[Effect of recombinant human superoxide dismutase (r-h-SOD) on reperfusion-induced irreversible arrhythmia in anesthetized rats].
Using anesthetized rats, we performed a dose-response study of the ability of r-h-SOD to reduce the mortality caused by reperfusion-induced irreversible arrhythmia. The hearts were subjected to regional ischemia by the occlusion of the left coronary artery for 4 min followed by reperfusion for 7 min. First, the relation between the anti-arrhythmic effect of r-h-SOD and the size of the ischemic zone was examined. The protective effect of r-h-SOD was easily detected in rats with an ischemic zone size of 40-55% of the total heart weight, but not in rats with other zone sizes. Intravenous infusion of r-h-SOD at rates of 430 to 130,000 U/kg/min beginning 1 min after regional ischemia significantly reduced the mortality after reperfusion. R-h-SOD at the doses used did not affect the blood pressure, heart rate or arrhythmia during the ischemic period. R-h-SOD at rates of 130 to 130,000 U/kg/min was intravenously infused into anesthetized rats, and its plasma level was measured at 3 min after the beginning of the infusion. The plasma level of r-h-SOD increased dose-dependently (8.5 to 6,600 U/ml). In conclusion, r-h-SOD reduced mortality after reperfusion over a wide range of doses and its effective plasma level was estimated to be 28 to 6,600 U/ml in this model.
Ohoi
I
I
Pharmacology Section, Research Laboratories, Nippon Kayaku Co., Ltd, Tokyo, Japan.
Ozawa
N
N
Nakamura
K
K
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology*
D011994:Recombinant Proteins; D013482:Superoxide Dismutase