Concordance of structural and functional alterations in myocardial ischemic states.
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Animals↗
Biomedical subjects
E Röth
Publications and source records attributed to E Röth.
Effects of antioxidant therapy in experimentally induced heart infarcts.
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.
Administration, Oral↗
Lipid peroxidation and scavenger mechanism in experimentally induced heart infarcts.
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.
Animals↗
Effect of the ultrashort-acting beta-blocker Brevibloc on free-radical-mediated injuries during the early reperfusion state.
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 beta-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 alpha (PGF1 alpha) 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 alpha 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.
6-Ketoprostaglandin F1 alpha↗
Free radical mediated injuries after coronary artery occlusion.
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.
Animals↗
Threshold level of NF-kB activation in small bowel ischemic preconditioning procedure.
Ischemic preconditioning (IPC), which is obtained by exposure to brief periods of vascular occlusion, improves organ tolerance to prolonged ischemia. The aim of this study was to evaluate the threshold level of NF-kB activation in small intestine during an IPC procedure. Various intestinal IPC were performed on 20 Wistar rats in seven groups: group I (GI, nonpreconditioned); group II (GII, 1-minute ischemia and 1-minute reperfusion); group III (GIII, two cycles of 1-minute ischemia and 1-minute reperfusion); group IV (GIV, 2-minutes ischemia and 2-minutes reperfusion); group V (GV, two cycles of 2-minute ischemia and 2-minute reperfusion); group VI (GVI, 5-minute ischemia and 10-minute reperfusion); group VII (GVII, two cycles of 5-minute ischemia and 10-minute reperfusion). Bowel biopsies were collected after laparotomy (control) as well as at 30, 60, and 120 minutes following IPC. We determined the cytoplasmic and nuclear NF-kB by a chemiluminescence-based ELISA method. Our results showed low, constant NF-kB levels in GI. In the preconditioned groups (GII-GVII), NF-kB was significantly elevated at 30 minutes following IPC (P < .05 vs control). After 1 hour, NF-kB activity decreased to the control level. However, 2 hours after IPC both forms of NF-kB were elevated significantly again, which was independent of the number of IPC cycles (P < .05 vs control). Our experiments revealed that one cycle of 1-minute ischemia and 1-minute reperfusion is a critical threshold level for NF-kB activation during small bowel IPC. Longer and more IPC cycles did not result in further elevation of NF-kB activation.
Animals↗
Effect of Ca-antagonists, beta-blockers and antioxidant during reperfusion period.
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.
6-Ketoprostaglandin F1 alpha↗
Effects of lidocaine on cerebral lipid peroxidation and neutrophil activation following complete compression ischemia.
The effect of lidocaine on brain lipid peroxidation, as reflected by jugular vein malondialdehyde concentrations, and of polymorphonuclear leukocyte activation in peripheral venous blood samples following transient global cerebral ischemia, were studied. In normothermic dogs subjected to a 10 min elevation of cerebrospinal fluid pressure and a subsequent 60 min reperfusion, the malondialdehyde concentration during the first 3 min of reperfusion increased significantly (p < 0.05) in the jugular vein. Lidocaine (10 mg/kg, i.v.), administered 10 min before ischemia, not only prevented the elevation of the malondialdehyde concentrations during ischemia, but also provoked a significant transient decrease 10 min after the start of reperfusion. A 10 min ischemia and a 60 min reperfusion caused no significant changes in the polymorphonuclear leukocyte radical production, neither following ischemia nor after addition of lidocaine. These results suggest that lidocaine exerts a scavenging action on free radical processes but that it has no direct effect on the polymorphonuclear leukocyte activation in the early phase of reperfusion following ischemia.
Animals↗