Circulation, Vol 82, 1402-1412, Copyright © 1990 by American Heart Association
PS Tsao, N Aoki, DJ Lefer, G Johnson 3d and AM Lefer
Myocardial ischemia and reperfusion have been shown to impair coronary
vasorelaxation to endothelium-dependent vasodilators. To examine the time
course of this dysfunction, occlusion of the left anterior descending (LAD)
coronary artery (90 minutes) was followed by reperfusion for 0, 2.5, 5, 20,
180, or 270 minutes. Coronary arterial rings from the ischemic LAD and
control left circumflex (LCx) arteries were tested for responsiveness to
the endothelium-dependent receptor- mediated vasodilator, acetylcholine
(ACh), and the endothelium- dependent nonreceptor-mediated vasodilator,
A23187, as well as the endothelium-independent vasodilator, NaNO2. ACh
relaxation was not impaired after 90 minutes of ischemia without
reperfusion. However, 2.5 minutes of reperfusion resulted in depressed ACh
responses (36 +/- 10% of control) that was further reduced to 16 +/- 6% at
20 minutes, and remained comparably depressed at every time thereafter.
A23187 vasodilator responses were also attenuated after reperfusion,
although the reduced response occurred later (that is, at 20 minutes).
There was no significant decrease in response to NaNO2 in the LAD at any
time or to any vasodilator in LCx control rings. Treatment with recombinant
human superoxide dismutase (hSOD, 5 mg/kg/hr, that is, 15,545 SOD
units/kg/hr), starting 10 minutes before reperfusion, preserved the
vasodilator response to ACh (82 +/- 6%) and A23187, but treatment with the
hydroxyl ion scavenger N-(2-mercapto proprionyl)-glycine (MPG) (8 mg/kg/hr)
only protected the A23187 response. No damage to the surface of the
endothelium was observed by scanning electron microscopy at any time point.
Myocardial cell damage increased with time of reperfusion as assessed by
increasing plasma CK activities and amounts of necrotic tissue indexed to
area at risk. Significant myocardial injury occurred at 3 hours after
reperfusion. These findings suggest that endothelial dysfunction resulting
in reduced endothelium-derived relaxing factor release occurs before the
development of myocardial cell necrosis and may be due to oxygen-derived
free radicals produced rapidly on reperfusion.
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Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
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