Coenzyme Q10 in health and disease.

The literature concerning the importance of coenzyme Q10 in health and disease has been reviewed. Usual dietary intake together with normal in vivo synthesis seems to fulfil the demands for Q10 in healthy individuals. The importance of Q10 supplementation for general health has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases, including cardiomyopathy, relatively low levels of Q10 in myocardial tissue have been reported. Positive clinical and haemodynamic effects of oral Q10 supplementation have been observed in double-blind trials, especially in chronic heart failure. These effects should be further examined. No important adverse effects have been reported from experiments using daily supplements of up to 200 mg Q10 for 6-12 months and 100 mg daily for up to 6 y.

[Efficacy and safety of dietary supplementation containing Q10]. / Effekt og sikkerhed af kosttilskud indeholdende Q10.

The literature concerning the importance of Q10 for health and disease has been reviewed. Dietary intake together with normal in vivo synthesis seems to fulfil the body's demands for Q10 in younger, healthy individuals. The importance of Q10 in general well-being has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases a positive effect of oral Q10 supplementation has been reported, especially in chronic heart failure. These effects should be further examined. No important adverse side effects have been reported from experiments using daily supplements of up to 200 mg of Q10 for six to twelve months, and 100 mg daily for up to six years.

A comparison of three diuretic regimens in heart failure.

Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment 1) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The 'quality of life' did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 (P < 0.02) and 6.7% lower during treatment 3 (P < 0.05). In comparison with treatment 1, the maximal increase in rate-pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P < 0.05) and 18% lower during treatment 3 (P < 0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand.

Heart muscle ubiquinone and plasma antioxidants following cardiac transplantation.

Nine patients who underwent heart transplantation (one female; average age 48 +/- 11, range 19-58 years) were followed in respect to contents of right-sided heart septum, blood and plasma ubiquinone (UQ), plasma alpha-tocopherol (alpha T), and plasma free cholesterol (FC). In contrast to healthy persons, substantial inter- and intraindividual variations were observed; individually low values were seen with rejection. Heart muscle UQ in well-treated patients averaged 0.33 +/- 0.08, range 0.06-0.58 micrograms mg-1 (0.38 +/- 0.09 mumol g-1 dry weight) and was not different from healthy individuals. Plasma UQ, alpha T; and FC averaged 0.63 +/- 0.33 micrograms ml-1 (P < 0.05 versus sedentary controls), 8.1 +/- 4.0 micrograms ml-1 (P < 0.01), and 0.52 +/- 0.23 mg ml-1 (P < 0.05). Corresponding molar values were 0.73 +/- 0.37 (UQ), 2.0 +/- 1.1 mumol l-1 (alpha T), and 1.42 +/- 0.54 mmol l-1 (FC). Blood and plasma UQ values were identical. A saturation like relationship was found between heart and blood UQ:blood contents below 0.7 micrograms ml-1 (0.8 mumol l-1) corresponded to markedly lowered heart contents. In four patients in whom blood samples were taken close to a fatal complication it averaged 0.42 micrograms ml-1 (0.49 mumol l-1, P < 0.01). When low heart muscle and blood ubiquinone were present, other variables such as left ventricle cardiac output or cycle ergometer performance was markedly impaired. Plasma UQ and alpha T covaried with a marker of the lipoidal deposit volume, plasma FC.(ABSTRACT TRUNCATED AT 250 WORDS)

Ubiquinone and alpha-tocopherol in plasma; means of translocation or depot.

Ubiquinone (UQ) and alpha-tocopherol (AT) are two highly lipophilic antioxidants which can be dissolved only in lipid layers or attached to protein structures. Analyses of both UQ and AT in whole blood and plasma demonstrate identical values, which excludes any significant allocation to blood cells. The lipoidic plasma structures constitute the plasma lipoprotein fractions of high (HDL), low (LDL), and very low (VLDL) density in addition to chylomicrons. This means by definition that blood and plasma UQ and AT values are limited if not related to the lipoidic deposit volume. UQ and AT increase linearly with free cholesterol (FC). FC has therefore been suggested to be a good marker for the deposit volume. The ratios UQ and AT over FC--normalized UQ (N-UQ) and normalized AT (N-AT)--have been computed for inter- and intraindividual comparisons. With a plasma UQ content of 1 microgram/ml (approximately 1 mumol/l) and a plasma volume of 41, UQ makes up about 15% of the total heart content or under 1% of UQ in skeletal muscle. The corresponding value for the total extracellular UQ content is less than 2%. This means that extracellular UQ has no or a very minor role as a UQ depot. The same is true for AT. However, for transportation and allocation determinations of N-UQ and N-AT are relevant. Assuming only a lipoprotein-related transportation, healthy persons have saturated plasma UQ and AT values in only 25% and 10% of the population, respectively. All patient categories studied have been found nonsaturated. VLDL plus LDL constitute some 90% of the UQ deposit volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment and evaluation of the International Water Decade.

The International Drinking Water Supply and Sanitation Decade (1981-90) has ended without reaching its declared goal of providing all people with safe drinking water and proper sanitation. The effect of drinking water and sanitation on health has been established, and the 2 components have been included in the World Health Organization (WHO) global campaign for Health For All by the year 2000, and in the global Primary Health Care programme. The assessment of the achievements has been based on coverage rates expressed in percentage. The findings were computerised. High population growth rates in the developing countries hampered and reduced the coverage. Other hindering factors included the lack of appropriate technology, the preference of the small privileged urban areas over the vast rural areas, the lack of the simultaneous approach in the development of water and sanitation and poor involvement of health education in the activities of the Water Decade. The water and sanitation development activities of the last decade have to be carried forward and continued during the present decade, in a different approach and alternative methods.

Ischaemic heart disease, skeletal muscle fibres and exercise capacity.

Twenty-eight male patients with ischaemic heart disease (IHD) performed OBLA (onset of blood lactate accumulation) exercise stress tests and had muscle biopsies taken from their vastus lateralis muscle the day before coronary bypass grafting. All 28 patients showed the same exercise performance pattern as compared to healthy sedentary, age-matched, controls: a low exercise intensity eliciting a blood lactate concentration of 2.0 mmol x l-1 (WOBLA), WOBLA corresponded to a high fraction (% WOBLA) of WSL (symptom limited or 'maximal' capacity), and a low peak blood lactate concentration. The high % WOBLA and low peak blood lactate indicated a reduced glycogenolytic capacity ('anaerobic' performance). Muscle fibre composition disclosed a high mean value of fast twitch (FT), type II or 'white' muscle fibres, as compared to sedentary healthy controls. This indicated that this patient group constituted an extreme subgroup of the age-matched population. The distorted muscle fibre composition in IHD could reflect both heredity as well as adaptation to physical inactivity, degenerative cytosolic properties, etc. Muscle and blood contents of a mitochondrial electron translocator and nonspecific radical scavenger, ubiquinone or coenzyme Q10(CoQ10), were low, which coincided with an elevated frequency of the fibre subgroup FT(c). The presence of the FT(c) fibre type is assumed to reflect histological trauma.

Exercise-limiting factors in respiratory distress.

Exercise performance data, circulatory function and respiratory and leg muscle quality, expressed as muscle fiber composition, are reviewed and together with our own data discussed as possible limiting factors for physical performance in chronic obstructive pulmonary disease (COPD). COPD is regarded as synonymous with reduced physical performance, exaggerated breathlessness or dyspnea, muscle hypotrophy and/or wasting and, frequently, malnutrition. Impaired right ventricular circulatory function seems to be essential. The observed preponderance of fast twitch (FT), 'glycogenolytic' and capillary-poor muscle fiber type in the investigated muscles might reflect endowment, a 'hypoxic vasoconstriction'-related downregulation of the other main fiber type: the slow twitch (ST), capillary-rich, fatigue-resistant fiber, and/or selective muscle trauma to ST fibers. Ischemic heart disease (IHD) patients demonstrate a similar fiber type pattern in leg muscles. Both COPD and IHD patients have low leg muscle and plasma deposits of antioxidants such as coenzyme Q10 (CoQ10) and alpha-tocopherol. This could reflect a depressed resistance to radical induced cell trauma and/or malnutrition. The magnitude of the antioxidant reduction is less pronounced in patients rich in FT fibers indicating a ST fiber-related susceptibility to trauma. Treatment of other muscle disorders including heart muscle with, e.g., CoQ10 improves performance due to a causative enhanced antioxidant potential, reduced catabolism and/or an upregulated muscle anabolism, increased mitochondrial volume/function, etc. Such data are lacking in COPD.

Plasma ubiquinone, alpha-tocopherol and cholesterol in man.

Plasma ubiquinone, coenzyme Q10 or CoQ10 has been analyzed in plasma together with alpha-tocopherol and free cholesterol in healthy sedentary male subjects (SS), endurance trained male athletes (ET) and male patients with severe ischemic heart disease (IHD). Higher means were found in SS compared to both IHD and ET. Moreover, the ratios CoQ10 and alpha-tocopherol over free cholesterol were higher. In all groups significant relationships were found between the two products of the mevalonate pathway: CoQ10 and cholesterol (r ranged 0.66-0.86, p less than 0.01). The two lipophilic antioxidants, CoQ10 and alpha-tocopherol, were interrelated only in IHD (r = 0.86, p less than 0.001), borderline in SS (r = 0.51, p less than 0.05) but not in ET. It is assumed that plasma free cholesterol reflects the capacity to transport lipids and lipophilic compounds in blood. With metabolic stress and an elevated radical formation as in IHD and ET, the lower CoQ10 and alpha-tocopherol to cholesterol ratios mirror a subsequent toll on the scavenging potential. The difference in LDL levels between IHD and ET and the different storage capacity of CoQ10 and alpha-tocopherol might explain the tight coupling in IHD but not in ET. It is possible that the toll reflects both an intra- and extracellular radical quenching activity. The joint effect of the two lipophilic, extracellular antioxidants CoQ10 and alpha-tocopherol role in protecting e.g. LDL particles from peroxidation is suggested.

Coenzyme Q10, alpha-tocopherol and free cholesterol in HDL and LDL fractions.

Twenty-three randomly selected plasma samples from apparently healthy, middle aged men were analysed for coenzyme Q10 (CoQ10), alpha-tocopherol (AT) and free cholesterol (FC) in: 1) whole plasma, 2) the HDL lipoprotein fraction after LDL precipitation (VLDL + LDL). CoQ10, AT and FC in plasma averaged 0.69 +/- .11, 6.74 +/- 1.78 micrograms x ml-1 and 0.59 +/- .11 mg x ml-1 and in HDL 0.17, 3.24 micrograms x ml-1 and 0.17 mg x ml-1 or 29, 48 and 29% of plasma values. Amounts of CoQ10 and AT were correlated to that of FC in all pools. The amount of HDL-CoQ10 but not of HDL-AT fell, with the HDL-FC expressed as the fraction of plasma FC. In all pools, N-AT versus AT initially increased and then levelled off, indicating saturation like conditions in contrast to CoQ10. Thus, CoQ10 and AT are differently allocated in HDL and LDL. This might have a bearing both on the suggested lipoprotein protection against peroxidation by these two antioxidants, but also on the distribution and allocation in different organs of CoQ10 and AT by HDL and LDL transportation.

Muscle mass effect on arterial desaturation after maximal exercise.

We measured arterial oxygen saturation before and immediately after randomly allocated 6 min of "all-out" maximal arm cranking, treadmill running, and ergometer rowing in 10 men and women with a median maximal oxygen uptake of 4.47 (range 3.22-5.34) 1.min-1. Arterial saturation for oxygen was unaltered after arm cranking, but decreased 1.7 (-2.5-6.0) % (P less than 0.05) after running, and 2.2 (1.0-8.7) % (P less than 0.01) after rowing. Arterial saturation was inversely related to capillary blood lactate, which reached 11.8 (7.4-14.0), 12.6 (8.9-18 2), and 14.3 (12.0-19.3) mmol.l-1 (P less than 0.01), respectively, and arterial bicarbonate fell to 15.0 (13.0-23.6), 12.4 (7.2-20.4), and 10.8 (0.0-12.5) mmol.l-1 (P less than 0.01). Thus, pH decreased to 7.25 (7.22-7.40), 7.17 (6.95-7.35), and 7.09 (6.84-7.19) (P less than 0.01). When measured immediately post-exercise, arterial oxygen tension was unchanged or elevated from rest, eliminating the possibility that the arterial desaturation was caused by a pulmonary diffusion limitation. The results of this investigation show that arterial desaturation associated with maximal exercise takes place in proportion to the involved muscle mass, as do deviations in blood lactate, bicarbonate, and hydrogen concentrations.

Muscle fibre types, ubiquinone content and exercise capacity in hypertension and effort angina.

The composition of skeletal muscle fibre expressed as a percentage of slow twitch (ST), type I or "red" and fast twitch (FT), type II or "white" were determined in patients with hypertension (HT) or with severe ischaemic heart disease (IHD) and compared to age matched controls. Similarly, exercise capacity expressed as the cycle intensity eliciting a blood lactate concentration corresponding to 2.0 mmol x 1-1 were compared with healthy controls. Both patient groups had a higher percentage of FT fibres with relatively lower exercise capacities than their controls. The exercise capacities were reduced even when the relationship of decreased capacity with the percentage of increased FT was considered. There was an increase IHD but not in HT in patients with fibre subgroup FTc, which most probably reflected fibre trauma. Both patient groups were low in the skeletal muscle mitochondrial electron carrier and unspecific antioxidant ubiquinone, coenzyme Q10 or CoQ10. Patients with IHD but not HT showed, however, a faster fall in the ratio CoQ10 over ST% the higher the percentage value of ST. The ratio reflects the antioxidant activity related to CoQ10 in the fibre hosting most of the oxidative metabolism. A low ratio indicates a risk of metabolic lesion and cell trauma. This could explain fibre plasticity and offer an alternative cause to heredity in elucidating in deviating muscle fibre composition in patients with HT and IHD.

Effects of N-acetylcysteine on histamine release by sodium fluoride and compound 48/80 from isolated rat mast cells.

N-acetylcysteine (NAC) enhances the release of histamine induced by the fluoride-calcium system but not by compound 48/80. After preincubation of the cells for 2 h at room temperature (RT) as well as at 37 degrees C, NAC was found to enhance histamine release also when induced by compound 48/80. Both fluoride treatment and prolonged incubation at 37 degrees C (but not at RT) for 2 h decreased the ATP content of the cells. NAC was found to counteract the fall in ATP caused by prolonged incubation of the cells at 37 degrees C but not when induced by exposure to sodium fluoride. The results do not favor the concept that free radicals generated by fluoride treatment are responsible for the subsequent sensitivity of the cells to the secretory action of calcium. On the other hand, it cannot be excluded that free radicals generated during prolonged incubation of the cells at 37 degrees C might be involved in the decrease of the sensitivity of the cells to the secretory action of the fluoride-calcium system and of compound 48/80. This is supported by the finding that the presence of NAC not only activated the secretory response but also counteracted the decrease of the cellular ATP content noted following preincubation of the cells for 2 h at 37 degrees C.

Effects of long-term coenzyme Q10 and captopril treatment on survival and functional capacity in rats with experimentally induced heart infarction.

The effects of coenzyme Q10 (CoQ) and captopril on functional capacity, hemodynamics and survival were studied in 154 rats that recovered after experimental myocardial infarction. Rats were randomized into four groups receiving either CoQ, captopril, a combination of the two drugs or 1 ml of tap water once daily for 12 weeks from the day of coronary artery ligation. CoQ as well as captopril and the combined treatment significantly improved exercise capacity as evaluated by lactate production during a standardized treadmill exercise test. No significant changes in heart rate or mean blood pressure were observed during the study in the captopril-treated group. CoQ treatment increased the maximum heart rate significantly, whereas no effect on mean blood pressure was observed. Both captopril and CoQ decreased pulmonary congestion. Furthermore, the data may suggest that captopril prevents right ventricular hypertrophy seen in placebo-treated rats with large infarcts. This was not observed after CoQ treatment. Captopril treatment improved 3-month probability of survival (93%) as compared with placebo (74%) (P less than .05). CoQ and the combined treatment tended to improve survival, but this was, however, not statistically significant.

Isolation of cardiac ventricular myocytes from newborn rats by use of fractional elutriation centrifugation.

Isolation of cardiac ventricular myocytes from newborn rats (0-4 days old) by use of elutriation centrifugation is described. By the use of fractional centrifugation, a homogeneous myocyte population with high purity was obtained without any further procedures, yielding about 10(6) myocytes/rat. When 48-hr monolayer cultures were established, the cells showed normal pulsatory contractions. A morphological evaluation of such cultures is given.

Time course of functional deterioration after coronary artery ligation in rats.

The aim of this study was to investigate the time course of deterioration of functional capacity in the rat after ligation of the left coronary artery. Functional capacity was evaluated from the increase in blood lactate concentrations in 109 rats during a standardised treadmill test. Animals with myocardial infarction were compared with sham operated and normal controls. Functional capacity was followed during a 13 week period and estimations of the functional capacity were performed 1, 3, 7, 9 and 13 weeks after infarction. Coronary artery ligation produced a significant reduction in functional capacity, averaging 47% (p less than 0.01) over the first 3 weeks after myocardial infarction, irrespective of infarct size. In rats with large infarcts, functional capacity remained essentially unchanged throughout the observation period, but rats with small infarcts improved gradually until their measured exercise response was completely normal at the end of the 13 week period.

Ergogenic effect of inhaled beta 2-agonists in asthmatics.

To investigate the effect of beta 2-agonists on exercise performance, eight asthmatics performed an incremental exercise test on a treadmill. Five minutes before the start of the exercise, they were treated with inhaled salbutamol or placebo in a double-blind manner. The exercise started at a low intensity (2 mph, 10% inclination), and every 3 min the speed was increased by 0.5 mph at the same inclination until the subjects were exhausted. Every minute peak expiratory flow, heart rate, blood lactate concentration, and rating of perceived exertion were measured. The same parameters were also measured following the completion of the exercise. No significant difference was seen in total working time, maximal lactate concentration, heart rate, or rating of perceived exertion, whereas the decrease in peak expiratory flow was reduced following pretreatment with salbutamol. It is concluded that the release of inhaled beta 2-agonists for use in competitive events is justified as no ergogenic effect was seen.