Publications (46)61.33 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: The left descending coronary artery (LAD) was ligated for 45 min or 90 min followed by 1-h reperfusion. During experiments the animals in Group I (15 dogs) received saline infusion, in Group II (20 dogs) they received the ultrashort-acting β-blocker Brevibloc (esmolol HCl). The marker of lipid peroxidation the malondialdehyde (MDH) as well as endogen scavengers, the glutathione (GSH), and superoxide dismutase (SOD) were measured in the heart tissue homogenates. In blood and heart tissue samples the 6-keto-prostaglandin F1 α. (PGF1 α) and thromboxane B2 (TXB2) were determined. Biochemical measurements revealed that esmolol HCl has beneficial effect on the free-radical-meduated-damage reducing the MDA content in the ischemic area. In Group I the value of MDA after 90 min of LAD ligature was 138 ± 5.6 %, in Group II the elevation was only 107.4 ± 3.2 %. After treatment with Brevibloc the GSH content of ischemic-reperfused areas decreased slightly (81.75 ± 3.5 % of the normal value), moreover, in Group I the depletion of GSH was considerable (64.5 ± 4.2 %). Coronary reperfusion caused the release of eicosanoids in both groups, mainly in the first 10 min. The highest value of thromboxane in blood samples could be measured in Group I after 90 min of LAD ligature (24.8 ± 3.6 pmol/ml; the normal value 8–12 pmol/ml). In Group II during the same period of experiments the TXB2 in the blood was 14 ± 3.7 pmol/ml. In heart tissue samples the amount of endoperoxides increased in ischemic and non-ischemic areas of Group I and II. Nevertheless, the calculated ratio of PGF1 α and TXB2 was near to the normal after Brevibloc treatment (0.85–0.9; the normal values were 1–1.2). These results indicate that esmolol HCl can modulate both the free-radical-mediated reaction and arachidonic acid metabolism.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study was to assess the influence of the radical scavenger (MTDQ-DA), Ca-antagonist (Verapamil) and ultrashort-acting beta-blocker (Brevibloc) on arachidonic acid metabolism and free radical mediated damage. In dog experiments, the left descending coronary artery (LAD) was ligated for 45 min or 90 min followed by one hour reperfusion. Blood samples were taken at different times of occlusion and recirculation for determination of 6-keto PGF1 alpha and TXB2. At the end of the experiments heart tissue samples were excised from injured areas and from the intact part of the left ventricular muscle. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) as well as prostacyclin and thromboxane were determined in tissue samples. Free radical mediated damage (increased lipid peroxidation and exhaustion of endogenous scavengers) could be diminished significantly by antioxidant treatment and moreover, therapy of Verapamil and Brevibloc preserved reduced. It was characteristic that release of endoperoxides was present in each case but the highest values were measured in non-treated animals. Tissue content of prostacyclin and thromboxane varied in differently treated groups, however the altered ratio of PGF1 alpha and TXB2 showed strong influence of the antioxidatnt, Ca-antagonist and beta-blocker.
- [Show abstract] [Hide abstract] ABSTRACT: The left descending coronary artery (LAD) of mongrel dogs was ligated for one month to evaluate the effect of a dihydroquinoline-type antioxidant (MTDQ-DA) during the healing process of myocardial infarction. Thirty animals were divided into three groups: I) control animals (10 dogs) were treated with saline infusion during operation and postoperative days; II) 10 dogs were treated with intravenous MTDQ-DA during the operation followed by postoperative oral treatment, and III) 10 animals were treated with preoperative and postoperative oral treatment plus intraoperative MTDQ-DA infusion. The antioxidant effects were evaluated by measurements of the lipid peroxidation and product malondialdehyde (MDA) and of endogenous scavengers: reduced glutathione (GSH) and superoxide dismutase (SOD) in the ischemic and in intact areas. Ultrathin sections were investigated by JEOL 100 C electron microscope. Elevation of lipid peroxidation (LPO) was present in each group. The most remarkable changes were seen in the control ischemic areas (152 +/- 6.7%). GSH was depleted in the infarcted areas of the control hearts (60 +/- 5.6%), in the antioxidant treated animals this thiol compound was only slightly decreased (81 +/- 5.6%). SOD activity showed a sharp decline (group I) in both ischemic (52 +/- 8.3 U/g) and non-ischemic parts of the left ventricle (78 +/- 7 U/g). After MTDQ-DA treatment (groups II, III) SOD activity diminished only in the ischemic area (83 +/- 8.5 U/g); other parts showed normal (123 +/- 7.2 U/g) activity. According to ultrastructural examinations, MTDQ-DA diminished the degree of structural injury.
- [Show abstract] [Hide abstract] ABSTRACT: In an ischaemic heart model the lipid peroxidation, scavenger state and ultrastructure were studied, to determine the action of a new antioxidant of dihydroquinoline type (MTDQ-DA). In dog experiments, the left descending coronary artery (LAD) was ligated permanently (30 minutes, 1, 2 or 3 hours) or temporarily (30 minutes, 1 or 2 hours of ischaemia followed by 1 hour of recirculation). The experimental protocol involved two groups: control animals without antioxidant treatment and animals treated with antioxidant infusion during the ischaemic and reperfusion period. In both groups, the thiobarbituric acid reactive product, the malondialdehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured, to illustrate the injured or scavenged state of the membrane system. In nontreated animals the permanent and temporary LAD increased the MDA content, decreased GSH concentration (mainly during reperfusion) and reduced SOD activity. Treatment with MTDQ-DA diminishes the characteristic biochemical changes. According to ultrastructural investigations, irreversible alterations (Ca deposits in the mitochondria, disruption of intramitochondrial membranes, hypercontraction bands) occurred only in the control group. Anti-oxidant therapy is able to reduce the myocardial damages both quantitatively and qualitatively.
- [Show abstract] [Hide abstract] ABSTRACT: Studies were undertaken using a synthetic free radical scavenger (MTDQ-DA) on regional ischaemic dog hearts; it was found that the rate of malignant ventricular arrhythmias and fibrillation after coronary ligature unexpectedly decreased. According to experiments on 22 dogs, the intravenous MTDQ-DA therapy decreases the unfavourable ECG consequences of left anterior descending branch ligature: already 5 to 10 minutes after drug administration the ST segment elevation, the QT interval lengthening and the occurrence of ventricular extrasystoles and salvos are diminishing. The so-called epicardial ST map ameliorates rapidly. MTDQ-DA as a blocking agent of free radicals is able to prevent the irritative stimuli around and in the border zone of an infarct, has a vigorous anti-arrhythmogenous effect and greatly reduces the electric heterogeneity. These unexpected results may lead to a promising therapy for the acute heart infarction.
- [Show abstract] [Hide abstract] ABSTRACT: Experiments were performed on dog hearts following coronary ligation and treatment with synthetic antioxidant of dihydroquinoline type. Experimental groups were: control dogs, dogs with ligation of descendens anterior coronary branch, coronary ligated dogs with antioxidant pretreatment and dogs with coronary ligation and simultaneous antioxidant infusion therapy. The heart infarction per se is accompanied by the disintegration of membrane polyunsaturated fatty acids expressed by increase of malondialdehyde (MDA) concentration and the impairment of natural scavenging characterized by the decrease of superoxide dismutase (SOD) and reduced glutathione (GSH) content. The oral pretreatment with antioxidant for 8 days prevented or decreased the unfavourable pathobiochemical responses. The acute infusion therapy exerted no immediate protection, nonetheless, it could decrease the severity of pathological signs.
- [Show abstract] [Hide abstract] ABSTRACT: Rat experiments were undertaken to describe the range of the endogenous lipid peroxidation (measured by formation of malondialdehyde [MDA] in lung tissue) and to analyze the effects of hyperoxic, hypoxic and ischemic influences. The acute hyperoxia caused a moderate increase in lipid peroxidation. The MDA formation in lungs of rats was perceptibly higher in low oxygen environment, while the highest values were found in ischemic lungs. The cytotoxic metabolites cause unfavourable influences on the lung structure (perivascular, interstitial and alveolar edema, destroyed epithelial lining with disintegration of lamellar membranes of the type II-pneumocytes). The findings suggest that potential danger of the oxygen free radicals is an increased lipid peroxidation of lung tissue causing alveolocapillary destruction and extensive exudation with pathologic dwindling of lung function.
- [Show abstract] [Hide abstract] ABSTRACT: Dog experiments were performed to establish the lipid peroxidation of heart tissue (measured by formation of malone-dialdehyde--MDA) and the natural scavenger action (measured by determination of superoxide dismutase--SOD and of reduced glutathione--GSH). Experimental groups were: control dogs having intact heart, dogs ventilated with hypoxic gas (N2O and O2 at a ratio of 10:1) for 1, 2 and 3 hours and dogs having acute coronary ligature for 1, 2, 3 and 24 hours. Acute hypoxia caused a gradual increase of MDA concentration, a moderate increase of the GSH level and a sharp decrease in SOD activity. In ischaemic heart tissue, these changes were very distinctive. High MDA values were found after 3 hours. GSH level and SOD activity decreased continually. Increased MDA formation indicates breakdown of polyunsaturated fatty acids (PUFA) in the membranes, decreased GSH and SOD levels indicate impairment of the natural scavenging, clearly outlining the extent of disintegration of the membrane structure and function due to the effect of toxic free oxygen radicals.
- [Show abstract] [Hide abstract] ABSTRACT: Dog experiments were performed to describe the time course of lipid peroxidation after various ischemic influences of the heart measured by formation of malondialdehyde (MDA), and the scavenger action determined by reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Experimental groups consisted of control dogs having intact hearts and dogs with acute ramus descendens anterior ligature (LAD) having ischemic areas through 15, 30, 45 minutes and 1, 2, 3, 24 hours. Heart tissue for biochemical assays was excised from both the ischemic areas and from nonischemic left ventricle. The acute ischemia caused characteristic alterations in the biochemical parameters: MDA level gradually increased with its peak value being found at the end of 3 hours ligature. GSH levels decreased moderately, whereas SOD levels reduced sharply. As increased MDA formation indicates breakdown of the polyunsaturated fatty acids (PUFA) in the membranes and decreased GSH and SOD levels indicate impairment of the natural scavengering, the observed changes clearly outline the extent of disintegration of membrane structure and function.
- [Show abstract] [Hide abstract] ABSTRACT: Rat and dog experiments were undertaken to describe the range of the endogenous lipid peroxidation (measured by formation of malondialdehyde in heart tissue) and to analyze the effects of hyperoxic, hypoxic and ischemic influences. The acute hyperoxia caused a moderate increase in the lipid peroxidation. The malondialdehyde formation was perceptibly higher in hypoxia, while the highest values were found in ischemic hearts. It can be concluded that the cytotoxic oxygen metabolites cause unfavourable influences on the heart structure and function, for this reason an antioxidant therapy is to be recommended.
- [Show abstract] [Hide abstract] ABSTRACT: Experiments were undertaken on rats and dogs to study the range of endogenous lipid peroxidation (measured by formation of malondialdehyde in heart tissue) and to analyse the effects of hyperoxic, hypoxic and ischaemic influences. The acute hyperoxia caused a moderate increase in lipid peroxidation. The malondialdehyde formation was perceptibly higher in hypoxia, while the highest values were found in ischaemic hearts. It can be concluded that the cytotoxic oxygen metabolites cause unfavourable influences on heart structure and function, for this reason an antioxidant therapy is to be recommended.
- [Show abstract] [Hide abstract] ABSTRACT: Experiments were performed on 10 dog hearts undergone 15 to 90-minute normothermic arrests and 60-minute reperfusion in a special heart-lung model. The purpose of the experiments was to characterize the global ischaemic effects recorded on epicardial electrograms. The duration of QRS complexes and of RR intervals, the integral of ST segment shifts (sigma ST), the number of points showed ST segment displacements (NoST) and the ST segment isopotential map obtained by computer control were evaluated. Only a minor ST segment deviation, a small increase in duration of QRS complexes and of RR intervals with bradycardia and a tendency to electrical stability were found after global ischaemic influences. These observations indicate that pathological electrical manifestations occurring after a global ischaemia are less serious than those occurring after a focal ischaemia.
- [Show abstract] [Hide abstract] ABSTRACT: Ultrastructural changes following ischaemic myocardial injury have been investigated in dogs. After 15 to 120 min global normothermic ischaemia the hearts were reperfused in a special heart-lung model for 60 min and then subjected to electron microscopic examination. The degree of morphological alterations and the duration of ischaemia were approximately interrelated. The ischaemic hearts showed characteristic changes such as mitochondrial, sarcolemmal and myofibrillar defects (swelling, disruption of cristae, loss of matrical density and contractile bands, myofibrillar rupture and lysis, blurred Z-lines). The hypercontractions are no artifacts but consequences of irreversible cellular injury and the observed stiffness during reperfusion is a good marker of the myocardial damage suffered.
- [Show abstract] [Hide abstract] ABSTRACT: Unprotected and preserved myocardial ultrastructures were analyzed in prepump and postreperfused states. The experiments were divided into three groups: group 1 - normal hearts functioning 60 min in a special heart-lung model; group 2 - hearts with 30, 60, 90 and 120 min of normothermic ischemia plus 60 min of recirculation; group 3 - hearts with 30, 60, 90 and 120 min of hypothermic cardioplegia plus 60 min of recirculation. Anoxic hearts could be set in motion, but after longer anoxia the symptoms of stone-heart regularly appeared. Reperfusion induced grave ultrastructural changes both in the energy system (mitochondrial edema, rupture and lysis of cristae) and myofibrils (hypercontraction, elongation, Z line anomalies). Cardioplegic hearts showed a dynamic recovery. However, after reperfusion, characteristic sporadic signs of ischemia could always be demonstrated.
- [Show abstract] [Hide abstract] ABSTRACT: The protective effect of Collins or Sacks solutions was reduced after warm ischemia in preserved and reperfused dog kidneys. The degree of the developed pathologic alterations was connected with the length of the warm ischemic period. Functional changes as decrease of microcirculation and proteinuria and structural sequences as edema and diverse disintegration in glomeruli and tubuli were produced.
- [Show abstract] [Hide abstract] ABSTRACT: An analysis of the ultrastructural features of 35 canine kidneys after hypothermic preservation in Rheomacrodex, Collins3 and Sacks II solutions, and subsequent autologous reperfusion for 2 to 3 hours is presented. Signs of irreversibility (intramitochondrial crista fragmentation, cell membrane rupture, detachment of the brush borders in the area of the proximal tubular system) were confined to the Rheomacrodex-preserved kidneys. Other abnormal features (cytoplasmic vacuolation, mitochondrial swelling in the proximal tubules, vacuolation of the visceral epithelial cells, heteromorphism in the glomerular system) found in the acute stage of revascularization may be regarded as reversible and account for the transitory functional disorders of renal transplants.
University of Pécs
Fuenfkirchen, Baranya, Hungary
- Institute of Pathology