Coronary endothelial dysfunction from ischemia and reperfusion: effect of reactive oxygen metabolite scavengers.
Using anesthetized mongrel dogs exposed to 60 min of ligation of the left anterior descending coronary artery followed by 60 min of reperfusion, we examined the effect of superoxide dismutase (SOD) and dimethylthiourea (DMTU) on evidence of endothelial injury in coronary rings studied in vitro. In 13 dogs treated with saline rings from the normal left circumflex coronary artery (LCF) relaxed by 98 +/- 4% when exposed to 10(-5) M acetylcholine whereas rings from the left anterior descending coronary artery (LAD) relaxed by 79 +/- 7% (p less than 0.05). In the same rings maximum relaxation with the ionophore A23187 was 107 +/- 5% versus 87 +/- 8% (p less than 0.05) for the LCF and the LAD, respectively. Comparisons of concentration-response curves through a range of doses of both acetylcholine and A23187 revealed significant differences for both vasodilators between the LCF and the LAD (p less than 0.01 for each). Nine dogs were treated with bovine SOD infused in the left atrium the last 20 min of ligation and throughout reperfusion (140 units/kg/min) and six other dogs were treated with DMTU 500 mg/kg i.v. given the last 30 min of the ligation period. Neither SOD nor DMTU prevented endothelial injury in the LAD. Despite pretreatment with these agents, there were significant reductions in maximum relaxation and in total concentration-response curves in the LAD as compared with the results in rings from the LCF with both acetylcholine and A23187. There were normal responses to nitroprusside in both the LCF and LAD in all three experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Horwitz
L D
LD
Division of Cardiology, University of Colorado Health Sciences Center, Denver.
VanBenthuysen
K M
KM
Sheridan
F M
FM
Lesnefsky
E J
EJ
Dauber
I M
IM
McMurtry
I F
IF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects*; D005609:Free Radicals; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D010100:Oxygen / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D005609:Free Radicals; D000001:Calcimycin; C038983:1,3-dimethylthiourea; D013482:Superoxide Dismutase; D013890:Thiourea; D000109:Acetylcholine; D010100:Oxygen