La Deposition Research Articles

Lanthanum deposition of the gastric mucosa in a dialysis patient.

A 49-year-old man presented for a screening esophagogastroduodenoscopy (EGD) as part of his registration for a donated kidney transplant. He had been on hemodialysis for 4 years for end-stage renal disease (ESRD) due to diabetic nephropathy. He was taking lanthanum carbonate (LaC) for hyperphosphatemia. A plain abdominal radiograph and CT showed the radiopaque appearance of LaC. EGD disclosed whitish spots resembling xanthomas in the stomach. Biopsies showed deposition of granular crystalline-like material and phagocytosis of these by multinucleated giant cells on HE staining. These histiocytes were positive for CD68. La deposition was suspected because of the long-term oral administration of LaC. LaC is commonly used to treat hyperphosphatemia in patients with ESRD. La deposition on the gastric mucosa presents with various endoscopic findings, including whitish spots, annular whitish mucosa, and diffuse whitish mucosa. The gastric endoscopic findings of La deposition reflect the infiltrated histiocytes and not the LC deposition itself. Our case highlights the importance of recognizing the rare but characteristic imaging findings of gastrointestinal La deposition in hemodialysis patients who are taking LaC.

Growth performance, nutrient digestibility, blood profile, gut health and La deposition of weaning rabbits fed with a low dosage of La2O3

The previous studies found that livestock supplemented with lanthanum (La) complex such as rare earth element-enriched yeast had better growth performance and gut microbiota, and it is assumed that these results may be mainly due to La3+. This study was conducted to evaluate whether La3+ could improve growth performance, nutrient digestibility, blood profile and gut health, also had no La deposition problem in weaning rabbits. La3+ was supplemented to the rabbit diet as La2O3 which dosage was low. A total of 216 weaning rabbits were randomly allotted into 3 treatments, with 6 replicates per treatment and 12 rabbits per replicate in a feeding trial. Treatments included: 1) basal diets (CON); 2) CON + 100 mg/kg of La2O3 (LA1); 3) CON + 200 mg/kg of La2O3 (LA2). Overall, gain-to-feed ratio was increased quadratically (P < 0.05) as increasing level of La2O3 in diets. At the end of the feeding trial, rabbits in the LA1 group had higher (quadratic, P < 0.05) duodenal villus height and calmodulin mRNA expression level in the duodenal epithelial cells respect to the other groups. No difference was found in La deposition in muscle between groups. Chyme samples were collected in the sacculus rotundus from CON, LA1, LA2 and diarrheal rabbits for analyzing gut microbial. Gut microbial in the LA1 group was associated with a higher (P < 0.05) alpha diversity by Shannon index compared to the CON and diarrheal rabbits. It was found that the count of g_Lactobacillus, g_Romboutsia, g_Alistipes and f_Ruminococcaceae was higher (P < 0.05) and the count of g_Escher ichia-Shigella was lower (P < 0.05) in no-diarrheal rabbits compared with diarrheal ones. Thus, weaning rabbits fed with a low dosage of La2O3 had better growth performance and gut health, and the deposition problem of La was not found in muscle, which relieved the weaning stress and could be a novel and functional additive in diets of weaning mammals.

A Periplasmic Lanthanide Mediator, Lanmodulin, in Methylobacterium aquaticum Strain 22A

Methylobacterium and Methylorubrum species oxidize methanol via pyrroloquinoline quinone-methanol dehydrogenases (MDHs). MDHs can be classified into two major groups, Ca2+-dependent MDH (MxaF) and lanthanide (Ln3+)-dependent MDH (XoxF), whose expression is regulated by the availability of Ln3+. A set of a siderophore, TonB-dependent receptor, and an ABC transporter that resembles the machinery for iron uptake is involved in the solubilization and transport of Ln3+. The transport of Ln3+ into the cytosol enhances XoxF expression. A unique protein named lanmodulin from Methylorubrum extorquens strain AM1 was identified as a specific Ln3+-binding protein, and its biological function was implicated to be an Ln3+ shuttle in the periplasm. In contrast, it remains unclear how Ln3+ levels in the cells are maintained, because Ln3+ is potentially deleterious to cellular systems due to its strong affinity to phosphate ions. In this study, we investigated the function of a lanmodulin homolog in Methylobacterium aquaticum strain 22A. The expression of a gene encoding lanmodulin (lanM) was induced in response to the presence of La3+. A recombinant LanM underwent conformational change upon La3+ binding. Phenotypic analyses on lanM deletion mutant and overexpressing strains showed that LanM is not necessary for the wild-type and XoxF-dependent mutant’s methylotrophic growth. We found that lanM expression was regulated by MxcQE (a two-component regulator for MxaF) and TonB_Ln (a TonB-dependent receptor for Ln3+). The expression level of mxcQE was altered to be negatively dependent on Ln3+ concentration in ∆lanM, whereas it was constant in the wild type. Furthermore, when exposed to La3+, ∆lanM showed an aggregating phenotype, cell membrane impairment, La deposition in the periplasm evidenced by electron microscopy, differential expression of proteins involved in membrane integrity and phosphate starvation, and possibly lower La content in the membrane vesicle (MV) fractions. Taken together, we concluded that lanmodulin is involved in the complex regulation mechanism of MDHs and homeostasis of cellular Ln levels by facilitating transport and MV-mediated excretion.

Sources and fluxes of rare earth elements in wet deposition at a Chinese coastal city downstream of the Asian continental outflow

Atmospheric deposition is an important source of dissolved rare earth elements (REEs) to the oceans, but the flux estimating from various sources of REEs in atmospheric wet deposition (AWD) have received little attention to date. To quantify the contributions of the fluxes of REEs in AWD, 38 wet deposition samples were collected for a year in Qingdao, China, a coastal city on the transport path of the continental aerosols heading toward the Pacific Ocean as they are carried on the westerlies. According to the results from Post-Archean Australian Sedimentary rock (PAAS) normalization, REEs in wet deposition showed four types of patterns during observation. Types A (47% of a total of 38 AWD samples) and B (34%) were the main REE patterns, showing a convex-up pattern and Heavy REE enrichment, respectively. Both Types C and D were characterized by higher Light REE with significant La anomalies, while Type C tended to be relatively flat and Type D transitioned downward from Tb to Lu. Meanwhile, the optimum multiparameter method was used to quantify the contribution from each source. Consequently, loess-dust (46% ± 19%) and coal fly ash (38% ± 17%) were the main contributors in Type A, while loess-dust (45% ± 15%) and sea salt (44% ± 14%) account for high proportions in Type B. Fluidized-bed catalytic cracking contributes extra La in types C and D. Annual total REE flux was 55.3 μg m−2 y−1, of which loess-dust contributed 63%, coal fly ash 20%, sea salt 13%, and the catalyst of fluidized-bed catalytic cracking 5% of annual La deposition flux. Furthermore, since aerosols can be transported over long distances, human activities could significantly increase the input fluxes of REEs to the ocean's surface, especially for Middle REE and La.

Investigation of the clinical significance and pathological features of lanthanum deposition in the gastric mucosa

BackgroundThere are often specific endoscopic findings caused by deposition of lanthanum (La) in the gastric mucosa of patients taking lanthanum carbonate (LaC), a novel phosphate binder for patients on hemodialysis. We conducted a retrospective study to investigate the clinical significance of La deposition in the gastric mucosa, and the association between endoscopic features and histologic findings in the same population.MethodsWe compared background factors in patients taking LaC with and without La deposition in their gastroscopic biopsy specimen. We also investigated the relationship between gastric endoscopic biopsy specimens with La deposition and the concurrent endoscopic images.ResultsThere was a significant difference in the total dose of LaC between the La-positive and La-negative groups (990 g [180–3150 g] vs. 480 g [225–1328 g]; p = 0.013). In 27 biopsy specimens with specific whitish mucosa, 10 showed mild histiocytic infiltration and 17 showed severe infiltration. In contrast, among 24 specimens with non-whitish mucosa, 5 showed no histiocytic infiltration, 10 showed mild infiltration, and 9 showed severe infiltration. There was a significant relationship between endoscopic features and the degree of histiocytic infiltration (p = 0.026).ConclusionsWe demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body’s normal response to foreign bodies.Trial registry The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038929, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044393).

Deposition patterns of iatrogenic lanthanum and gadolinium in the human body depend on delivered chemical binding forms

BackgroundRecently, gadolinium from linear GBCAs has been reported to deposit in various regions of the body. Besides gadolinium, other lanthanides are used in medical care. In the current study, we investigated deposition of lanthanum in two patients who received lanthanum carbonate as a phosphate binder due to chronic kidney injury and compared it to additionally found Gd deposition. MethodsTissue specimens of two patients with long-term application of lanthanum carbonate as well as possible GBCA application were investigated. Spatial distribution of gadolinium and lanthanum was determined by quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging of tissue sections. The deposition of gadolinium and lanthanum in different organs was compared, and the ratio of Gd concentration to La concentration (Gd-to-La-ratio) was investigated on an individual pixel base within the images. ResultsDeposition of Gd and La was found in all investigated tissues of both patients. Gd and La exhibited high spatial correlation for all samples, with the main deposition being located in the middle coat (tunica media) of blood vessels. The Gd-to-La-ratio was similar in the tissues investigated (between 8 ± 4 (mean ± standard deviation) and 10 ± 2), except for the thyroid vasculature and surrounding tissue (90 ± 17) as well as the cerebellum (270 ± 18). Here, the ratio was significantly increased towards higher Gd concentration. ConclusionThe results of this study demonstrate long-term deposition of La and comparable localization of additionally found Gd in various tissues of the body. La deposition was relatively low, considering the total administered amount of lanthanum carbonate of up to 11.5 kg, indicating a low absorption and/or high excretion of lanthanum. However, the total amount of deposited La is significant and raises questions about possible adverse side effects. The ratio-approach allows for the usage of the additionally generated Gd data, without detailed knowledge about possible GBCA applications. The significantly decreased Gd-to-La-ratio in the brain might be explained by the lanthanum being released and taken up as free La3+ ion in the stomach that impedes a crossing of the blood-brain-barrier while the intravenously injected GBCAs might dechelate first when they have already crossed the blood-brain-barrier.

Lanthanum Deposition in the Gastroduodenal Mucosa of Dialysis Patients.

Lanthanum (La) carbonate (LC) is one of the most popular phosphate binders used in dialysis patients with end-stage renal disease. Only a small amount of LC is believed to be absorbed from the gastrointestinal (GI) tract because LC strongly binds to dietary phosphate and forms insoluble complexes. La deposition in the gastroduodenal mucosa has been recently identified. Endoscopically, La deposition is demonstrated as whitish lesions of varying sizes and shapes in the gastroduodenal mucosa. Microscopically, La deposition is characterized by histiocytic reaction or small foreign body granulomas containing gray or brown materials mainly in the lamina propria of the GI mucosa. Some histiocytes containing La can migrate into regional lymph nodes via the lymphatic flow. The amount of La deposition in the gastroduodenal mucosa is correlated with the total dose of LC administration, and La deposition is almost consistently observed in LC-treated dialysis patients. Although the detailed mechanism of La deposition in the GI tract is still unclear, several factors, such as gastric pH and metaplastic change of the mucosal epithelium, may be involved in the La deposition in the gastroduodenal mucosa. Here we present an overview of the feature of La deposition in the GI tract.

Lanthanum-Induced Mucosal Alterations in the Stomach (Lanthanum Gastropathy): a Comparative Study Using an Animal Model.

Lanthanum (La) carbonate (LC) is one of the most potent phosphate binders that prevents the elevation of serum phosphate levels in patients with end-stage renal diseases undergoing dialysis. LC binds strongly to dietary phosphate and forms insoluble complexes that pass through the gastrointestinal tract. La deposition in patients treated with LC is a recently documented finding particularly observed in gastric mucosa. We herein describe the detailed gastric mucosal lesions in 45 LC-treated patients and address the potential underlying pathologic mechanism using oral LC administration in rats. Microscopically, La deposition, as shown by subepithelial collections of plump eosinophilic histiocytes or small foreign body granulomas containing coarse granular or amorphous inclusion bodies, was found in the gastric mucosa of 44 (97.8%) of the 45 dialysis patients in the study cohort, which was most frequently associated with foveolar hyperplasia (37.8%). Using oral administration of rats with 1000mg/day LC for 2 or more weeks, La deposition was consistently detectable in the gastric mucosa but not in other organs examined. In addition, various histologic alterations such as glandular atrophy, stromal fibrosis, proliferation of mucous neck cells, intestinal metaplasia, squamous cell papilloma, erosion, and ulcer were demonstrated in the rat model. Thus, orally administered LC can induce mucosal injury, designated here as La gastropathy, which may alter the local environment and result in La deposition in the gastric mucosa, thereby potentially inducing abnormal cell proliferation or neoplastic lesions.

Correlation of lanthanum dosage with lanthanum deposition in the gastroduodenal mucosa of dialysis patients.

Lanthanum (La) deposition has been observed in gastrointestinal mucosa of dialysis patients treated with La carbonate to treat hyperphosphatemia in the 6 years since its authorization in Japan. We investigated gastrointestinal biopsies from 112 dialysis patients, and found 15 cases of histiocytic aggregation with crystalloids and one case of duodenitis with histiocyte aggregation without crystalloids in the 30 patients treated with La carbonate. No histiocytic lesions were observed in the 82 patients without La carbonate administration. So far in total 70 cases of La deposition in the alimentary tract have been reported, including our 16 cases. Neither clinical nor histological findings other than histiocytic aggregation were specific in the patients with La deposition. We also compared the groups with and without La deposition, revealing that the daily and total doses of La carbonate showed statistically significant correlations with La deposition. However the causality with their histologic features, e.g. intestinal metaplasia and degree of inflammation, were inconclusive between the two groups. Although no critical symptoms have been reported, it is necessary to accumulate more cases to clarify the mechanism of La deposition, because dialysis patients must take phosphate buffers for a long period.

Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonate.

Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined "gastric lanthanosis", was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron-microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high-density linear appearance by CT, reflective bright-white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron-dense particles in the histiocytes. The particles had burr-like skeletons resembling La crystals. Gastric lanthanosis is an under-reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.

Bioaccumulation and effects of lanthanum on growth and mitotic index in soybean plants

Rare earth elements such as lanthanum (La) have been used as agricultural inputs in some countries in order to enhance yield and improve crop quality. However, little is known about the effect of La on the growth and structure of soybean, which is an important food and feed crop worldwide. In this study, bioaccumulation of La and its effects on the growth and mitotic index of soybean was evaluated. Soybean plants were exposed to increasing concentrations of La (0, 5, 10, 20, 40, 80, and 160µM) in nutrient solution for 28 days. Plant response to La was evaluated in terms of plant growth, nutritional characteristics, photosynthetic rate, chlorophyll content, mitotic index, modifications in the ultrastructure of roots and leaves, and La mapping in root and shoot tissues. The results showed that the roots of soybean plants can accumulate sixty-fold more La than shoots. La deposition occurred mainly in cell walls and in crystals dispersed in the root cortex and in the mesophyll. When La was applied, it resulted in increased contents of some essential nutrients (i.e., Ca, P, K, and Mn), while Cu and Fe levels decreased. Moreover, low La concentrations stimulated the photosynthetic rate and total chlorophyll content and lead to a higher incidence of binucleate cells, resulting in a slight increase in roots and shoot biomass. At higher La levels, soybean growth was reduced. This was caused by ultrastructural modifications in the cell wall, thylakoids and chloroplasts, and the appearance of c-metaphases.

Electrodeposition of Mg-Li-Al-La Alloys on Inert Cathode in Molten LiCl-KCl Eutectic Salt

Electrochemical preparation of Mg-Li-Al-La alloys on inert electrodes was investigated in LiCl-KCl melt at 853 K (580 °C). Cyclic voltammograms (CVs) and square wave voltammograms (SWVs) show that the existence of AlCl3 or AlF3 could promote La deposition on an active Al substrate, which is predeposited on inert electrodes. All electrochemical tests show that the reduction of La3+ is a one-step reduction process with three electrons exchanged. The reduction of La(III)→La(0) occurred at –2.04 V, and the underpotential deposition (UPD) of La was detected at –1.55 V (vs Ag/AgCl). The same phenomena concerning La UPD were observed on two inert cathodes, W and Mo. In addition, Mg-Li-Al-La alloys were obtained by galvanostatic electrolysis on the W cathode from La2O3 in LiCl-KCl-MgCl2-KF melts with aluminum as the anode. X-ray diffraction (XRD) measurements indicated that various phases like the Al2La, Al12Mg17, and βLi phase (LiMg/Li3Mg7) existed in the Mg-Li-Al-La alloys. The distribution of Mg, Al, and La in Mg–Li–Al-La alloys from the analysis of a scan electron micrograph (SEM) and energy dispersive spectrometry (EDS) indicated that the elements Mg, Al, and La distributed homogeneously in the alloys.

Lanthanum deposition in a dialysis patient

Lanthanum carbonate (LaCO(3)) is an oral phosphate binder widely used in end-stage renal disease (ESRD). Preclinical animal studies reported the highest La concentrations outside the gut to be in mesenteric lymph nodes. We observed previously unreported La deposition visible by light microscopy and confirmed by scanning electron microscopy with energy dispersive x-ray spectroscopy in a mesenteric lymph node at autopsy of a 38-year-old female ESRD patient 3 years following LaCO(3) administration. Although LaCO(3) is generally thought to be minimally absorbed, this demonstration suggests the need for further investigation of the extent and potential effects of such absorption.

Effect of La Surface Coatings on Oxidation Behavior of Aluminum Alloy/SiCp Composites

The oxidation behavior of aluminum-matrix-composites (A3 xx.x/SiCp) has been studied after La deposition with conversion and electrolytic treatments. Kinetics data of the corrosion process were obtained from gravimetric tests performed at different temperatures (350, 425 and 500°C). The nature of the corrosion products and the influence of the microstructure on the morphology and growth of the oxidation layer were analyzed by scanning-electron and atomic-force microscopy, X-ray photoelectron spectroscopy and X-ray diffraction. The extent of oxidation degradation in untreated composites was characterized by a phenomenon of oxidation preferentially localized in matrix/SiCp interfaces favoring MgO formation. La coatings favored a homogeneous oxidation of the composite surface favoring MgAl2O4 spinel formation. In addition, this oxide increased the surface hardness of materials.

めっき法によるNi-Al-La合金膜のコーティングとその耐サイクル酸化性

The formation of coating layer of a Ni aluminide containing La on a Ni-10 at%Cr-8 at%Al alloy substrate was tried by the electrodeposition of La, Ni and Al. The cyclic oxidation resistance for the alloys covered with the coating was then evaluated. Ni was deposited by aqueous solution electrolysis. La and Al were deposited by molten salt electrolysis. For the sample treated with the Ni and Al depositions, a layer consisting of Ni2Al3 was uniformly formed. On the other hand, for the sample treated with the La deposition for 0.6 ks, followed by the Ni and Al depositions, a Ni-rich layer and a Ni2Al3 layer were formed in that order from the substrate alloy. Further, when electrodeposition time of La became long to 1.2 and 1.8 ks, a La-rich layer, a Ni-rich layer and a Ni2Al3 layer were formed in that order from the substrate alloy. The cyclic oxidation test showed that for the untreated sample and the sample with Ni and Al depositions, the mass reduction due to exfoliation of a scale took place. However, for the sample treated with La deposition for 0.6 and 1.2 ks, followed by the Ni and Al depositions, mass reduction was not observed. For this sample after the cyclic oxidation test, a scale consisting of α-Al2O3 adhering to the substrate was formed. Consequently, it was found that a cyclic oxidation resistance of the alloy was improved by the La, Ni and Al electrodepositions.

Immunoglobulin deposition in thickened basement membranes of aging strial capillaries

The presence of immunoglobulins in the thickened basement membrane (BM) of aging strial capillaries was investigated as a possible indicator of autoimmunity in the genesis of atypical BM. Cochleas from young and old Mongolian gerbils raised in quiet were examined by immunostaining at the light microscopic level for IgG and IgM and for the BM components laminin (La) and type IV collagen (IV-C). Another age-graded series of cochleas was stained for IgG at the ultrastructural level. No immunoreactive IgG was detected in specimens from animals less than 6 months old. In contrast, 2 of 12 cochleas from 20- to 28-month-old gerbils and 11 of 20 cochleas from gerbils 30 months or older showed positive staining for IgG in strial capillary BM. IgM was not detected at any age. At the electron microscope level, no immunoreactive IgG was detected in the stria of cochleas younger than 30 months. However, labeling demonstrative of IgG was observed in the thickened BM of some strial capillaries in all six cochleas from gerbils older than 33 months. Lysosome-like granules in endothelial cells and the superiormost marginal cells also stained for content of IgG as did fibrillar material in edematous regions in the intrastrial space. In addition to showing accumulation of IgG, the findings confirm our prior demonstration of increased La deposition in the thickened strial capillary BM of all cochleas from old gerbils. The BM alterations appear confined to strial capillaries in old gerbils, since morphological observations and immunostaining for La and IgG failed to detect changes in BMs at any other site in a wide survey of aged gerbil organs including vessels in other regions of the affected cochleas. The results point more towards the development of an age-dependent permeability to IgG selectively in strial capillaries than to autoimmunity as an explanation of the IgG in BM.

AES study of the La/Si interface with gold interlayers

An AES investigation of the processes of La deposition on the Si(111) surface with one and five monolayers of preliminary adsorbed gold has been performed. The interdiffusion and chemical interaction between the contacting components are observed for the La/Au(θ=5)/Si system. For La/Au(θ=1)/Si chemical interaction at the interface does not lead to the breaking of chemical bonds in the substrate and interdiffusion of the contact components.

Impairment of sarcolemmal permeability in the acute ischemic myocardium--a study with ionic lanthanum probe method.

Impairment of sarcolemmal permeability after the initiation of acute ischemic myocardial injury was studied using an ionic lanthanum (La3+) probe in electron microscopy. Acute ischemic myocardium was induced by ligation of the left anterior descending coronary artery in dogs. In normal cardiac myocytes La is localized exclusively in the extracellular space. i.e. on the glycocalyx, in the T-system and in intercalated discs, with normal fine structures. In ischemic myocardial cells, La deposits were found in the cytosolic space in 22% of subendocardial cells with mild to moderate, but non-necrotic, fine structural changes as early as 30 min. The number of myocytes with La deposition increased with advancing ischemic injury, and necrotic fine structural changes were recognized following ischemia for 60 min. These results indicate that deposition of La occurs before the appearance of irreversible morphologic alterations in ischemic myocardial cells, and suggest an increased permeability of the sarcolemma for Ca2+ and the development of degradation of plasma membrane integrity.

Abnormal lanthanum accumulation due to ischemia in isolated myocardium: effect of chlorpromazine.

The progression of functional, structural, and membrane permeability alterations in the isolated, perfused rabbit interventricular septal preparation was examined at 1, 1.5 or 2 h of ischemia and during 1 h of postischemic reflow. Two other groups of rabbits were pretreated with chlorpromazine (15 and 25 mg/kg), a drug with inhibitory effects on Ca influx and phospholipase activation. The ability of the septa to contract decreased markedly during the ischemic period, but a graded recovery response in physiological contractile parameters was observed upon reperfusion. In septa with comparable preischemic contractile function, pretreatment with chlorpromazine resulted in better functional recovery than that of nontreated septa. Ultrastructural examination showed more extensive and severe damage with increasing periods of ischemia. Ionic La-probe studies of altered membrane integrity showed extensive abnormal intracellular La deposition with ischemic periods of 1.5 h or longer followed by reperfusion. Septa pretreated with chlorpromazine showed better preservation of cell integrity and less intracellular lanthanum deposition. Thus, in this model, a good correlation was found between the extent of functional, structural, and membrane permeability alterations caused by ischemia, and a protective effect of chlorpromazine was shown.

Effect of glucose availability on functional membrane integrity, ultrastructure and contractile performance following hypoxia and reoxygenation in isolated feline cardiac muscle

Isolated, isometrically contracting feline papillary muscles were used to evaluate the effects of glucose availability during hypoxia and reoxygenation on interrelationships between changes in ultrastructure, contractile parameters and functional membrane integrity tested by an ionic lanthanum La probe technique. La 3+ is an electron dense trivalent ion with size and electrochemical properties similar to those of the calcium ion (Ca 2+). Thirty-five muscles were maintained in HEPES-buffered media, containing either 5 m m glucose or glucose-free (0 m m). After the final measurement of contractile parameters, muscles were exposed to media containing 5 m m LaCl 3 for 1 h and then fixed for microscopic study. Control oxygenated muscles, with or without glucose, remained stable for 3 h and showed normal ultrastructure. La remained extracellular in these muscles as confirmed by both transmission and analytical electron microscopy of fixed tissue sections as well as unfixed, frozen-dried sections. With 5 m m glucose medium, muscles reoxygenated after 1 h and 15 min of hypoxia (pO 2 < 40 mmHg) showed significant functional recovery and general preservation of ultrastructure although deposition of intracellular La was noted in focal areas. With glucose deficient media (0 m m), muscles reoxygenated after 1 h and 15 min and 2 h of hypoxia exhibited a progressive impairment in functional recovery and a progressive increase in extent of cellular injury with intracellular La accumulation. Ultrastructural examination revealed a mixed population of muscle cells including severely damaged cells with marked intracellular La deposition on myofibrils and within mitochondria, ultrastructurally intact muscle cells with mild cytoplasmic La deposition and ultrastructurally normal muscle cells devoid of La. La deposition generally was not associated with detectable structural defects in membranes with the possible exception of some severely damaged cells. Thus, in isolated feline papillary muscle, glucose availability influences the potential for recovery of hypoxia-induced contractile depression, ultrastructural alterations and membrane injury associated with increased permeability of plasma and mitochondrial membranes. The data also provide additional evidence for a correlation between the development of irreversible hypoxic injury and a membrane alteration associated with intracellular accumulation of large cations.