Reduction of reperfusion injury with mannitol cardioplegia.

Forty consecutive patients undergoing myocardial revascularization were divided into two equal groups: group 1 received standard cardioplegic solution, and group 2 received a solution containing mannitol, 59.8 mmol/L. In 6 patients in each group, myocardial biopsies were done before ischemia and at the time of reperfusion. Samples were assessed by chemiluminescence to determine oxidative stress and by electron microscopic studies. A significant reduction in atrial arrhythmias was observed in the mannitol group. Chemiluminescence in group 1 showed a photoemission of 37.6 +/- 3.5 cpm/mg of protein x 10(-3) for the preischemia samples and 74.8 +/- 16 cpm/mg of protein x 10(-3) for the reperfusion samples (p less than 0.001). In group 2, the values for chemiluminescence were 37.7 +/- 3.4 cpm/mg of protein x 10(-3) and 40 +/- 6.1 cpm/mg of protein x 10(-3), respectively (p = not significant). Electron microscopic studies showed, for group 1, increased grades of damaged mitochondria in the reperfusion biopsy specimens compared with the preischemia biopsy specimens (p less than 0.01). In group 2, differences for damaged mitochondria were not significant. These results support the hypothesis that mannitol reperfusate significantly reduces myocardial damage in patients undergoing open heart procedures. They also suggest that this protective effect may be in part secondary to the antioxidant property of mannitol, although other mechanisms may have accounted for or contributed to the improved outcome after ischemia.

Oxidative stress in skeletal muscle during sepsis in rats.

Skeletal muscle is a target organ during sepsis; nevertheless, there is no evidence of a possible free radical overproduction with tissue damage in this situation. We studied Sprague Dawley female rats in two groups: a septic group with cecal ligation and double cecal perforation and a control group that was sham operated. Hind limb adductor muscles spontaneous chemiluminescence was measured at 2, 4, 6, 12, 24, and 30 hr after the surgical procedure as the expression of oxygen excited species generation. Muscle samples were also taken and activity of the principal antioxidant enzymes--superoxide dismutase (SOD), catalase, and glutathione peroxidase--as well as myeloperoxidase, an index of neutrophil infiltration was determined. CPK seric assays at 12 and 24 hr were used to reflect muscle injury and revealed high levels. Previously administered bovine superoxide dismutase was employed to prevent or attenuate oxidative stress. The results showed that light emission by rat skeletal muscle doubled from 4 to 12 hr of sepsis and could be attenuated with SOD pretreatment. Observed changes may be attributed to the production of oxygen free radicals that do not depend on local neutrophil infiltration. The detoxifying antioxidant enzyme activities in skeletal muscle were diminished (Mn SOD 46% at 6 hr, catalase 83% at 12 hr glutathione peroxidase 55% at 12 hr), which would also facilitate muscle septic damage.