Improved myocardial function using a Na+/H+ exchanger inhibitor during cardioplegic arrest and cardiopulmonary bypass.
BACKGROUND
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.


CONCLUSIONS
Na(+)/H(+) exchanger inhibition improves systolic but not diastolic function after CPB/CPA. This is not due to a reduction in MWC.
Cox
Charles S
CS
Department of Surgery, Center for Microvascular and Lymphatic Studies at the University of Texas-Houston, Medical School, Houston, TX, USA. Charles.S.Cox@uth.tmc.edu
Allen
Steven J
SJ
Sauer
Henning
H
Laine
Glen A
GA
D000818:Animals; D002315:Cardiopulmonary Bypass; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006324:Heart Arrest, Induced; D008297:Male; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D017923:Sodium-Hydrogen Exchangers