title: Sodium/hydrogen exchange activity in sepsis and in sepsis complicated by previous injury: 31P and 23Na NMR study.
abstract: OBJECTIVE
  Sepsis or septic shock occurs frequently in sick and injured patients and is associated with a significant mortality. Myocardial contractile dysfunction has been proposed to be a major determinant of sepsis-related mortality. This study was directed to examine the role of Na/H exchange activity in myocardial defects after sepsis or after sepsis complicated by a previous burn injury.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Sprague-Dawley rats (300-350 g, males).
  
  
  METHODS
  Cardiac function, cellular Na and Ca, myocardial pH, and high-energy phosphates were examined in perfused hearts harvested after sepsis alone (intratracheal Streptococcus pneumoniae, 0.4 mL of 1 x 10 CFU/mL), after sepsis complicated by previous burn injury (40% total body surface area), and after amiloride (a selective inhibitor of Na/H exchange) treatment of either sepsis alone or sepsis plus burn.
  
  
  RESULTS
  The ratio of Na signal from the intracellular compartment (Nai) compared with an external standard (monitored by Na-NMR spectroscopy, TmDOTP shift reagent) increased by 70% in sepsis alone and by 41% in sepsis complicated by previous burn injury compared with shams. Cardiac adenosine triphosphate and intracellular pH (P nuclear magnetic resonance spectroscopy) were unchanged by sepsis or sepsis plus burn. Left ventricular pressure and maximal change in pressure over time were reduced after sepsis or after sepsis plus burn injury. Amiloride treatment in either sepsis or sepsis complicated by a previous burn injury prevented myocardial Na and Ca accumulation, attenuated sepsis-related lactic acidosis, and improved left ventricular function.
  
  
  CONCLUSIONS
  Our results suggest that sepsis-related cardiac dysfunction is mediated, in part, by Na/H exchange activity, and inhibition of Na/H exchange activity improves cardiac function after sepsis alone or sepsis complicated by a previous injury.
authors.affiliation: UT Southwestern Medical Center Department of Surgery, Dallas, Texas, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sikes
authors.forename: Piyu
authors.initials: P
authors.lastname: Zhao
authors.forename: David L
authors.initials: DL
authors.lastname: Maass
authors.forename: Jean
authors.initials: J
authors.lastname: White
authors.forename: Jureta W
authors.initials: JW
authors.lastname: Horton
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002056:Burns / Q000150:complications*; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007474:Ion Exchange; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011015:Pneumonia, Aspiration / Q000150:complications / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
chemical_list: D000584:Amiloride; D012964:Sodium