Mikko Vuolle

Effect of ischaemic preconditioning, cardiopulmonary bypass and myocardial ischaemic/reperfusion on free radical generation in CABG patients.

OBJECTIVE To investigate the free radicals (FR) generation after ischaemic preconditioning and cardiopulmonary bypass and during reperfusion in CABG patients, and the role of ischaemic preconditioning. METHODS Forty-three CABG patients were randomised into an ischaemic preconditioning and a control group. The protocol for ischaemic preconditioning was two cycles of 2-min ischaemia followed by 3-min reperfusion. Free radicals were measured using electron spin resonance spectroscopy. Global and right heart functions were collected. RESULTS The free radicals generation in coronary sinus blood in the ischaemic preconditioning group was 9.7 and 16.6% after the ischaemic preconditioning protocol and 10 min after declamping, 6.8 and 13.3% in the controls. The free radicals in arterial samples were, respectively, 21, 14, 10 and 9% at 10 min, 1, 2 and 24 h after reperfusion. Cardiac index (CI) and right ventricular ejection fraction (RVEF) were improved by ischaemic preconditioning. CONCLUSION Both ischaemic preconditioning and cardiopulmonary bypass induced free radicals generation. Although ischaemic preconditioning had no effect on free radicals generation after the operation, it protected against postoperative stunning.

Effect of Allopurinol on Myocardial Oxygen Free Radical Production in Coronary Bypass Surgery

OBJECTIVES Allopurinol protects the heart from reperfusion injury. The aim of this study was to investigate myocardial free radical production during reperfusion with and without allopurinol treatment in coronary artery bypass grafting patients randomized into allopurinol (n = 14) or placebo (n = 13) groups. DESIGN Allopurinol (1 g) was given blind prior to cardiopulmonary bypass and prior to opening the aorta. Oxygen free radicals were measured before anesthesia in arterial blood, before cross-clamping and 1 and 10 min after reperfusion in arterial and coronary sinus blood. Levels were measured as relative concentrations by the electron spin resonance method. RESULTS One minute after reperfusion the level of spin-trapped radicals in arterial blood was elevated significantly (p = 0.016) in the allopurinol group, from 7.7 (SE: 0.8) to 8.6 (1.4) and non-significantly (p = 0.074) in the placebo group, from 7.3 (0.7) to 8.3 (0.8). Ten minutes after reperfusion the arterial values were 8.6 (1.5) in the allopurinol and 7.6 (0.7) in the placebo group, the sinus values being 7.6 (1.3) and 8.3 (0.8), respectively. Myocardial free radical production was -0.94 (1.21) in the allopurinol and +0.79 (0.96) in the placebo group after 10 min reperfusion, the difference being significant (p = 0.043). CONCLUSIONS All patients in both groups had an increasing tendency to free radical production during early reperfusion. Patients treated with allopurinol showed less myocardial production of free radicals, indicating that its protective effect may be due to its antioxidative properties.Objectives - Allopurinol protects the heart from reperfusion injury. The aim of this study was to investigate myocardial free radical production during reperfusion with and without allopurinol treatment in coronary artery bypass grafting patients randomized into allopurinol (n = 14) or placebo (n = 13) groups. Design - Allopurinol (1 g) was given blind prior to cardiopulmonary bypass and prior to opening the aorta. Oxygen free radicals were measured before anesthesia in arterial blood, before cross-clamping and 1 and 10 min after reperfusion in arterial and coronary sinus blood. Levels were measured as relative concentrations by the electron spin resonance method. Results - One minute after reperfusion the level of spin-trapped radicals in arterial blood was elevated significantly (p = 0.016) in the allopurinol group, from 7.7 (SE:0.8) to 8.6 (1.4) and non-significantly (p = 0.074) in the placebo group, from 7.3 (0.7) to 8.3 (0.8). Ten minutes after reperfusion the arterial values were 8.6 (1.5) in the allopurinol and 7.6 (0.7) in the placebo group, the sinus values being 7.6 (1.3) and 8.3 (0.8), respectively. Myocardial free radical production was-0.94 (1.21) in the allopurinol and +0.79 (0.96) in the placebo group after 10 min reperfusion, the difference being significant (p = 0.043). Conclusions - All patients in both groups had an increasing tendency to free radical production during early reperfusion. Patients treated with allopurinol showed less myocardial production of free radicals, indicating that its protective effect may be due to its antioxidative properties.

Electron spin resonance, ENDOR and TRIPLE resonance of some 9,10-anthraquinone and 9,10-anthraquinol radicals in solution

E.s.r., ENDOR and TRIPLE resonance spectra have been recorded for 2-methylanthraquinone, anthraquinone-2-sulphonate and anthraquinone-2,6-disulphonate radical anions, and in a strongly acidic medium for 2-methylanthraquinol, anthraquinol-2-sulphonate and anthraquinol-2,6-disulphonate radical cations.The hyperfine coupling constants (h.f.s.) and g factors are given. The ENDOR spectra show there to be more h.f.s. than were detected earlier by e.s.r. spectroscopy. The spectra of the di-deutero radicals of the anthraquinols and the assignment of h.f.s. are discussed.

TEMPERATURE DEPENDENCE OF THE ISOTROPIC HYPERFINE COUPLING CONSTANTS IN 1,4-HYDROQUINONE AND 1,4-DIHYDROXYNAPHTHALENE CATION RADICALS

The temperature dependences of hydroxyl group proton and ring proton isotropic hyperfine coupling constants (IHFC) of 1,4‐hydroquinone (HQ) and 1,4‐dihydroxynaphthalene (NQ) cation radicals were measured by electron paramagnetic resonance spectroscopy. The spectral parameters were obtained in the temperature range 150–300 K using various solvents. The hydroxyl group proton IHFC data obtained were fitted to the theoretical temperature dependence model, yielding the hydroxyl group rotation barrier height and completely planar hydroxyl proton IHFC value. Experimental results are discussed with reference to theoretical density functional calculations. The new experimental rotation barrier heights for HQ and NQ cation radicals are 59±4 and 37±4 kJ mol‐1 in nitromethane, respectively.

Molecular orbital study of the isotropic hyperfine coupling constants of hydroquinone and tetramethylhydroquinone cation radicals

The isotropic hyperfine coupling constants (IHFC) of hydroquinone and tetramethylhydroquinone cation radicals have been studied with the UB3LYP and UB3PW91 density functional methods. The ability of various basis sets to reproduce the experimental IHFCs was tested. The effects of the zero-point and temperature-dependent torsional oscillations of the hydroxy groups to the IHFCs were calculated by solving the torsional Schrodinger equation. Consideration of torsional zero-point and temperature-dependent oscillations were essential in order to reproduce the hydroxy proton IHFC experimental results with the computational methods. The applied theory predicts a considerable temperature dependence for the hydroxy proton IHFC and a very small temperature dependence for the ring-proton IHFCs in both cis and trans isomers.

Electron paramagnetic resonance, ENDOR and TRIPLE resonance of some 9,10-anthraquinone radicals in solution. Part 3.—Hydroxyanthraquinones

EPR, ENDOR and TRIPLE resonance spectra have been recorded for 1,4-dihydroxy-9,10-anthraquinone, 1,5-dihydroxy-9,10-anthraquinone, 1,8-dihydroxy-9,10-anthraquinone, 2,6-dihydroxy-9,10-anthraquinone, 1,2-dihydroxy-9,10-anthraquinone, 1,2-dihydroxy-9,10-anthraquinone-3-sodium sulphonate and 1,2,5,8-tetrahydroxy-9,10-anthraquinone anion radicals. The hyperfine coupling constants and g factors are given. Use of a modified additivity relationship allowed assignment of the constants. The spectra of deuterated radicals are discussed.

Electron spin resonance, ENDOR and TRIPLE resonance of some 9,10-anthraquinone radicals in solution. Part 2.—Anthraquinonesulphonates

We report studies on radical anions of 9,10-anthraquinone-1-sulphonate, 9,10-anthraquinone-1,5-disulphonate, 9,10-anthraquinone-2-sulphonate, 9,10-anthraquinone-2,6-disulphonate and 9,10-anthraquinone-1,2-dihydroxy-3-sulphonate in alkaline ethanol and water mixtures carried out by multiple resonance spectroscopy. The hyperfine coupling constants and relative signs were determined in ENDOR and TRIPLE resonance experiments. The temperature dependence of the coupling constants was measured and the g values were also estimated. Use of a modified additivity relationship suggested a new assignment of the coupling constants.

Molecular orbital study of conformational isomers and rotational barriers of methyl substituted hydroquinone cation radicals

Abstract The torsional potential energy curve of the hydroxyl group of hydroquinone and tetramethyl-hydroquinone cation radicals were explored with various ab initio methods. The minimum and the torsional transition state geometries and energies were computed by using high accuracy density functional methods yielding the rotation barrier height and the energy difference between the cis- and trans-isomers. The obtained minimum energy geometry for the hydroquinone cation radical indicates that the CO bond has shortened when compared to the neutral species. We attribute this to the increased double-bond character of this bond. The energy minima were located for methyl-hydroquinone, 2,3-dimethyl-hydroquinone, 2,5-dimethyl-hydroquinone, 2,6-dimethylhydroquinone and trimethyl-hydroquinone cation radicals. By assuming the Boltzman distribution among the energy levels of the cis- and trans-isomers of these compounds the ratio of expected isomers at 230K was obtained.

Comparison of Spin Density Calculation Methods for Various Alkyl‐Substituted 9,10‐Anthraquinone Anion Radicals in the Solution Phase

EPR and ENDOR spectra were recorded for 2‐methyl‐9,10‐anthraquinone (2‐methylAQ), 2‐ethylAQ, 2‐tert‐butylAQ and 2,3‐dimethylAQ anion radicals in the solution phase. The EPR spectra were simulated with the help of ENDOR data. The experimental isotropic hyperfine coupling constants (IHFCs) were compared with calculated values from semi‐empirical INDO, spin‐restricted AM1/CI and B3PW91 density‐functional methods. The best computational methods for the IHFCs were the semi‐empirical AM1/CI method and the B3PW91 density‐functional method with a large basis set.

Electron paramagnetic resonance, ENDOR and TRIPLE resonance study of methyl-substituted benzoquinol radical cations

EPR and ENDOR spectra have been recorded for hydroquinone, methylhydroquinone, 2,3-dimethylhydroquinone, 2,5-dimethylhydroquinone, 2,6-dimethylhydroquinone, 2,3,5-trimethylhydroquinone and tetramethylhydroquinone radical cations. The radicals were generated by Ce4+ or Zr4+ oxidation in FSO3H or FSO3H and CH3NO2 solution. The radical cations were stable in strongly acidic media, where they existed in double-protonated form. The splittings of hydroxyl protons were assigned by deuteriation and other coupling constants by the additivity relationship. The cis–trans isomerism of the double-protonated cation radicals showed up clearly in EPR and ENDOR spectra of four of the radicals.