title: Role of nucleoside transport and purine release in a rabbit model of myocardial stunning.
abstract: Previously, we have demonstrated the role of nucleoside transport and purine release in post-ischemic reperfusion injury (myocardial stunning) in several canine models of ischemia. Since rabbits are deficient of xanthine oxidase, it is not known whether selective blockade of purine release is beneficial in a rabbit model of coronary artery occlusion and reperfusion (stunning). Therefore, we determined the hemodynamic and metabolic correlates in response to myocardial stunning in the presence or absence of selective nucleoside transport blocker (p-nitrobenzylthioinosine, NBMPR) and adenosine deaminase inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine, EHNA). Sixty adult anaesthetized rabbits were surgically prepared for hemodynamic measurements. After stabilization period, the left anterior descending coronary artery was occluded for 15 min and reperfused for 30 min. Transmural myocardial biopsies were obtained from the ischemic LAD area and from the non-ischemic posterior (circumflex, CFX) segment of the myocardium. Rabbits (n = 60) were randomly assigned to either the control or the EHNA/NBMPR-treated group (n = 30 each). Each group was further divided to either functional or metabolic groups (n = 15 each subgroup). Each animal received intravenously 30 ml of either a vehicle solution or 100 M EHNA and 25 M NBMPR 10 min before ischemia. Although administration of EHNA/NBMPR did not affect the heart rate, it did cause mild hypotension (about 20-30%). Fifteen minutes of LAD occlusion resulted in significant ATP depletion and concomitant accumulation of nucleosides in both groups (p < 0.05 vs. baseline and non-ischemic CFX segment). AMP was higher in the LAD compared to the CFX segment. Significant accumulation of adenosine was observed in the treated group compared to the control group. It is concluded that EHNA/NBMPR induced site specific entrapment of adenosine of nucleoside transport in the rabbit heart, in vivo.
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0532, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Abd-Elfattah
authors.forename: R P
authors.initials: RP
authors.lastname: Maddox
authors.forename: M E
authors.initials: ME
authors.lastname: Jessen
authors.forename: I M
authors.initials: IM
authors.lastname: Rebeyka
authors.forename: A S
authors.initials: AS
authors.lastname: Wechsler
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D033703:Nucleoside Transport Proteins; D011687:Purines / Q000378:metabolism*; D011817:Rabbits; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000227:Adenine Nucleotides; D058892:Adenosine Deaminase Inhibitors; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D011687:Purines; D013868:Thioinosine; C010192:9-(2-hydroxy-3-nonyl)adenine; C001789:4-nitrobenzylthioinosine; D000225:Adenine