Circulation, Vol 82, 595-608, Copyright © 1990 by American Heart Association
JW Homeister, PT Hoff, DD Fletcher and BR Lucchesi
The endogenous compound adenosine may play a role in limiting myocardial
ischemia-reperfusion injury through its ability to cause vasodilation,
modulate cardiac adrenergic responses, inhibit neutrophil function, or
modulate energy supply and demand of the myocardium. The local anesthetic
lidocaine has been shown to be protective against myocardial
ischemia-reperfusion injury, although its mechanism of action remains
unresolved. We hypothesized that administration of exogenous adenosine
during reperfusion would limit the size of the infarct that results from a
period of ischemia and reperfusion only when the animals are treated with
lidocaine. Male, mongrel dogs (13.0- 20.0 kg) were anesthetized (30 mg/kg
i.v. sodium pentobarbital), and a left thoracotomy was performed. The left
circumflex coronary artery (LCx) was isolated and instrumented with an
electromagnetic flow probe, a 25-gauge nonobstructing intracoronary
catheter, and a critical stenosis. The dogs were allocated randomly to one
of four groups: 1) control, n = 13, (saline), 2) adenosine, n = 13, (0.15
mg/kg/ml/min i.c. for the first hour of reperfusion), 3) lidocaine, n = 9,
(2.0 mg/kg i.v. given immediately before coronary artery occlusion and just
before reperfusion), or 4) adenosine plus lidocaine, n = 11. The LCx was
occluded for 90 minutes and reperfused for 6 hours. Regional myocardial
blood flow (RMBF) was determined (n = 6 per group) at 80 minutes of
occlusion and at 45 minutes of reperfusion with radiolabeled microspheres.
RMBF determinations revealed an increase in blood flow to the inner two
thirds of the myocardium at 45 minutes of reperfusion only in the presence
of the combined treatment. Adenosine treatment alone or lidocaine treatment
alone did not affect RMBF. Quantification of infarct size
(triphenyltetrazolium method) expressed as a percent of the area at risk
revealed a significant limitation of infarct size only in the group treated
with both adenosine and lidocaine: control, 47.8 +/- 6.6%; adenosine, 45.0
+/- 3.2%; lidocaine, 46.9 +/- 6.0%; and adenosine and lidocaine, 20.8 +/-
5.6%. Statistical analyses were performed with two-way analysis of variance
to account for the two individual drug treatments. The findings show that
intracoronary administration of exogenous adenosine, at the dose used, is
only effective at limiting myocardial infarct size when administered to
lidocaine-treated animals.
ARTICLES
Combined adenosine and lidocaine administration limits myocardial reperfusion injury
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
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