Helen W. Richter

Study of the superoxide radical chemistry by stopped-flow radiolysis and radiation induced oxygen consumption. [Electron beams]

The chemical reactivity of the superoxide radical has been studied at pH 10 and 23/sup 0/C by absorption spectroscopy in a fast kinetics spectrophotometer and by radiation induced oxygen consumption in a modified stopped-flow radiolysis apparatus on line with a Van de Graaff electron generator. The latter method differentiates between oxidation and reduction reactions and yields information on the corresponding stoichiometry. A number of examples are used to demonstrate the versatility of these techniques. Rate constants were determined for the reaction of superoxide radicals with: ferricytochrome c, k = 2.6 +- 0.2 x 10/sup 5/ M/sup -1/ s/sup -1/ at pH 9.0; ascorbate, k = 1.52 +- 0.1 x 10/sup 5/ M/sup -1/ s/sup -1/ at pH 9.9; nitroblue tetrazolium, k = 5.94 +- 0.5 x 10/sup 4/ M/sup -1/ s/sup -1/ at pH 9.8. Some 19 other compounds (buffers, carboxylic acids, chelating agents, etc.) were shown to be inert toward superoxide radicals.

Maintenance of left ventricular function (90%) after twenty-four-hour heart preservation with deferoxamine

During 24-h in vitro heart preservation and reperfusion, irreversible tissue damage occurs caused by reactive oxygen intermediates, such as superoxide radicals, singlet oxygen, hydrogen peroxide, hydroperoxyl, hydroxyl radicals, as well as the peroxynitrite radical. Reduction of the related oxidative damage of reperfused ischemic tissue by free radical scavengers and metal chelators is of primary importance in maintaining heart function. We assessed whether deferoxamine (DFR) added to a cardioplegia solution decreased free radical formation during 24-h cold (5 degrees C) heart preservation and normothermic reperfusion (37 degrees C) in the Langendorff isolated perfused rat heart. The deferoxamine treated hearts were significantly (p less than .001) better preserved than the control hearts after 24 h of preservation with regard to recovery of left ventricular diastolic pressure, contractility (+dP/dt), relaxation (-dP/dt), creatine kinase release, and lipid peroxidation. DFR preserved cell membrane integrity and maintained 93% of left ventricular contractility. The evidence suggests that DFR reduces lipid peroxidation damage by reducing free radical formation and thereby maintaining normal coronary perfusion flow and myocardial function.

The effects of mannitol, albumin, and cardioplegia enhancers on 24-h rat heart preservation

During 24 h in vitro heart preservation and reperfusion, tissue damage occurs that seriously reduces cardiac function. Prevention of free radical production during preservation and reperfusion of ischemic tissue using free radical scavengers is of primary importance in maintaining optimal heart function in long-term preservation protocols. We examined whether mannitol (68 mM) and albumin (1.4 microM) in combination with other cardioplegia enhancers decreased free radical formation and edema and increased cardiac function during 24-h cold (5 degrees C) heart preservation and warm (37 degrees C) reperfusion in the Langendorff-isolated rat heart. The performance of mannitol-treated hearts was significantly decreased compared with that of hearts without mannitol treatment after 24 h of preservation with regard to recovery of diastolic pressure, contractility (+dP/dt), relaxation (-dP/dt), myocardial creatine kinase release, coronary flow, and lipid peroxidation. Albumin-treated hearts demonstrated higher cardiac function (contractility and coronary flow especially) than hearts not treated with albumin or hearts treated with mannitol, and this appears to be due to the positive effects of increased cellular metabolism and the enhancement of membrane stability.During 24 h in vitro heart preservation and reperfusion, tissue damage occurs that seriously reduces cardiac function. Prevention of free radical production during preservation and reperfusion of ischemic tissue using free radical scavengers is of primary importance in maintaining optimal heart function in long-term preservation protocols. We examined whether mannitol (68 mM) and albumin (1.4 μM) in combination with other cardioplegia enhancers decreased free radical formation and edema and increased cardiac function during 24-h cold (5°C) heart preservation and warm (37°C) reperfusion in the Langendorff-isolated rat heart. The performance of mannitol-treated hearts was significantly decreased compared with that of hearts without mannitol treatment after 24 h of preservation with regard to recovery of diastolic pressure, contractility (+dP/d t), relaxation (-dP/d t), myocardial creatine kinase release, coronary flow, and lipid peroxidation. Albumin-treated hearts demonstrated higher cardiac function (contractility and coronary flow especially) than hearts not treated with albumin or hearts treated with mannitol, and this appears to be due to the positive effects of increased cellular metabolism and the enhancement of membrane stability.