Myocardial protection during elective coronary artery bypasses grafting by pretreatment with omega-3 polyunsaturated fatty acids

Abstract

Background/Aim. Despite recent advances in coronary artery bypass grafting (CABG), cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) are still associated with myocardial injury. Accordingly, the efforts have been made lately to improve the outcome of CPB by glucose-insulinpotassium, adenosine, Ca2+-channel antagonists, L-arginine, N-acetylcysteine, coenzyme Q10, diazoxide, Na+/H+ exchange inhibitors, but with an unequal results. Since omega-3 polyunsatutated fatty acids (PUFAs) have shown remarkable cardioprotection in preclinical researches, the aim of our study was to check their effects in prevention of ischemia reperfusion injury in patients with CPB. Methods. This prospective, randomized, placebo-controlled study was performed with parallel groups. The patients undergoing elective CABG were randomized to receive preoperative intravenous omega-3 PUFAs infusion (n = 20) or the same volume of 0.9% saline solution infusion (n = 20). Blood samples were collected simultaneously from the radial artery and the coronary sinus before starting CPB and at 10, 20 and 30 min after the release of the aortic cross clamp. Lactate extraction/excretion and myocardial oxygen extraction were calculated and compared between the two groups. The levels of troponin I (TnT) and creatine kinase-myocardial band (CK-MB) were determined before starting CPB and 4 and 24 h postoperatively. Results. Demographic and operative characteristics, including CPB and aortic cross-clamp time, were similar between the two groups of patients. The level of lactate extraction 10 and 20 min after aortic cross-clamp time has shown negative values in the control group, but positive values in the PUFAs group with statistically significant differences (-19.6% vs 7.9%; p < 0.0001 and -19.9% vs 8.2%; p < 0.0008, respectively). The level of lactate extraction 30 minutes after reperfusion was not statistically different between the two groups (6.9% vs 4.2%; p < 0.54). Oxygen extraction in the PUFAs group was statistically significantly higher compared to the control group after 10, 20 and 30 min of reperfusion (35.5% vs 50.4%, p < 0.0004; 25.8 % vs 48.7%, p < 0.0001 and 25.8% vs 45.6%, p < 0.0002, respectively). The level of TnT, 4 and 24 h after CPB, was significantly higher in the control group compared to PUFAs group, with statistically significant differences (11.4 vs 6.6, p < 0.009 and 12.7 vs 5.9, p < 0.008, respectively). The level of CK-MB, 4 h after CPB, was significantly higher in the control group compared to PUFAs group (61.9 vs 37.7, p < 0.008), but its level, 24 h after CPB, was not statistically different between the two groups (58.9 vs 40.6, p < 0.051). Conclusion. Treatment with omega-3 PUFAs administered preoperatively promoted early metabolic recovery of the heart after elective CABG and improved myocardial protection. This study showed that omega-3 emulsion should not be considered only as a nutritional supplement but also as a clinically safe and potent cardioprotective adjunct during CPB.Uvod/Cilj. Uprkos tehnoloskom napretku srcani zastoj izazvan kardioplegijom i vantelesni krvotok (cardiopulmonary bypass - CPB) tokom operacije revaskularizacije srcanog misica i dalje dovode do ostecenja srcanog misica. Napor da se poboljsa ishod posle CPB primenom glukoze-insulin-kalijuma, adenozina, blokatora Ca2+-kanala, L-arginina, N-acetilcisteina, koenzima Q10, diazoksida, inhibitora razmene Na+/H+ nije dao zeljene rezultate. Omega-3 nezasicene masne kiseline (polyunsaturated fatty acids - PUFAs), u preklinickim ispitivanjima, pokazale su znacajno kardioprotektivno dejstvo. Cilj ovog rada bio je ispitivanje efekata primene PUFA u prevenciji ishemijsko reperfuzionih ostecenja srcanog misica nakon revaskularizacije sa primenom CPB. Metode. Ova prospektivna, randomizovana, placebo-kontrolisana studija sprovedena je na paralelnim grupama. Bolesnici sa elektivnim operacijama revaskularizacije srcanog misica slucajnim izborom podeljeni su u dve grupe. Prva grupa (n = 20) preoperativno je dobijala infuziju PUFAs (PUFAs grupa), dok je kontrolna grupa (n = 20) dobijala istu kolicinu 0,9% rastvora NaCl. Uzorci krvi su istovremeno uzimani iz radijalne arterije i koronarnog sinusa pre pocetaka CPB i 10, 20 i 30 minuta posle skidanja kleme sa aorte. Ekstrakcija laktata i kiseonika iz srcanog misica izvedena je primenom poznatih formula. Nivo troponina I (TnT) i miokardne frakcije kreatin-kinaze (CK-MB) odredjivana je pre pocetka CPB i 4 i 24 h posle operacije. Rezultati. Demografske i operativne karakteristike, ukljucujuci trajanje CPB i klemovanja aorte, bili su slicni u obe grupe. Nivo ekskrecije laktata 10 i 20 min nakon deklemovanja aorte imao je negativne vrednosti u kontrolnoj grupi, dok su vrednosti u PUFAs grupi bile pozitivne, sa statisticki znacajnom razlikom (-19,6% prema 7,9%; p < 0,0001 i -19,9% prema 8,2%; p < 0,0008, respektivno). Nivo ekstrakcije laktata 30 min nakon skidanja kleme sa aorte bio je bez statisticki znacajne razlike izmedju dve grupe (6,9% prema 4,2%; p < 0,54). Ekstrakcija kiseonika 10, 20 i 30 min posle skidanja kleme sa aorte bila je veca u PUFAs grupi sa statisticki znacajnom razlikom u odnosu na kontrolnu grupu (35,5% prema 50,4%, p < 0,0004; 25,8 % prema 48,7%, p < 0,0001 i 25,8% prema 45,6%, p < 0,0002, respektivno). Nivo TnT, 4 i 24 sata nakon CPB, bio je statisticki znacajno visi u kontrolnoj grupi nego u PUFAs grupi (11,4 prema 6,6 ng/mL p < 0,009 i 12,7 prema 5,9 ng/mL p < 0,008). Nivo CK-MB, 4 h nakon CPB, bio je statisticki znacajno visi u kontrolnoj grupi nego u PUFA grupi (61,9 prema 37,7 U/L; p < 0,008), dok je nivo CK-MB 24 h nakon CPB bio bez statisticki znacajne razlike izmedju dve grupe bolesnika (58,9 prema 40,6 U/L; p < 0,051). Zakljucak. Preoperativna primena omega-3 PUFAs pomaze u ranom metabolickom oporavku srca nakon revaskularizacije tako sto stiti srcani misic. Ovo istrazivanje je pokazalo da omega-3 PUFAs nisu samo nutricioni dodatak vec i klinicki bezbedan i snazan kardioprotektor tokom CPB.