Cardiac contractile function following repetitive brief ischemia: effects of nucleoside transport inhibition.
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.
Kirkebøen
K A
KA
University of Oslo, Institute for Experimental Medical Research, Ullevål Hospital, Norway.
Ilebekk
A
A
Tønnessen
T
T
Leistad
E
E
Naess
P A
PA
Christensen
G
G
Aksnes
G
G
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
D009705:Nucleosides; D010879:Piperazines; C072040:draflazine