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Effects of specific sodium/hydrogen exchange inhibitor during cardioplegic arrest
I O Choy1, V D Schepkin, T F Budinger
1Center for Functional Imaging, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
Insights
This study shows that HOE 694, a sodium/hydrogen exchange inhibitor, reduces intracellular sodium buildup during heart ischemia and reperfusion. This leads to better recovery of heart function after the ischemic event.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Pharmacology
Background:
- Intracellular sodium accumulation during myocardial ischemia impairs cardiac recovery post-reperfusion.
- This sodium influx is linked to inappropriate calcium influx and reduced cardiac function.
- The study investigates the role of the sodium/hydrogen exchange inhibitor HOE 694.
Purpose of the Study:
- To evaluate the effects of HOE 694 on intracellular sodium levels during myocardial ischemia and reperfusion.
- To assess the impact of HOE 694 on post-ischemic cardiac recovery and function.
Main Methods:
- Isolated rat hearts were treated with St. Thomas' cardioplegia with or without HOE 694.
- Global normothermic ischemia was induced, and intracellular sodium was measured using 23Na nuclear magnetic resonance spectroscopy.
- Hemodynamic variables were recorded before and after the ischemic period.
Main Results:
- HOE 694 significantly attenuated intracellular sodium accumulation during ischemia and early reperfusion.
- Hearts treated with HOE 694 demonstrated improved recovery of left ventricular developed pressure and rate-pressure product.
- No significant difference in post-ischemic coronary flow recovery was observed between groups.
Conclusions:
- HOE 694 effectively reduces intracellular sodium during myocardial ischemia and reperfusion.
- This reduction in sodium overload is associated with improved recovery of cardiac contractile function.
- HOE 694 may mitigate sodium and calcium overload in ischemic myocardium, enhancing recovery.
Background:
The accumulation of intracellular sodium during myocardial ischemia couples an inappropriate calcium influx and depressed cardiac recovery during subsequent reperfusion. The effects of the selective sodium/ hydrogen exchange inhibitor HOE 694 are evaluated during myocardial ischemia and reperfusion.
Methods:
Ten isolated rat hearts were subjected to a 2-minute infusion of St. Thomas' cardioplegia +/- 1 mumol/L HOE 694 followed by 50 minutes' normothermic (37 degrees C) global ischemia. Intracellular sodium accumulation was continuously measured using triple quantum filtered 23Na nuclear magnetic resonance spectroscopy without chemical shift reagents. Hemodynamic variables were assessed before and after ischemia.
Results:
The addition of 1 mumol/L HOE 694 to St. Thomas cardioplegic solution (n = 5) attenuated the accumulation of intracellular sodium after 50 minutes' ischemia (160.5% +/- 9.1% versus 203.4% +/- 10.9% [mean +/- standard error], HOE 694 versus control, respectively; p = 0.014) and after the initial reperfusion period (first 30 minutes) (288.7% +/- 10.2% versus 335.9% +/- 10.3%; p = 0.008). HOE 694-treated hearts showed significantly improved postischemic recovery of left ventricular developed pressure (53.5% +/- 8.4% versus 26.4% +/- 6.6%; p = 0.036) and rate-pressure product (40.2% +/- 6.9% versus 13.2% +/- 5%; p = 0.014). Postischemic recovery of coronary flow was not significantly different between the two groups (68.6% +/- 5.9% versus 55.5% +/- 4.6%, HOE 694 versus control, respectively; p = 0.11).
Conclusions:
The addition of 1 mumol/L HOE 694 to cardioplegic solution attenuates the increase of intracellular sodium during myocardial ischemia and early reperfusion. This is coupled with an improved recovery of contractile function, possibly as a result of decreased sodium and calcium overload of ischemic myocardium.