Antioxidant status of patients after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: It has been convincingly established that cardiopulmonary bypass routinely used in cardiac surgery induces an oxidative stress. The extensive production of reactive oxygen species occurring during cardiopulmonary bypass has a deleterious effect on the endogenous antioxidant defense pool. The recovery of antioxidant enzyme activities as well as other antioxidatively substances is one of the important tasks for the effective defense of patients in the postoperative period. AIM OF THE STUDY: Oxidative stress markers and the antioxidant status and the activities of some antioxidant enzymes were studied in patients during one-week period after cardiac revascularization performed using cardiopulmonary bypass and the results were compared with patients operated by off-pump technique. PATIENTS AND METHODS: Thirty-nine patients undergoing elective surgical revascularization (coronary artery bypass grafting) were divided in two groups: twenty-two patients operated using cardiopulmonary bypass (group A) and a group B of seventeen patients undergoing pump-off surgery. Blood samples were drawn before operation and then in course of the first week after surgery. The following biochemical parameters were estimated: plasma levels of total antioxidant status (TAS) and of thiobarbituric acid reactive substances (TBARS) as well as erythrocyte activities of two antioxidant enzymes--superoxide dismutase (SOD) and glutathione peroxidase (GPx). RESULTS: There was a significantly decreased preoperative and also postoperative levels of TAS associated with a preoperatively increased level of TBARS in group A only. In both groups of patients (especially in group B), markedly decreased activity of SOD was observed. The increase of GPx activity--especially on the third postoperative day--was not significant. CONCLUSIONS: Regardless of the surgical technique, both groups of patients had a markedly decreased antioxidant capacity with a significantly increased production of lipid peroxides especially in patients operated with cardiopulmonary bypass. The decreased antioxidant status was connected with decreased erythrocyte activity of SOD. Therefore, we recommend the regular supply of antioxidant acting substances (antioxidant vitamins and coenzyme Q10) be included in their standard therapeutic strategy especially in the preoperative period. (Tab. 2, Fig. 4, Ref: 22.)

Inhibition of NO synthase activity in nervous tissue leads to decreased motor activity in the rat.

The nitric oxide/cGMP system has been shown to play a crucial role in the mechanism of learning and memory. The aim of the present study was to investigate whether the inhibition of NO synthase in brain regions leads to alterations of spontaneous behavior in rats. Male Wistar rats were treated with NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) at the dose of 40 mg/kg/day. After 4 weeks of L-NAME treatment, NO synthase activity was significantly decreased by 75% in the cerebellum, by 71% in the cerebral cortex and by 72% in the thoracic spinal cord. Decreased NO synthase activity in the nervous tissue was associated with decreased motor horizontal and vertical activities as well as by lowered frequency of sniffing, cleaning and defecation. It is concluded that the inhibition of NO synthase activity has a suppressive effect on spontaneous behavior of rats.

[Parameters of energy metabolism in patients after vascular reconstructive surgical procedures]. / Niektoré parametre energetického metabolizmu u pacientov pocas cievneho rekonstrukcného chirurgického výkonu.

Revascularization surgery in patients with peripheral arterial occlusive disease presents an acceptable clinical model for studying the rate of ischaemia-reperfusion injury of cells and other structures of skeletal muscle of the affected extremity. Validity of carefully chosen set of biochemical parameters for determination of this injury during and after surgery as well as in the early and late reperfusion periods and during the readaptation to situation after restoration of blood circulation was verified. Blood samples were taken from the regional common femoral vein which allowed to obtain information directly from the ischaemized extremity. Analyzed biochemical parameters have given useful information about the situation in acid-base regulation, in energy metabolism as well as antioxidant capacity. These parameters were estimated in four time intervals: before aorta cross-clamping (preischaemic phase), then 30 min (early reperfusion) and 18 hours (readaptation period) after aorta-declamping. In the early reperfusion period a marked acidosis and raised carbon dioxide tension, significant increase of lactate and pyruvate levels as well as increased hypoxanthine plasma level were observed. On the contrary, in this period the lowest lipoperoxide level was found, evident in the wake of relative stability of concentration of endogenous antioxidants documented by a constant glutathione redox status that at the first postoperative day even significantly decreased as a consequence of a drop of oxidized and increased of reduced form of glutathione. Therefore, the applied biochemical parameters allow to monitor the ischaemia-reperfusion damage of afflicted region and could be used even in the study of compounds with a protective effect against possible injury of ischaemized and reoxygenized tissues. (Tab. 3, Fig. 4, Ref. 32.)

[The effect of uric acid, creatine phosphate and carnitine on lipid peroxidation in cerebral cortex and myocardium homogenates]. / Vplyv kyseliny mocovej, kreatínfosfátu a karnitínu na lipoperoxidáciu v homogenátoch mozgovej kôry a myokardu.

BACKGROUND: Uric acid as the product of purine nucleotide degradation is an integrate component of blood plasma. This metabolite is considered to be one of the important naturally occurring antioxidants building up the antioxidation system of the organism. Creatine phosphate and carnitine are important substances participating in energy metabolism of the cells. Energy production is closely related to the level of reduction systems and thus also to the antiradical ability of the cell. By this mechanism could creatine phosphate and carnitine improve the antioxidative capacity of the cell. METHODS: In homogenates of rat brain cortex and myocardium was the production of oxygen radicals stimulated by mixture of Fe2+ ions and ascorbate. Oxygen radicals may induce lipid peroxidation by the means of the reaction with lipid structures. We tried to inhibit the process of lipid peroxidation by addition of uric acid, creatine phosphate and carnitine into the incubation medium. Intensity of lipoperoxidation was measured by detection of substances giving positive reaction with thiobarbituric acid (TBA) in homogenates of brain cortex and myocardium. RESULTS: Uric acid in concentrations of 1 and 0.5 mmol.l-1 markedly inhibits the production of compounds reacting with TBA. This effect was not found in 0.05 mmol.l-1 concentration. Creatine phosphate and carnitine in 1 mmol.l-1 concentrations also decreased the value of lipid peroxides in homogenates of brain cortex, but their effect was lower than the effect of uric acid. This effect was not seen in myocardium homogenates.

[Biochemical parameters in the blood of patients during open-heart surgery. I. Monitoring changes in energy metabolism]. / Sledovanie niektorých biochemických parametrov v krvi pacientov pocas operácie na otvorenom srdci. I. Monitorovanie zmien energetického metabolizmu.

Levels of lactate, inorganic phosphate and uric acid in arterial, mixed venous and coronary sinus blood were studied in patients during open-heart surgery. It was found that the determination of mentioned biochemical parameters can provide information regarding the energetic metabolism status of the whole organism, but selectively, also of the patient's myocardium. The results of biochemical analyses demonstrate a significant loading of the organism manifested by metabolic alterations, especially after long-term cardiopulmonary bypass. The study of mentioned biochemical parameters can be employed for investigation of a more efficient protection of myocardium against ischemia-reperfusion injury. (Fig. 6, Ref. 18).

Role of natural prostaglandins in the control of murine mammary tumor virus expression.

The regulation of murine mammary tumor virus (MuMTV) production by mammotropic hormones, hormonomimetic substances, and cyclic nucleotides was investigated. The virus produced in control and treated mammary tumor cell cultures was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly(rC).oligo(dG) as template-primer. Two days after exposure, the synthetic glucocorticoid, dexamethasone (DXMT), increased spontaneous MuMTV production at optimal concentration (0.1 mumol) up to ten times. Dibutyryl derivative of cyclic AMP had no effect on spontaneous MuMTV production, whereas the drug potentiated suboptimal concentrations of the glucocorticoid. Natural prostaglandins, potent agonists of adenylate cyclase catalyzing intracellular synthesis of cyclic AMP, enhanced both basal (up to five times) and DXMT-stimulated (up to 1.6 times) MuMTV replication. The MuMTV-stimulating activity of prostaglandins decreased in the order of PGA1 greater than PGE1 greater than PGB1 greater than PGF2 alpha. Prostaglandins can be replaced partially by norepinephrine and isoproterenol by enhancing the DXMT-mediated MuMTV stimulation, whereas these drugs remained without effect on spontaneous MuMTV production. Theophylline, an antagonist of cAMP-phosphodiesterase converting cAMP to AMP, enhanced the virus-stimulating activity of DXMT as well as of prostaglandins. The enhancement of MuMTV production by adenylate cyclase agonists do not correlate absolutely with the estimates of intracellular cAMP levels, since the highest amounts of cAMP has been repeatedly observed in cells treated with PGE1 and norepinephrine. The results indicate that besides hormones, other hormone-like substances and cyclic nucleotides may be involved in the complex mechanism of hormone-regulated MuMTV genome expression.