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Biomedical subjects

S Curello

Publications and source records attributed to S Curello.

At least 55 records · Page 3Linked to original sources
PubMed1995

Oxidative stress during reperfusion of human hearts: potential sources of oxygen free radicals.

OBJECTIVE: The aim was to examine the role of neutrophil activation in the genesis of oxidative stress during the early phases of reperfusion after ischaemia in patients subjected to aortocoronary bypass grafting. METHODS: Ten selected patients were studied. All had normal ejection fraction and normal left ventricular end diastolic pressures before operation. Each patient required at least three grafts, so that the duration of aortic crossclamping exceeded 30 min, the minimum ischaemic period required to detect oxidative stress upon reperfusion. Oxidative stress was assessed by measuring the formation and release of oxidised glutathione (GSSG) in the coronary sinus 1 min before and 3 min after the start of the cardiopulmonary bypass, and then 1, 5, 10, and 20 min after removal of the aortic clamp, and again 5 and 10 min after the end of the cardiopulmonary bypass. The arterial-coronary sinus difference for neutrophils, elastase-alpha 1 protease complex (elastase), and creatine phosphokinase was also monitored at the same intervals. RESULTS: Before clamping GSSG was undetectable in arterial and coronary sinus blood. There was no significant arterial-coronary sinus difference for neutrophils or elastase [53(SEM 66) cell.ml-1 and 1.10(2.49) micrograms.litre-1, respectively[. Five minutes after re-establishment of coronary blood flow, there was both a release of GSSG into the coronary sinus [arterial-coronary sinus difference: 11(2.6) nmol.dl-1] and an accumulation of neutrophils in the heart [arterial-coronary sinus difference: 262(33), P < 0.01 cell.ml-1], whereas no elastase release from the heart was measured [arterial-coronary sinus difference 7.6(4.46) microgram.litre-1, NS]. The arterial levels of elastase increased progressively during the operation from 48(5) microgram.litre-1 (preclamping) to 405(62) microgram.litre-1, P < 0.01 (end of the cardiopulmonary bypass). CONCLUSIONS: These data indicate that, in man, neutrophils do accumulate in the myocardium during early reperfusion. However, they are not activated when oxidative stress occurs. It is unlikely that the neutrophil localisation in the heart has pathological significance in the production of oxygen free radicals during early reperfusion. Free radical accumulation in the coronary vessels may contribute to disorders of coronary flow associated with reperfusion.

Coronary Artery Bypass↗
PubMed1994

Extraction and assay of creatine phosphate, purine, and pyridine nucleotides in cardiac tissue by reversed-phase high-performance liquid chromatography.

The levels of creatine phosphate, purine, and pyridine nucleotides in tissues provide important information on energetic and oxidative cellular states. Nevertheless, technical, theoretical, and methodological difficulties in extraction and quantification procedures have so far limited our understanding of the exact role that these substances play in metabolic processes which take place in cells. The objective of our study was to find an easy and rapid method for extracting, separating, and quantifying creatine phosphate, purine, and pyridine nucleotides in solid tissues. We adapted the classic acid-extraction procedure with HClO4 for purine and oxidized pyridine nucleotides and then developed a new alkaline extraction with phenol in a phosphate buffer solution (pH 7.8) for reduced pyridine nucleotides. Biopsies of myocardial tissue were frozen and ground at -180 degrees C using the appropriate extraction procedure. The separation and quantification of the metabolites were performed using a reversed-phase 3-microns Supelchem C18 column, with the addition of tetrabutylammonium as an ion-pair agent to the buffer solution, by ultraviolet detection. The recovery of the external and internal standards always exceeded 90%. The autooxidation or interconversion processes were almost insignificant for each reduced form. This technique allowed us to avoid complex enzymatic procedures and difficulties in the selective assay of pyridine nucleotides with chemiluminescence and surface spectroscopy.

Chromatography, High Pressure Liquid↗
PubMed1993

Plasma levels of atrial natriuretic factor (ANF) and urinary excretion of ANF, arginine vasopressin and catecholamines in children with congenital heart disease: effect of cardiac surgery.

We studied the changes in the plasma concentration of atrial natriuretic factor (ANF) and the urinary excretion of ANF, arginine vasopressin (AVP) and catecholamines in 22 children with congenital heart disease, divided into two groups. Group 1 included 11 children with congestive heart failure (CHF), treated with digitalis and diuretics. Group 2 included 11 children without CHF and without medical treatment. Each group was compared with a control group of 15 healthy, age-matched children. The plasma concentration of ANF was raised in both groups, but it was significantly higher in group 1 (235.5 +/- 82.9 pg/ml), compared to group 2 (48.4 +/- 29.4 pg/ml, P < 0.002). Urinary excretion of ANF was measurable in both groups and higher in group 1 (185.9 +/- 116.2 pg/kg per h) than in group 2 (48.5 +/- 30.7 pg/kg per h), but not significantly so. Urinary excretion of AVP and catecholamines was not different in children with congenital heart disease and healthy children. Twenty-four hours after surgery, plasma ANF diminished in group 1 (from 235.5 +/- 82.9 to 93.4 +/- 53.8 pg/ml, P < 0.003), but did not change in group 2. The urinary excretion of ANF was unchanged in both groups. In contrast, urinary excretion of AVP and catecholamines rose significantly in both groups. These data show that plasma ANF is increased in children with congenital heart disease, even in the absence of CHF. The measurement of urinary ANF is less reliable than a plasma assay. The postoperative increases in AVP and catecholamine urinary excretions could be responsible for the vasoconstriction and water retention typical of the postoperative period.

Adolescent↗
PubMed1993

Cardioprotection by nisoldipine: role of timing of administration.

Nisoldipine was administered at 10(-9) M, a dose lacking negative inotropism, to isolated and perfused rabbit hearts submitted to 60 min ischaemia (1 ml.min-1) followed by 30 min reperfusion. The drug was delivered either 30 min before ischaemia, at the onset and after 30 min of ischaemia and during reperfusion only. Cardiac protection was evaluated in terms of recovery of left ventricular pressure during reperfusion, release of creatine phosphokinase (CPK), mitochondrial function, tissue content of adenosine triphosphate (ATP) and creatine phosphate (CP), calcium homeostasis and the occurrence of oxidative stress, established measuring content and release of reduced and oxidized glutathione. The cytoprotective action of nisoldipine occurs in the absence of negative inotropism and is closely related to the time of administration. Optimal myocardial preservation is achieved when nisoldipine is given before or at the onset of ischaemia. Prophylactic administration of nisoldipine improved the recovery of the developed pressure from 15.9 +/- 1.0 (SE) mmHg to 47.8 +/- 1.9 mmHg, P < 0.01 and reduced the release of CPK from 830 +/- 29 to 229 +/- 27 mU.min-1 g-1 wet wt, P < 0.01. The accumulation of tissue and mitochondrial calcium was reduced from 58 +/- 11 and 49 +/- 9 to 14 +/- 6 and 10 +/- 4 mmol.kg-1 dry wt respectively, P < 0.01. This resulted in a significant (P < 0.01) preservation of all indices of mitochondrial function, allowing a higher recovery of ATP and CP after reperfusion (from 4.1 +/- 0.7 and 10.0 +/- 0.6 to 16.1 +/- 1.0 and 29.9 +/- 0.2 mumol.g-1 dry wt respectively, P < 0.001). Reperfusion-induced myocardial accumulation and release of oxidized glutathione were reduced from 0.493 +/- 0.07 nmol.mg-1 protein and 0.768 +/- 0.063 nmol.min-1 g-1 wet wt to 0.225 +/- 0.07 and 0.157 +/- 0.038 respectively, P < 0.01. Similar data were obtained when nisoldipine was given at the time of ischaemia, while administration 30 min after the onset of ischaemia showed only a trend towards protection. Nisoldipine lost its protective effect when given on reperfusion. A multifactorial analysis of the data suggest that the cardioprotective effect of nisoldipine is related to the maintenance of membrane integrity, possibly since nisoldipine is highly lipophilic.

Adenosine Triphosphate↗
PubMed1993

Myocardial damage during ischaemia and reperfusion.

Reperfusion, without doubt, is the most effective way to treat the ischaemic myocardium. Late reperfusion may, however, cause further damage. We attempted to identify the nature and time-course of metabolic changes occurring during ischaemia followed by reperfusion either in isolated and perfused rabbit hearts or in coronary artery disease (CAD) patients undergoing intracoronary thrombolysis or aortocoronary bypass grafting. In isolated hearts, reperfusion after prolonged ischaemia causes exacerbation of cell damage, leading to a breakdown of the permeability barrier of ions as well as of larger molecules, such as creatine phosphokinase. As consequence, reperfusion results in a large increase in intracellular calcium, leading to mitochondrial calcium overload with subsequent damage to the mitochondrial structure and loss of the ability to produce adenosine triphosphate (ATP). The ultimate mediator of the membrane damage is not known. It has been suggested that myocardial production of oxygen free radicals above the neutralizing capacity of the myocytes is an important cause of reperfusion damage. There is evidence that prolonged ischaemia reduces the naturally occurring defence mechanisms of the heart against oxygen free radicals, particularly mitochondrial manganese superoxide dismutase, and the intracellular pool of reduced glutathione. Consequently, reperfusion results in severe oxidative damage, as evidenced by tissue accumulation and release of oxidized glutathione. An oxygen free radical-mediated impairment of mechanical function also occurs during reperfusion of the human heart. During surgical reperfusion of CAD patients, we observed a prolonged and sustained release of oxidized glutathione; the degree of oxidative stress can inversely correlated with recovery of mechanical and haemodynamic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Occurrence of oxidative stress during myocardial reperfusion.

Reperfusion, without doubt, is the most effective way to treat the ischaemic myocardium. Late reperfusion may however cause further damage. Myocardial production of oxygen free radicals above the neutralizing capacity of the myocytes is an important cause of this reperfusion damage. There is evidence that prolonged ischaemia reduces the naturally occurring defence mechanisms of the heart against oxygen free radicals, particularly mitochondrial manganese superoxide dismutase, and intracellular pool of reduced glutathione. Consequently, reperfusion results in a severe oxidative damage, as evidenced by tissue accumulation and release of oxidized glutathione. An oxygen free radical-mediated impairment of mechanical function also occurs during reperfusion of human heart. In fact we observed during surgical reperfusion of coronary artery disease (CAD) patients, a prolonged and sustained release of oxidized glutathione; the degree of oxidative stress was inversely correlated with recovery of mechanical and haemodynamic function. These findings represent the rationale for therapeutic interventions which increase the cellular antioxidant capacities and improve the efficacy of myocardial reperfusion.

Animals↗
PubMed1992

Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action.

We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state. At concentrations > 10(-6) M, zofenopril, but not captopril, caused a reduction in myocardial NE content. At 10(-4) M, both drugs caused a reduction in developed pressure and an increase in diastolic pressure and release of creatine phosphokinase (CPK). Second we investigated their effects on ischemic and reperfused myocardium. Both drugs exerted a cardioprotection; zofenopril was always more potent than captopril. Recovery of developed pressure on reperfusion improved, and peak release of NE was reduced, as was release of CPK. Calcium homeostasis and mitochondrial function were maintained. Captopril had no effect on occurrence of oxidative stress during reperfusion, whereas zofenopril reduced it. In hearts treated with the converting enzyme inhibitors, peak release of NE was correlated to mitochondrial calcium content, production of ATP, and recovery of mechanical function on reperfusion. These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE.

Adenosine Triphosphate↗
PubMed1991

Oxygen free radicals and myocardial damage: protective role of thiol-containing agents.

It has been suggested that the sudden presence of oxygen during reperfusion after a period of ischemia may be toxic for the myocardial cell. The oxygen molecule is capable of producing reactions in the cell, forming highly reactive free radicals, and inducing lipid peroxidation of membranes, altering their integrity and increasing their fluidity and permeability. The ischemic and reperfused cardiac cell is the prime candidate for this reaction sequence and may explain the molecular mechanism underlying the pathologic events related to membrane dysfunction and calcium homeostasis. However, the myocardium has a series of defense mechanisms including the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase plus other endogenous antioxidants such as vitamin E, ascorbic acid, and cysteine to protect the cell against the cytotoxic oxygen metabolites. The prerequisite for oxygen free radical involvement in ischemia and reperfusion damage is that ischemia alters the defense mechanisms against oxygen toxicity. It is known that ischemia may impair mitochondrial SOD and, with reperfusion, oxidative stress may occur as shown by tissue accumulation and release of oxidized glutathione. This tripeptide molecule in the cofactor of glutathione peroxidase, the enzyme that removes hydrogen and lipid peroxides. Its formation and subsequent release is a reliable index of oxidative damage. In our study, we investigated the effects of N-acetylcysteine on oxidative damage in the isolated rabbit heart. N-acetylcysteine increases, in a dose-dependent manner (from 10(-7) to 10(-5) M), the myocardial glutathione content and provides an important degree of protection against ischemia and reperfusion. Oxidative stress does not occur, mitochondrial function is maintained, enzyme release is reduced, and contractile recovery is increased. Similarly, we administered N-acetylcysteine in the pulmonary artery of coronary artery disease patients undergoing coronary bypass grafting (150 mg/kg in 1 hour followed by 150 mg/kg in 4 hours). The degree of oxidative stress on reperfusion was reduced and recovery of cardiac function improved. In this article, we review the cardioprotective role of thiol-containing agents.

Animals↗
PubMed1991

The occurrence of oxidative stress during reperfusion in experimental animals and men.

Reperfusion is the prerequisite for the ischemic myocardium to recover its metabolic and mechanical function. However, reperfusion after a prolonged period of ischemia in the experimental animal may exacerbate, or at least accelerate, the occurrence of ischemic injury, whilst in humans at the least it is not beneficial. This entity has been called reperfusion damage, since much of the damage is believed to be caused by events occurring at the moment of reperfusion rather than by changes occurring during ischemia. The existence of reperfusion damage, however, has been questioned, and evidence in favour of the concept is sparse. At the moment the molecular events occurring at the time of reperfusion are not completely understood, and the relative importance of several proposed deleterious mechanisms is not yet established. One of the most fashionable ideas for the cause of reperfusion damage is that the function of cell membrane is modified by oxygen radicals generated at the moment of reperfusion. Evidence in favour of and against this hypothesis is described in detail in the present article.

Animals↗
PubMed1991

The effect of propionyl-L-carnitine on the ischemic and reperfused intact myocardium and on their derived mitochondria.

To assess whether propionyl-L-carnitine protects rabbit heart against the deterioration caused by ischemia and reperfusion, isolated hearts were infused with a medium containing it in different concentrations. During control, normoxic perfusion, and 60 minutes of low-flow ischemia (37 degrees C) followed by 30 minutes of reperfusion, diastolic, and developed pressures were monitored; coronary effluent was collected and assayed for lactate and creatine phosphokinase (CPK); mitochondria were harvested and assayed for oxidative phosphorylation and calcium content; and tissues for concentration of adenosine triphosphate (ATP) and creatine phosphate. Propionyl-L-carnitine reduced the ischemic deterioration of mitochondrial function and the depletion of tissue stores of ATP. On reperfusion, hearts treated with it recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. The reperfusion-induced mitochondrial calcium overload and release of CPK were also reduced. The effect of propionyl-L-carnitine was dose dependent. At 10(-8) M it failed to modify ischemic and reperfusion damage but protected well at 10(-7) M. No further protection was obtained at 10(-6) M. Propionyl-L-carnitine thus protects the myocardium against some of the deleterious effects of ischemia and reperfusion. In particular it protects mitochondrial function, perhaps partly by preventing mitochondrial calcium overload. Because this protection occurs in the absence of a negative inotropic effect during normoxia or of a coronary dilatatory effect during ischemia, it cannot be attributed to an energy-sparing effect or to the improvement of oxygen delivery.

Adenosine Triphosphate↗
PubMed1991

Time course of human atrial natriuretic factor release during cardiopulmonary bypass in mitral valve and coronary artery diseased patients.

We determined the time-course of the release of atrial natriuretic factor (ANF) during cardiopulmonary bypass (CPB) in six patients undergoing coronary artery bypass (CAD) and eight patients undergoing valve replacement for mitral stenosis (MS). Before CPB, the arterial ANF was significantly higher in MS patients than in CAD patients (243 +/- 38 and 29 +/- 5.8 pg/ml respectively, P less than 0.01). With the onset of CPB, the acute pressure unloading of the atria induced a significant, rapid decrease of ANF only in MS patients (-64% of pre-CPB value at 5 min) and no major changes in CAD patients. Clamping of the aorta induced a further progressive reduction of ANF release to almost zero in both groups. Readmission of coronary flow to the empty atria with declamping resulted in an increase in the plasma level of ANF in both groups to reach the concentration present in MS patients before CPB. After CPB, the ANF levels decreased in CAD patients while remaining elevated in MS patients. These data suggest that ANF release from human atria depends on atrial filling pressure and other unknown factors.

Adult↗
PubMed1991

Role of oxygen free radicals in ischemic and reperfused myocardium.

In recent years there has been considerable interest concerning the role of oxygen radicals in myocardial ischemia and reperfusion injury. The sequential univalent reduction of oxygen gives rise to very reactive intermediate products. Normally, the tissue concentration of these intermediate products of oxygen is limited and the aerobic myocardium survives because of the existence of a delicate balance between the generation of the various oxidants and the maintenance of the antioxidant defense mechanism. Several possible sources have been identified for the production of active oxygen species after ischemia and reperfusion and these sources may be mutually interactive. The ability of scavengers of oxygen free radicals, including vitamin E, to improve mechanical, mitochondrial, and sarcoplasmic reticulum function in animal models of ischemic-reperfusion injury also suggests that oxygen free radicals are partly responsible for myocardial damage in these models, although caution in the interpretation of these data is necessary.

Animals↗
PubMed1991

Evaluation of phospholipid peroxidation as malondialdehyde during myocardial ischemia and reperfusion injury.

Peroxidation of membrane phospholipid polyunsaturated fatty acids is considered a major mechanism of the damage occurring on reperfusion of the myocardium after a prolonged period of ischemia. The evidence in support of this mechanism of damage is based on tissue malondialdehyde quantitation by the thiobarbituric acid test (TBA test). In an attempt to verify this topic, we have subjected isolated and Langendorff-perfused rabbit hearts to a period of 60 min of severe ischemia plus 30 min of reperfusion. At appropriate time points, malondialdehyde was determined in the tissue by means of TBA test and directly by reversed-phase, high-pressure liquid chromatography (HPLC). We have found no correlation between the two compared assays. During reperfusion, there was the formation of non-lipid-related, malondialdehyde-like, TBA-reactive substance that leads to overestimation of the extent of lipid peroxidation. On the contrary, by direct HPLC quantitation, there was a decrease of tissue malondialdehyde during ischemia and during the early phases of reperfusion. Our results demonstrate that TBA test is not a reliable index of lipid peroxidation in organ systems.

Animals↗
PubMed1991

[Is lipid peroxidation responsible for the damage caused by postischemic reperfusion?].

Peroxidation of membrane phospholipid polyunsaturated fatty acids is considered a major mechanism of the damage occurring during post-ischemic reperfusion. The evidences in support for this mechanism of damage are based on tissue malondialdehyde (MDA) quantitation by the thiobarbituric acid test (TBA-test). In an attempt to verify this topic we have subjected isolated and Langendorff perfused rabbit hearts to a period of 60 min of severe ischemia plus 30 min of reperfusion. At appropriate time points MDA was determined in the tissue by means of TBA-test and directly by reversed phase, high pressure, liquid chromatography (HPLC). We have found no correlation between the 2 compared assays. During reperfusion, there was the formation of non-lipid related, MDA like, TBA-reactive substance which leads to overestimation of the extent of lipid peroxidation. On the contrary, by direct HPLC quantitation, there was a decrease of tissue MDA during ischemia and during the early phases of reperfusion. Our results demonstrate that TBA-test is not a reliable index of lipid peroxidation in organ systems and that MDA accumulation does not precede the evidence of the functional alterations occurring on reperfusion of the previously ischemic myocardium. These results are of relevance in the understanding of the exact mechanism of reperfusion damage as, in the same experimental model, oxy radicals have been shown to be generated and antioxidants are protective.

Animals↗
PubMed1991

[Toxicity of fatty acids during myocardial reperfusion: a new possible mechanism of action].

To assess the value of myocardial substrate in the occurrence of ischemic-reperfusion damage, isolated, electrically paced rabbit hearts were perfused for 60 min under aerobic condition (25 ml/min with oxygenated Krebs-Henseleit solution containing glucose 11 mM). Thereafter the hearts were made ischemic for 30 min by reducing coronary flow to 3 ml/min. During ischemia, 3 different substrates were used glucose 11 mM (Group I), palmitate 1.2 mM (Group II) and palmitate 1.2 mM + glucose 11 mM (Group III). The hearts were then reperfused (25 ml/min) for 30 min under aerobic condition using glucose 11 mM as the only substrate. In the presence of glucose with or without palmitate (Group I and III) ischemic damage was mild. Recovery of the developed pressure was 95% and there was no contracture during ischemia and or reperfusion. During ischemia and reperfusion there was a small release of CPK, GSSG and GSH. In the presence of palmitate (Group II) ischemic and reperfusion damage was profound. Recovery of developed pressure was reduced (25%) and diastolic pressure significantly increased (68 +/- 5.1 vs 3 +/- 1.5, 5 +/- 1.8 mmHg). These mechanical data were concomitant with an important release of CPK (580 +/- 50 vs 180 +/- 35, 210 +/- 48 mU/min/gww) and oxidised glutathione (0.38 +/- 0.3 vs 0.05 +/- 0.001, 0.09 +/- 0.003 nmoles/min/gww). In addition the redox state of the cells of the Group II was significantly shifted through the oxidative state at the end of ischemia and of reperfusion. These results indicate that palmitate as substrate increases the deleterious effects of ischemia; glucose is able to overcome the negative effects of palmitate.

Aerobiosis↗