Focal Coagulative Necrosis Research Articles

COMPARISON OF LAPAROSCOPIC SALINE INFUSED TO DRY RADIO FREQUENCY ABLATION OF RENAL TISSUE: EVOLUTION OF HISTOLOGICAL INFARCT IN THE PORCINE MODEL

We investigated and compared the gross and histopathological features of radio frequency (RF) ablated renal tissue using saline infused RF ablation (RFA) vs dry RFA in a porcine model. Ten porcine kidneys underwent laparoscopic RFA. The lower and upper poles of each right kidney were treated with 1 and 2 cycles of saline augmented (wet) RFA, respectively. The upper pole of each left kidney was RF ablated without saline infusion (dry RFA) and a control lesion was created in the lower pole. The animals were sacrificed immediately after ', 2 and 9 days after (subacute), and 14 and 21 days after (chronic) treatment, respectively. Gross pathological and histological changes caused by the different RF treatments were compared. Mean time to attain target temperature was shorter with wet than with dry RFA. Grossly the lesion sizes achieved were larger using wet RFA but independent of the number of wet RFA treatment cycles. Gross lesion sizes decreased with time for each treatment modality. No histopathological differences were seen between the 2 RFA treatment modalities as well as between 1 vs 2 cycles of wet RFA. In the acute phase hematoxylin and eosin staining of ablated tissue revealed focal areas of alterations in renal tubular histology. However, nicotinamide adenine dinucleotide staining of corresponding areas confirmed the lack of cellular viability except for glomeruli. In the subacute phase there were focal coagulation necrosis and thrombosed blood vessels. Within the necrotic areas the glomeruli were the last structures to lose viability. In the chronic phase fibrosis with decreased lesion size was seen. Nicotinamide adenine dinucleotide staining demonstrated that the cellular kill was permanent during the entire study period. The effects of RFA of renal tissue has 2 phases, namely initial direct thermal ablation causing acute cell death and a later subacute phase causing subsequent infarction of the distal arterial vascular supply to the ablated region, resulting in more cell death and coagulative necrosis. Glomeruli are the last structures to lose viability in necrotic areas. Most importantly cellular death caused by RFA is permanent.

Clinical histopathology and ultrastructural analysis of myocardium following microwave energy ablation.

Due to weaknesses of conventional modes for treating atrial fibrillation (AF), surgical energy ablation methods and tools to cure AF have been under rapid development. One of these methods, microwave energy, is beginning to be applied clinically. The purpose of this study was to examine histology and ultrastructure of lesions produced by microwave energy in the myocardium. Fifteen consecutive patients underwent surgical microwave energy ablation (Microwave Ablation System with FLEX 4 probe, AFx Inc., Fremont, CA) concomitant to a valve procedure. Epicardial ablation was carried out on the beating normothermic heart prior to performing the valve procedure. Two tissue specimens (1cm(2)) were obtained from each patient; one from the lesion site (right appendage) and the other from an adjacent, non-ablated site, which was used as control. Tissue samples were fixed and stained as appropriate for histological and ultrastructural analysis. All ablated samples revealed observable microscopic alteration, including loss of nuclei, foci of coagulative necrosis or induced irregular bands of contraction. Ultrastructurally, ablated cells demonstrated architectural disarray, loss of contractile filaments, mitochondrial swelling and focal interruption of plasma membrane. Histologic appearance of lesions created by epicardial microwave energy ablation was consistent over tissue samples, although acute findings demonstrated differences from cryoablation. In most of the cases, lesions were transmural, as was demonstrated by loss of cellular viability throughout the depth of tissue specimens.

An Outbreak of Yersinia pseudotuberculosis Infection in Lambs

Movassaghi, A.R. and Rad, M. 2002. An outbreak of yersinia pseudotuberculosis infection in lambs. J. Appl. Anim. Res. 22: 125–128. Yersinia pseudotuberculosis, a gram-negative coccobacillus, is primarily a pathogen of rodents. In addition to farm and domestic animals, birds are also natural reservoirs. Five affected lambs were presented with the signs of diarrhoea and emaciation. Grossly, there were intestinal effusions and enlargement of mesenteric lymph nodes. The most important macroscopic finding was whitish hepatic foci. Histopathological examination revealed fibrinohemorrhagic enterocolitis and multiple foci of coagulative necrosis associated with microabscess formation in the liver. The isolated organism, based on morphological and biochemical characteristics confirmed as Yersinia pseudotuberculosis.

Emerging and future indications of interventional endosonography

After reading all of the preceding articles in this issue of Techniques in Gastrointestinal Endoscopy, it is clear that interventional endoscopic uhrasonography (EUS) provides a myriad of possibilities for improving diagnosis and therapy. Because interventional EUS is able to sample lesions within and outside the gastrointestinal tract, it is a field that is emerging to show its usefulness not only in gastroenterology but other body systems and specialties (eg, staging of nonsmall cell lung cancer). Apart from the techniques discussed in this issue, many other interventional techniques are being investigated. In a preliminary study to extend EUS-guided therapy to pancreatic cancer, activated T-lymphocytes were injected into unresectable pancreatic cancers as a form of immunotherapy with improved survival over standard chemotherapy with gemcitabine. 1 Radiofrequency ablation under EUS guidance has also been attempted recently in an experimental swine model. After localizing the pancreas with linear array endosonography, transgastric pancreatic puncture was performed with a needle under real-time EUS guidance. Radiofrequency current was then delivered to the pancreas with pathologic examination showing foci of coagulation necrosis in the pancreas at the site of current delivery. It was hypothesized that such technique could be used in the future for tumor ablation. 2 Another concept regarding EUS-guided therapy is the potential for using high-intensity focused ultrasound (H1FU). Ultrasound

An Experimental Study on Hepatic Ablation Using an Expandable Radio-Frequency Needle Electrode

Purpose : The purpose of this study was to determine the factors influencing on the size of thermal lesions after ablation using an expandable radio-frequency needle electrode in porcine liver. Materials and Methods : Ablation procedures involved the use of a monopolar radio-frequency generator and 15-G needle electrodes with four and seven retractable hooks (RITA Medical System, Mountain View, Cal.,U.S.A.). The ablation protocol in fresh porcine liver comprised of combinations of varying hook deployment, highest set temperature, and ablation time. Following ablation, the maximum diameter of all thermal lesions was measured on a longitudinal section of the specimen. Ten representive lesions were examined by an experienced pathologist. Results : At 3-cm hook deployment of the needle electrode with four lateral hooks, the size of spherical thermal lesions increased substantially with increases in the highest set temperature and ablation time until 11 minutes. After 11 minutes lesion size remained similar, with a maximum diameter of 3.3 cm. At 2-cm hook de-ployment, sizes decreased to about 2/3 of those at 3 cm, and at 1-cm hook deployment lesions were oblong. At 3-cm hook deployment of a needle electrode with seven hooks, the size of thermal lesions increased with in-creasing ablation time until 14 minutes, and the maximum diameter was 4.1 cm. Microscopic examination showed a wide zone of degeneration and focal coagulation necrosis. Conclusion : The size of thermal lesions produced by the use of an expandable radio-frequency needle electrode were predictable, varying according to degree of hook deployment, highest set temperature, and ablation time .

Study on the etiopathogenesis of multiple spongy necrosis of the pontine base in three autopsy cases.

The etiopathogenesis of multiple spongy necrosis (MSN) of the pontine base was analyzed by examining the spatial relationship with intra- and extrafascicular vascular structures by reconstruction of serial sections of nine lesions from three autopsy cases. All nine lesions in the fascicles were distributed without any spatial relationship to the intrafascicular vessels. Instead, these lesions were distributed in parallel with arterial and venous transverse main branches between the anteromedial and anterolateral groups of the pontine vessels. On the other hand, all lesions in the middle cerebellar peduncle were arranged obliquely along the arterial and venous main trunks of the lateral group vessels with sparing of the perivascular narrow zone of the white matter. Moreover, narrow fascicles, even though located in the dorsomedial region of the pontine base, which is consistently involved in MSN, were spared, and thick transverse and longitudinal fascicles were selectively involved. The marginal zone of fascicles was spared, and focal coagulation necrosis was sometimes found in MSN lesions. Additionally, normal fascicles did not have their own nutritional arteries, and were nourished by arterioles and capillaries from the surrounding pontine gray matter. Neither severe organic stenosis nor occlusion of pontine vessels was found. On the basis of the close topographical relationship of MSN lesions with the pontine vascular architecture in addition to preferential involvement of thick fascicles with sparing of the marginal zone and inclusion of focal coagulation necrosis, it is proposed that the etiopathogenesis of MSN is pontine ischemia on a background of the characteristic parenchymal and vascular architecture of the pontine base. As to the cause of the ischemia, it is proposed that some functional disorder such as arterial vasoconstriction in the pontine base or the vertebrobasilar artery is responsible, rather than organic changes in the vessels.

Histopathologic Findings in 107 Uterine Leiomyomas Treated with Leuprolide Acetate Compared with 126 Controls

The reported histopathologic findings in leiomyomas treated with leuprolide acetate (LA) differ. We examined 233 myomectomy specimens, including 107 myomas from 30 patients (mean age, 34.7 +/- 4.6 years) treated with LA. Their histopathologic findings were compared with those from a control group of 126 myomas from 30 untreated patients (mean age 32.7 +/- 5.3 years). The LA-treated leiomyomas had myxoid change (n = 2; 1.9%), total necrosis (n=4; 3.7%), focal necrosis (n = 5; 4.7%), calcifications (n = 5; 4.7%), hemorrhage (n = 8, 7.5%), vascular changes (n = 12; 11.2%), hydropic degeneration (n = 22; 20.5%), and hyalinization (n = 61; 57.0%). None of these changes differed significantly from the untreated controls. None of the LA-treated leiomyomas had nuclear atypia, whereas nuclear atypia occurred in four (3.2%) of the untreated leiomyomas; this difference was also not significant. Mitotic figures were present in 8.4% of the LA-treated myomas and 8.5% of untreated controls. The number of mitotic figures per 10 high-power fields was slightly higher in the untreated myomas, but the difference was not statistically significant (range, 0-3 for treated, 0-5 for controls). The degree of cellularity did not differ between the two groups. In conclusion, (a) LA-treated myomas do not significantly differ from untreated myomas with respect to nuclear atypia, calcification, total coagulative necrosis, focal coagulative necrosis, hemorrhage, vascular changes, myxoid change, hydropic degeneration, hyalinization, mitotic activity, or cellularity; and (b) the mechanism leading to a reduction in the size of myomas treated with LA is not apparent from routine histologic examination.

Hepatic arterial infusion of recombinant platelet factor-4 suppresses metastases to the lungs from tumors implanted into the livers of rabbits

This study evaluated the toxicity (Part I) and antitumor effects (Part II) associated with hepatic arterial infusion of recombinant platelet factor-4 (rPF4), an antiangiogenic protein. Healthy rabbits (Part I) and rabbits with tumors implanted in their livers (Part II) received saline or rPF4 via hepatic arterial infusion. Three saline-receiving and four rPF4-receiving animals died 2-3 days postinfusion from gastroduodenal thromboembolism. The remaining animals were necropsied 3, 7, 10, or 14 days postinfusion. Blood analyses and hepatic angiography were performed before infusion and at the time of sacrifice. In Part I, focal coagulation necrosis of the hepatic parenchyma was observed in 1 of 11 rabbits that received saline and in 6 of 10 that received rPF4. In Part II, hepatic arterial infusion of rPF4 had no effect on growth of the implanted liver tumors. However, the protein significantly reduced the incidence of lung metastasis. Intraarterial infusion of rPF4 significantly reduced the incidence of lung metastasis. Nonheparin systemic anticoagulation may be needed during catheterization and infusion procedures to prevent thromboemboli.

Effects of Trypanosoma congolense on pituitary and adrenocortical function in sheep: changes in the adrenal gland and cortisol secretion

The effect of trypanosomiasis on adrenal function was studied in 10 pubertal Scottish blackface rams infected with Trypanosoma congolense and nine uninfected controls. Plasma cortisol concentration was measured by radioimmunoassay in samples obtained twice a week for three weeks before infection and three times a week for 79 days after infection. There was a significant (P<0·001) increase in cortisol concentration in all the infected rams after the onset of parasitaemia nine to 16 days after infection. This was followed by a transient non-significant decrease in cortisol levels between 19 and 41 days and a variable and parasitaemia-dependent increase in cortisol levels between 44 and 79 days after infection. Marked hypertrophy of the zona fasciculatareticularis, infiltration of mononuclear cells into the cortical and medullary zones, hyperaemia and focal coagulative necrosis were evident in the adrenal glands of infected rams killed at the end of the study. Trypanosome infection induced a low grade persistent pyrexia, marked anaemia, reduced growth rates and general loss of body condition. These results demonstrate that T congolense infection in sheep causes marked pathological changes in the adrenal cortex and changes in the secretion of cortisol.

Failure of protection against endotoxin hepatotoxicity by selenium

The present study was undertaken in rats to test the ability of selenium to prevent endotoxin hepatotoxicity. There were no significant morphological changes in the liver and no abnormalities of liver function in rats given 0, 6.25 or 12.5 mumol of selenium. Endotoxin administration to these rats induced focal hepatocellular coagulative necrosis and increased serum transaminase activities. However, endotoxin hepatotoxicity and mortality of the rats given endotoxin after treatment with 6.25 or 12.5 mumol of selenium were not significantly lower than in those given endotoxin alone. These facts suggest that selenium does not prevent endotoxin hepatotoxicity.

Pathomorphological studies in European bison (Bison bonasus Linnaeus, 1758) with seropositive reaction to Coxiella burnetii.

Comprehensive serological and histopathological examinations of 47 free living European bison (Bison bonasus Linnaeus, 1758) were performed. Of these animals, 36 were serologically positive due to Coxiella burnetii, which confirmed the presence of Q fever epizootic foci in this population of wild animals in Poland. The presence of multiple foci of mononuclear cells typical for Q fever was a consistent finding in all tissues of the majority of C. burnetii seropositive animals under study. Pathomorphological changes observed in myocardium as the focal coagulation necrosis, and in kidneys, resembled the glomerular lesion observed in humans with Q fever, as well as in the experimental Q-fever infections in laboratory animals. These changes were absent in bison showing a C. burnetii seronegative reaction.

Role of activated macrophages in augmentation of endotoxin hepatotoxicity.

In this study, to clarify the role of activated macrophages in the augmentation of endotoxin hepatoxicity, rats were pretreated with zymosan, an activator of macrophages, before the induction of endotoxin hepatotoxicity, and some were given pentoxifylline, an inhibitor of tumour necrosis factor production. The intravenous injection of zymosan induced many granulomas composed of macrophages in the lungs and the liver, while the intraperitoneal injection caused granulomas in the greater omentum. Endotoxin hepatotoxicity. as shown by focal and random hepatocellular coagulative necrosis and elevation of serum transaminase activities, was more intense in the rats pretreated with zymosan than in those which were not injected with zymosan. This augmented endotoxin hepatotoxicity was significantly inhibited by pentoxifylline treatment. These findings indicate that endotoxin hepatotoxicity may be augmented in the presence of activated macrophages which produce chemical mediators, particularly tumour necrosis factor.

Augmentation of endotoxin hepatotoxicity by zinc.

The present study was undertaken in rats to determine whether zinc protects against endotoxin hepatotoxicity and mortality. Treatment with zinc (50-200 mumol/kg body weight) alone or endotoxin (lipopolysaccharide B, Escherichia coli 026:B6, Difco, 2 mg/kg body weight) alone did not induce significant morphological changes in the liver parenchyma or any abnormalities in liver function tests. The mortality rate was 0%. In the rats pretreated with 100 mumol of zinc and then injected with endotoxin, the mortality rate, the incidence of focal hepatocellular coagulative necrosis and serum transaminase activity increased markedly. Eleven of the 12 rats pretreated with 200 mumol of zinc died within 4 h after endotoxin injection. In the rats pretreated with 50 mumol of zinc and then injected with endotoxin, there was no conspicuous change, in the mortality rate, liver function tests or morphology of the liver. These experimental data indicate that zinc increases the mortality rate in endotoxemic rats and augments biochemical and morphological evidence of endotoxin hepatotoxicity.

Role of lipid peroxidation in enhancement of endotoxin hepatotoxicity

The present study was undertaken in the rats to examine whether endotoxin hepatotoxicity is enhanced by increased lipid peroxidation. The rats were given 10 ml of water, corn oil or heated and oxygenated corn oil per kg body weight by stomach tube twice a day for 14 days, and then they were injected physiological saline solution or endotoxin (2 or 2.5 mg per kg body weight) into the tail vein. In the rats pretreated with water or corn oil, the activity of serum glutamic pyruvic transaminase was within the normal limit, and there was no conspicuous morphological change in the liver, except for accumulation of fine fat droplets in few liver cells. On the other hand, in the rats pretreated with heated and oxygenated corn oil, containing a large amount of lipid peroxides, accumulation of small fat droplets in the liver cells and a slight elevation of serum transaminase activity were induced. The challenge with endotoxin (2.5 mg per kg body weight) caused focal hepatocellular coagulative necrosis and a marked elevation of serum transaminase activity, irrespective of the sorts of pretreatment, and there was no significant difference in the biochemical change and the histopathological damage between the rats pretreated with water, corn oil and heated and oxygenated corn oil. These results suggest that increased lipid peroxidation does not contribute to the enhancement of endotoxin hepatotoxicity, although it is thought that carbon tetrachloride and ethanol enhance endotoxin hepatotoxicity by synergism between endotoxin and the chemicals through lipid peroxidation.

Relation of the reticuloendothelial function to endotoxin hepatotoxicity

The present study was undertaken in rats to clarify whether endotoxin hepatotoxicity can be modified by phagocytic activity of the reticuloendothelial system. Pretreatment with cortisone acetate, diethylstilbestrol, methyl palmitate, triolein or gadolinium chloride markedly improved the mortality rate from endotoxemia and prevented the development of focal random coagulative hepatocellular necrosis and the elevation of serum transaminase activities due to endotoxemia. Cortisone acetate, methyl palmitate and gadolinium chloride are the well-known depressors of reticuloendothelial phagocytic activity: Diethylstilbestrol and triolein are the stimulators. This suggests that phagocytic activity of the reticuloendothelial system does not relate to not only the mortality rate but also the degree of hepatic injury following endotoxemia.

Neoplasms and nonneoplastic liver lesions in winter flounder, Pseudopleuronectes americanus, from Boston Harbor, Massachusetts.

A variety of neoplasms and nonneoplastic hepatic lesions have been noted in winter flounder, Pseudopleuronectes americanus, from Boston Harbor, Massachusetts. Inflammatory lesions include cholangiitis, pericholangiitis, pericholangial fibrosis, hepatitis, and pancreatitis. Necrotic lesions consist essentially of focal coagulative necrosis and a distinctive vacuolated cell lesion of the hepatic parenchyma. The most conspicuous and numerous proliferative lesion is macrophage aggregate hyperplasia and hypertrophy. Preneoplastic lesions include principally basophilic foci of cellular alteration and hepatocellular adenoma. Carcinomas consist of several morphologic varieties: hepatocarcinoma, cholangiocarcinoma, and anaplastic adenocarcinoma. The pathogenesis of the lesions observed is discussed with respect to anthropogenically introduced chemical contaminants and the resistant hepatocyte model of hepatocarcinogenesis. This study, and others of bottom-living food fish with enzootic neoplastic disease, warrants further evaluation, particularly with respect to possible bioaccumulation of chemical contaminants in edible tissues.

Toxic effects for lambs of cytotoxic necrotising factor from Escherichia coli

The lethal effect, clinical signs and lesions caused by the intravenous inoculation into six lambs (seven to 10 days old) of a partly purified preparation of cytotoxic necrotising factor (CNF) from Escherichia coli, strain BM2-1, were investigated. Two control preparations were also tested in two lambs each: (i) the same as above but heated for one hour at 60°C, a treatment which inactivates CNF and preserves residual endotoxic activity; and (ii) purified material from a CNF-defective mutant of BM2-1. Whereas none of the lambs in either of the control groups died or showed significant clinical signs or lesions, all the lambs inoculated with partly purified CNF developed severe clinical signs starting six hours after inoculation which consisted mainly of neurological signs and mucoid diarrhoea. The most striking lesions were oedema and haemorrhages in the central nervous system, and foci of coagulation necrosis in the myocardium. Mucus hypersecretion in the gastrointestinal tract was not associated with cellular inflammation.

The lethal principle of Poa huecu (Coiron Blanco): a plant indigenous to Argentina

A. B. Pomilio, R. D. Rofi, M. P. Gambino, C. A. Mazzini and R. T. Debenedetti de Langenheim. The lethal principle of Poa huecu (Coiron Blanco): a plant indigenous to Argentina. Toxicon 27, 1251–1262, 1989.—The lethality of Poa huecu, a plant toxic to cattle and sheep, was followed by injection of chromatographic fractions in mice. The lethal aqueous extract was administered i.p. to Rockland mice of either sex and produced motor incoordination, transient ataxia, rough hair coat, tremors and muscle contractions and, occasionally, blindness. Doses greater than 1.5 g/kg mouse were always lethal. Fractionation of this lethal extract included dialysis, column chromatography on Sephadex G-25 and fractional precipitation with ethanol. Precipitates obtained with 70% and 85% ethanol were further purified on a DEAE-cellulose column. Eight fractions were obtained, each was injected into mice. Only fractions 3–6 were toxic. Fraction 3 produced slight hepatosis and hyperemia in the liver and gliosis in the brain. None of the other tissues exhibited histological lesions. Fractions 4 and 5 caused death of all animals within 30 min to 4 hr after injection. Polyacrylamide gel electrophoresis and acid hydrolysis showed that fractions 4 and 5 contained a glycoprotein of nearly the same mol. wt (67,000–94,000). Microscopic pathology in the mice treated with the lethal glycoprotein of fraction 4 included hyperemia in the kidneys, megakaryocytes in the spleen, slight hepatosis and focal coagulative necrosis with nuclear pyknosis and karyonexis in the liver, gliosis, intracellular brain edema with axon degeneration and swollen astrocytes in the brain. These brain injuries may relate to the motor incoordination of cattle that causes a delayed righting reflex. The major monosaccharides of the lethal glycoprotein are glucose and mannose, while rhamnose, arabinose, xylose and galactose are present in low percentages. Proline and the acidic amino acids (glutamic and aspartic acids) are the most abundant in the peptidic residue.

Infections with Francisella tularensis biovar palaearctica in hares (Lepus timidus, Lepus europaeus) from Sweden.

The occurrence of tularemia was studied in 1,500 hares submitted to the National Veterinary Institute, Uppsala, Sweden for postmortem examination during 1973 through 1985. A total of 109 tularemia cases was recorded based on the fluorescent antibody (FA) test for Francisella tularensis and on the gross and microscopic pathology. Tularemia was diagnosed only in the varying hare (Lepus timidus) and not in the European brown hare (Lepus europaeus). The geographical distribution of the 109 cases indicates that tularemia has not spread in Sweden during the last 45 yr, with the exception of an endemic occurrence of the disease on the island of Stora Karlsö in the Baltic sea. The disease was most frequent in the autumn and only a few cases were recorded during winter. Cases were not seen in the spring. The annual prevalence varied, with several cases in 1974 and 1981, but there were no cases in 1976 and 1980. The postmortem findings in hares dying of tularemia in the autumn were characterized by focal coagulative necrosis in liver, spleen and bone marrow, with high numbers of bacteria FA-positive for F. tularensis. In hares dying during winter months, the most characteristic findings were hemorrhagic enteritis and typhlitis, although necrotic lesions could occur in liver, spleen and bone marrow. Diseased hares on the island of Stora Karlsö were demonstrated to be infected with ticks, while hares on the mainland of Sweden generally were fed upon by mosquitoes. Twenty-six of the 109 hares with tularemia were examined bacteriologically and F. tularensis biovar palaearctica was isolated from eight. The lung extract antibody test for F. tularensis was performed in 18 of the 109 hares. All were negative. In addition to the field study, an experimental study with F. tularensis biovar palaearctica was performed. Four varying hares and three European brown hares were inoculated. None of the hares died from tularemia, and generalized infection was not demonstrated.

On the Pathogenesis of Hepatic Dysfunction and Necrosis Following Acute Circulatory Failure

To clarify whether diminished hepatic blood flow and portal endotoxaemia interact in the pathogenesis of hepatic dysfunction secondary to acute circulatory failure, such as shock, prolonged hypotension, or left-sided heart failure, the present study was undertaken in rats. Reduced hepatic perfusion, which was produced by partial obstruction of the portal vein, caused elevation of serum transaminase activities and electron microscopic abnormalities of hepatocytic structure, namely, disruption of plasma membrane, swelling of mitochondria, vesiculation and disruption of endoplasmic reticulum, etc. Portal endotoxaemia, which was induced by infusion of endotoxin into the portal vein, led to a rise of serum transaminase activities and random, focal coagulative hepatocellular necrosis. In contrast, massive hepatic necrosis and excessive elevation of serum transaminase activities, which are similar to those seen in patients with shock, etc., were produced when portal endotoxaemia was superimposed upon poor hepatic perfusion. These experimental results suggest that acute hepatic failure and massive hepatic necrosis secondary to acute circulatory failure may be induced by the coexistence of reduced hepatic blood flow and portal endotoxaemia.