title: Sodium/hydrogen-exchanger inhibition during cardioplegic arrest and cardiopulmonary bypass: an experimental study.
abstract: OBJECTIVE
  We sought to determine whether pretreatment with a sodium/hydrogen-exchange inhibitor (EMD 96 785) improves myocardial performance and reduces myocardial edema after cardioplegic arrest and cardiopulmonary bypass.
  
  
  METHODS
  Anesthetized dogs (n = 13) were instrumented with vascular catheters, myocardial ultrasonic crystals, and left ventricular micromanometers to measure preload recruitable stroke work, maximum rate of pressure rise (positive and negative), and left ventricular end-diastolic volume and pressure. Cardiac output was measured by means of thermodilution. Myocardial tissue water content was determined from sequential biopsy. After baseline measurements, hypothermic (28 degrees C) cardiopulmonary bypass was initiated. Cardioplegic arrest (4 degrees C Bretschneider crystalloid cardioplegic solution) was maintained for 2 hours, followed by reperfusion-rewarming and separation from cardiopulmonary bypass. Preload recruitable stroke work and myocardial tissue water content were measured at 30, 60, and 120 minutes after bypass. EMD 96 785 (3 mg/kg) was given 15 minutes before bypass, and 2 micromol was given in the cardioplegic solution. Control animals received the same volume of saline vehicle. Arterial-coronary sinus lactate difference was similar in both animals receiving EMD 96 785 and control animals, suggesting equivalent myocardial ischemia in each group.
  
  
  RESULTS
  Myocardial tissue water content increased from baseline in both animals receiving EMD 96 785 and control animals with cardiopulmonary bypass and cardioplegic arrest but was statistically lower in animals receiving EMD 96 785 compared with control animals (range, 1.0%-1.5% lower in animals receiving EMD 96 785). Preload recruitable stroke work decreased from baseline (97 +/- 2 mm Hg) at 30 (59 +/- 6 mm Hg) and 60 (72 +/- 9 mm Hg) minutes after cardiopulmonary bypass and cardioplegic arrest in control animals; preload recruitable stroke work did not decrease from baseline (98 +/- 2 mm Hg) in animals receiving EMD 96 785 and was statistically greater at 30 (88 +/- 5 mm Hg) and 60 (99 +/- 4 mm Hg) minutes after bypass and arrest compared with control animals.
  
  
  CONCLUSIONS
  Sodium/hydrogen-exchanger inhibition decreases myocardial edema immediately after cardiopulmonary bypass and cardioplegic arrest and improves preload recruitable stroke work. Sodium/hydrogen-exchange inhibition during cardiac procedures with cardiopulmonary bypass and cardioplegic arrest may be a useful adjunct to improve myocardial performance in the immediate postbypass or arrest period.
authors.affiliation: Department of Surgery and Anesthesiology-Center for Microvascular and Lymphatic Studies, University of Texas-Houston, Medical School, USA. Charles.S.Cox@uth.tmc.edu
authors.forename: Charles S
authors.initials: CS
authors.lastname: Cox
authors.forename: Henning
authors.initials: H
authors.lastname: Sauer
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Allen
authors.forename: L Maximilian
authors.initials: LM
authors.lastname: Buja
authors.forename: Glen A
authors.initials: GA
authors.lastname: Laine
mesh_terms: D000818:Animals; D002314:Cardioplegic Solutions / Q000008:administration & dosage; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006324:Heart Arrest, Induced / Q000379:methods*; D006334:Heart Function Tests; D006439:Hemodynamics / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D012016:Reference Values; D012680:Sensitivity and Specificity; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D002314:Cardioplegic Solutions; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C118397:eniporide