M. Hori et al., AICA RIBOSIDE IMPROVES MYOCARDIAL-ISCHEMIA IN CORONARY MICROEMBOLIZATION IN DOGS, American journal of physiology. Heart and circulatory physiology, 36(4), 1994, pp. 80001483-80001495
This study was undertaken to examine whether 5-amino-4-imidazolecarbox
amide (AICA) riboside (acadesine), which augments adenosine release in
ischemic myocardium, further attenuates ischemic injury after acute c
oronary microembolization. The left anterior descending corollary arte
ry was cannulated and perfused with blood from the left carotid artery
in 46 dogs, and coronary blood flow (CBF) of the perfused area was me
asured. In 12 dogs, 15-mu m microspheres (5.0 x 10(4)/ml) were injecte
d repeatedly until CBF approached zero. Changes in CBF, fractional sho
rtening, lactate extraction ratio. and adenosine release were measured
with and without administration of AICA riboside. In the control grou
p (n = 7), CBF increased to 154 +/- 11 ml.100 g(-1).min(-1) at 16-30%
of total coronary embolization, and adenosine release was 6.1 +/- 1.0
nmol.100 g(-1).min(-1). Administration of AICA riboside (n = 5) enhanc
ed coronary hyperemia (187 +/- 8 ml.100 g(-1).min(-1), P < 0.05), aden
osine release (11.9 +/- 0.9 nmol.100 g(-1).min(-1), P < 0.001), and my
ocardial adenosine content (0.434 +/- 0.069 vs. 0.118 +/- 0.019 nmol/m
g wet wt, P < 0.01) and attenuated decreases in fractional shortening
and lactate extraction ratio. AICA riboside preserved myocardial tissu
e ATP content of the embolized area. The administrations of 8-phenylth
eophylline (n = 12) and alpha,beta-methyleneadenosine 5'-diphosphate (
n = 10) abolished the beneficial effects of AICA riboside. Furthermore
, AICA riboside increased ectosolic and cytosolic 5'-nucleotidase acti
vity of the embolized myocardium (n = 12). Thus we conclude that AICA
riboside attenuates contractile and metabolic dysfunction by enhancing
adenosine release via activation of ectosolic 5'-nucleotidase and ind
ucing local hyperemia in acute coronary microembolization.