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Improved Myocardial Function Using a Na+/H+ Exchanger Inhibitor During Cardioplegic Arrest and Cardiopulmonary Bypass

Improved Myocardial Function Using a Na+/H+ Exchanger Inhibitor During Cardioplegic Arrest and Cardiopulmonary Bypass

Charles S Cox Jr, Steven J Allen, Henning Sauer, Glen A Laine

Chest. 2003 Jan;123(1):187-94.

PMID: 12527621

Abstract:

Introduction:
We have demonstrated that a component of post-cardiopulmonary bypass (CPB)/cardioplegic arrest (CPA) myocardial dysfunction is related to myocardial edema. Myocardial ischemia/reperfusion that occurs with CPB/CPA activates the Na(+)/H(+) exchanger to normalize intracellular pH, with intracellular Na(+) (and water) accumulation. We hypothesized that Na(+)/H(+) exchanger inhibition with a selective inhibitor (EMD 87580) would decrease myocardial edema and improve myocardial performance after CPB/CPA.
Methods:
Anesthetized dogs (n = 14) were instrumented with myocardial ultrasonic crystals, and left ventricular (LV) micromanometer, to study myocardial function. Myocardial tissue water (MWC) was determined using microgravimetry. Treated animals (n = 5) received EMD 87580 (5 mg/kg IV pretreatment and 10 mol/L cardioplegia); control animals (n = 9) received a saline vehicle. After baseline, hypothermic CPB/CPA was initiated for 2 h, followed by reperfusion/rewarming for 45 min and separation from CPB. Myocardial function parameters and MWC were measured at 30 min, 60 min, and 120 min after CPB.
Results:
Preload recruitable stroke work did not decrease from baseline in EMD 87580-treated animals, and was significantly greater in EMD 87580-treated animals than control animals at 120 min after CPB. At a similar LV end-diastolic volume, the maximal rate of rise of LV pressure (dp/dtMAX) was significantly decreased from baseline at all time points in control animals, and unchanged in EMD 87580-treated animals. MWC increased with CPB/CPA in both groups, with no difference between groups. There was no difference in - dp/dtMAX or slope of the end-diastolic pressure-volume relationship.
Conclusion:
Na(+)/H(+) exchanger inhibition improves systolic but not diastolic function after CPB/CPA. This is not due to a reduction in MWC.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP187870786	EMD-87580		187870-78-6	Price

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