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C Vial

Publications and source records attributed to C Vial.

At least 127 records · Page 7Linked to original sources
PubMed1987

Only one of the two interconvertible forms of mitochondrial creatine kinase binds to heart mitoplasts.

When analyzed by cellulose acetate electrophoresis, solubilized pig or rabbit heart mitochondrial creatine kinase is shown to exist under two distinct forms. The less cathodic one (form 1) is a dimer and the other having a higher cathodic mobility (form 2) has a molecular weight of about 350,000. The latter form can be converted into the former by incubation at alkaline pH or when the enzyme forms a reactive or an abortive complex with its substrates. This conversion is a reversible phenomenon and is not due to proteolysis. When rabbit heart mitoplasts are treated with the creatine kinase releasing agents, the enzyme is always solubilized as its form 2 and conversion to form 1, when it occurs, always take place after solubilization. Form 2 is also the only form which can be bound to pig or rabbit mitoplasts. Thus form 2 may be the actual form associated with heart mitochondria in vivo.

Animals↗
PubMed1987

Interaction of creatine kinase and hexokinase with the mitochondrial membranes, and self-association of creatine kinase: crosslinking studies.

Covalent coupling of protein by crosslinking reagents have been used to study the interaction of mitochondrial creatine kinase (CKm) and hexokinase (HK) with the mitochondrial membranes. The effects of crosslinkers were studied either by following the inhibition of solubilization of enzymatic activities or by modification of the electrophoretic patterns of proteins solubilized from mitochondria after treatment with different crosslinkers. Dimethylsuberimidate (DMS) efficiently reduced the amount of HK activity solubilized by various agents but it did not modify solubilization of CKm from mitochondria. The effect of DMS on HK solubilization did not result from non specific crosslinking since it did not impede the solubilization of adenylate kinase. Bissuccinimidyl another class of crosslinker has been tested. Ethyleneglycol bis (succinimidyl succinate)(EGS) efficiently reduced HK solubilization, but in addition it induced osmotic stabilization of mitochondria and thus impeded release of soluble or solubilized proteins from the intermembrane space. Furthermore this agent drastically inhibited CKm activity and thus, in a second set of experiments the effect of crosslinkers have been studied by the disappearance of protein bands in the electrophoretic pattern of soluble fractions obtained from mitochondria, the outer membranes of which have been ruptured to allow free release of soluble proteins. Results of these experiments showed that succinimidyl reagents and Cu++-Phenanthroline substantially reduced the amount of CKm released from mitochondria and confirmed that bisimidates were ineffective in inhibiting CKm solubilization. In addition crosslinking reagents have been used to study subunits interactions in purified CKm. Our results showed, in contrast with control experiments with a non oligomeric protein (ovalbumin) which did not give rise to polymers, that in the same conditions electrophoresis of crosslinked CKm resolved a set of species with molecular weights roughly equal to integral multiples of the protomer. These results proved that the polymeric form of CKm was an octamer.

Adenylate Kinase↗
PubMed1987

Significance of release of adenosine triphosphate and adenosine induced by hypoxia or adrenaline in perfused rat heart.

The status of ATP as a possible coronary vasodilator remains poorly understood. The onset of hypoxia induced a rapid and transient increase of the ATP concentration in the coronary effluent of the isolated perfused rat heart from 0.8 +/- 0.2 nM to the average peak value of 1.3 +/- 0.2 nM (P less than 0.01) at 2 +/- 0.5 min; at the same time the coronary flow increased 2-fold so that the rate of ATP release increased from 10.2 +/- 2.9 to 21.4 +/- 4.2 pmol/g/min (P less than 0.005). Hypoxia also produced a peak rate release of adenosine of 93 +/- 5 nM/g/min occurring only after the peak increase of coronary flow and also after the peak release of ATP; at peak coronary flow, however, the adenosine concentration was sufficient for vasodilation (0.31 +/- 0.19 microM). Peak release of ATP and of adenosine preceded that of lactate dehydrogenase. 10(-6) M adrenaline induced a rapid increase of coronary flow and release of ATP, the concentration of which rose from 0.9 +/- 0.3 nM to an average peak of 1.7 +/- 0.2 nM (P less than 0.01) at 2 +/- 0.3 min. The rate of increase of ATP in the coronary effluent paralleled the rate of early rise of coronary flow, yet adenosine had also risen to vasodilatory values (0.28 +/- 0.5 microM). The absolute changes in the measured concentrations of ATP in the coronary effluent were more variable and 1000 X less in concentration than those of adenosine. Hence coronary dilation could be explained by adenosine without involving ATP, although an additional vasodilatory role for ATP could not be excluded, especially in the early phases of vasodilation. In one condition, hypoxic K-arrested hearts, the increase in coronary flow could not be linked to release of either adenosine or ATP. The changes in concentrations of potential vasodilators measured in the coronary effluent do not necessarily reflect changes in the interstitial fluid.

Adenosine↗
PubMed1987

[Amnesic ictus and cerebral blood flow].

Cerebral blood flow determinations using the Xenon inhalation test in two patients with transient global amnesia showed overall decreases during the attack with a more marked fall in temporal-inferior frontal flow in one case and in temporal flow in the other. In the latter patient the temporal anomaly was reversible after naloxone injection but clinical improvement was lacking. Blood flow determinations in a further patient with transient global amnesia, after 2 mg of ergotamine tartrate plus caffeine, showed a global decline in flow without focal anomaly, with recovery after ten days. Values obtained in two other patients 24 and 38 hours respectively after typical transient global amnesia attacks were normal. The effect of naloxone appears related to a direct neuronal action although the role of endorphins in this affection is not conclusive. Comparison of these anomalies with those noted by Reichle with position emission tomography imaging suggests a primary neuronal mechanism.

Aged↗
PubMed1986

Interaction of creatine kinase with phosphorylating rabbit heart mitochondria and mitoplasts.

This paper demonstrates that the mitochondrial isoenzyme of creatine kinase (CKm) can be solubilized from rabbit heart mitochondria, the outer membrane of which has been removed or at least broken by a digitonin treatment or a short hypotonic exposure, but which has retained an important part of the capacity to phosphorylate ADP. Phosphate, ADP, or ATP, at concentrations which are used to study oxidative phosphorylation and creatine phosphate synthesis, solubilize CKm; the same is true with MgCl2 and KCl. The effect of adenine nucleotides does not seem to be due to their interaction with the adenine nucleotide translocase. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that CKm is the main protein released in the described conditions; however, it does not amount to more than 1% of the total protein content of the mitoplasts. When the apparent Km for ATP of CKm was estimated by measuring creatine phosphate synthesis, the values obtained using water-treated mitochondria (0.21 mM) were slightly higher than those of intact mitochondria (0.12 mM) but the difference was not significant. In the former preparation 77% of CKm was in a soluble state. If we can extrapolate these results to intact mitochondria and suppose that in this case a fraction of CKm is also soluble in the intermembrane space, this does not support the theory of functional association between CKm and the adenine nucleotide translocase.

Adenine Nucleotides↗
PubMed1986

[Clinical amyotrophic lateral sclerosis syndromes in gammapathies: clinical, electrophysiologic and histoimmunologic aspects].

Eleven patients with motor neuron disease associated with a monoclonal gammopathy were studied. One patient had a previously known multiple myeloma. In the other patients neurological symptoms preceded diagnosis of the gammopathy by one month to 8 years. They were 5 multiple myeloma, 1 macroglobulinemia, 1 chronic lymphatic leukemia, 1 lymphoma and 3 benign monoclonal gammopathies. EMG and motor conduction velocities results were consistent with anterior horn cell disease but sensory conduction studies were abnormal in seven cases out of eight. Superficial peroneal nerve biopsy performed in all patients confirmed peripheral nerve involvement. The relations between gammopathy, clinical symptoms and electrophysiological data are discussed. The interest of sensory conduction studies in every patient with motor neuron disease is emphasized.

Aged↗
PubMed1985

[Benign acute cerebral angiopathy. 4 cases].

Presenting symptoms in 4 patients with acute benign cerebral angiopathy were headaches over several days, with a transient neurologic disorder in two cases. Angiography showed diffuse and segmental distal narrowing alternating with dilatations. In one patient, the radiologic anomalies persisted to a milder degree in the same region 2 months later, while the reduced cerebral blood flow failed to return to normal. The pathophysiology of this syndrome would appear to result initially of vasospasm in particularly reactive subjects, especially young women. Its cause appears to vary from one case to another: post-partum disorders, infection or inflammation, meningeal hemorrhage, paroxysmal hypertension. Adjuvant factors could be unusual effort, medication or a migraine context. In spite of this pathogenetic uncertainty this angiopathy in usually considered as an isolated, benign and non-relapsing disease.

Acute Disease↗
PubMed1983

Effects of SH group reagents on creatine kinase interaction with the mitochondrial membrane.

Solubilization of the specific mitochondrial isoenzyme of creatine kinase (CKm) from rabbit heart mitochondria by treatment with SH group reagents has been studied. From the various compounds tested only the negatively charged organomercurials are able to induce an extensive solubilization of the enzyme. This effect is fully reversible since the solubilized enzyme readily reassociates with the membrane when the bound organomercurial is removed by treatment of the homogenate by an excess of dithiothreitol. Solubilization by negatively charged organomercurials can be partly prevented by pretreatment of mitochondria with either disulfide or uncharged organomercurials. No clear-cut relationship has been pointed out when the amount of SH titrated by various reagents has been compared with the extent of CKm solubilization. More detailed studies with para-chloromercuribenzoate (pCMB) show that extensive CKm solubilization (about 75%) occurs for pCMB concentration as low as 25 microM, whereas pronounced inhibition of the enzyme is observed only for concentrations greater than 200 microM. By cross-reassociation of enzyme solubilized either by para-hydroxymercuribenzoate (pHMB) or by 20 mM sodium phosphate (NaPi) with mitochondria depleted of CKm by pHMB or by NaPi treatment, SH groups whose titration impedes CKm reassociation with the mitochondrial membrane have been tentatively located on the enzyme. Thus, negatively charged organomercurials, could induce a reversible conformational modification of the enzyme which is no longer able to bind on the inner mitochondrial membrane. Furthermore, our results show that the binding of an excess of mitochondrial CK, which has been previously reported, could reflect unspecific binding since it occurs only on mitoplasts incubated in very hypotonic medium, but not in isotonic medium.

Animals↗
PubMed1980

[Myocardial metabolism during coronary perfusion at 10 degrees C with or without cardioplegia associated with potassium].

Myocardial metabolism was studied during coronary perfusion at 10 degrees c with haemodiluted blood by sampling the coronary sinus blood of 20 patients undergoing aortic valve replacement. The patients were divided into four groups : Group 1 with continuous coronary perfusion at 10 degrees c ; Group 2 : continuous perfusion at 10 degrees c with Potassium cardioplegia ; Group 3 : discontinuous coronary perfusion at 10 degrees c ; Group 4 : discontinuous perfusion at 10 degrees c with Potassium cardioplegia. In groups 1 and 2, coronary blood flow remained constant at an average of 200 ml/mn. Cardioplegia did not affect the peripheral coronary resistances at this temperature. During coronary perfusion the average myocardial oxygen consumption was 1.38 vol/mn (Group 1) and 0.18 vol/mn (Group 2), p < 0.01. This reduced oxygen consumption results in a fall in the average amount of oxygen extracted from 4.8 p.100 (Group 1) to 1.2 p.100 (Group 2) p < 0.01. At the end of coronary perfusion lactic acid production was not observed in Groups 1 and 2. Ten minutes after coming off bypass, the percentage of oxygen extraction was nearly the same in both groups (Group 1 : 38.4 p.100 ; Group 2 : 43.2 p.100). Systemic arterial lactic acid levels tended to be higher than those of coronary sinus blood in both groups. With discontinuous coronary perfusion and an average period of myocardial anoxia of 45 mn, metabolic acidosis was observed, greater in Group 3 than in Group 4 (p < 0.05) when the aorta was unclamped. Ten minutes after the end of bypass, despite normal levels of oxygen extraction, myocardial lactate production was observed in both groups. The enzyme levels, in particular the CPK MB isoenzyme, in the coronary sinus blood, remained low throughout operation in all four groups. Deep, stable and constant myocardial hypothermia (10 degrees c) induced by coronary perfusion with haemodiluted blood, affords excellent myocardial protection ; it was not possible to show the complementary benefits of Potassium cardioplegia at such low temperatures.

Aortic Valve↗
PubMed1980

[Comparative study of myocardial protection by coronary perfusion in deep hypothermia (10 degrees C) with or without potassium cardioplegia. Clinical, electrocardiographic, enzymatic results; biochemical and histological controls].

A technique of coronary perfusion with diluted blood, giving homogenous myocardial cooling (10-12 degrees C) under lignocaine perfusion, with or without potassium (K) cardioplegia is presented. The first 75 operated cases were used to adjust the optimal lignocaine (5 mg/min) and K (2 meq/min in continuous coronary perfusion, 5 meq/min in discontinuous coronary perfusion) dosage in the myocardial protection circuit. Then, 123 operated patients (78 aortic valve replacement, 30 mitro-aortic double valve replacement, 15 other operations on the ascending aorta) were classified into four groups prospectively: 1. Continuous coronary perfusion 10 degrees C, 2. Continuous coronary perfusion 10 degrees C with associated K cardioplegia, 3. Discontinuous coronary perfusion 10 degrees C, 4. Discontinuous coronary perfusion 10 degrees C with K cardioplegia. The best return of cardiac activity was observed in Group 1 and this was statistically significant with a high percentage of spontaneous heart beating after declamping the aorta (average 10 minutes), immediate efficacity of left ventricular contraction, and absence of arrhythmias, especially the transient conduction defects observed with K cardioplegia. In Group 1, during mitro-aortic valve replacement, after over 60 minutes aortic clamping, no significant reduction of ATP or myocardial phosphocreatinine or changes of hexosemonophosphates were observed, contrary to the findings after 15 minutes aortic clamping at 28 degrees C in a control group of mitral valve replacements (n = 10). Myocardial changes on electron microscopy in the subendocardial region of the left ventricle were minimal or absent, especially with respect to the mitochondria. The early post-operative course was the same in all four groups: of the 123 patients operated, early mortality was 2.4 p. 100 (1.6 p. 100 from intercurrent causes), severe arrhythmias were observed in 1.6 p. 100, supraventricular arrhythmias in 4.9 p. 100, myocardial infarction in 0.8 p. 100, electrocardiographic ischaemia in 0.8 p. 100, and atrioventricular block in 0.8 p. 100. The average enzyme level (CPK, SGOT, LDH) in the early postoperative period were low, with no correlation with the duration of aortic clamping.

Chemical Phenomena↗
PubMed1980

Effects of isoproterenol on the metabolism of normal and ischemic heart.

A study has been made of the simultaneous evolution of cardiac activity and metabolism in the dog heart in situ, during the perfusion of isoproterenol in a dose comparable to therapeutic doses (1 micrograms x kg-1 x min-1, 30 min). A total cardiopulmonary by-pass system allowed of taking the repeated myocardial tissue samples necessary for the determination of the main energetic substrate and high-energy phosphate content. Samples were taken from subendocardial and subepicardial layers separately. The acceleration of heart rate due to isoproterenol was quickly regressive but, in the well-irrigated heart, the drug elicited a rapid fall in glycogen content and a considerable rise in lactate content, a slower reduction in free fatty acid concentration restricted to the subendocardial layer, and no significant variation of creatine phosphate or ATP. In the ischemic heart, isoproterenol aggravated the glycolysis disturbances without completely losing its effects on lipolysis when the ischemia was not too marked.

Adenosine Triphosphate↗
PubMed1979

[Biochemical effects of reperfusion after regional myocardial ischemia of different duration in the open chest dog].

Restoration of blood flow after 15 or 45 min. of ischemia induced an immediate recovery of phosphocreatine level and adenylate energy charge whereas ATP and total adenine nucleotides remained significantly below their normal values. These results prove that oxidative phosphorylations are not impaired but that a pool of myocardial adenine nucleotides is lost during ischemia which cannot be restored shortly after reperfusion. The significance of energy charge as a regulatory parameter in the myocardium is discussed.

Adenine Nucleotides↗
PubMed1979

Myocardial biochemical modifications induced by theophylline with reference to its value as antianginal drug.

Theophylline-induced variations of cardiac metabolism have been investigated by determining concentrations of various energetic substrates and of high-energy phosphates in myocardial tissue, the repeated sampling of myocardium being made possible by an extracorporal circulation system. When administered in therapeutic, or even slightly higher doses, theophylline does not modify triglyceride, glycerol and free fatty acid content or phosphocreatine and ATP content in subepicardial and subendocardial layers, but it does lower glycogen and raise lactate concentration. Consequently, the changes in anaerobic glycolysis due to myocardial ischemia may be enhanced if, as is probably the case, theophylline fails to restore the supply of oxygen.

Angina Pectoris↗
PubMed1978

Studies on the energy-linked Ca2+ accumulation in pig heart mitochondria - role of Mg2'ons.

Comparative intracellular distribution of Ca2+, Mg2+ and adenine nucleotides has been studied in pig heart by differential centrifugation or fractional extraction and has shown that Mg2+ and ATP are associated mainly with soluble fractions whereas Ca2+ and ADP are more tightly bound to subcellular structures. Ca2+ accumulation and Ca2+ stimulated respiration were studied in pig heart mitochondria under different energetic conditions in the absence or presence of phosphate. Ca2+ concentrations of about 1200 nmoles/mg protein inhibit Ca2+ accumulation, site I substrate oxidation and induce an efflux of mitochondrial Mg2+. These deleterious effects of Ca2+ on respiration occur even in the absence of phosphate or oxidizable substrate; they are completely prevented by ruthenium red only, and partially prevented by the addition of M2+ to the medium. The kinetics of Ca2+ uptake become of the sigmoidal type when Mg2+ is present. This cation strongly inhibits the rate of Ca2+ uptake in the presence of added phosphate and decreases the affinity of Ca2+ for its transport system. In the absence of phosphate, Mg2+ has no effect on Ca2+ uptake. The possible physiological implications of these findings are discussed

Adenine Nucleotides↗