Myocardial infarction and purine transport inhibition in anaesthetised ferrets.
The potential cytoprotective effect of the purine transport inhibitor S-(p-nitrobenzyl)-6-thioinosine (NBTI) in a model of myocardial ischaemia and reperfusion was investigated in the anaesthetised ferret. The left anterior descending coronary artery (LAD) was occluded for 90 min, producing ischaemia in 53 +/- 3% of the left ventricular free wall, followed by 240 min reperfusion. NBTI (0.5 mg kg-1, i.v.) was given prior to ischaemia or prior to reperfusion. In addition the effect of purine transport inhibition was investigated in animals subjected to ischaemia without reperfusion. NBTI reduced infarct size from 84.0 +/- 1.7 to 71.4 +/- 3.7% of the area at risk (P < 0.05) when given prior to occlusion of the LAD. NBTI was ineffective however when given 15 min prior to reperfusion. NBTI had no effect upon infarct size produced by ischaemia without reperfusion. The effect of NBTI was independent of significant changes in myocardial blood flow during ischaemia and reperfusion or upon neutrophil infiltration.
Poucher
S M
SM
Cardiovascular Department, Zeneca Pharmaceuticals, Mereside, Macclesfield, Cheshire, UK.
Brooks
R
R
Pleeth
R M
RM
Conant
A R
AR
Collis
M G
MG
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D005289:Ferrets; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013868:Thioinosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D013868:Thioinosine; D001262:Atenolol; D009195:Peroxidase; C001789:4-nitrobenzylthioinosine; D000241:Adenosine