PEG-SOD and myocardial protection. Studies in the blood- and crystalloid-perfused rabbit and rat hearts.
BACKGROUND
Polyethylene glycol, covalently linked to superoxide dismutase (PEG-SOD), has a long plasma half-life (greater than 30 hours) and has been proposed as an effective agent for reducing free radical-mediated injury ischemia and reperfusion.


RESULTS
Using an isolated rabbit heart perfused with arterial blood from a support rabbit, we have demonstrated that pretreatment with PEG-SOD (30,000 units/kg, intravenous bolus, 12-24 hours before 60 minutes of normothermic global ischemia), combined with addition of PEG-SOD to the blood perfusion circuit (30,000 units/kg to the support rabbit) and inclusion of PEG-SOD (150 micrograms/ml) in a cardioplegic solution, enhanced the postischemic recovery of left ventricular developed pressure (LVDP) from 51 +/- 6 to 74 +/- 9 mm Hg (p less than 0.05; n = 9 per group). In further studies we showed that, whereas maximum protection was obtained when PEG-SOD was given as a combined pretreatment and additive to both the cardioplegic and the reperfusate solutions (postischemic LVDP recovery increased from 44 +/- 4% in the control group to 70 +/- 3% in the PEG-SOD group), the administration of PEG-SOD during pretreatment plus cardioplegia or during reperfusion alone also resulted in a significant improvement in postischemic function (62 +/- 7% and 60 +/- 3%, respectively). However, the use of PEG-SOD as a cardioplegic additive alone failed to afford protection (47 +/- 4% recovery of LVDP). In dose-response studies (with 0, 3,000, 6,000, 12,000, 30,000, or 60,000 units/kg; n = 8 per group), maximum recovery of LVDP was obtained with the administration of 12,000 units/kg of PEG-SOD. Studies of the plasma activity of PEG-SOD confirmed its long half-life and showed that the treatment with PEG-SOD either 1 hour or 12-24 hours before the study resulted in similar levels of plasma activity. In an attempt to assess any involvement of blood-borne elements in the protection afforded by PEG-SOD, studies were also carried out in the crystalloid-perfused rabbit heart, and no protection was observed. Similarly, no protection was observed at any one of a variety of doses in the crystalloid-perfused rat heart.


CONCLUSIONS
PEG-SOD can afford protection in the blood-perfused rabbit heart; this protection is dose dependent and probably involves some action of PEG-SOD on blood-borne elements, possibly leukocytes.
Galiñanes
M
M
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, UK.
Qiu
Y
Y
Ezrin
A
A
Hearse
D J
DJ
D000818:Animals; D001639:Bicarbonates; D001769:Blood; D002122:Calcium Chloride; D002314:Cardioplegic Solutions; D000077324:Crystalloid Solutions; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers; D007552:Isotonic Solutions; D008274:Magnesium; D008297:Male; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010952:Plasma Substitutes; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011189:Potassium Chloride; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology*
D001639:Bicarbonates; D002314:Cardioplegic Solutions; D000077324:Crystalloid Solutions; D016166:Free Radical Scavengers; D007552:Isotonic Solutions; D010952:Plasma Substitutes; C041711:St. Thomas' Hospital cardioplegic solution; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D011189:Potassium Chloride; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D008274:Magnesium; D002122:Calcium Chloride