title: Cardiac contractile function following repetitive brief ischemia: effects of nucleoside transport inhibition.
abstract: The effects of nucleoside transport inhibition on cardiac contractile function were examined in anesthetized pigs subjected to five 6-min left anterior descending coronary artery (LAD) occlusions, separated by 20-min reperfusion, and followed by 150-min reperfusion. In group 1 (n = 8), saline was infused. In group 2 (n = 9), endogenous myocardial accumulation of adenosine was increased by intracoronary infusion of the specific nucleoside transport inhibitor R-75 231. Left ventricular segment lengths were recorded by ultrasonic crystals in the inner one-third of the myocardium. Percent systolic segment length shortening (SS) (normalized to percent of preischemic value) was significantly better maintained in the R-75 231 group compared with the saline group after each occlusion. SS in the saline group reached a nadir of 30% (22-40) at 30-min reperfusion after the last occlusion compared with 66% (54-73) in the R-75 231 group. In the R-75 231 group, but not in the saline group, maximal postischemic decline in SS and decline at 20-min reperfusion were significantly reduced following the last occlusion. We conclude that R-75 231, which inhibits nucleoside transport, attenuates contractile dysfunction following repetitive brief ischemia and results in a preconditioning-like effect against stunning in the pig. On the basis of the well-documented biochemical effects of R-75 231, increased accumulation of endogenous adenosine most likely explains these findings.
authors.affiliation: University of Oslo, Institute for Experimental Medical Research, Ullevål Hospital, Norway.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirkebøen
authors.forename: A
authors.initials: A
authors.lastname: Ilebekk
authors.forename: T
authors.initials: T
authors.lastname: Tønnessen
authors.forename: E
authors.initials: E
authors.lastname: Leistad
authors.forename: P A
authors.initials: PA
authors.lastname: Naess
authors.forename: G
authors.initials: G
authors.lastname: Christensen
authors.forename: G
authors.initials: G
authors.lastname: Aksnes
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000503:physiopathology*; D017682:Myocardial Stunning; D009705:Nucleosides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D013552:Swine; D013599:Systole
chemical_list: D009705:Nucleosides; D010879:Piperazines; C072040:draflazine