Brain injury by ischemic anoxia: Hypothesis extension — A tale of two ions?

Scatchard analysis of methane sulfinic acid production from dimethyl sulfoxide: A method to quantify hydroxyl radical formation in physiologic systems

“…Oxygen centered free radicals may play a central role in the initiation or exacerbation of tissue damage in heart attack, stroke, organ transplantation, acute pancreatitis, liver cirrhosis, arthritis, Parkinson's disease, and the toxicity of and redox cycling drugs and chemicals. [1][2][3][4][5][6][7][8][9][10][11] Perhaps of greatest clinical importance is the amplification of tissue damage during reperfusion of previously ischemic tissues, including heart, 12 kidney, [13][14] small intestine, [15][16][17] skin, 18 and skeletal muscle. 19 Widespread acceptance of pathogenic mechanisms invoking formation of oxygen radicals has been limited by their inability of investigators to convincingly detect and quantify such radicals in isolated tissues or in animal models.…”

A rapid, widely applicable screen for drugs that suppress free radical formation in ischemia/reperfusion

“…In interpreting the results of such experiments, it is helpful to clarify the distinction between what White et al have called ischemic hypoxia versus hypoxic hypoxia (White et al, 1984), as well as the terms reperfusion and reoxygenation. Ischemia hypoxia is hypoxia without capillary perfusion.…”

Effect of deferoxamine on late deaths following CPR in rats

“…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].…”

“…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]. If, in fact, irreversible damage to the brain and other organs by such mechanisms occurs during the period of reperfusion rather than during the period of anoxia, the corresponding pathophysiologic entity, "reperfusion injury" ,may be treatable as part of advanced cardiac life support (ACLS).…”

“…It is water soluble, yet crosses the blood brain barrier, and does not interfere significantly with the oxygen transport function of hemoglobin [9]. Blaine C. White [3] recently proposed that free iron ions liberated from intracellular stores during ischemic anoxia may play a major role in the genesis of reperfusion injury by oxidative free radicals. Our study was designed as a preliminary test of the potential of deferoxamine to prevent late deaths following initially successful CPR.…”