Elevated serum uric acid reduce heart damage in patients undergoing open-heart surgery

Abstract

Objectives: Peroxynitrite is species claimed to propagate ischemia/reperfusion damage. In this report levels of serum uric acid (UA), a peroxynitrite scavenger, are compared with creatine phosphokinase (CPK) in male patients before and after open-heart surgery in order to asses if increased levels of UA may protect heart from biochemical damage induced by peroxynitrite during the coronary by-pass grafting (CABG) intervention. Methods: 45 male patients (16 carvedilol pretreated (6.25 mg/ daily, during 6 weeks before surgery, mean age 55.3±1.7 years, range 50-71) and 29 patients without carvedilol pretreatment (mean age 58.3±1.4 years, range 47-73) underwent elective CABG were examined. Study inclusion criteria were CABG performed on two and more coronary-vessels with aortic crossclamp during 30-40 minutes. For assessment of patients objective health status before operations Euro- SCORE were used. Serum uric acid (UA) levels and creatine phosphokinase (CPK) were measured spectrophotometricaly by using a quantitative enzymatic assay. Results: Carvedilol pretreated patients had higher amount of serum UA (p<0.05) comparing to non-treated patients. During the surgical procedure patients are subjected to temporary ischemia due to transfer from corporeal to extracorporeal circulation. In this period of time the amount of UA decreased in carvedilol pretreated group (406±46 (t1) vs. 300±22 mmol/L (t2)) to the level of non-treated patients (328±14 (t1) vs. 322±18 mmol/L. Carvedilol pretreated patients and non-treated patients had the same level of CPK at the beginning of the surgical procedure (t1) (78±6 vs. 83+13 U/L) but lower increase (p<0.05) in CPK activity in carvedilol pretreated patients in respect to nontreated patients (338±46 vs. 644±103 U/L) at the end of procedure (t2). Such results suggest that open heart surgery led to elevated CPK levels, but this effect was less pronounced in patients with higher level of UA. Conclusions: Our results suggest possible role of UA in the protection from reperfusion injury. Increase of UA before surgery may be beneficial factor during CABG procedure in patients treated with carvedilol by decreasing level of peroxynitrite as one of molecular causes of reperfusion injury. Our results showed influence of UA on CPK levels at the end of surgical procedure, indicating that increased levels of UA may protect heart from biochemical damage induced by peroxynitrite during the CABG intervention.

Ciljevi: Postoji mišljenje da Peroxynitrite širi - pojačava oštećenja koja potiču od ishemije /reperfuzije. U ovom radu poređen je nivo mokraćne kiseline (UA) u serumu, sakupljača peroksinitrita, sa nivoom kreatin fosfokinaze (CPK) kod muškaraca pre i nakon operacije na otvorenom srcu, a u cilju procene da li povećani nivoi UA mogu služiti kao zaštita od biohemijskih oštećenja izazvanih upotrebom peroksinitrita tokom hirurške CABG intervencije. Metode: Ispitivano je 45 bolesnika (16 je prethodno primalo karvedilol - 6.25 mg dnevno, tokom 6 nedelja pre operacije, prosečne starosti 55.3±1.7 godina, 55-71, i 29 bolesnika koji nisu primali karvedilol, prosečne starosti 58.3±1.4 godina, 47-73) koji su bili podvrgnuti CABG hirurškoj intervenciji. Kriterijumi za uključenje u studiju su bili izvođenje CABG na dva ili više sudova sa klemovanjem aorte u trajanju od 30 - 40 minuta. Za procenu zdravstvenog stanja bolesnika pre operacije korišćen je EuroSCORE. Nivoi UA i kreatin fosfokinaze (CPK) u serumu su mereni uz pomoć spektrofotometrije korišćenjem kvantitativnog enzimskog eseja. Rezultati: U bolesnika koji su prethodno primali karvedilol uočeni su uvećani nivoi UA u serumu (p< 0.05) u poređenju sa bolesnicima koji nisu primali pomenuti lek. Tokom hirurške procedure bolesnici su podvrgnuti privremenoj ishemiji zbog prebacivanja sa telesnog na vantelesni krvotok. U tom periodu vrednosti UA su snižene u bolesnika koji su prethodno primali karvedilol (406+46 (t1) naspram 300±22 mol/L (t2)) bolesnika koji ga nisu primali (328±14 (t1) naspram 322±18 mol/L). Bolesnici koji su primali karvedilol i oni koji nisu imali su isti nivo CPK na početku hirurške procedure (t1) (78±6 naspram 83±13 U/L) ali je na kraju procedure uočen niži porast aktivnosti CPK (p<0.05) u bolesnika koji su primali karvedilol u poređenju sa bolesnicima koji nisu (338±46 prema 644±103 U/L) (t2). Ovakvi rezultati sugerišu da intervencija na otvorenom srcu dovodi do povećanja nivoa CPK, ali je taj efekat bio manje izražen u bolesnika koji su imali viši nivo UA. Zaključak: Naši rezultati ukazuju na moguću pozitivnu ulogu mokraćne kiseline u zaštiti od oštećenja koja može prouzrokovati reperfuzija. Povećanje nivoa UA pre operacije može predstavljati koristan faktor tokom CABG procedure u bolesnika koji su primali karvedilol, jer snižava nivo peroksinitrita kao jedan od uzroka oštećenja od reperfuzije. Naši rezultati pokazuju uticaj UA na nivoe CPK pri kraju hirurške intervencije, što pak ukazuje na to da uvećani nivoi UA mogu štititi srce od biohemijskih oštećenja izazvana peroksinitritom tokom CABG intervencije.