Paschalis Tossios

N-acetylcysteine prevents reactive oxygen species–mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial

OBJECTIVEnReactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8-iso-prostaglandin-F(2)alpha and nitrotyrosine formation. We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery.nnnMETHODSnForty patients undergoing coronary artery surgery (mean age +/- SD, 66 +/- 9 years; 9 women and 31 men) were randomized to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1), n = 20) or placebo (n = 20). Patients and clinical staff were blinded to group assignment. Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining against 8-iso-prostaglandin-F(2)alpha (primary measure) as an indicator for reactive oxygen species-mediated lipid peroxidation and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated tissue injury. Cardiomyocyte staining was quantitatively determined by using densitometry (in gray units). Global left ventricular function was measured on the basis of fractional area of contraction by using transesophageal echocardiography.nnnRESULTSnPatient characteristics in both groups were comparable. The change in left ventricular cardiomyocyte staining (end of cardiopulmonary bypass--before cardiopulmonary bypass) differed significantly between groups for both primary measures: 8-iso-prostaglandin-F(2)alpha, -1.8 +/- 7.5 gray units (mean +/- SD, N-acetylcysteine group) versus 5.0 +/- 4.1 gray units (placebo group; 95% confidence interval, 2.6-11.0, P =.003); nitrotyrosine, -6.4 +/- 10.0 gray units (N-acetylcysteine group) versus 9.2 +/- 8.4 gray units (placebo group; 95% confidence interval, 9.4-21.7, P <.001). Hemodynamics and clinical outcomes were comparable in both groups.nnnCONCLUSIONSnReactive oxygen species scavenging with N-acetylcysteine attenuates myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest.

Renal protection by radical scavenging in cardiac surgery patients

ABSTRACT Objective: Renal function impairment is a common complication in cardiac surgery patients. Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals, which have been shown to impair various organs including the kidneys, radical scavenging may protect renal function. Therefore, the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine (NAC) versus placebo on peri-operative renal function in cardiac surgery patients. Research design and methods: We reanalyzed the data of our previous study in which 40 coronary artery surgery patients (66 ± 9 [SD] years, 9 women and 31 men) with normal pre-operative renal function had been randomized in a double-blind fashion to receive either NAC (100u2009mg/kg into the cardiopulmonary bypass prime followed by infusion at 20u2009mg/kg/h; n = 20) or placebo (n = 20). We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication. Creatinine clearance was calculated according to Cockcroft and Gault. Results: Biometric and intra-operative patient data were similar between both groups. In the placebo group, serum creatinine increased from 93.1 ± 35.4 µmol/L pre-operatively to 115.9 ± 47.2 µmol/L on post-op day 1 (u2009p < 0.001). In contrast, serum creatinine in the NAC group remained unchanged (92.3 ± 31.3 µmol/L pre-op; 99.3 ± 25.4 µmol/L on post-op day 1; p = 0.084). Accordingly, creatinine clearance decreased by 16.9 ± 14.3 mL/min in the placebo group as compared to 7.5 ± 17.7 mL/min in the NAC group (u2009p = 0.039). Urinary output and diuretic medication were similar between NAC and placebo. Conclusions: Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass.

Effect of prophylactic bisoprolol plus magnesium on the incidence of atrial fibrillation after coronary bypass surgery: results of a randomized controlled trial

ABSTRACT Objective: Bisoprolol, a highly cardioselective β1‐blockers, is widely used to treat elderly patients with hypertension, coronary artery disease and heart failure. The current literature lacks evidence regarding its potency to prevent atrial fibrillation (AF) following cardiac surgery. Therefore the aim of this study was to evaluate the efficacy of bisoprolol plus magnesium (Mg) in the prophylaxis of AF after coronary artery bypass graft (CABG) surgery. Research design and methods: A total of 100 consecutive patients subjected to elective on-pump CABG (84 men, age 65 ± 8 [SD] years), with no prior AF history, were randomly assigned to the prophylaxis group (u2009n = 50) receiving after surgery bisoprolol (5u2009mg/day) plus Mg (intravenous infusion of 2u2009g of Mg on arrival in the intensive care unit, followed by oral Mg at 1800u2009mg/day for 1 week), or to the control group (u2009n = 50), receiving no combined study medication but remaining on their preoperative drugs, including β‐blockers. All patients were continuously monitored to identify the onset of AF. Results: In the prophylaxis group the incidence of postoperative AF was significantly lower, with 20% (10 / 50) compared to 42% (21 / 50) among controls (u2009p = 0.030, 95% confidence interval [CI] for absolute risk reduction [ARR], 2–42%). Particularly in the elderly, bisoprolol plus Mg was effective in preventing AF; in the prophylaxis group only six of 36 (17%) patients ≥ 65 years of age developed AF, compared to 13 of 20 (65%) in the control group (u2009p < 0.001, 95% CI for ARR, 17–65%). This was associated with significantly (u2009p = 0.022) shorter hospital stays in the prophylaxis group (median of 7 vs. 9 days, 95% CI for difference in medians, 0–3 days). Conclusions: The combination of bisoprolol plus Mg effectively reduces the incidence of postoperative AF following on-pump CABG, particularly in elderly patients, and is associated with a shorter hospital length of stay.

No evidence of myocardial restoration following transplantation of mononuclear bone marrow cells in coronary bypass grafting surgery patients based upon cardiac SPECT and 18F-PET

BackgroundWe tested the hypothesis, that intramyocardial injection of mononuclear bone marrow cells combined with coronary artery bypass grafting (CABG) surgery improves tissue viability or function in infarct regions with non-viable myocardium as assessed by nuclear imaging techniques.MethodsThus far, 7 patients (60 ± 10 [SD] years) undergoing elective CABG surgery after a myocardial infarction were included in this study. Prior to sternotomy, bone marrow was harvested by sternal puncture. Mononuclear bone marrow cells were isolated by gradient centrifugation and resuspended in 2 ml volume of Hanks buffered salt solution. At the end of CABG surgery 10 injections of 0.2 ml each were applied to the core area and borderzones of the infarct. Global and regional perfusion and viability were evaluated by ECG-gated 99mTc-tetrofosmin myocardial single-photon emission computed tomograph (SPECT) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in all study patients < 6 days before and 3 months after the intervention.ResultsNon-viable segments indicating transmural defects were identified in 5 patients. Two patients were found to have non-transmural defects before surgery. Concomitant surgical revascularisation and bone marrow cell injection was performed in all patients without major complications. The median total injected mononuclear cell number was 7.0 × 107 (range: 0.8–20.4). At 3 months 99mTc-tetrofosmin SPECT and 18F-FDG-PET scanning showed in 5 patients (transmural defect n = 4; non-transmural defect n = 1) no change in myocardial viability and in two patients (transmural defect n = 1, non-transmural defect n = 1) enhanced myocardial viability by 75%. Overall, global and regional LV ejection fraction was not significantly increased after surgery compared with the preoperative value.ConclusionIn CABG surgery patients with non-viable segments the concurrent use of intramyocardial cell transfer did not show any clear improvement in tissue viability or function by means of non-invasive bioimaging techniques.

Anti-oxidative therapy protects renal function in cardiac surgery patients

Objectives: Oxygen-derived free radical formation induced by cardiopulmonary bypass (CPB) may contribute to renal dysfunction associated with cardiac surgery. As anti-oxidants have been shown to attenuate free radical-induced renal dysfunction in medical patients, we hypothesized that the anti-oxidant N-acetylcysteine (NAC) protects renal function in patients subjected to cardiac surgery on CPB. Material and Methods: Forty coronary artery surgery patients (66±9[SD] years, 9 women and 31 men) with normal preoperative renal function (serum creatinine <0.9mg/dl) subjected to CPB and CA were randomized in a double-blind fashion to receive either NAC (100mg/kg into CPB prime followed by infusion at 20mg/kg/h; n=20) or Placebo (n=20). We measured serum creatinine levels pre- and post-operatively (1. day post CPB) as well as urinary output and diuretic medication. Creatinine clearance was calcuted using the Cockroft equation. Results: In the Placebo group, serum creatinine increased from 93.1±35.4 mmol/l pre-operatively to 115.9±47.2 mmol/l on post-op day 1 (p<.001, 95% CI for mean change: 13.9 to 31.7). In the NAC group, change in serum creatinine was not statistically significant (92.3±31.3 mmol/l pre-operatively; 99.3±25.4 mmol/l on post-op day 1; p=.084, 95% CI for mean change: –0.5 to 14.5). Creatinine clearance decreased significantly in the Placebo group compared to NAC (–16.9±3.2ml/min vs. –7.5±4.2ml/min, p=0.04). Hemodynamics as well as clinical outcome were similar between NAC and Placebo. Conclusions: Our data show that NAC protects renal function post CPB, thus, radical-scavenging may reduce renal dysfunction associated with cardiac surgery.