Reactive oxygen metabolite scavengers decrease functional coronary microvascular injury due to ischemia-reperfusion.
The role of reactive oxygen metabolites in ischemia-reperfusion coronary microvascular injury is unclear. To investigate this problem, we tested the effects of the reactive oxygen metabolite scavengers superoxide dismutase (SOD) and dimethylthiourea (DMTU) on ischemia-reperfusion-induced coronary microvascular dysfunction. As an index of vascular function, we assessed microvascular permeability with a double radioisotope protein leak index (PLI) method. Anesthetized dogs underwent 60 min of ischemia via left anterior descending (LAD) occlusion followed by 60 min of reperfusion. Untreated animals (n = 7) received saline. SOD-treated animals (n = 6) received 140 U.kg-1.min-1 (6.6 mg.kg-1.min-1) bovine SOD throughout ischemia and reperfusion. DMTU-treated animals (n = 5) received a 500 mg/kg bolus 30 min before ischemia. At the beginning of reperfusion, radiolabeled autologous protein (113mIn transferrin) and red blood cells (99mTc) were given intravenously for the assessment of permeability. In untreated dogs, ischemia-reperfusion increased the PLI of ischemic (flow less than 20 ml.min-1.100 g-1) myocardium more than threefold compared with that of nonischemic (flow greater than 100 ml.min-1.100 g-1) myocardium (ischemic-to-nonischemic PLI ratio = 3.49 +/- 0.48). SOD reduced the PLI of ischemic myocardium by 45% and DMTU reduced it by 66% (PLI = 9.25 +/- 1.30, 5.04 +/- 1.18, and 3.16 +/- 0.94, untreated, SOD, and DMTU, respectively). The PLI was increased proportional to the regional severity of ischemic blood flow. Both SOD and DMTU reduced the increase in protein leak at all levels of regional ischemic blood flow. Neither SOD nor DMTU increased regional myocardial blood flow to the occluded LAD zone.(ABSTRACT TRUNCATED AT 250 WORDS)
Dauber
I M
IM
Division of Cardiology, Veterans Administration Medical Center, Denver 80220.
Lesnefsky
E J
EJ
VanBenthuysen
K M
KM
Weil
J V
JV
Horwitz
L D
LD
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008833:Microcirculation; D010100:Oxygen / Q000378:metabolism*; D011506:Proteins / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D016166:Free Radical Scavengers; D011506:Proteins; C038983:1,3-dimethylthiourea; D013482:Superoxide Dismutase; D013890:Thiourea; D010100:Oxygen