Effect of the Na+/H+ exchange inhibitor eniporide on cardiac performance and myocardial high energy phosphates in pigs subjected to cardioplegic arrest.
BACKGROUND
Pharmacologic Na(+)/H(+) exchange inhibition has been suggested to ameliorate cardiac performance depression associated with myocardial ischemia/reperfusion. The purpose of our experimental study was to investigate the impact of the novel Na(+)/H(+) exchange inhibitor Eniporide (EMD 96785) on cardiac performance and high energy phosphate content in a clinically relevant pig model of cardioplegic arrest.


METHODS
We subjected 21 pigs (47 +/- 12 [SD] kg) to cardiopulmonary bypass (CPB) and 60 minutes cold (4 degrees C) crystalloid cardioplegic arrest (Bretschneider). The pigs were randomized to receive either systemic infusion of 3 mg/kg Eniporide before cardioplegia with added 2 micromol/L Eniporide (ENI-CP+iv; n = 7); 3 mg/kg Eniporide in cardioplegia only (ENI-CP; n = 7); or no Eniporide (control; n = 7). For cardiac performance determination we measured preload recruitable stroke work and Tau, the time constant of left ventricular (LV) isovolumic relaxation using sonomicrometry and micromanometry before CPB as well as 30, 60, and 120 minutes after weaning off CPB. LV and right ventricular myocardial adenine nucleotides (ATP, ADP, and AMP), glycogen, and water content were determined at the end of the experiments.


RESULTS
Neither for standard hemodynamics including vascular pressures and cardiac index nor for cardiac performance factors did we find statistically significant differences between the groups. Similarly, myocardial adenine nucleotides, glycogene, and water content did not differ significantly between the groups.


CONCLUSIONS
In this acute study we did not find significant effects of the Na(+)/H(+) exchange inhibitor Eniporide on cardiac performance and high energy phosphate content in healthy pig hearts subjected to ischemia/reperfusion induced by crystalloid cardioplegic arrest.
Klass
Oliver
O
Department of Cardiothoracic Surgery, University of Cologne, Cologne, Germany.
Fischer
Uwe M
UM
Perez
Elisabeth
E
Easo
Jerry
J
Bosse
Marfalda
M
Fischer
Juergen H
JH
Tossios
Paschalis
P
Mehlhorn
Uwe
U
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D006003:Glycogen / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011292:Premedication; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000494:pharmacology*; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000227:Adenine Nucleotides; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C118397:eniporide; D006003:Glycogen