Role of iron ions in the genesis of reperfusion injury following successful cardiopulmonary resuscitation: Preliminary data and a biochemical hypothesis

Effect of deferoxamine on late deaths following CPR in rats

“…Recent unpublished computer simulations of the kinetics of lipid peroxidation reactions suggest that such reactions may continue and even accelerate for hours to days after their initiation (Charles F Babbs, MD, unpublished data). Thus the time course of the survival curves is consistent with the type of smoldering oxidative reactions that we have proposed as a biochemical mechanism for post-resuscitation brain injury [4].…”

“…Late deaths following initially successful CPR may be related to specific and preventable phenomena that occur during the reperfusion period [1][2][3][4]. Indeed, a large proportion of the total injury seen after five-minute to 15-minute periods of circulatory arrest may develop during the reperfusion phase, due to 1) the no-reflow phenomenon [5], in which cerebral vascular resistance rises during reperfusion after ischemic anoxia, decreasing perfusion to areas of the brain; 2) continued calcium influx through cell membranes damaged during anoxia, leading to intracellular calcium intoxication during reperfusion [2,3,6,7]; or 3) production of oxidative free radicals, causing progressive lipid peroxidation in cell membrane systems, particularly in the lipid-rich brain [l, 3,8].…”

Free radicals and the etiology of colon cancer

“…This hypothesis derives from an earlier conjecture by Graf and Eaton [1], coupled with the serendipitous discovery in our laboratory that highly reactive HO radicals can be produced abundantly by suspensions of feces under aerobic conditions. As do many other hypotheses for the pathogenic effects of oxygen centered free radicals in biologic systems [2][3][4][5][6], this one also invokes the superoxide driven Fenton reaction:…”

“…It is consistent with many established facts of the epidemiology of the disease [79][80][81][82] including increased incidence of colon cancer in people who 1. ingest a high meat diet (which provides more iron), 2. ingest a high fat diet (which provides more procarcinogens and stimulates bile secretion), 3. ingest a low fiber diet (which allows for greater fecal concentration of both iron, procarcinogens, oxidizable lipids, and bile salts), or 4. suffer from chronic ulcerative colitis (which provides peri-mucosal superoxide from activated leukocytes, heme iron from chronic bleeding, and which also may dictate supplementation of the diet with iron to correct for chronic blood loss and consequent iron deficiency anemia).…”

“…This hypothesis derives from an earlier conjecture by Graf and Eaton [1], coupled with the serendipitous discovery in our laboratory that highly reactive HO radicals can be produced abundantly by suspensions of feces under aerobic conditions. As do many other hypotheses for the pathogenic effects of oxygen centered free radicals in biologic systems [2][3][4][5][6], this one also invokes the superoxide driven Fenton reaction:In feces a ready biologic source of superoxide is the respiratory activity of bacteria [7][8][9][10], notably E. coli [11], perhaps together with spontaneous autoxidation of ferrous iron chelates that have been previously reduced by metabolites of the anerobic subpopulation of fecal flora. Another intriguing source of colonic superoxide is the lipoxygenase activity of normal or sloughed colonic epithelial cells [12].…”