title: Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury.
abstract: BACKGROUND
  The heart is a tumor necrosis factor-alpha (TNF-alpha)-producing organ. Recent basic experimental and clinical evidence suggests that TNF-alpha is an important mediator of myocardial injury during acute myocardial infarction, chronic heart failure, cardiac allograft rejection, and cardiopulmonary bypass operations. Although it is known that the myocardium itself is capable of producing TNF-alpha in response to endotoxin, it is unknown whether there is an increase in myocardial tissue TNF-alpha levels after ischemia-reperfusion injury. We hypothesized that ischemia-reperfusion induces the production of TNF-alpha by the heart.
  
  
  METHODS
  To avoid blood-borne TNF-alpha as a potentially confounding variable, we examined myocardial TNF-alpha production in a crystalloid-perfused model of cardiac ischemia-reperfusion injury. Isolated rat hearts were perfused with crystalloid solution and subjected to ischemia-reperfusion. Postischemic myocardial TNF-alpha was measured using an enzyme-linked immunosorbent assay and correlated with developed pressure, coronary flow, end-diastolic pressure, and creatine kinase loss (assay of activity in coronary effluent).
  
  
  RESULTS
  Ischemia-reperfusion induced a marked increase in myocardial TNF-alpha that was associated with decreased myocardial contractility and coronary flow and with increased end-diastolic pressure and postischemic creatine kinase loss.
  
  
  CONCLUSIONS
  The heart produces TNF-alpha in response to ischemia-reperfusion. Ischemia-induced TNF-alpha production may contribute to postischemic myocardial stunning, necrosis, or both. Strategies designed to limit ischemia-induced myocardial TNF-alpha production may have therapeutic utility in the settings of planned myocardial ischemic events.
authors.affiliation: Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Meldrum
authors.forename: J C
authors.initials: JC
authors.lastname: Cleveland
authors.forename: B S
authors.initials: BS
authors.lastname: Cain
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.forename: A H
authors.initials: AH
authors.lastname: Harken
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D000077324:Crystalloid Solutions; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008297:Male; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010952:Plasma Substitutes; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D014409:Tumor Necrosis Factor-alpha; D003402:Creatine Kinase