title: Action of aprotinin in myocardial ischemia - an investigation using a plasma-free model.
abstract: BACKGROUND
  The protease inhibitor aprotinin has been reported to have an anti-ischemic effect on left-ventricular myocardium in patients undergoing cardiopulmonary bypass operation. To examine the anti-ischemic properties beside its antifibrinolytic and inhibitory action on the kallikrein-bradykinin system, we investigated this substance in buffer-perfused rat hearts.
  
  
  METHODS
  24 isolated isovolumically contracting rat hearts received a 10-minute infusion of either 10000 units aprotinin or pure saline followed by 30 minutes of no-flow global ischemia and 45 minutes of reperfusion. Hemodynamics, high-energy phosphates, and troponin T as molecular marker of cardiac injury were studied.
  
  
  RESULTS
  During 15 minutes of reperfusion steady state function was identical in both groups, with a recovery of the developed left-ventricular pressure to 81.9+/-1.5% after protease inhibition and 83.0+/-2.6% in the controls. Coronary flow, myocardial oxygen consumption, and contractile reserve after maximum Ca++ stimulation were also identical. High-energy phosphates were comparably reduced in both groups (adenine nucleotides: 3.1+/-0.3 micromol/g ww after aprotinin vs. controls 2.7+/-0.4 micromol/g ww and creatine phosphate: 6.5+/-0.9 micromol/g ww vs. controls 4.7+/-1.1 micromol/g ww). However, release of the cardiac specific marker troponin T was lower after ischemia at several measurements (p<0.05). The total release of troponin T was 44+/-10 ng in the aprotinin treated hearts vs. 90+/-17 ng in the postischemic control hearts (p<0.05).
  
  
  CONCLUSIONS
  The findings demonstrate that aprotinin in a moderate dose is effective in reducing postischemic troponin release in a non-blood perfused system. Measurement of myocardial high-energy phosphates after aprotinin use was performed for the first time and indicates that not a reduction in severity of direct myocardial ischemic intensity but a beneficial action on processes causing release of troponin is the mode of action of this effect.
authors.affiliation: Department of Cardiology, Center for Internal Medicine, Eberhard-Karls University, Tübingen, Germany.
authors.forename: H M
authors.initials: HM
authors.lastname: Hoffmeister
authors.forename: M
authors.initials: M
authors.lastname: Fischer
authors.forename: S
authors.initials: S
authors.lastname: Kazmaier
authors.forename: W
authors.initials: W
authors.lastname: Heller
authors.forename: L
authors.initials: L
authors.lastname: Seipel
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology*; D004195:Disease Models, Animal; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion / Q000379:methods; D010725:Phosphocreatine / Q000378:metabolism; D010949:Plasma; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D020107:Troponin T / Q000378:metabolism; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D015842:Serine Proteinase Inhibitors; D020107:Troponin T; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D007611:Aprotinin