Lee R B, Stewart J R, Merrill W H, Frist W H, Hammon J W, Bender H W
Department of Cardiac and Thoracic Surgery, Vanderbilt University, Nashville, TN 37232.
Circulation. 1989 Nov;80(5 Pt 2):III25-9.
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.
在实验性犬全身体温过低性心肌缺血模型中，我们评估了在再灌注前给予重组人超氧化物歧化酶（rHSOD）后的血浆清除情况。成年杂种犬接受体外循环，将核心体温降至25摄氏度。使用间歇性晶体心脏停搏液维持体温过低性全心肌缺血90分钟。在再灌注前5分钟，通过泵氧合器推注给予rHSOD。在注射后0、3、5、10、20、30、60和120分钟测量血浆rHSOD水平。动物复温并脱离体外循环。三个实验组分别接受4、8或16mg/kg的rHSOD。根据先前报道的剂量反应数据，我们得出结论，16mg/kg的rHSOD可达到理想的血清峰值浓度。在体温过低性体外循环和全心肌缺血的情况下，由于血清半衰期延长，在再灌注前单次推注给予rHSOD是一种有效的方法。
