Dimethylthiourea, but not dimethylsulfoxide, reduces canine myocardial infarct size.
We studied the effect of treatment with two diffusible, low molecular weight scavengers of toxic oxygen metabolites, dimethylthiourea (DMTU) and dimethylsulfoxide (DMSO), on canine infarcts caused by 90 min of ischemia and 3 h of reperfusion. Infarct size was determined by incubating ventricular slices with triphenyl tetrazolium chloride. Areas at risk were determined by autoradiography of 99Tc microspheres injected in vivo during ischemia and were similar (p greater than 0.05) in DMTU, DMSO, and saline treated dogs. However, the ratio of infarct size to area at risk was reduced (p less than 0.05) in dogs treated 30 min before reperfusion with 500 mg/kg DMTU (31.1 +/- 4.6%, n = 9) compared with saline treated dogs (53.4 +/- 4.6% n = 9). In contrast, the ratio of infarct size to area at risk was not significantly different (p greater than 0.05) in dogs treated with 2000 mg/kg DMSO 30 min before reperfusion (43.7 +/- 4.3%) compared to saline treated dogs. The serum concentration of DMTU (4.5 mM) was one-tenth that of DMSO (48 mM) in early reperfusion. Therefore, DMTU but not DMSO protected against post-ischemic cardiac reperfusion injury.
Portz
S J
SJ
Division of Cardiology, University of Colorado, Denver.
Lesnefsky
E J
EJ
VanBenthuysen
K M
KM
Repine
J E
JE
Parker
N B
NB
McMurtry
I F
IF
Horwitz
L D
LD
D000818:Animals; D001784:Blood Gas Analysis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004285:Dogs; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D008863:Microspheres; D009203:Myocardial Infarction / Q000503:physiopathology*; D009994:Osmolar Concentration; D015427:Reperfusion Injury / Q000503:physiopathology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
C038983:1,3-dimethylthiourea; D013890:Thiourea; D004121:Dimethyl Sulfoxide