Glycerol-induced acute renal failure (ARF) in rats is a model of acute trauma in which intra-muscular injection of 50% glycerol causes rapid myoglobinuria, oliguria, and a rapid reduction in glomerular filtration rate. We found that plasma tumor necrosis factor-alpha (TNF-alpha) is rapidly induced in glycerol injected rats. It can be detected in some animals as early as 30 minutes post-injection, peaks at one hour (range: 4 to 32 U/ml) with no significant difference between blood from renal vein and vena cava, and decreases by three hours. None was detected in control saline injected rats (P < 0.001). Four out of five rats infused with neutralizing anti-TNF-alpha antiserum (200 microliters/300 g body wt) immediately prior to glycerol injection had significantly protected kidney function (P = 0.001). In these rats, plasma urea (104.8 +/- 58.9 mg%) and creatinine (1.16 +/- 0.38 mg%) were lower and creatinine clearance higher (0.34 +/- 011 ml/min) than in glycerol injected animals pretreated with normal serum (291.8 +/- 41.8 mg%, 3.15 +/- 0.74 mg%, and 0.03 +/- 0.03 ml/min, respectively) or animals injected with glycerol alone (302.6 +/- 76.8 mg%, 3.45 +/- 0.97 mg%, and 0.03 +/- 0.03 ml/min, respectively). These results imply a direct role for TNF-alpha in pathogenesis of glycerol induced ARF in rats.

Increased Troponin I levels and pro-inflammatory cytokines have been reported in most patients undergoing cardiac surgery, ascribed to the type and extent of surgery, reperfusion injury, and the method of myocardial protection. We investigated their levels in patients undergoing on-pump (CCAB) or off-pump (OPCAB) coronary artery bypass surgery and whether these correlated with the extent of myocardial injury. One hundred twenty patients were prospectively randomized to undergo OPCAB (n = 60) or CCAB (n = 60). Hemodynamic and respiratory data, as well as serum CK-MB mass fraction, Troponin I, and interleukin (IL)-6, IL-8, and IL-10 levels, were collected perioperatively. Demographic, hemodynamic, and respiratory parameters were similar between the two groups. Troponin I was significantly lower in the OPCAB than in the CCAB group, either at the end of ischemia, end of surgery, 6-hour and 24-hour postoperatively (4 +/- 3, 5 +/- 3, 7 +/- 5, and 8 +/- 3 microg/L, vs. 19 +/- 18, 27 +/- 19, 28 +/- 13.5, and 33 +/- 8.5 microg/L, respectively, p < 0.05). Serum cytokine levels in the OPCAB patients were lower compared to the CCAB group at the end of surgery (32 +/- 35, 25 +/- 30, and 40 +/- 30 pg/ml for IL-6, IL-8, and IL-10 vs. 230 +/- 30, 140 +/- 70, and 125 +/- 50 pg/ml, respectively, p < 0.05). Plasma IL-6 levels correlated with the Troponin I levels at the end of surgery in both groups (r = 0.45, p = 0.01). Thus, OPCAB surgery is associated with reduced levels of Troponin I and activation of cytokines, compared to those in the CCAB group. High levels of these factors could correlate with myocardial damage during coronary artery bypass surgery. This finding warrants further laboratory and clinical confirmation in the future.