Spontaneous superoxide formation by human neutrophils of patients with stable angina after physical exercise*1 (original) (raw)
Related papers
Occurrence of oxidative stress during reperfusion of the human heart
Circulation, 1990
We have investigated the relation between occurrence of myocardial oxidative stress and functional recovery during postischemic reperfusion in 20 selected patients subjected to aortocoronary bypass grafting. Patients were selected for having normal percent ejection fraction and left ventricular end-diastolic pressure before the operation. Occurrence of oxidative stress was assessed by measuring the formation and release of oxidized glutathione (GSSG) in the coronary sinus immediately before aortic cross-clamp, 1, 5, 10, and 20 minutes after removal of aortic cross-clamp, and 10 and 20 minutes after the end of cardiopulmonary bypass. Reduced glutathione (GSH), lactate, and creatine phosphokinase release were also monitored with the same timing. Standard hemodynamic measurements were recorded by means of a triple-lumen thermodilution pulmonary artery catheter before sternotomy, 15 minutes after the end of cardiopulmonary bypass, and during the 24 hours after termination of cardiopulmona-ry bypass. Reperfusion in patients after a short period of ischemia (less than 30 minutes; group 1) resulted in a small and transient release in the coronary sinus of GSSG and GSH and in a progressive improvement of hemodynamic parameters reaching a stable state 4 hours after the operation. In patients with a period of ischemia longer than 30 minutes (group 2), reperfusion induced a marked and sustained release of lactate, GSH, and GSSG; the arteriocoronary sinus difference for GSSG was still negative after the end of cardiopulmonary bypass. The arteriocoronary sinus difference for creatine phosphokinase also remained negative for as long as 20 minutes after cardiopulmonary bypass, and the rate of functional recovery was significantly delayed, reaching the values of group 1 only 12 hours after the operation. In these patients there was a positive correlation (r=0.88, p<0.01) between the duration of ischemia and the myocardial arteriovenous difference for GSSG. In addition, there was a negative correlation between the arteriocoronary sinus difference for GSSG and cardiac index measured 2, 4, and 6 hours after the operation. These data suggest for the first time that, depending on the severity of the ischemic period, oxidative stress occurs during reperfusion of patients with coronary artery disease who are subjected to heart surgery and that it may be linked with a delay in postoperative recovery of cardiac function. (Circulation 1990;81:201-211) T nhe availability of techniques such as surgical reperfusion, angioplasty, and thrombolysis for the restoration of blood flow to the ischemic myocardium has revived interest in the molecular events occurring during reperfusion.1-5 It is clear that reperfusion occupies a central role in
Free Radical Research, 2003
The aim of this study was to analyse the level and progression of oxidative stress, in both plasma and erythrocytes, during heart surgery involving cardiopulmonary bypass. Materials and Methods: Twenty two patients undergoing cardiac surgery and considered to present a high/severe level of surgical risk were selected. We took five blood samples at different times during the cardiac surgery and analysed TBARS, a-tocopherol, coenzyme Q and retinol in plasma and TBARS (baseline levels and induced by Fe 2þ-ascorbate oxidation), a-tocopherol, coenzyme Q and catalase, superoxide dismutase and gluthatione peroxidase activity in erythrocytes. Results: Plasma results shown a decrease in both a-tocopherol and retinol concentration after starting CPB with respect to the reference level ð13:6^1:5 nmol ml 21 vs. 22:0^3:0 nmol ml 21 and 1:2^0:1 nmol ml 21 vs. 1:8^0:2 nmol ml 21 ; respectively ðp , 0:05ÞÞ: In comparison, in erythrocytes, all antioxidants, both enzymatic and non-enzymatic, increased in activity or concentration after starting CPB. Erythrocyte TBARS, both baseline levels and induced levels, followed a similar pattern, with an increase after starting CPB with respect to the reference level (3:9^0:6 nmol mg 21 of protein vs. 2:3^0:2 nmol mg 21 of protein and 10:6^0:8 nmol mg 21 of protein vs. 6:7^0:6 nmol mg 21 of protein, respectively ðp , 0:05ÞÞ: Conclusion: These results reveal an increase in oxidative stress after CPB, both in plasma and erythrocytes, and although the organism is capable of attenuating this stress by means of various antioxidative defence mechanisms, there is an increased possibility of post-CPB complications and thus of mortality.
Cardiovascular Research, 2007
Objective: In animal models, formation of oxidants during postischemic reperfusion may exert deleterious effects ("oxidative stress"). Cardioplegic arrest/reperfusion during cardiac surgery might similarly induce oxidative stress. However, the phenomenon has not been precisely characterized in patients, and therefore the role of antioxidant therapy at cardiac surgery is a matter of debate. Thus, we wanted to ascertain whether the relationship between oxidant formation and development of myocardial injury also translates to the situation of patients subjected to cardioplegic arrest. Methods: In 24 patients undergoing coronary artery bypass, trans-cardiac blood samples and myocardial biopsies were taken before cardioplegic arrest and again following reperfusion. Results: Cardiac glutathione release (marker of oxidant production) was negligible at baseline (0.02 ± 0.04 μmol/L), but it increased 15 min into reperfusion (1.10 ± 0.40 μmol/L; p b 0.05); concomitantly, myocardial concentration of the antioxidant ubiquinol decreased from 144.5 ± 52.0 to 97.6 ± 82.0 nmol/g (p b 0.05). Although these changes document cardiac exposure to oxidants, they were not accompanied by evidence of injury. Neither coronary sinus blood nor cardiac biopsies showed increased lipid peroxide concentrations. Furthermore, electron microscopy showed no major ultrastructural alterations. Finally, full recovery of left ventricular systolic and diastolic function was observed. Conclusions: Careful investigation reveals that while oxidant production does occur during cardiac surgery in patients with chronic ischemic heart disease, cardiac oxidative stress may not progress through membrane damage and irreversible injury.
Heart, 1998
Objective-To determine whether preoperative left ventricular ejection fraction (LVEF) is related to the degree of myocardial oxidative stress during bypass surgery in man. Design-Observational study. Setting-Tertiary care centre. Patients and interventions-31 patients (LVEF range was 20% to 68%) undergoing elective coronary bypass surgery with blood cardioplegic reperfusion were studied. Arterial and coronary sinus blood was collected before aortic cross clamping (T0) and at 0 (T1), 15 (T2), and 30 (T3) minutes after unclamping. Transmural left ventricular biopsies were also obtained from 15 patients at T0 and at T1. Main outcome measures-Glutathione and adenine nucleotides were measured in myocardial biopsies, while coronary sinus-artery diVerences for glutathione, nucleotides, and products of lipid peroxidation were calculated from blood specimens. Creatine kinase (myocardial band; CK-MB) was measured in plasma at four and 12 hours after operation. Results-Myocardial glutathione and adenine nucleotides were correlated (p < 0.02) with preoperative LVEF both at T0 (r = 0.909 and 0.672) and T1 (r = 0.603 and 0.605). Oxidised glutathione released from the heart during reperfusion was inversely correlated with LVEF (r = −0.448, −0.466, and −0461 at T1, T2, and T3, p < 0.01), while reduced glutathione (r = 0.519 and 0.640 at T1 and T2) and glutathione redox ratio (r = 0.647, 0.714, 0.645, and 0.702 at T0, T1, T2, and T3) showed a direct correlation (p < 0.01). Lipid peroxidation at T1 was negatively related to LVEF (r = −0.492). CK-MB was also negatively related to LVEF (r = −0.440 at 4 h and −0.462 at 12 h). Conclusions-The capacity to counterbalance oxidative burst following ischaemia and reperfusion appears to be related to the functional ability of the heart.
Leukocytes, oxygen radicals, and myocardial injury due to ischemia and reperfusion
Free Radical Biology and Medicine, 1988
Ischemic myocardium generates stimuli for neutrophil chemotaxis before the final extent of irreversible ischemic injury is attained. Reperfusion accelerates the infiltration of ischemic myocardium by neutrophils. Oxygen radicals released by the activated neutrophils may exacerbate the tissue damage caused by ischemia. Neutrophil depletion by antiserum was shown to limit infarct size in dogs undergoing coronary occlusion for 90 minutes followed by reperfusion for 6 or 72 hours, but not in dogs undergoing occlusion for 4 hours. Prostacyclin, which inhibits the generation of superoxide anions by neutrophils, also limited canine myocardial injury despite no effect on collateral blood flow. Iloprost, an analogue of prostacyclin that inhibits neutrophils also reduced infarct size, while SC39902, an analogue that does not inhibit neutrophils, did not alter infarct size. The results suggest that oxygen radicals released by activated neutrophils play a role in the pathophysiology of myocardial injury due to ischemia followed by reperfusion.
Biomedicine & Pharmacotherapy, 2002
Myocardial and endothelial damage is still a widely debated problem during the ischemia-reperfusion sequence in heart surgery. We evaluated myocardial purine metabolites, antioxidant defense mechanisms, oxidative status and endothelial dysfunction markers in 14 patients undergoing coronary artery bypass graft (CABG). Heart biopsies were taken before aortic cross-clamping (t1), before clamp removal (t2) and 30 min after reperfusion (t3); perchloric extracts of the tissue were analyzed for glutathione, NAD, nucleotide nucleoside and base content by capillary electrophoresis (CE). In plasma samples from the coronary sinus we evaluated: nitrate and nitrite concentrations by CE, plasma glutathione peroxidase (plGPx) by ELISA, endothelin-1 (ET-1) by RIA and reactive oxygen metabolites (ROM) by colorimetric assay. During the ischemic period (t2) we observed a reduction in cellular NAD and GSH levels, as well as nitrate, nitrite and plGPx. ATP and GTP levels decreased and their catabolic products AMP, GMP, IMP, adenosine, inosine and hypoxanthine accumulated. The energy charge, ATP/ADP ratio, and nucleotide/(nucleoside + base) ratios decreased. At t3, levels of plasma ET-1 increased and monophosphate nucleotides tended to return to basal values. The energy charge did not increase but the nucleotide/(nucleoside + nucleobase) ratio recovered to some extent. Levels of nitrates plus nitrites continued to decrease. No significant variation in ROM levels was observed. Our data indicate that oxidative stress and endothelial damage are major events during CABG, overwhelming the scavenging capacity of the myocyte and preventing restoration of the normal energy balance for 30 min after reperfusion. The AMP deaminase pathway leading to IMP production is active during ischemia and adenosine is not the main compound derived from ATP breakdown in the human heart. The possible role of extracorporeal circulation is also discussed.
Antioxidant defence during cardiopulmonary bypass surgery
2010
Objective: Cardiac surgery may lead to severe oxidative stress due to formation of oxidation products generated during ischemia and reperfusion. We investigated to which extent oxidative stress influences a number of endogenous antioxidants and markers of cellular activation. Methods: At six time points blood was withdrawn from patients undergoing coronary artery bypass grafting, using the on-pump procedure. Results: Both glutathione peroxidase and superoxide dismutase show a gradual and strong increase in activity during surgery (40 and 30%, respectively), returning to baseline values 24 h after surgery. The total antioxidant capacity has a maximum increase of 60%. Markers of cellular activation, such as eosinophil cationic protein and tryptase also increase during the procedure. Conclusion: Cardiac surgery results in systemic inflammation accompanied or caused by severe oxidative stress. The human body has a strong innate oxidative defence screen, which is probably not sufficient to fully compensate for the total amount of oxidative damage. q
Objectives: To determine whether oxidative stress occurs in unstable angina and to examine the state of oxidative stress during reperfusion state following myocardial infarction and bouts of recurrent ischemia in unstable angina. Methods: Blood samples were taken from 16 with acute myocardial infarction (AMI), 11 with unstable angina (UA) and 34 healthy volunteers. The concentration of plasma and neutrophil SOD, catalase, MDA, ceruloplasmin, Cu+2, Zn+2 and thiols were etermined at first and seventh day of onset of chest pain following complete clinical response. Results: The means of serum total creatine phosphokinase enzyme activity and the neutrophil count were significantly increased (P<0.001) with increase in both plasma Cu+2 and ceruloplasmin concentration (P<0.01) and significant decrease in the mean neutrophil SOD activity in AMI group within the first day of onset of chest pain in comparison to the control mean values ( P<0.05). The means of plasma Cu+2, and neutrophil Cu+2 were increased by 26.8, and 13.7%, respectively after seven days of onset of chest pain (P < 0.01) in UA group. The activity of neutrophils catalase revealed 14% decrease in UA at day seven as compared to those of the first day of chest pain. In AMI group, the catalase activities showed a near significant reduction (18.4, P < 0.07), on the seventh day, while the mean of SOD activities was significantly increased to 8.4% over the first day reported mean enzyme activity (P < 0.01). Significant decrease in thiols and MDA (10.3% , 22.6%.P<0.01) in UA and MDA values was increased in AMI to 25.7% (P<0.01) as compared to the day one mean concentration. Conclusion: There was more alleviation in the oxidative stress effect (MDA and thiols, SOD, catalase, ceruloplasmin) in UA as compared to AMI at reperfusion state.