Infarct size reduction with the nucleoside transport inhibitor
r75231 in swine.
Martin, Bradley J., Robert D. Lasley, and Robert M. Mentzer.
Department of Surgery, Division of Cardiothoracic Surgery,
University of Wisconsin School of Medicine, Madison, WI 53792 USA
APStracts 3:0507H, 1996.
Adenosine (ADO) has been reported to be cardioprotective in several
models of myocardial ischemia. The nucleoside transport inhibitor
R75231 (R75) has been reported to enhance local adenosine
concentrations and postischemic recovery of function, but little is
known regarding its effects on myocardial infarct size. The purpose
of the present study was to determine the effects of R75 on infarct
size and measure myocardial regional adenosine concentrations.
Studies were conducted in pentobarbital anesthetized swine undergoing
60 min coronary artery occlusion and 2 hr reperfusion. Control pigs
(n=8) were compared to those receiving R75231 (0.1mg/kg IV) 15 min
prior to either occlusion (Pre R75, n=8) or reperfusion (Rep R75,
n=8). Interstitial fluid (ISF) ADO,coronary venous ADO, and infarct
size (% of the region at risk) were measured. In the Pre R75 group,
ISF ADO concentrations were significantly increased prior to and
during ischemia, reaching a peak value of 71.8+/-8.6 [mu]M (vs
16.8+/-0.8 [mu]M in control). ISF inosine and hypoxanthine
concentrations were significantly reduced during ischemia in Pre R75
animals. Infarct size was smaller in Pre R75 when compared to control
(21.6+/-1.9% vs 38.4+/-2.6%, p<0.05). Rep R75 resulted in
significantly elevated coronary venous ADO concentrations, but no
increases in ISF ADO or reduction in infarct size (33.5+/-3.5%).
These data indicate that R75 increases myocardial ADO and reduces
infarct size when administered prior to coronary occlusion. The R75
-induced reduction in infarct size appears to be related to the
augmentation of ISF ADO prior to ischemia, rather than increased
plasma ADO during reperfusion.
Received 10 April 1996; accepted in final form 9 October 1996.
APS Manuscript Number H315-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996