intracellular Ca++ was 1764±142 nmol l -1 in control group and 694±213 in HOE group (P<0.05). Infarct size was measured at 28±4% in control group vs. 17±2% in HOE group (P<0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared with control (P<0.05). The beneficial effect of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups. Conclusion NHE inhibition was effective in protecting myocardium from I/R injury in aged rats, whereas APC was not. 5HD failed to block the protective effect of NHE inhibition.

AB - Background and objective Ageing is associated with an increase in myocardial susceptibility to ischaemia/reperfusion (I/R) injury. Na +/H+ exchange (NHE) inhibition and anaesthetic preconditioning (APC) are shown to protect myocardium from I/R injury. We set out to investigate whether NHE inhibition can induce protection against I/R injury and whether KATP channel inhibition can enhance this effect in aged rat myocardium. Methods Hearts from 24-month-old rats were assigned to four groups: control group; APC group perfused with 2.5% sevoflurane before ischaemia; HOE group perfused with (3-methylsulfonyl-4-piperidinobenzoyl) guanidine methanesulfonate (HOE-694) prior to ischaemia; and HOER5HD group perfused with both HOE and 5-hydroxydecanoic acid before ischaemia. We measured intracellular Na+ and Ca++ to quantitate the severity of myocardial injury. Results Both intracellular Na+ and Ca++ were significantly increased at the end of ischaemia and both were attenuated by NHE inhibition. Intracellular Na+ was 134±12 mEqkg -1 dry weight in control group and 55±7 in HOE group (P<0.05). Intracellular Ca++ was 1764±142 nmol l -1 in control group and 694±213 in HOE group (P<0.05). Infarct size was measured at 28±4% in control group vs. 17±2% in HOE group (P<0.05). High-energy phosphates and myocardial function were better preserved in HOE group compared with control (P<0.05). The beneficial effect of HOE on myocardial preservation was not blocked by 5HD nor were there any differences between APC and control groups. Conclusion NHE inhibition was effective in protecting myocardium from I/R injury in aged rats, whereas APC was not. 5HD failed to block the protective effect of NHE inhibition.

KW - Aged

KW - Anaesthetic preconditioning

KW - Ischaemic/reperfusion injury

KW - Myocardium

KW - Na/H exchange inhibition

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