The purpose of this study was to use a direct method, that of electron spin resonance (ESR) spectroscopy, to demonstrate that reperfusion after a period of ischemia results in a sudden increase in the production of free radicals in the myocardium. The isolated buffer-perfused rat heart was used with N-tert-butyl-alpha-phenylnitrone (PBN) as a spin-trapping agent. Samples of coronary effluent were taken and extracted into toluene for detection of radical adducts by ESR spectroscopy. After 15 minutes of total, global ischemia, aerobic reperfusion resulted in a sudden burst of radical formation that peaked at 4 minutes. When hearts were reperfused with anoxic buffer, no dramatic increase in radical production was observed. Subsequent reintroduction of oxygen, however, resulted in an immediate burst of radical production of a similar magnitude to that seen in the wholly aerobic reperfusion experiments. The ESR signals obtained (aN = 13.60 G, aH = 1.56 G) are consistent with the spin-trapping by PBN of either a carbon-centered species or an alkoxyl radical, both of which could be formed by secondary reactions of initially-formed oxygen radicals with membrane lipid components.

1. Phosphorus-nuclear-magnetic-resonance measurements were made on perfused rat hearts at 37 degrees C. 2. With the improved sensitivity obtained by using a wide-bore 4.3 T superconducting magnet, spectra could be recorded in 1 min. 3. The concentrations of ATP, phosphocreatine and Pi and, from the position of the Pi resonance, the intracellular pH (pHi) were measured under a variety of conditions. 4. In a normal perfused heart pHi = 7.05 +/- 0.02 (mean +/- S.E.M. for seven hearts). 5. During global ischaemia pHi drops to 6.2 +/- 0.06 (mean +/- S.E.M.) in 13 min in a pseudoexponential decay with a rate constant of 0.25 min-1. 6. The relation between glycogen content and acidosis in ischaemia is studied in glycogen-depleted hearts. 7. Perfusion of hearts with a buffer containing 100 mM-Hepes before ischaemia gives a significant protective effect on the ischaemic myocardium. Intracellular pH and ATP and phosphocreatine concentrations decline more slowly under these conditions and metabolic recovery is observed on reperfusion after 30min of ischaemia at 37 degrees C. 8. The relation between acidosis and the export of protons is discussed and the significance of glycogenolysis in ischaemic acid production is evaluated.

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We report the development of a prototype positron emission tomography (PET) scanner compatible with clinical magnetic resonance imaging (MRI) scanners and nuclear magnetic resonance (NMR) spectrometers. This single slice PET system consists of 72 2 x 2~5 mm lutetium oxyorthosilicate (LSO) crystals coupled by 2 mm diameter, 4 meter long double clad optical fibers to three multi-channel photomultiplier tubes (MC-PMT's) shielded inside an aluminum closure. The ring diameter is 54 mm and the slice thickness is -1 mm FWHM. Measurements with a point source demonstrate that this PET system has a reconstructed resolution of 2.1 mm, a coincidence time resolution of 26 ns and a typical energy resolution of 45%. Simultaneously acquired PET and MR phantom images show no significant artifacts or distortions. We also obtained simultaneous NMR spectra and PET images from an isolated, perfused rat heart, demonstrating the power of obtaining temporally correlated PET and NMR information in biological systems. Again, no artifacts in the PET or NMR data were apparent, despite the high field strength of 9.4T. The challenge for the future is to scale up the design to develop a high resolution, high sensitivity device that can be used in simultaneous PET and MR studies of in vivo systems.

The extended medical degree programme at King’s College London shows that widening participation in medicine can be successful, but requires appreciable extra commitment by academic staff