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Biomedical subjects

S Curello

Publications and source records attributed to S Curello.

85 records · Page 5Linked to original sources
PubMed1985

Changes in the cardiac glutathione status after ischemia and reperfusion.

In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.

Animals↗
PubMed1985

Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity.

The possibility that myocardial ischaemia alters the defence mechanisms against oxygen toxicity has been investigated. Ischaemia was induced in isolated, perfused rabbit hearts by reducing coronary flow from 25 ml/min to 1 ml/min for 90 min. Two different degrees of ischaemic damage have been achieved using either spontaneously beating or electrically stimulated hearts. The effects of post-ischaemic reperfusion were also followed for 30 min. Tissue activity of superoxide dismutase (SOD), glutathione peroxidase and reductase (GPD and GRD) have been determined together with tissue content of reduced and oxidized glutathione (GSH and GSSG) and of protein SH groups. The changes in myocardial ATP and CP content and release of CPK and of GSH and GSSG were also determined. Systolic and diastolic pressures were continuously monitored. In the spontaneously beating hearts ischaemia induced a reduction of tissue GSH and protein SH groups. On reperfusion there was a recovery of mechanical function, a transient release of GSH into the coronary effluent and an increase of tissue GSH. In the paced hearts, ischaemia resulted in 50% reduction of mitochondrial SOD activity together with a reduction of tissue GSH and protein SH groups. Reperfusion induced a massive release of CPK and of GSH and GSSG, a further reduction of tissue GSH concomitant with an increase of GSSG and no recovery of mechanical function. GPD and GRD activity were not affected by ischaemia and reperfusion. These data indicate that severe ischaemia induces a reduction of the protective mechanisms against oxygen toxicity.

Adenosine Triphosphate↗
PubMed1985

Role of oxygen in myocardial ischaemic and reperfusion damage: effect of alpha-tocopherol.

There is evidence that oxygen-derived free radicals may play a role in myocardial ischaemic and reperfusion injury. Major sources of O2 free radicals formation during ischaemia and reperfusion are: the enzyme xanthine oxidase, activated neutrophils and the myocardial mitochondria. However, in the heart there are defense mechanisms against the toxic oxygen metabolites. They include the enzyme superoxide dismutase, catalase and glutathione peroxidase plus endogenous antioxidants like vitamin E, ascorbic acid and cysteine. We have investigated in the isolated rabbit hearts the effects of ischaemia and reperfusion on these defence mechanisms. 90 min of ischaemia and/or hypoxia induced a significant reduction of mitochondrial superoxide dismutase, and of reduced glutathione/oxidized glutathione ratio which was further declined after reperfusion indicating that an oxidative stress has occurred. These alterations are associated with massive tissue and mitochondrial calcium accumulation, loss of mitochondrial function and severe membrane damage. The effects of vitamin E on these parameters have been investigated. Administration of 1.1 mg of dl-alpha-tocopherol acetate showed a protective effect on mitochondrial function but it failed to improve the recovery of mechanical function during reperfusion.

Animals↗
PubMed1984

Reversible and irreversible ischaemic damage: importance of energy metabolism.

In this study the effects of different degrees and duration of coronary flow reduction on pressure development of the isolated and perfused rabbit hearts has been studied. Three different degrees of ischaemia lasting for 30, 60 and 90 minutes have been investigated, after which the effects of post-ischaemic reperfusion have been followed. The effects of substituting FFA for glucose as myocardial substrate has also been investigated. Reperfusion resulted in a recovery of mechanical function or in a further worsening of mechanical function, depending upon the degree, duration of flow reduction and substrate employed. To establish the causes of reperfusion damage, in a separate series of experiments the effects of reperfusion after 90 minutes of severe ischaemia on lactate, CPK and Mg++ release, tissue and mitochondrial calcium content tissue ATP and CP concentration and mitochondrial function have been determined. The ultrastructural damage of the myocardial cell have also been established. The results obtained suggest that mitochondria play an important role in reperfusion damage.

Adenosine Triphosphate↗
PubMedDate not supplied

Protective effect of propionyl-L-carnitine against ischaemia and reperfusion-damage.

Reperfusion of isolated rabbit heart after 60 min of ischaemia resulted in poor recovery of mechanical function, release of reduced (GSH) and oxidized glutathione (GSSG), reduction of tissue GSH/GSSG ratio and shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. Pretreatment of the isolated heart with propionyl-L-carnitine (10(-7) M) improved the functional recovery of the myocardium, reduced GSH and GSSG release and attenuated the accumulation of tissue GSSG. This effect was specific for propionyl-L-carnitine as L-carnitine and propionic acid did not modify myocardial damage.

Animals↗
PubMedDate not supplied

Relation between energy metabolism, glycolysis, noradrenaline release and duration of ischemia.

We studied the effect of 12-36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = -0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline 10x (p < 0.05). Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x, and 200x, (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r = -0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.

Adenosine↗
PubMedDate not supplied

Effect of D-600 on ischemic and reperfused rabbit myocardium: relation with timing and modality of administration.

In this study we have investigated the possibility that D-600, a phenylalkylamine calcium antagonist, protects the isolated rabbit heart against ischemia and reperfusion-induced damage. D-600 was either subcutaneously injected (2mg/kg, twice daily for 5 to 6 days) in the rabbit before isolation of the heart, or delivered to the isolated hearts in the perfusate (10(-7) M), either at the onset of ischemia and during reperfusion, or only during post-ischemic reperfusion. Ischemia (90 min) was induced by reducing coronary flow from 25 to 1 ml/min, followed by 30 min of reperfusion. Myocardial damage was determined in terms of mechanical function, release of creatine phosphokinase (CPK) and noradrenaline, mitochondrial function, calcium homeostasis, and endogenous stores of ATP and creatine phosphate (CP). Administration of D-600 to the rabbits or to the isolated hearts at the time of ischemia exerted protection. There are four groups of evidence in support of this conclusion: 1) the rise in diastolic pressure during ischemia was diminished with greater recovery of developed pressure during reperfusion; 2) CPK and noradrenaline release during reperfusion were reduced; 3) the oxygen consumption and ATP generating capacities of mitochondria were better maintained; and 4) associated with this preservation of mitochondrial function was the maintenance of near normal calcium homeostasis and of endogenous ATP and CP stores. The two different modalities of administration did not produce substantially different results. When administered to the isolated hearts after the ischemic period, D-600 failed to improve mechanical recovery and release of endogenous substances. However, it reduced mitochondrial calcium overload and improved ATP production. The mechanism of the protective effect of D-600 seems to be multiple: energy-sparing effect, reduction of the toxicity mediated by endogenous catecholamines, and direct inhibition of mitochondrial calcium transport.

Adenosine Triphosphate↗
PubMedDate not supplied

No evidence of oxygen free radicals-mediated damage during the calcium paradox.

Reperfusion of an isolated mammalian heart with a calcium-containing solution after a brief calcium-free perfusion results in irreversible cell damage: the calcium paradox. We investigated whether the calcium paradox is associated with oxidative damage. We measured the tissue changes of glutathione status and the release of oxidized glutathione from isolated perfused rabbit hearts as indicators of cellular oxidative events. After 10 min of calcium-free perfusion, tissue content of reduced (GSH) and oxidized (GSSG) glutathione, and of protein and non-protein sulfhydryl groups were not significantly different from control values. Restoration of the calcium concentration resulted in an immediate and massive release of GSH and a depletion of tissue content of GSH, GSSG, and non-protein sulfhydryl groups. However, only a minimal release of GSSG into the coronary effluent was observed. In addition, the characteristic features of the calcium paradox were present: development of an irreversible contracture and massive release of creatine kinase. The calcium paradox did not lead to a decrease of the tissue content of protein sulfhydryl groups. These observations indicate that the calcium paradox is not associated with oxidative damage.

Animals↗
PubMedDate not supplied

Tumor necrosis factor in congestive heart failure: a mechanism of disease for the new millennium?

Tumor necrosis factor alpha (TNF-alpha), a protein belonging to the family of cytokines, is one of the leading mediators of the immune response to inflammation. Its widespread biological effects are modulated by two circulating binding proteins corresponding to the extracellular domain of the membrane receptors, namely soluble TNF receptors. TNF-alpha was first supposed to be linked with congestive heart failure (CHF) on a cachexia-inducing basis. In patients with advanced CHF, elevated levels of circulating TNF-alpha and soluble TNF receptors have been found. The pathophysiological implications of activation of the TNF system in CHF seem to rely mainly on its effects on the heart and the endothelium. TNF-alpha exerts a negative inotropic effect both directly and indirectly, this latter being mediated by enhancement of nitric oxide production. Moreover, TNF-alpha has been suggested to trigger the apoptotic process in cardiac myocytes. There is consensus on the detrimental role played by TNF-alpha in CHF further supported by the evidence of a temporal association between TNF activation and transition from asymptomatic to symptomatic CHF.

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PubMedDate not supplied

Superoxide dismutase: possible therapeutic use in cardiovascular disease.

Superoxide dismutase (SOD) for parenteral administration is in clinical use in several European countries, where it is prescribed principally for treatment of musculoskeletal inflammation, especially osteoarthritis. However, new possibilities for its usefulness are arising from recent progresses of the pathophysiology of several diseases. From the beginning of this decade there has been a virtual explosion of the available informations about the mechanisms and control of free radical-mediated tissue injury. This progress has led us to the threshold of what will probably be broad clinical applications in the next future. Taking into account the mortality and morbidity caused by cardiovascular injury, the most promising application of SOD in human therapy seems to relay in the protection against ischaemia and post-ischaemic reperfusion damage of various organs and tissues but, particularly, of the myocardium. A large body of evidence suggests that myocardial damage following both global or regional ischaemia can be ameliorated by the blockade of free radical mediated injury. SOD has been proposed as a protective agent in various experimental models. The premises of this action, and the available results will be reviewed.

Animals↗
PubMedDate not supplied

[New findings on calcium antagonism].

The family of calcium antagonist substances is continuously increasing. Often it is difficult, if not impossible, to have clear, objective criteria to differentiate between the available molecules. We have considered some molecular aspects of calcium channels and of the effects of calcium antagonists which may be relevant for the clinical utilization of these drugs. In particular, differences between L and T type of calcium channels in the myocytes and between VOC and ROC calcium channels in the smooth muscle are described. Then we have considered the main differences in the mechanism of action and clinical use of the three prototypes of calcium antagonists: phenilalkilamines, dihydropyridines and benzothiazepines. Finally, we have synthetically depicted the characteristic of the second generation agents such as nisoldipine, amlodipine, felodipine, isradipine, lacidipine and gallopamil.

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