Hong Liu1, Peter G Moore. 1. Department of Anesthesiology and Pain Medicine, University of California Davis, Sacramento, California 95817, USA. hualiu@ucdavis.edu
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 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.
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.
Authors: M Tani; Y Suganuma; H Hasegawa; K Shinmura; Y Ebihara; Y Hayashi; X Guo; M Takayama Journal: J Mol Cell Cardiol Date: 1997-11 Impact factor: 5.000
Authors: Andre Heinen; Ragnar Huhn; Kirsten M A Smeele; Coert J Zuurbier; Wolfgang Schlack; Benedikt Preckel; Nina C Weber; Markus W Hollmann Journal: Anesthesiology Date: 2008-11 Impact factor: 7.892