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Previous in vitro studies have shown that isolated mitochondria can generate oxygen radicals. However, whether a similar phenomenon can also occur in intact organs is unknown. In the present studwy,e tested the hypothesis that resumption of mitochondrial respiration upon reperfusion might be a mechanism of oxygen radical formation in postischemic hearts, and that treatment with inhibitorosf mitochondrial respiration might prevent this phenomenon. Three groups of Langendorff- perfused rabbit hearts were subjected to 30 min of global ischemia at 37 “C, followed by reflow. Throughout ischemia and early reperfusion the hearts received, respectively: (a) 6 mM KC1 (controls), (b) 6 mM sodium amobarbital (Amytal“, which blocks mitochondrial respiration at Site I, at the level of NADH dehydrogenase), and (c) 6 mM potassium cyanide (to block mitochondrial respiration distallya, t the level of cytochrome c oxidase). The hearts were thperonc essed to directly evaluatoex ygen radical generationb y electron paramagnetic resonances pectroscopy, or to measure oxygen radical-induced membrane lipid peroxidation by malonyl dialdehyde (MDA) content of subcellular fractions. Severity of ischemia, as assessed by “P-nuclear magnetic resonance measurements of cardiac ATP, phosphocreatine, and pH, was similar in all groups. Oxygen-centered free radical concentration averaged 3.84 f 0.64 PM in reperfused control hearts, and it was significantly reduced by Amytal treatment (1.98 2 0.26; p < 0.06), but not by KCN (2.68 f 0.96 PM; p = not significant (NS)), consistent with oxygen radicals being formed in them itochondrial respiratory chain at Site I. Membrane lipid peroxidation of reperfused hearts was also reduced by treatment with Amytal, but not with KCN. MDA content of the mitochondrial fraction averaged 0.76 f 0.06 nM/mg protein in controls, 0.72 f 0.06 in KCN-treated hearts, and0 .64groups). Similarly, MDA content of lysosomal membrane fraction was0 .64 f 0.09 nM/mg protein in controls, 0.79 C 0.16 in KCN-treated hearts, and 0.43 2 0.06 in Amytal-treated hearts ( p 0.06 versus both groups). Since the effects of Amytal are known to be reversible, in a second series of experiments we investigated whether transient mitochondrial inhibition during the initial1 0 min of reperfusion wasa lso associated with beneficial effects on subsequent recovery of cardiac function after wash-out of the drug. At the end of the experiment, recoveroyf left ventriculaer nddiastolic and of developed pressure was significantly greater in those hearts that had been treated with Amytal during ischemia and earlyre flow, as compared to untreated hearts. In conclusion, our data demonstrate that in intact hearts electron flow through the respiratory chain may be an important source of oxygen radicals, which may form at the sites of interactions between Fe-S clusters and ubiquinone, and that resumption of mitochondrial respiration upon reoxygenation might contribute to reperfusion injury.

Skin ulcers are a dangerous and uncommon complication of vasculitis. We describe the case of a teenager suffering from Systemic Lupus Erythematosus with digital ulcer resistant to conventional therapy, treated successfully with Hyperbaric Oxygen Therapy. The application of hyperbaric oxygen, which is used for the treatment of ischemic ulcers, is an effective and safe therapeutic option in patients with ischemic vasculitic ulcers in combination with immunosuppressive drugs. Further studies are needed to evaluate its role as primary therapy for this group of patients.

The relationship between either heart rate or diastolic time and ST segment depression has been evaluated during supine and upright exercise in 16 coronary artery disease patients. Diastolic perfusion time and ST segment depression were related by a linear regression, which was independent of exercise posture. The entity of ST segment depression was greater during supine than in upright exercise for the same heart rate. The assessment of the relationship between heart rate and diastolic perfusion time during two exercises showed that at the same heart rate, diastolic perfusion time was shorter in supine posture. In conclusion, the greater entity of ST segment depression induced by supine rather than upright exercise might be explained by the effect of supine posture on diastolic perfusion time.

The lipophilic probe 1,6-diphenyl-1,3,5-hexatriene was incorporated into erythrocyte ghosts of either normal or obese humans, and the polarization of fluorescence was measured between 0 and 40 C. The membrane lipid fluidity, evaluated by fluorescence polarization, was consistently higher in the ghosts from obese subjects. A strong correlation was found between increased 1,6-diphenyl-1,3,5-hexatriene fluorescence polarization and excess body weight. Measurements of cholesterol and phospholipids indicated increased cholesterol and decreased phospholipids in erythrocyte ghosts from obese subjects. These data suggest that alterations in lipid composition in erythrocytes of obese subjects are responsible for abnormal physical properties of plasma membranes, which, in turn, may cause altered enzymatic activities.

The mitogenic effect of thyrotropin on functional rat thyroid cells of the line FRTL-5 is correlated with membrane lipid fluidity as evaluated by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. Continued exposure of FRTL-5 cells to a medium lacking thyrotropin causes cessation of cell proliferation and a decrease in membrane lipid fluidity which reaches its minimum in approximately 8 days. The change in lipid fluidity is due to an absolute increase (greater than 2-fold) of membrane cholesterol, with an increased cholesterol/phospholipid ratio and an increased ratio of saturated to unsaturated fatty acids of the membrane phospholipids, contributed primarily by a nearly 4-fold increase in the ratio of saturated to unsaturated C16 fatty acids. It is also associated with a variation of the relative proportions of the major membrane phospholipids; thus, phosphatidylinositol and phosphatidylethanolamine decrease while phosphatidylcholine increases. Both membrane fluidity and lipid composition can be restored by thyrotropin to their original levels, i.e. levels measured under continuous exposure to the hormone. Complete reversal requires at least 48 h, i.e. approximately the same time required for resumption of growth when FRTL-5 cells, starved in thyrotropin, are re-exposed to the hormone. Changes in lipid composition and fluidity can be prevented or can be reversed if FRTL-5 cells are exposed to dibutyryl cAMP while being deprived of thyrotropin. Dibutyryl cAMP has only a modest direct effect on growth; however, this pretreatment eliminates the 48-h lag phase with respect to thyrotropin stimulation. It is proposed that the effects of thyrotropin on growth of FRTL-5 cells requires a modification of the molecular structure and the physical state of cell membranes, which can be mediated by cAMP, although cAMP is not sufficient by itself to promote growth.

Diastolic perfusion time is a critical determinant of myocardial oxygen supply when coronary artery flow is limited by a significant stenosis of the coronary vessel. Diastolic time adjustment of the ST segment depression occurring during effort enhances stress test prediction of the coronary impairment severity. Effective diastolic adjustment of ST segment requires a stable and simple to perform measurement of the diastolic perfusion time during stress test execution. The authors investigated the reproducibility of the diastolic measurements obtained using the arterial pulse of the lobulus auriculae compared to the classical phonocardiographic data. The results obtained indicate that ear arterial pulse measurement of the diastolic time is reliable avoiding the difficulties rising from using the phonocardiographic method.