Circulation, Vol 86, 986-994, Copyright © 1992 by American Heart Association
CF Toombs, S McGee, WE Johnston and J Vinten-Johansen
BACKGROUND. We hypothesized that 1) endogenous adenosine released during
ischemia conferred an inherent cardioprotection, and 2) a pretreatment dose
of adenosine before ischemia would provide additional protection
independent of hemodynamic effects. METHODS AND RESULTS. Thirty-six
anesthetized New Zealand White rabbits underwent 30 minutes of regional
ischemia produced by coronary occlusion followed by 2 hours of reperfusion.
The adenosine group (ADO, n = 9) received a 5-minute pretreatment infusion
of 140 micrograms/kg/min of adenosine before ischemia. A control group
(SAL, n = 9) received saline before ischemia. To separate the effects of
adenosine used as a pretreatment versus the effects during ischemia, a
third group (ADO+SPT, n = 9) received adenosine as pretreatment followed by
10 mg/kg 8-p-sulfophenyl theophylline (8-SPT), an A1/A2-receptor antagonist
given before ischemia, thus allowing pretreatment with adenosine but
antagonizing its effects during ischemia. To preclude any protection from
endogenous adenosine released during ischemia, the fourth group (SAL+SPT, n
= 9) received saline as pretreatment and 8-SPT before ischemia. Area of
necrosis within the area at risk (infarct size) was determined with
tetrazolium and Evans blue stains, and transmural blood flow was measured
using radioactive microspheres. Collateral blood flow in the area at risk
was similar in all groups, as was the size of the area at risk. Infarct
size was reduced by adenosine pretreatment (ADO, 8.4 +/- 7.2%) in contrast
to saline vehicle (SAL, 27.8 +/- 6.3%; p less than 0.05 versus ADO). alpha
1/alpha 2-Receptor blockade after adenosine pretreatment abolished the
ischemic protection provided by pretreatment adenosine (ADO+SPT, 42.7 +/-
8.3%; p less than 0.05 versus ADO). Finally, receptor blockade of
endogenously released adenosine without adenosine pretreatment increased
infarct size by 24% over the nonpretreated saline group (SAL+SPT, 51.5 +/-
9.0%; p less than 0.05 versus SAL). CONCLUSIONS. We conclude that 1)
endogenous adenosine building up during ischemia is cardioprotective, and
2) pretreatment with adenosine confers cardioprotection independent of
hemodynamic effects. Whether pretreatment effects of adenosine subsequently
modulate the effects of endogenous adenosine (through alterations in
receptor population or sensitivity) or endogenous and exogenous adenosine
represent additive compartments is unclear.
ARTICLES
Myocardial protective effects of adenosine. Infarct size reduction with pretreatment and continued receptor stimulation during ischemia
Department of Cardiothoracic Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1096.
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