Nitecapone inhibits myeloperoxidase in vitro and enhances functional performance after 8 h of ischemia in experimental heart transplantation.
Nitecapone (NC) has been shown to have beneficial effects on the functional recovery of rat hearts in Langendorff-preparation. The present study was executed to evaluate the effect of NC on preservation of grafts in heart transplantation and the role of NC in the inhibition of granulocyte infiltration. Donor hearts were perfused and stored at +4 degrees C for 8 h in either Ringer solution in the control-group (C-group, n = 26) or in NC (50 microM) added Ringer solution (NC-group, n = 18). The heterotopic heart transplantation was performed. The rats in both groups were killed at either 10 min or 60 min after release of the aortic clamp and tissue samples were obtained for antioxidative capacity, myeloperoxidase activity, and lipid peroxidation measurements. In vitro studies were performed using sodium azide or nitecapone to inhibit myeloperoxidase (MPO) activity of isolated human leukocytes. A total of 61% of the grafts began to beat in the NC-group, compared to 46% in the control group. Using an arbitrary scale of functional performance, only 33% (4/12) of the grafts were classified as well functioning in the control group, compared to 82% (9/11) in the NC-group (P<0.05). MPO activity was equal in both groups after 10 min but significantly lower after 60 min in the NC-group as compared to the control group (P<0.05). In vitro studies demonstrated that NC inhibits 50% of purified MPO activity at a concentration of 10 microM. NC did not significantly affect lipid peroxidation or the preservation of endogenous antioxidants. Since NC inhibited myeloperoxidase both in vitro and in vivo, it seems that the positive effects of NC on graft preservation may be mediated via the inhibition of granulocyte infiltration.
Vento
A E
AE
Department of Thoracic and Cardiovascular Surgery, Helsinki University Central Hospital, Finland.
Rämö
O J
OJ
Nemlander
A T
AT
Ahotupa
M
M
Nissinen
E
E
Holopainen
A
A
Mattila
S P
SP
D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology; D010422:Pentanones / Q000494:pharmacology*; D009195:Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002396:Catechols; D004791:Enzyme Inhibitors; D010422:Pentanones; C057364:nitecapone; D009195:Peroxidase; D005978:Glutathione