title: Dual effects of tumor necrosis factor alpha on myocardial injury following prolonged hypoperfusion of the heart.
abstract: OBJECTIVE
  To examine the dose response of TNFα in an ex vivo rat model of myocardial ischemia reperfusion.
  
  
  RESULTS
  Seventy-two rat hearts were mounted on Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solutions. Ischemia was induced by reducing the perfusate flow rate. During reperfusion, incremental doses of recombinant TNFα were infused as a part of perfusate. TNFα was blocked with monoclonal TNFα antibody. Myocardial function was measured by dP/dT and relaxation time (IVRT). Cellular injury was assessed by released myoglobin and tissue concentration of malondialdehyde activity of the heart homogenates. Baseline +dP/dT was 1645 ± 125 mmHg/sec, -dP/dT was 945 ± 73 mmHg/sec and IVRT was 65 ± 5 msec. At the conclusion of reperfusion period, lower doses of TNFα increased +dP/dT and lowered IVRT. In contrast, the higher doses of TNFα decreased +dP/dT and prolonged IVRT. Pretreating the hearts with monoclonal TNFα antibody completely abolished the effects of TNFα on myocardial contractility and relaxation comparable to ischemia controls.
  
  
  CONCLUSIONS
  Low dose TNFα improved myocardial function and decreased resultant cellular injury while high dose TNFα decreased myocardial function and increased myocardial injury following ischemia and reperfusion.
authors.affiliation: Department of Medicine, University Hospitals , Cleveland, Ohio , USA .
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Asgeri
authors.forename: Leili
authors.initials: L
authors.lastname: Pourafkari
authors.forename: Amita
authors.initials: A
authors.lastname: Kundra
authors.forename: Hassan
authors.initials: H
authors.lastname: Javadzadegan
authors.forename: Sohrab
authors.initials: S
authors.lastname: Negargar
authors.forename: Nader D
authors.initials: ND
authors.lastname: Nader
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008315:Malondialdehyde / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009211:Myoglobin / Q000378:metabolism; D009924:Organ Culture Techniques; D010477:Perfusion; D051381:Rats; D020318:Rats, Long-Evans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D009211:Myoglobin; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde
keywords: Myocardial infarction; TNF alpha; ventricular function