Myocardial protection of MCI-186 in rabbit ischemia-reperfusion.
We observed that 3-methyl-1-1phenyl-2-pyrazolin-5-one (MCI-186), a newly-developed free radical scavenger, attenuated necrosis in the in vivo rabbit hearts upon reperfusion after prolonged ischemia. In rabbits undergoing 1 hour ligation of the anterior ventricular coronary artery, a single bolus injection of MCI-186 (1.5 mg/kg) was introduced into the post-ischemic heart immediately before 4 hour reperfusion. Compared to negligible necrosis in sham-operated control animals and 33.81 +/- 13.50% necrosis in the area at risk for the saline control group (n = 8), the MCI-186 - treated group (n = 8) had a necrosis of 13.27 +/- 4.60% (p < 0.05 vs saline control group). The pressure-rate index had a slight decrease in MCI-186 treated group compared to the control group (p > 0.05). However, the blood levels of malondialdehyde (MDA) in MCI-186 treated group (2.08 +/- 0.23 microM) was significantly smaller than that of 2.65 +/- 0.31 microM in control animals (p < 0.01), while sham control had an average MDA level of 1.91 +/- 0.40 microM, with p > 0.05 relative to that in the MCI-186 treated group. These data support our contention that MCI-186 reduces reperfusion injury in perfused hearts with prolonged ischemia and the mechanism for the in vivo efficacy of MCI-186 is predominantly related to its antioxidant activities.
Wu
Tai-Wing
TW
Department of Clinical Biochemistry, University of Toronto and Center for Cardiovascular Research, The Toronto Hospital, Western Division, Canada. taiwu@hotmail.com
Zeng
Ling-Hua
LH
Wu
Jun
J
Fung
Kwok-Pui
KP
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D001794:Blood Pressure; D004195:Disease Models, Animal; D000077553:Edaravone; D004562:Electrocardiography; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008315:Malondialdehyde / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D011817:Rabbits
D016166:Free Radical Scavengers; D008315:Malondialdehyde; D000077553:Edaravone; D000983:Antipyrine