UC Davis

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 HOE+5HD 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 mEq kg(-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.