Circulation, Vol 83, 237-247, Copyright © 1991 by American Heart Association
CJ Pitarys 2d, R Virmani, HD Vildibill Jr, EK Jackson and MB Forman
Adenosine influences the function of several cell types thought to be
involved in the pathogenesis of myocardial reperfusion injury. We have
previously demonstrated that intracoronary administration of adenosine
enhances myocardial salvage 24 hours after reperfusion. To determine if
these beneficial effects could be obtained during a prolonged period of
reperfusion using an intravenous route of administration, 22 closed- chest
dogs were subjected to 90 minutes of proximal left anterior descending
coronary artery occlusion and 72 hours of reperfusion. Animals randomly
received either intravenous adenosine (0.15 mg/kg/min) or an equal volume
of Ringer's lactate during the first 150 minutes of reperfusion. The area
at risk was defined in vivo with Monastral blue, and infarct size was
measured histologically with Mallory's trichrome stain. Serial global and
regional ventricular function were determined with contrast
ventriculography and analyzed using a computerized radial shortening
method. Biopsies were obtained from the central ischemic zone to assess
endothelial ultrastructure and capillary obstruction. No significant
effects in heart rate or blood pressure were noted during adenosine
infusion. Transmural collateral blood flow during ischemia was similar in
the groups. Infarct size expressed as a percentage of the anatomical area
at risk was significantly less in the adenosine- treated group (35.3 +/-
4.3% in controls versus 17.1 +/- 4.3% in treated animals, p less than
0.01). A progressive decrease in transmural blood flow was noted in control
animals during reperfusion, resulting in a significant reduction at 3 hours
compared with the preocclusion value (0.69 +/- 0.11 ml/min/g [at baseline
versus 0.45 +/- 0.10 ml/min/g at 3 hours, p less than 0.05]). In contrast,
flow in adenosine animals at 3 hours was similar to baseline values (0.91
+/- 0.15 ml/min/g at baseline versus 0.98 +/- 0.14 ml/min/g at 3 hours, p =
NS) and was significantly higher (p less than 0.05) than the control group.
Radial shortening in the ischemic zone was significantly improved at 3
(-2.6 +/- 2.8% in controls versus 11.6 +/- 3.3% in treated animals, p less
than 0.01) and 72 hours (5.5 +/- 2.0% in controls versus 17.3 +/- 3.5% in
treated animals, p less than 0.01) after reperfusion in treated animals.
Electron microscopy showed reduced neutrophil and erythrocyte plugging of
capillaries with relative preservation of endothelial cell structure in the
adenosine group.(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Reduction of myocardial reperfusion injury by intravenous adenosine administered during the early reperfusion period
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tenn.
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