Pharmacokinetics of superoxide dismutase during hypothermic cardiopulmonary bypass.
We evaluated the plasma elimination of recombinant human superoxide dismutase (rHSOD) when given before reperfusion in an experimental canine model of global hypothermic myocardial ischemia. Adult mongrel dogs were placed on cardiopulmonary bypass, and core temperature was reduced to 25 degrees C. Hypothermic global myocardial ischemia was maintained for 90 minutes with intermittent crystalloid cardioplegic solution. Five minutes before reperfusion, rHSOD was administered via the pump oxygenator as a bolus injection. Plasma rHSOD levels were measured at 0, 3, 5, 10, 20, 30, 60, and 120 minutes after injection. Animals were rewarmed and weaned from bypass. Three experimental groups received either 4, 8, or 16 mg/kg rHSOD. Based on previously reported dose-response data, we conclude that desirable peak serum concentrations are achieved with 16 mg/kg rHSOD. In the setting of hypothermic cardiopulmonary bypass and global myocardial ischemia, single bolus administration of rHSOD before reperfusion is an effective method due to the prolonged serum half-life.
Lee
R B
RB
Department of Cardiac and Thoracic Surgery, Vanderbilt University, Nashville, TN 37232.
Stewart
J R
JR
Merrill
W H
WH
Frist
W H
WH
Hammon
J W
JW
Bender
H W
HW
D000818:Animals; D002315:Cardiopulmonary Bypass; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors
D005609:Free Radicals; D011994:Recombinant Proteins; D013482:Superoxide Dismutase