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Biomedical subjects

C Muscari

Publications and source records attributed to C Muscari.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mitochondrial production of oxygen free radicals in the heart muscle during the life span of the rat: peak at middle age.

Mitochondria extracted from Wistar rat hearts at 3, 14-18 and 24 months of age showed no change in state 3-mitochondrial respiration measured in the presence of glutamate or succinate. Again no changes were found in the SMP-O2- production at the level of the rotenone-inhibited region, whilst at the level of the antimycin-inhibited region there was a marked increase in O2- production in the group of 14-18-month-old rats. In the same age period, the production of mitochondrial H2O2 supported by glutamate or succinate and the level of GSSG increased in comparison to the young group, accompanied by a decrease in the GSH level. Mitochondrial TBARS levels did not change during a life span, while a progressive accumulation in the mitochondrial lipofuscin content with age was measured.

Aging↗
PubMed1992

[Coenzyme Q9 biosynthesis in the aging myocardium after ischemia and reperfusion].

The purpose of the present study was to evaluate the biosynthesis of coenzyme Q9 (CoQ9) in isolated and perfused young (6 months) and aged (24 months) rat hearts, either under aerobic perfusion condition or during postischemic reperfusion. The young and aged hearts have been divided into 2 groups: Group A, aerobic perfusion for 60 min with recirculating Krebs-Henseleit solution, containing 0.8 microM p-OH-[U-14C]benzoate plus 2.5 mM mevalonlactone; Group B, severe ischemic perfusion for 30 min, followed by 60 min of reperfusion under the same experimental condition of Group A. At the end of the reperfusion the mitochondrial content of CoQ9 was lower in young than aged rat hearts (p < 0.01). In Group A the incorporation of the labeled precursor into mitochondrial CoQ9 was greater in the hearts of aged than young rats (p < 0.01); on the contrary, in Group B this incorporation was significantly reduced in aged than in young rats (p < 0.05). Thus, it is possible that, in the aged rat heart, the higher activity of CoQ9 biosynthesis is related to an elevated turnover of the coenzyme due to the aging process; moreover, this activity is partially reduced by an ischemic-reperfusion stress.

Aerobiosis↗
PubMed1992

Biochemical correlates with myocardial aging.

Both contraction and relaxation times are prolonged in cardiac muscle of senescent animals. This is in part explained by an alteration of excitation-contraction coupling due to an increased duration of the action potential, reduced biosynthesis of the Ca(2+)-stimulated ATPase pump of sarcoplasmic reticulum, and prevalence of the V3 isoform of myosin with slow ATPase activity. The response to catecholamine decreases with aging because of a defective transmission of alpha and beta adrenergic stimulation mediated respectively by phosphoinositide hydrolysis and adenylate cyclase. Cardiac energetics is also impaired in the aged myocardium, since ATP and creatine phosphate levels are reduced by about 20%. This reduction seems in part the consequence of defective mitochondrial function, especially in fatty acid oxidation and ATP translocation to the cytoplasm. In this paper we have discussed the possibility that oxygen free radicals may be a cause of myocardial senescence, by damaging the nuclear and mitochondrial genomes as well as membranes and other cellular components.

Aging↗
PubMed1991

[The inhibitory effect of magnesium on mitochondrial calcium uptake in ischemic and reperfused rat hearts].

Several studies suggest that the protection exerted by Mg2+ on the reperfused myocardium may be mostly due to its competitive effect with respect to Ca2+. The aim of this research was to evaluate the inhibitory action of Mg2+ on mitochondrial Ca2+ uptake in the reperfused myocardium. Hearts of male Wistar rats (250-300 g) were isolated and perfused by the Langendorff technique. Aerobic control hearts (n = 6) were perfused with a constant flow of 10 ml/min/g for 65 min. In a second group (n = 6) the hearts were aerobically equilibrated for 20 min, then subjected to 30 min of ischemia (98% reduction of coronary flow) and subsequently reperfused for 15 min at the same preischemic flow. The hearts of both groups were electrically stimulated at 300 b/min. Then, the hearts were pooled in groups of 2 each and homogenized for the isolation of mitochondria. One part of mitochondrial suspension was used to evaluate the respiratory function by a polarographic technique. The remaining part was incubated with fura-2/AM for 10 min at 30 degrees C in order to determine the kinetics of Ca2+ transport within mitochondria in the presence of succinate as substrate. Ca2+ uptake was reduced in the mitochondria of reperfused hearts with respect to control, particularly in the presence of elevated extramitochondrial Ca2+ concentrations (greater than 10 nM). On the contrary the initial rate of Ca2+ uptake was increased in the reperfused mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[The biochemical bases of cardiovascular aging].

The majority of reports concerning the performance of senescent heart in both human and animal models states that, at rest, most hemodynamic parameters are substantially unchanged during aging, with the exception of a prolongation of left ventricular ejection time and a decrease in the early diastolic filling rate. A biochemical rationale for the increased early diastolic filling time with age seems to be the enhanced stiffness of left ventricular wall due to either myocardial hypertrophy or collagen tissue accumulation. The prolonged time of contraction and the inadequate response to stress of cardiac muscle in elderly subjects may be the consequence of changes in different steps of the excitation-contraction coupling, namely altered intracellular calcium homeostasis, reduced availability of highly energetic compounds, and impaired response to adrenergic stimulation. These defects can cause major hemodynamic changes when the heart is subjected to volume or pressure overload. In fact, during exercise, elderly subjects can reach a maximal heart rate slower than that of younger people. The possibility that the toxicity of oxygen reactive forms may provoke some age-related myocardial lesions such as structural alteration of membranes and enzyme inactivation is very attractive but the linkage between the most functional perturbations of aged hearts and peroxidative stress remains to be clarified.

Aging↗
PubMed1990

Mitochondrial function and superoxide generation from submitochondrial particles of aged rat hearts.

A decrease in heart function with ageing might be related to an impairment of mitochondrial function, since these organelles produce the greatest fraction of ATP in the myocyte. Mitochondria extracted from Wistar rat hearts at 3, 14, 18 and 24 months of age were employed to evaluate the changes of the respiratory activity during lifetime. A slight decrease of the respiratory rate (QO2) was observed in the 14 month group with respect to the 3 month group when succinate was used as substrate, whereas the respiratory control index (RCI) in the presence of glutamate or succinate increased in the 24 month group. The latter result may be related to a condition of moderate hypertrophy that generally occurs in the ageing heart. Submitochondrial particles (SMP) were also prepared to study the superoxide radicals (O2-) production at the level of rotenone or antimycin-inhibited regions of the respiratory chain. A strong elevation in the O2- generation was observed in the antimycin-inhibited region at 14 months of age; on the contrary, the rate of O2- production remained unchanged in the 24 month group in comparison to the youngest group. These observations correlate well with the enhanced tissue level of oxidized glutathione that was observed at 14 and 18 months of age. The products of lipid peroxidation (TBARS) did not change in the rat heart at any of the ages measured, whereas the levels of fluorescent substances progressively increased beginning from 18 months of age, with a greater extent in the mitochondrial compartment. The present study suggests that age does not substantially affect mitochondrial respiration and energy output in the rat heart, while a greater production by cardiac mitochondria of superoxide anions in the adult rats (14 months) might accelerate the fluorescent pigment formation.

Aging↗
PubMed1990

Receptors for atrial natriuretic factor in cardiomyocytes and aortic smooth muscle.

The aim of this work was to investigate whether specific receptors for atrial natriuretic factor (ANF) are present in ventricular cardiomyocytes and aortic smooth muscle membranes. 125I-ANF was employed to test the binding of the radioligand to isolated rat cardiomyocytes. Calcium-tolerant ventricular cardiomyocytes were obtained by retrograde perfusion with collagenase. 125I-ANF binding to cardiomyocytes was highly specific (70-80%) with a KD value of 72.6 pM and a Bmax of 9.37 fmol/mg protein. In other studies, 125I-ANF binding was investigated with a membrane preparation obtained from calf thoracic aorta, from which the endothelium had been previously stripped off. In this preparation too the interaction of 125I-ANF (70-80%) was highly specific, with a KD value of 70.4 pM and a Bmax of 8.78 fmol/mg protein. These results suggest that specific receptors to atrial natriuretic factor are present both in isolated rat cardiomyocytes and in the smooth muscle of calf thoracic aorta. This second observation is in agreement with the hypothesis that the vasodilator effect of atrial natriuretic factor is due to a direct interaction between this peptide and vascular smooth muscle cells.

Animals↗
PubMed1990

Changes in myocardial mitochondrial respiration after ligation of the coronary artery in pigs.

After ligation of the left coronary artery, porcine cardiac mitochondria were isolated by homogenizing the tissue and treating the myofibrillar pellet with nagarse. When compared with unligated controls, the ischemic myocardium showed decreases in phosphocreatine (to 41%), ATP (to 56%) and in the mitochondrial respiratory control index (to 69% and 78% as measured with glutamate and succinate respectively). No changes were found in the corresponding P/O ratios. Similar results were obtained upon separation of the mitochondria into two main fractions by a density gradient technique, though only one of these fractions showed a fall in succinate-supported respiration. The results suggest that ischemia decreases the NADH-dehydrogenase activity of cardiac mitochondria.

Adenosine Diphosphate↗
PubMed1990

Influence of age on oxidative damage in mitochondria of ischemic and reperfused rat hearts.

Hearts from rats aged 3 months and 24 months respectively were isolated and subjected to a brief ischemia. The extent of myocardial injury, measured by release of creatine phosphokinase into coronary effluents and by developed tension, was greater in the young rats than in the old when compared with their corresponding non-ischemic controls. The amount of peroxidation, measured in the isolated mitochondria using the malondialdehyde method, was also greater in the younger rats. In contrast, when mitochondria from non-ischemic hearts were incubated for 20 minutes in a medium containing FeCl3, NADPH and ADP, known to generate hydroxyl radicals, significant peroxidation (together with a decrease in respiratory control indices) was obtained only from mitochondria isolated from the older rats. If, as the in vitro results suggest, the mitochondria of the old rats are not less sensitive to peroxidative attack, the difference between the effects of ischemia in the two age groups may be due to a lower rate of formation of reactive species of oxygen or to a greater anti-oxidative cytosolic capacity in the hearts of older rats. Alternatively, the overall oxidative stress following ischemia may be due to the effects of different radicals which target different parts of the mitochondrial membrane.

Aging↗
PubMed1989

Anti oxy-radical properties of trimetazidine.

Trimetazidine at concentrations above 100 microM competed with cytochrome c in scavenging O2.- radicals formed by the reaction catalyzed by the xanthine oxidase enzyme upon xanthine. This scavenger effect was also observed when O2.- were generated by active human neutrophils in which the rate of O2.- formation was monitored by following the reduction of cytochrome c or the emission of luminol-dependent chemiluminescence. An additional scavenger effect of trimetazidine was measured in a OH. chemical generating system whereby the breakdown of deoxyribose by the thiobarbituric acid assay was detected. This study suggests that trimetazidine might function as an antioxy radical compound in conditions of increased oxy radical production.

Deoxyribose↗
PubMed1988

Beneficial effects of trimetazidine on mitochondrial function and superoxide production in the cardiac muscle of monocrotaline-treated rats.

The administration of a single dose of monocrotaline (105 mg/kg) after 21 days produced in rats a reduction of cardiac mitochondrial function at the level of complexes I, II and IV of the respiratory chain, associated with the formation of heart hypertrophy, prevalently of the right ventricle. Moreover, in these rats, the submitochondrial particles produced more O2- and in the cardiac tissue there was an elevation of malondialdehyde content. The repeated administration of trimetazidine (5 mg/kg/24 hr) improved the cardiac mitochondrial function, particularly in state 3 of respiration. In addition, the treatment with trimetazidine reduced, in the heart muscle, both the production of mitochondrial O2- and the content of tissue malondialdehyde. Trimetazidine added alone did not significantly change either the cardiac mitochondrial activity, or the mitochondrial O2- production in comparison to control rats. Also, the content of tissue malondialdehyde was not modified by the repeated administration of trimetazidine. In all the experimental conditions examined, the content of cardiac water-soluble fluorescence substrates did not significantly change in comparison to control rats.

Animals↗
PubMed1987

The effect of treatment with coenzyme Q10 on the mitochondrial function and superoxide radical formation in cardiac muscle hypertrophied by mild aortic stenosis.

A 40% reduction of the diameter of the ascending aorta maintained for 60 days induced the formation of a compensate cardiac hypertrophy in rabbits without changing the value of the azide insensitive Ca2+-ATPase activity in comparison to control hearts. The cardiac mitochondria isolated from constricted animals assayed in presence of glutamate and succinate did not show a change in the R.C.I. and ADP/O values in comparison to the controls, whilst the QO2 value enhanced or decreased respectively when determined with glutamate or succinate. The intramuscular injections of CoQ10 (12 mg/kg body weight/48 h) enhanced the mitochondrial CoQ10 concentrations both in the control and in the constricted animals and further increased the QO2 value determined in both groups of animals when glutamate was used as the substrate. The production of O2.- radicals by the level of the complexes I and III of the respiratory chain, did not change in the constricted animals, nor in the animals administered with CoQ10 in comparison to the control. CoQ10 augmented the rate of oxygen consumption by the submitochondrial particles only in the constricted animals. Moreover, the treatment with the coenzyme or the constriction of the aorta, did not modify the cardiac superoxide dismutase activity, but increased the glutathione peroxidase activity only in the banded animals. In addition, in the CoQ10 treated animals there was a reduction of NADH-diaphorase activity both in the control and constricted animals, while the malondialdehyde, generated during the thiobarbituric acid test, and the cardiac content of lipofuscin were decreased.

Animals↗