Oxygenated perfluorocarbon, recombinant human superoxide dismutase, and catalase ameliorate free radical induced myocardial injury during heart preservation and transplantation.
The effect of free radical scavengers on free radical-induced myocardial injury during heart preservation and transplantation was examined. Four groups of nine hearts each were harvested from mongrel dogs (12.5 to 16.5 kg) and orthotopically transplanted to size-matched recipients. All hearts received a continuous perfusion of oxygenated modified Collins' solution (group A). In addition, groups B, C, and D received Fluosol DA and albumin. Preservation perfusion was performed for 18 hours, at 4 degrees C, pH = 7.4, and 20 mm Hg. In group C, recombinant human superoxide dismutase (4,080 U/mg, 20 mg/kg) and bovine catalase (46,200 U/mg, 20 mg/kg) were administered only during preservation perfusion. In group D, these scavengers were administered just before and during reperfusion for 1 hour. Hemodynamic studies were performed before excision of the donor hearts and 1 hour after the termination of cardiopulmonary bypass. Creatinine kinase MB isoenzyme and thiobarbituric acid reactive substance levels in the coronary effluent were determined during preservation perfusion and reperfusion. Only group A showed a significant heart weight gain (p less than 0.05) and a decline in passive compliance (p less than 0.05) during preservation. Lactate release was higher in group A than in the groups receiving Fluosol DA. In contrast, pyruvate levels in group A were lower than in other groups. The generation of free radicals stayed at a low level during preservation, but significantly increased during reperfusion and was associated with a corresponding increase in creatinine kinase MB isoenzyme. Perfusion with a perfluorochemical solution (group B) inhibited the sharp rise in levels of thiobarbituric acid reactive substances and of creatinine kinase MB isoenzyme and improved cardiac function during reperfusion (versus group A). Exogeneous free radical scavengers administered just before and during reperfusion (group D) significantly ameliorated thiobarbituric acid reactive substances and creatinine kinase MB isoenzyme levels and also induced a significant hemodynamic improvement during reperfusion. However, administration of scavengers during preservation did not. This study demonstrates that the generation of free radicals is primarily significant during reperfusion and reoxygenation after ischemia. Thus the best time for administration of scavengers is just before and just after the onset of reperfusion. Furthermore, perfusion with perfluorochemicals effectively maintains aerobic metabolism and ameliorates free radical damage during this period.
Bando
K
K
Department of Surgery II, Okayama University Medical School, Japan.
Teramoto
S
S
Tago
M
M
Seno
S
S
Murakami
T
T
Nawa
S
S
Senoo
Y
Y
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D005466:Fluorocarbons / Q000494:pharmacology*; D005609:Free Radicals; D016027:Heart Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000473:pathology / Q000628:therapy; D007527:Isoenzymes; D007773:Lactates / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009926:Organ Preservation; D009929:Organ Size; D011773:Pyruvates / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013858:Thiobarbiturates
D005466:Fluorocarbons; D005609:Free Radicals; D007527:Isoenzymes; D007773:Lactates; D011773:Pyruvates; D011994:Recombinant Proteins; D013858:Thiobarbiturates; D002374:Catalase; D013482:Superoxide Dismutase; D003402:Creatine Kinase