No abstract

BACKGROUND We tested the hypothesis that secondarily produced free radicals can be detected in venous coronary effluent without the need for direct exposure of postischemic tissue to the spin trapping agent alpha-phenyl-tert-butylnitrone (PBN). METHODS AND RESULTS The left anterior descending coronary artery (LAD) of pigs was ligated for 15, 30, 40, or 60 minutes, and the tissue was subsequently reperfused for 60 minutes. Venous effluent (6.5 ml) from the risk area was withdrawn sequentially at 1.5-minute intervals during reperfusion. The effluent blood was immediately infused (4.5 ml/min) with an isotonic saline solution containing 120 mM PBN: Preischemic control effluent samples were collected in an identical fashion. Plasma from each sample was extracted in organic solvent and subsequently analyzed by electron spin resonance (ESR) spectroscopy. Another group of pigs received an infusion of the metal chelator deferoxamine mesylate (25 mg/kg/hr) into the right atrium starting 1 hour before the 40-minute ligation and continuing throughout ligation and reperfusion. We were able to demonstrate the postischemic production of ESR signals for PBN adduct(s) from untreated hearts having spectral characteristics similar to an alkoxyl adduct (PBN-RO.; hyperfine splitting constants for beta-hydrogen [alpha H] = 2.0-2.25 G; nitrogen [alpha N] = 13.5-13.75 G). The reperfusion time course of PBN adduct production had a unique pattern: 1) multiple low-level bursts during the initial 15 minutes of reperfusion, and 2) a prominent PBN adduct signal during a relatively late time (20-25 minutes) of reperfusion. Total postischemic PBN adduct production rose with increasing duration (15-60 minutes) of ischemia and was associated with a progressive elevation of total lactate dehydrogenase in the effluent. Infusion of deferoxamine markedly diminished PBN adduct production as well as total release of lactate dehydrogenase. CONCLUSIONS These data suggest the potential feasibility of using an ex vivo ESR spin trapping technique in blood-perfused models of cardiovascular injury and that chelatable free iron contributes to the production of alkoxyl radicals.

Objectives-Critical vascular surgery of the brain or the heart occasionally requires total cessation of the circulatory system. Profound hypothermia is used to protect the brain from ischaemic injury. This study explores the use of microdialysis to measure metabolic indices of ischaemia: glutamate, lactate, and pH, and cerebral temperature during profound hypothermia and circulatory arrest. Methods-EZuent from a microdialysis catheter placed in the cerebral cortex of three patients undergoing complete circulatory arrest was continuously sampled. Samples were pooled over 10 minute periods and glutamate and lactate concentrations were measured postoperatively. Brain temperature and pH were measured on line intraoperatively. Electroencephalography and monitoring of somatosensory evoked potentials and brainstem auditory evoked potentials were simultaneously carried out. Results-Patient 1 had normal glutamate and lactate. PH was 6.75 to 6.85 and increased to 6.9 after warming ensued. Patient 2 had raised glutamate and lactate during most measurements. The glutamate concentrations peaked at 305 µM/l at the start of the measurements and fell below 20 µM/l after warming. The lactate concentrations peaked at 680 µM/l before cooling, rose to 1040 µM/l during the cooling process, decreased to 212 µM/l during circulatory arrest, and rose again to 620 µM/l after warming. The pH started at 7.06 and continued a downward course until stabilising at a pH of 6.5 after circulatory arrest. Patient 3 had a transient, mild increase in glutamate and lactate during the cooling and warming period. pH was stable throughout. Conclusion-Microdialysis combined with temperature and pH measurements of the cerebral cortex promises to be an important tool in detecting cerebral ischaemia. Further studies are needed to validate our findings and test the feasibility of modifying ischaemic changes. (J Neurol Neurosurg Psychiatry 1998;64:611-618)