Inability of dimethylthiourea to limit tissue necrosis during acute myocardial infarction in rabbits.
This study examined the effect of treatment with dimethylthiourea (DMTU), a highly cell-permeable scavenger of hydroxyl radicals, on tissue necrosis in rabbit hearts during myocardial ischemia and reperfusion. Sixty-two rabbits underwent 45 minutes of coronary occlusion with, or without, coronary reperfusion for 3 hours. A saline vehicle, or DMTU (500 mg/kg intravenously [iv]) was administered over 45 minutes starting either 10 minutes before or 10 minutes after coronary occlusion, or 10 minutes before coronary reperfusion. Anatomic risk zone size was assessed using microsphere autoradiography, and the area of necrosis was determined using tetrazolium staining. Cardiac hemodynamics and risk zone size were similar for all treatment groups. No differences were observed in the extent of tissue necrosis (normalized to risk zone size) for saline- and DMTU-treated rabbits subjected to 45 minutes (61.2 +/- 23.1% vs. 70.6 +/- 16.5%) or 225 minutes (82.8 +/- 5.4% vs. 78.3 +/- 5.9%) of permanent coronary occlusion without reperfusion. Similarly, tissue necrosis in rabbits with 45 minutes coronary occlusion followed by 3 hours reperfusion was not significantly reduced when DMTU was administered either 10 minutes before coronary occlusion, 10 minutes after coronary occlusion, or 10 minutes before coronary reperfusion (67.0 +/- 9.9%; 57.6 +/- 10.6%; 68.3 +/- 13.3%) compared to saline-treated controls (76.6 +/- 10.5%). These results demonstrate that the hydroxyl radical scavenger DMTU does not appear to influence the progression of myocyte injury in this experimental model of acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Kingma
J G
JG
Department of Medicine, Faculty of Medicine, Laval University, Quebec, Canada.
Yellon
D M
DM
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D011817:Rabbits; D013890:Thiourea / Q000031:analogs & derivatives* / Q000627:therapeutic use
C038983:1,3-dimethylthiourea; D013890:Thiourea