Passive smoking impairs endothelium-dependent relaxation of isolated rabbit arteries.

The aim of the present study was to examine the effect of prolonged passive smoking (lasting 3 weeks) on plasma catecholamine levels and reactivity of isolated rabbit arteries. Plasma noradrenaline, adrenaline and dopamine levels were determined radioenzymatically. Isolated rings of the thoracic aorta and carotid artery were suspended in organ chambers and connected to a force transducer for the recording of isometric tension. Plasma noradrenaline levels were found to be significantly elevated in rabbits subjected to passive smoking for 3 weeks. Plasma adrenaline and dopamine levels were not changed. Transmural nerve stimulation of arterial rings evoked frequency-dependent contractions. Prolonged passive smoking did not affect neurogenic contractions of the arteries tested. On the other hand, endothelium-dependent relaxations of phenylephrine-precontracted arteries were significantly impaired. Furthermore, hypertrophy of the left ventricle was observed. In conclusion, passive smoking impairs endothelium-dependent relaxations but not neurogenic contractions of systemic arteries. The impaired relaxations of arteries may be, at least in part, mediated through the degradation of released nitric oxide by superoxide anions derived from cigarette smoke.

[The cytoprotective effect of magnesium in global myocardial ischemia]. / Cytoprotectívny úcinok magnézia v podmienkach globálnej ischémie myokardu.

BACKGROUND: Administration of magnesium in the therapy of ischaemic heart diseases does not belong to the standard procedures. The results of clinical trials with application of this cation are mutually contradictive, mechanisms of its effect are not solved yet. Many physicians consider magnesium to represent a classical placebo, or an uncertain light sedative. MAIN PURPOSE AND OBJECTIVES: The study is aimed at proving the direct effect of magnesium on the heart muscle under ischaemic conditions which exclude the placebo effects. These conditions are mostly fulfilled by the model of isolated heart. MATERIAL AND METHODS: The authors used isolated rabbit hearts according to Langedorff with Krebs-Henseleit (KH) perfusion solution, the only variable of which is represented by concentration of magnesium. The following groups of patients were formed: 1. Control group-30-minute perfusion with normal Mg concentration (0.5 mmol/l) in KH solution. 2. Hypomagnesemia-30-minute perfusion with KH solution Mg-free. 3. Normomagnesemia+ischaemia-30-minute perfusion with normal concentration succeeded by a 60-minute global ischaemia. 4. Hypomagnesiaemia+ischaemia-30-minute perfusion with KH solution magnesium-free succeeded by a 60-minute global ischaemia. 5. Hypermagnesiemia +ischaemia-30-minute perfusion with increased Mg concentration in KH solution to 2.0 mmol/l succeeded by a 60-minute global ischaemia. The investigated parameters: after completion of perfusion the authors isolated mitochondria and evaluated individual parameters of oxidative phosphorylation by means of oxygraph/Gilson/with Clark's oxygen electrode. The calcium uptake by mitochondria was observed by means of calcium-sensitive electrode Orion (oxygraph Gilson). The formation of free oxygen radicals was observed indirectly by spectrophotometric assessment of malondialdehyde production. Concentration of mitochondrial nucleotides (AMP, ADP, ATP) was assessed by using HPLC. RESULTS: Hypomagnesemia lasting 30 minutes had a negative effect on the index of oxidative phosphorylation (ADP:O p < 0.005) the uptake of calcium (p < 0.002), ATP concentration in mitochondrial ATP (p < 0.05) and the production of free radicals significantly increased (p < 0.001). Normomagnesemia indicated practically no cytoprotective effect before global ischaemia of myocardium lasting for 60 minutes. Hypermagnesemia indicated a direct cytoprotective effect before global ischaemia affecting respiration of isolated heart mitochondria in state of S3 (p < 0.001), respiration control index RCI (p < 0.001), the rate of oxidative phosphorylation OPR (p < 0.001) and on the index of oxidative phosphorylation ADP:O (p < 0.05) on the uptake of calcium by mitochondria (p < 0.002) and on concentration of mitochondrial nucleotides ATP (p < 0.002). It was remarkable that also under conditions of moderate hypomagnesemia the production of malondialdehyde increased. CONCLUSIONS: Under our experimental conditions it was confirmed that magnesium yields direct cytoprotective effect on the subcellular level of the myocardium prior to global ischaemia, providing the process takes place under the condition of hypermagnesemia. (Tab. 1, Fig. 12, Ref. 45.) Key words: hypomagnesemia, normomagnesemia, hypermagnesemia, Langendorff's global ischaemia, mitochondrial metabolism, cytoprotective effect.

[Cardiomyopathies from the aspect of clinical and experimental cardiology]. / Problematika kardiomyopatií z hladiska klinickej a experimentálnej kardiológie.

The study represents a summary of the latest experience, definitions, classification and diagnostics in cardiomyopathologic diseases. The main attention is drawn to the pathogenesis of cardiomyopathies, especially regarding the metabolic disturbances of the cardiac muscle on the mitochondrial level: the disturbances of oxidative and related energetic processes which the authors have registered in coincidence with the cardiomyopathological alcohol and smoking experimental model. The conclusion includes a notice about the prospective possibility for human cardiology to study these metabolic disturbances in endomyocardial biopsies in order to assess the diagnosis in early thus still reversible stages.

[Cardiomyopathies and myocarditis]. / Kardiomyopatie a myokarditídy.

The authors discuss recent findings regarding cardiomyopathies, assembled recently due to the association of clinical and experimental cardiology. The main attention is paid to the pathogenesis of cardiomyopathies from the aspect of metabolic disorders of the heart muscle at the cellular and subcellular level. The differential diagnosis in relation to myocarditis is still a serious problem in cardiology: acute myocarditis is not a myocardiopathy, there exists, however, a close relationship between viral myocarditis and the development of dilatation cardiomyopathies. Echocardiography is one of the most important diagnostic examinations.

[Redox therapy in mitochondrial diseases using coenzyme Q10]. / "Redox terapia" mitochondriálnych chorôb koenzýmom Q10.

BACKGROUND: The biochemical and genetic analysis served as the basis for the definition of the following mitochondrial diseases (mt diseases) and the diseases of the mitochondrial deoxyribonucleic acid (mtDNA diseases): mitochondrial myopathy, encephalomyopathy, and cardiomyopathy. The therapy of mitochondrial diseases (in both practice and experiment) belongs to the current trends of research. AIM: The study does not present any new experimental results but in their literary review the authors indicate: a) new trend in biochemical studies of mitochondrial diseases, b) some current knowledge on mtDNA diseases, c) the current trend of mitochondrial disease "redox therapy" by CoQ10, d) significance of the therapeutic task of CoQ10 in four experimental models of the myocardial mitochondria impairment (by ageing, smoking, alcohol, ischemia). SIGNIFICANCE FOR PRACTICE AND RESEARCH DEVELOPMENT: The authors indicate a new perspective for the studies of mitochondrial diseases (mt diseases) and the diseases of the mitochondrial deoxyribonucleic acid (mtDNA diseases) and their therapy not only under experimental conditions, but also in the blood and bioptic samples of patients. (Tab. 3, Fig. 2, Ref. 43.)

[New findings on cardiomyopathies]. / Novsie poznatky o kardiomyopatiách.

In this review the authors summarize the newest knowledge on cardiomyopathies, which was obtained during the last ten years due to joint experimental and clinical in this field. It concerns the pathogenesis of cardiomyopathies from the point of view of metabolic damage of the heart on the cellular and subcellular level, the diagnosis--mainly by means of echocardiographic investigation, as well as the therapy of cardiomyopathies--medicamental and surgical (transplantation of the heart). (Ref. 6.)

[Significance of mitochondrial Ca2+ transport in ischemic injury and myocardial protection]. / Význam transportu Ca2+ mitochondriami pri ischemickom poskodení a ochrane srdcového svalu.

The role of calcium regarding the origin of irreversible impairment of the myocardial tissue is being intensively studied. An important role in this process is played by mitochondria which by means of the active Ca2+ uptake stimulate its oxidative metabolism and intervene into the Ca2+ homeostasis in mitochondrial cells. The study investigates the influence of cardioprotective substances with distinct mechanisms of the mitochondrial Ca2+ uptake effect. The experiments were performed on chinchilla buck rabbits of 2500-3000 g of body weight. Isolated hearts were perfused according to the method of Langendorff, ischemia was evoked by a 60-minute stoppage of the coronary blood flow. The cardioprotective substances were added into the perfusion solution prior to ischemia inducement. We investigated the following cardioprotective substances: Spirapril (ACE inhibitor), magnesium (Mg2+), and MDL 73,404 (antioxidant, synthetic analogue of alpha-tocopherol). After the 60-minute ischemy the mitochondrial Ca2+ uptake decreased by 43% in comparison with the control group (p < 0.01), Spirapril caused its accretion by 35% in comparison with the ischemic group (p < 0.05), and magnesium increased the uptake even by 52% (p < 0.001). The MDL 73,404 substance had no effect on the mitochondrial Ca2+ uptake. On the basis of experimental results we assume that the cardioprotective effects of Spirapril and magnesium can be besides other factors intermediated also by the increase of intramitochondrial enzymatic activity in consequence of augmented transport of Ca2+ into mitochondria. The cardioprotective effect of the MDL 73,404 substance is assumedly caused by its antioxidant properties. (Fig. 4, Ref. 21.)

[Alcoholic mitochondrial cardiomyopathy]. / Alkoholová mitochondriálna kardiomyopatia.

The effect of alcohol on oxidative phosphorylation, activity of cytochrome oxidase and the content of cytochromes in mitochondria of the heart muscle was studied in rabbits after 14- and 21-day subcutaneous administration of 20% alcohol solution. Alcohol was found to exert an inhibitory effect on oxygen consumption and on the rate of energy production in mitochondria of the heart muscle, to decrease the specific activity of cytochrome oxidase and to increase the cytochrome content in the mitochondria. The authors classify these metabolic derangements under the concept of alcoholic mitochondrial cardiomyopathy and discuss broader aspects of mitochondrial diseases in medicine.

Metabolic adaptation of myocardial mitochondria to mild altitude hypoxia.

We studied the metabolic parameters of myocardial mitochondria (respiration, respiratory control index, oxidative phosphorylation rapidity and coefficient of oxidative phosphorylation) in two groups of rats: one living at an altitude of 140 m above sea level (control group) and the other living from birth at an altitude of 1350 m above sea level for 2 and 4 months (experimental group). Compared with the control rats, the experimental rats during 2 and 4 months of mild altitude acclimatization increased their basal and stimulated respiration, as well as the rapidity of energy production by myocardial mitochondria. The coefficient of oxidative phosphorylation under mild altitude hypoxia decreased but the respiratory control index did not change. We explain these alterations of heart muscle metabolism at the mitochondrial level as an adaptation to the mild hypoxic conditions.

[The role of mitochondrial energy metabolism and oxygen free radicals in the pathogenesis of experimental autoimmune myocarditis]. / O úcasti energetického metabolizmu mitochondrií a vol'ných kyslíkových radikálov v patogenéze experimentálnej autoimúnnej myokarditídy.

In a model of autoimmune myocarditis in guinea piga, the authors studied energy producing processes in mitochondria and the role of oxygen free radical generation in tissue injury. A significant decrease in the capacity of oxidative phosphorylation was detected in parameters QO2 (S3) on the basis of glutamate + malate (p < 0.005) and pyruvate (p < 0.05) measurements. Other parameters studied were however only insignificantly reduced in myocarditic heart mitochondria as compared to controls. The activity of mitochondrial cytochrome oxidase was also insignificantly reduced in animals with myocarditis. Generation of oxygen free radicals was in the presence of the inflammatory infiltrate in this model not significantly higher than in the intact myocardial tissue.

[A model of autoimmune myocarditis in guinea pigs]. / Model autoimúnnej myokarditídy u morciat.

A model of autoimmune myocarditis was developed in guinea pigs. The disease was induced by repeated subcutaneous administration of heterologous myocardial tissue and adjuvants. After immunization all experimental animals developed myocarditis, mostly of diffuse but also of focal character of the inflammatory process. The model of the disease can be used to study immunological and metabolic processes occurring in the course of myocarditis. (Fig. 2, Ref. 16.)

Effect of smoking on the oxidative processes of cardiomyocytes.

The effect of prolonged (14 days) passive smoking on the respiration of isolated cardiomyocytes in rabbits using various substrates (pyruvate, glutamate, succinate) was studied. The endogenous respiration of cardiomyocytes was not affected whereas stimulated respiration as well as the ratio of stimulated to endogenous respiration significantly decreased. These results complement previous studies in which the effect of smoking on the metabolic processes of heart muscle mitochondria was measured. In conclusion, prolonged smoking may provoke myocardial dysfunction and in this way may contribute to the development of heart failure in chronic smokers.

[The effect of alcohol on the mitochondrial respiratory chain in the cardiac muscle]. / Vplyv alkoholu na dýchací retazec mitochondrií srdcového svalu.

The authors investigated the action of prolonged 2- and 3-week action of ethanol on the main parameters of oxidative processes and on the cytochrome content of mitochondria in the heart muscle in 3-month-old rats. They found a statistically significant reduction of the oxidative phosphorylation coefficient, the rate of energy formation and a transient increase of the cytochrome oxidase activity in mitochondria. Under these experimental conditions an increase of cytochromes (cyt aa3, b, c, c1, bc1, c + c1) in mitochondria of the heart muscle occurred.

The functional state of the creatine kinase system of myocardial mitochondria in alcoholic cardiomyopathy.

The authors studied the chronic effect of ethanol on the functional state of creatine kinase system in myocardial mitochondria of adult rats. Mitochondrial functions were determined in skinned fibres prepared according to Veksler without mitochondria isolation. Compared with control values, ethanol was found to decrease statistically significantly the velocity of creatine-stimulated mitochondrial respiration (Vcr) and that of maximum ADP-induced stimulation of mitochondrial respiration (Vmax). The chronic action of alcohol also reduces the respiratory activation by creatine (%Cr) which ranks among the most sensitive indicators of mitochondrial respiration regulation by creatine kinase. The authors have demonstrated that the function of the creatine kinase system of myocardial mitochondria is impaired in alcoholic cardiomyopathy in the adult rat.

Use of myocardial skinned fibres for the study of mitochondrial oxidative phosphorylation during ischaemia.

The authors studied mitochondrial oxidative phosphorylation in the skinned myocardial fibres of the rat and the rabbit during ischaemia. Saponin action on tissue was used to remove the sarcolemma while leaving the interior of intracellular structures intact. Mitochondrial oxidative phosphorylation was measured by polarography using Clark's oxygen electrode in the presence of NAD- and FAD-substrates. The skinned fibre method is rapid and very simple. The fact no more than 5-10 mg of tissue is needed to perform it makes it suitable for the study of metabolic processes in experimental and clinical cardiology, under physiologic conditions as well as during ischaemia.

[Smokers' mitochondrial cardiomyopathy]. / Fajciarska mitochondríálna kardiomyopatia.

The authors analyze the metabolic background of mitochondrial myopathies of the skeletal musculature in humans. They summarize their results assembled over years pertaining to functional disorders of mitochondria of the heart muscle in experimental models of passive smoking in rabbits. Based on comparison of these disorders with disorders in mitochondrial myopathies they reach the conclusion that the concept of smokers' mitochondrial myopathy is justified.

[Left ventricular function in patients with recent onset of type I diabetes mellitus]. / Funkcia l'avej komory srdca u pacientov s krátkodobým trvaním diabetes mellitus I. typu.

Left ventricular heart function was investigated by means of two dimensional (2D) echocardiography and pulsed Doppler (PD) echocardiography in 17 young consecutive patients aged 17-38 years (mean 26.6 y.) with type I diabetes mellitus of short duration (mean 5.5 y.) whose stress ECG showed no signs of ischemic heart disease and who had no other organic complications of diabetes. The series was compared with 13 healthy volunteers (mean age 25.5 y.). No differences were found between diabetics and controls in systolic function parameters (left ventricular fractional shortening, interventricular septum shortening, left ventricular posterior wall shortening, left ventricular endsystolic dimension) as established by 2D. The parameters of left ventricular diastolic filling (maximal velocity of the rapid filling period E, its maximal time and duration of the whole phase) were established by PD and computer assisted approach. These parameters were studied also during atrial systole A and the E/A ratio was determined. All findings were comparable in the group of diabetics and controls, with the only statistically significant difference (p less than 0.05) in the duration of A which was shortened in the diabetics.

[The relation of myocarditis to the development of cardiomyopathy]. / Vztah myokarditídy k vývoju kardiomyopatie.

Dilated cardiomyopathy is a degenerative disease of the myocardium of unknown etiology. Evidence was provided in experiments on mice that it may develop as a late consequence of viral myocarditis. In experiments on mice it was also found that the damaging factor in the pathogenesis of myocarditis may be a reaction of the immune system rather than an infective agent. Research into myocarditis and dilated cardiomyopathy in humans is faced with the difficulty of accurate assessment of the diagnosis; frequently there is no sharp borderline between the two conditions. The possible pathogenetic role of immune reactions is apparent from several publications--the finding of cytotoxic antibodies against myocyte structures, evidence of a reduced function of suppressor T-lymphocytes, impaired function of NK cells. The assembled findings do not provide so far an unequivocal picture of the disease and do not make causal therapy possible.