Pathophysiological mechanism of renal injury induced by cardiopulmonary bypass [CPB]: is there a possible protective role of N-acetylcysteine [NAS] as a radical scavenger?

ABSTRACT

Despite improvements in surgical techniques, myocardial protection, and perioperative care, acute renal failure [ARF] after cardiopulmonary bypass [CPB] represents one of clinician problems as it associated with unacceptable high mortality. Oxygen free radicals are important components that may be involved in the pathophystological tissue alterations observed during ischemia/reperfusion [I/R]. we evaluated the possible renoprotective role of N-acetylcysteine [NAC] as a free radical scavenger against oxidative stress during I/R injury of the kidney induced by CPB in patients with normal renal function compared with placebo, a prospective randomized study where thirty patients of ischemic heart disease who underwent coronary artery bypass grafting [CABG] were divided into two groups. The study group [n=15] with mean age 61.20 +/- 8.01 received NAC intravenously in a dose of 50 mg/Kg/day, given as 25 mg/Kg' twice daily for successive 3 days, and the placebo group [n=15] with mean age 60.60 +/- 8.41 received 0.5 cc/kg saline twice in 24h for three days before CABG. Intraoperative as well as the clinical outcome in both groups such as the type of graft used perioperative myocardial infarction, pump time aortic cross clamp time, the need for intra-aortic balloon, incidence of arrhythmias, and the of ICU stay were evaluated. Arterial blood sampling were collected from both groups after induction of anesthesia, and, 241 after cessation of CPB to measure serum creatinine, creatinine clearance [as markers of glomerular function]. Biochemical assay performed to measure Myeloperoxidase activity [MPO], interlukin-6 [IL-6] as an indicator of inflammation, malondialdhyde [MDA] as an index of lipid peroxidation and C-reactive protein [CRP] level "acute phase protein level The blood sampling for those biochemical studies was withdrawn after induction of anesthesia [t[0]], them 10 min [t[10]], and 30 mm [t[30]] on bypass, at the end of surgery [t[end]] and after 6h [t[6h]] and 24h [t[24h]] after cessation of CPB. There was no significant differences between both group regarding operative, and post operative data except for the duration of ICU stay which was significantly longer in the placebo group MPO activity was significantly higher levels in placebo group compared with the study group starting from t[0] and throughout the study. P=0.001 at t[0]], [t[10]], [t[30]], t[end], t[6th] and t[24h] In addition, its activity had not returned to the preoperative level at 24h P=0.0, while in the study group there was no significant difference in MPO activity at and 24h after cessation of CPB. MDA value started to increase 10 min after commencement of CPB in the placebo compared with the study group, and remained significantly higher throughout the study. P=.03,.02, .001, .01, .01 at t[10], [t[30]], t[end], t[6th] and t[24h] respectively. Similar to the MPO, MAD value had not returned to the preoperative level at t 24h in the placebo group P=.00 Regarding IL-6 levels. The study group patients had significantly lower levels than the placebo at the periods of t30, tend, and t6h. P=.03,.00,.00 respectively. However, 24h after cessation of CPB, the IL-6 levels were similar in both groups. CRP also increased significantly in the placebo group starting 30 mm after commencement of CPB and throughout the study duration P=.001,. 001, .02, .001 at t[end], t[6th] and t[24h] time periods respectively. However CRP levels had not returned to the basal levels in both study and placebo groups after 24h of CPB cessation P=.001. In the placebo group, serum creatinine SC increased significantly from 0.69 +/- 0.32 mg/dL tol.25 +/- 0.33 mg/dL24h after cessation of CPB. P=.001. While the study group showed no significant ehange in its level. Moreover after 24h of CPB cessation the placebo group had significantly higher SC level than the study group .P=.001, In addition to SC elevation in the placebo group, creatinine clearance CC also significantly decreased after 24h compared to the basal value. P=.01, and similar to SC, CC decreased significantly in the placebo group after 24h compared to the study group P=.02. In conclusion, we believe that preioperative administration of NAC has a beneficial protective effect against renal injury induced by ischemia reperfusion due to CBP particularly in patients with normal preoperative renal function