title: Myocardial protection in beating heart cardiac surgery: I: pre- or postconditioning with inhibition of es-ENT1 nucleoside transporter and adenosine deaminase attenuates post-MI reperfusion-mediated ventricular fibrillation and regional contractile dysfunction.
abstract: OBJECTIVE
  To determine the role of the p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 (es-ENT1) in postmyocardial infarction reperfusion injury-mediated ventricular fibrillation and regional dysfunction. We used erythro-9 (2-hydroxy-3-nonyl)-adenine and p-nitrobenzylthioinosine to inhibit both adenosine deamination and transport in a canine model of off pump acute myocardial infarction.
  
  
  METHODS
  Anesthetized adult dogs (n = 37), instrumented to monitor the percentage of systolic segmental shortening and wall thickening using sonomicrometry, underwent 90 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Myocardial coronary blood flow, adenosine triphosphate pool, infarct size, and the incident of ventricular fibrillation and cardioversion were also measured. The dogs received an intravenous infusion of the vehicle (control) or 100 μM of erythro-9 (2-hydroxy-3-nonyl)-adenine and 25 μM p-nitrobenzylthioinosine before ischemia (preconditioning group) or just before reperfusion (postconditioning group).
  
  
  RESULTS
  In the control group, adenosine triphosphate depletion was associated with the accumulation of more inosine than adenosine during ischemia and washed out during reperfusion. Myocardial adenosine and inosine were the major nucleosides in the pre- and postconditioning groups during ischemia and remained detectable during reperfusion. In both groups, recovery of systolic segmental shortening and wall thickening and a reduction in the incidence of ventricular fibrillation (P < .05 vs the control group) coincided with retention of myocardial nucleosides. The infarct size in the 3 groups was not significantly different, independent of myocardial blood flow during ischemia.
  
  
  CONCLUSIONS
  Preconditioning or postconditioning with erythro-9 (2-hydroxy-3-nonyl)-adenine/p-nitrobenzylthioinosine significantly reduced the incidence of ventricular fibrillation and cardioversion and attenuated regional contractile dysfunction mediated by postmyocardial infarction reperfusion injury. It is concluded that p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 played a major role in these events.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0068, USA. aabdelfattah@mcvh-vcu.edu
authors.forename: Anwar Saad
authors.initials: AS
authors.lastname: Abd-Elfattah
authors.forename: Hamdy
authors.initials: H
authors.lastname: Aly
authors.forename: Scott
authors.initials: S
authors.lastname: Hanan
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Wechsler
mesh_terms: D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D033721:Equilibrative Nucleoside Transporter 1 / Q000494:pharmacology*; D019194:Ischemic Preconditioning / Q000379:methods*; D016018:Least-Squares Analysis; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D058892:Adenosine Deaminase Inhibitors; D033721:Equilibrative Nucleoside Transporter 1; D013868:Thioinosine; D000255:Adenosine Triphosphate; C001789:4-nitrobenzylthioinosine