[Inhibition of ventricular fibrillation in experimental acute coronary occlusion by means of free radical-binding compounds].
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Animals↗
Biomedical subjects
E Röth
Publications and source records attributed to E Röth.
Lipid peroxidation in lung of rats exposed to hyperoxic, hypoxic and ischemic effects.
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.
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Myocardial injuries mediated by free oxygen radicals.
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.
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[Lipid peroxidation in vivo--lipid-membrane interaction induced by hyperoxia, hypoxia and ischemia in the heart muscle].
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.
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Membrane perturbations in myocardium: oxygen radicals mediate injuries in experiments.
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.
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Ultrastructural consequences of reperfusion of the ischaemic myocardium.
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.
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Ultrastructural changes of the subendocardium in ischemic and cardioplegic states before and after reperfusion.
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.
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Ultrastructural features of canine kidneys after preservation with hyperthermic solutions and subsequent reperfusion.
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.
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[Value of organ preservation with Collins-3 and Sacks II solutions of warm ischemic and re-perfused kidneys].
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.
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[Susceptibility of the myocardium to injury in decreased coronary circulation].
In the experiments intact dog hearts with ligated descendents, hearts with aorta insufficiency and others with a cardiopulmonary bypass were perfused. It was demonstrated that both ischaemia and relative oxygen deficiency induce within a comparatively short time the same type of irreversible damage in the structure of the subendocardial layers of the myocardium (lysis and rupture of the myofilament, swelling of the mitochondrium, rupture and lysis of the crista, clearing of the matrix). Consequently, the aimed protection of the myocardium during cardiac surgery is of the greatest importance.
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Study of factors affecting the antigen structure of the donor kidney. I. Interpretation of the relationship between periodate pretreatment and the rejection phenomena of canine kidney allografts.
Donor kidneys were preserved in a Collins-4 solution containing periodate in concentrations of 10(-2) and 10(-4) mole/l, respectively, in an attempt to oxidize the carbohydrate components of the antigen-carrying membrane surfaces and thus to influence the rejection phenomena exhibited by the allogeneic kidney. All kidneys were, however, rejected as a result of a hyperacute reaction indicating that periodate did not react with the hydrophobic membrane structures in vivo. Not only did the antigen thus remain unchanged but the vulnerability of other renal structures to the destructive effect of the killer cells also increased as a result of toxic damage.
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The aminogram of the urine produced by the preserved kidney.
The function of autogenous canine kidneys may be considered even after successful preservation and reperfusion to be pathological for about 3 to 4 days, since a condition characterized by proteinuria and increased amino aciduria exists for a while.
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Description and interpretation of morphological changes in canine kidneys after preservation with hypothermic solutions and subsequent reperfusion.
The morphological appearance of canine kidneys preserved with hypothermic solutions of three different types (Rheomacrodex, Collins 3 and Sacks-II) was studied in acute autologous reperfusion models. While at the end of preservation the renal structure still seemed intact (with the exception of the Rheomacrodex model), reperfusion was associated with the manifestation of hitherto latent structural lesions. This is confirmed by light-microscopic features (hydropic swelling and destruction of the tubular epithelium), enzyme histochemical studies (positive alkaline phosphatase reaction of the Bowman space) and topo-optical reactions (loss of anisotropy of the cytomembranes in the presence of fairly well preserved birefringence of the basement membranes).
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Consequences of experimental mitral insufficiency induced by chordotomy.
In mitral insufficiency induced by chordotomy in dogs beside the common diagnostic data the values for tissue perfusion indicative of myocardial microcirculation have been studied. Unexpectedly, a decrease of subendocardial circulation was found; this reduced circulation manifested itself with alterations such as changes in mitochondrial structure, increased quantity of subsarcolemic sarcoplasma, and degenerative symptoms.
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Description and interpretation of functional changes in canine kidneys after preservation with hypothermic perfusates and subsequent reperfusion.
The function of canine kidneys stored with hypothermic solutions (Rheomacrodex, Collins4, Sacks) was studied in acute autologous reperfusion models. Changes in the perfusates (increase in LDH level and minor increase in K+ level), as well as the quantitative and qualitative properties (proteinuria) of the urine produced by the graft may be ascribed to storage and revascularization which affect the cells and their membranes. The alterations of the circulatory parameters demonstrable at the outset and during revascularization are due to an increase in renovascular resistance of hypothermic origin on the one hand, and to acute tubular epithelial damage inherent in the procedure, on the other.
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Description and interpretation of structural changes in canine kidneys after preservation with a hyperosmolar solution and reperfusion.
The effects of hypothermic preservation of canine kidneys for 24 hours by the use of the Sacks solution, and additional autogenous reperfusion were studied by means of submicroscopic morphological methods. While preservation with the Sacks solution was to ensure normal organization of the lipoprotein structures of the basement and cell membranes, in case of additional reperfusion, even of short duration, a substantial or complete loss of anisotropy of the cytomembranes was demonstrable. The present report is the first to be published in the literature on polarization microscopic studies concerned with the effects of kidney preservation and of reperfusion.
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Characteristics of hyperacute rejection of swine kidney xenografts perfused with canine blood.
Twenty-five swine kidney xenografts previously flushed with Collins-4 solution were perfused with canine blood and the functional and morphological changes resulting from xenoperfusion were studied. Blood flow of the kidneys practically ceased by the end of 8 minutes parallel with progressive swelling and cyanosis of the organ. Microscopic study of the kidneys revealed gross destruction of the glomerular and tubular apparatus, marked by extensive oedema, interstitial haemorrhages, diffuse capillary thrombosis and damage to the cell membrane.
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[Auto-perfused multi-organ preparations. III. Interpretation of histologic changes in perfused organs].
The functional instability of "multi-organ" preparations has been studied by morphological and histochemical assessment of 46 autoperfused heart-lung-kidney-liver-duodenopancreas preparations. The organs of the autoperfused preparations were damaged to different degrees, but the damage was always a function of perfusion time (1 to 3 hours). The liver suffered the most serious lesions (stagnation, oedema, hepatocytolysis, hydropic degeneration) but lesions such as interstitial haemorrhage and oedema though in a milder form appeared also in the kidney. The heart structure was comparatively well preserved.
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