scholarly journals THE ISOLATED PERFUSED BOVINE LIVER

1961 ◽  
Vol 113 (6) ◽  
pp. 981-996 ◽  
Author(s):  
Niles D. Chapman ◽  
Patrick D. Goldsworthy ◽  
Wade Volwiler ◽  
Lloyd M. Nyhus ◽  
Andrew J. Martinis

1. A procedure is described for surgically isolating and artificially perfusing the liver of the young bovine. Heparinized autogenous blood from the hepatectomized animal diluted with Krebs-Ringer-bicarbonate solution is employed as the perfusate. 2. This preparation has been satisfactorily reproducible in this laboratory in more than 90 separate sequential perfusions. Absence of a sensitive hepatic venous smooth musculature contributes to the ability to maintain satisfactory perfusion for as long as 24 hours. 3. The perfusate was usually maintained bacterially free for at least the first 12 hours of perfusion without the use of antibiotics. The perfusate was maintained at normal body temperature and, by varying the CO2 content of the oxygenating gas, within a physiological pH range. The importance of these features when studying problems of intermediary biochemistry and ultrastructure is emphasized. 4. The liver of the bovine calf is sufficiently large to permit (a) simultaneous and independent perfusion through the hepatic artery and portal vein, and (b) repeated sampling of hepatic tissue without interruption of the circulation. 5. Excellent, viable condition of the isolated liver, throughout many hours of perfusion, was demonstrated by steady state of oxygen consumption, efficient clearance of bromsulphalein dye, continuous secretion of bile, constancy of blood flows and pressures, and very minimal alterations from normal in histologic and ultrastructural detail.

1982 ◽  
Vol 202 (3) ◽  
pp. 661-665 ◽  
Author(s):  
D G Clark ◽  
M Brinkman ◽  
O H Filsell ◽  
S J Lewis ◽  
M N Berry

(Na+ + K+)-dependent ATPase activity, heat production and oxygen consumption were increased by 59%, 62% and 75% respectively in hepatocytes from tri-iodothyronine-treated rats. Ouabain at concentrations of 1 and 10 mM decreased oxygen uptake by 2-8% in hepatocytes from euthyroid rats and by 5-15% in hepatocytes from hyperthyroid animals. Heat output was decreased by 4-9% with the glycoside in isolated liver parenchymal cells from the control animals and by 11% in the cells from the tri-iodothyronine-treated animals. These results do not support the hypothesis that hepatic (Na+ + K+)-ATPase plays a major role in increased heat production in hepatocytes from hyperthyroid rats.


1983 ◽  
Vol 244 (6) ◽  
pp. G604-G612 ◽  
Author(s):  
G. B. Bulkley ◽  
P. R. Kvietys ◽  
M. A. Perry ◽  
D. N. Granger

The local hemodynamic response of the innervated but vascularly isolated colon to decreased systemic perfusion induced by cardiac tamponade was studied in anesthesized dogs as a model of nonocclusive mesenteric ischemia. Increasing levels of pericardial pressure caused progressive decreases in colonic blood flow associated with substantial increases in colonic vascular resistance. These increases in local colonic resistance were proportionately larger than concurrent increases in systemic resistance. The disproportionate response of the colonic resistance vessels was not diminished by colonic (sympathetic) denervation. Reductions of blood flow to 30 ml . min-1 . 100 g-1 resulted in compensatory increases in colonic oxygen extraction such that colonic oxygen consumption remained constant (flow independent) at about 1.5 ml . min-1 . 100 g-1. At blood flows below 30 ml . min-1 . 100 g-1 colonic oxygen consumption was markedly dependent on blood flow. This fundamental relation of colonic oxygen consumption to blood flow was the same whether ischemia was induced by cardiac tamponade, partial mechanical arterial occlusion, or vasoconstrictor (norepinephrine or digoxin) infusion. Furthermore, this relationship was not altered by vasodilation with isoproterenol after the induction of ischemia by any of the above means.


1959 ◽  
Vol 197 (3) ◽  
pp. 624-626 ◽  
Author(s):  
Ann Evringham ◽  
Edith M. Brenneman ◽  
Steven M. Horvath

Eleven mongrel dogs were trained to lie quietly while splanchnic blood flows and splanchnic metabolisms were determined. They were then anesthetized by means of intravenous injection of 28.4 mg/kg of sodium pentobarbital and studies of the hepatic circulation continued for an additional 70 minutes. Only minor, transitory alterations were observed in the parameters being measured. It was concluded that with this particular anesthetic agent splanchnic blood flows and oxygen consumption were essentially at control unanesthetized levels within 30–45 minutes postanesthesia.


1959 ◽  
Vol 14 (3) ◽  
pp. 390-392 ◽  
Author(s):  
William R. Beavers ◽  
Benjamin G. Covino

Six male human subjects were given 30 gm oral glycine. Oxygen consumption, skin and rectal temperatures, and forefinger blood flows were measured during an interval in a warm room and then during 75 minutes cold exposure (0°F). The same subjects receiving 30 gm glucose served as controls. Glycine increased heat production at rest in a warm room and also during cold exposure. The subjects when receiving glycine had a slightly higher rectal temperature and higher skin temperatures in areas other than fingers during the cold exposure period. Submitted on August 1, 1958


2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Tamsyn Clark ◽  
Georg Ebeling ◽  
Daniel Voyce ◽  
Luca Bau ◽  
Constantin Coussios ◽  
...  

Abstract Aims Up to 85% of patients with liver metastases have inoperable hepatic tumour burden. Isolated liver perfusion involves vascular isolation of the liver in situ and regional delivery of chemotherapy, avoiding dose-limiting extra-hepatic toxicity. In this series, we develop a surgical protocol to demonstrate the feasibility of isolated normothermic liver perfusion (INLP) and investigate short-term safety and feasibility of delivering high-dose chemotherapy. Methods Laparotomy and complete, vascular isolation of the liver was performed on 55-65Kg pigs (n = 6). The hepatic artery (HA), portal vein (PV) and inferior vena cava were cannulated and liver NMP established. Veno-venous bypass maintained systemic circulation. High-dose doxorubicin was administered to the isolated liver, circulated for 1 hour and vascular reconnection performed. Physiological parameters were measured and doxorubicin quantified in blood, bile and tissue by high-performance liquid chromatography. Results INLP with doxorubicin delivery achieved physiological flow rates (PV 0.7L/min (0.6-0.9L/min); HA 0.3L/min (0.2-0.4L/min)) and pH (median 7.3 (7.24-7.38)), with a median lactate of 0.42mmol/L. Median peak AST and ALT were 1045 U/L and 47 U/L respectively. Doxorubicin decay was fitted with a 2-compartmental model; distribution half-life was 1.9 minutes and plasma Cmax was higher than if given systemically resulting in mean hepatic tissue levels of 26+/-11.6 µg/g. There was no leak during INLP and doxorubicin was undetectable in kidney or heart. Conclusions Surgical isolation and NMP of the liver in situ, with concurrent veno-venous bypass is feasible and enables high-dose drug delivery resulting in therapeutic tissue levels with no off-target toxicity. Further safety studies are required.


1954 ◽  
Vol 11 (2) ◽  
pp. 125-133 ◽  
Author(s):  
V. L. VIDOVIC ◽  
V. POPOVIC

SUMMARY Hibernation in the ground squirrel ends within 1–2 hr after total adrenalectomy and does not recur. Survival time after adrenalectomy in laboratory-kept ground squirrels during November and December was longer than it was during September-October and February-March. Body temperature during hibernation (4–18° C) was restored to normal (37° C) within 1–2 hr after adrenalectomy, the animals being kept in a room at 17° C. Oxygen consumption was measured in ground squirrels on the 6th and 7th days after adrenalectomy at 31–32° and 4° C respectively. Maximum consumption occurred at 4° C; normal body temperature was retained. The 131I uptake by the thyroid of non-hibernating ground squirrels is considerably smaller in early Autumn (September-October) than during the winter months. Radioactive iodine is not accumulated by the thyroid gland of the hibernating ground squirrel, but 3 days after adrenalectomy the amount of 131I accumulated is equivalent to that taken up by the gland of the non-hibernating animal. The effects of adrenalectomy in the hibernating and non-hibernating ground squirrel are compared with those obtained in hypothermic rats maintained in similar environmental conditions.


1987 ◽  
Vol 253 (2) ◽  
pp. H422-H431 ◽  
Author(s):  
J. D. Bristow ◽  
E. O. McFalls ◽  
C. G. Anselone ◽  
G. A. Pantely

During myocardial ischemia, we tested whether coronary blood flow would increase in response to tachycardia, thereby employing known coronary flow reserve. We instrumented the left anterior descending (LAD) coronary circulation in anesthetized pigs and performed three sets of experiments while coronary pressure was controlled and several heart rate increases were produced. Pacing-induced tachycardia at normal LAD pressure was characterized by increased LAD flow and myocardial oxygen consumption, without production of lactate. Tachycardia at a mean LAD pressure of 38 mmHg was associated with a lower, fixed coronary flow and oxygen consumption. At average heart rates of 90 and 150 beats/min, LAD flow was 19.6 and 19.4 ml/min and corresponding myocardial blood flows were 0.59 and 0.54 ml X g-1 X min-1. Lactate was produced at all rates and local myocardial function declined progressively. Coronary flow at low LAD pressure doubled during tachycardia when intracoronary adenosine was added. The increase to the subepicardium was greater than 100%, whereas subendocardial flow changed little. There is persistent coronary flow reserve during moderately severe myocardial ischemia, even when metabolic demand is increased by tachycardia. This reserve, however, is predominantly subepicardial.


1994 ◽  
Vol 141 (2) ◽  
pp. 353-358 ◽  
Author(s):  
H C Freetly ◽  
C L Ferrell

Abstract The objective of this study was to determine whether circulating concentrations or prior exposure to oestradiol-17β (OE2) and progesterone affected their uptake by splanchnic tissues. Catheters were surgically placed in the portal vein, a branch of the hepatic vein, a mesenteric vein and the abdominal aorta of three multiparous ovariectomized Dorset ewes. Blood and plasma flow across the portal-drained viscera (PDV) and the liver, and net uptake of OE2 and O2 consumption in these same tissues were determined in ovariectomized ewes (control), during OE2 infusion into the jugular vein, 7 days after an OE2 implant had been given, and during OE2 infusion into the jugular vein 7 days after an OE2 implant. The above treatments were repeated for progesterone. Plasma flows across visceral organs were determined by marker dilution (para-aminohippuric acid), and OE2 and progesterone concentrations were determined by radioimmunoassay. During the infusion with OE2, OE2 arterial concentration (mean ± s.d.) was 346 ± 199 pg/ml, PDV net uptake was 9·7±5·6 μg OE2/h and hepatic net uptake was 15·5 ± 9·5 μg OE2/h. Hepatic uptake was 82% of the jugular OE2 infusion rate. Blood flow and oxygen consumption by hepatic tissue increased when ewes were exposed to an OE2 implant for 7 days. During the infusion with progesterone, progesterone arterial concentration (mean ± s.d.) was 8·8 ±3·4 ng/ml, PDV net uptake was 220 ± 118 μg progesterone/h and hepatic net uptake was 238 ± 52 μg progesterone/h. Hepatic net uptake was 23% of the progesterone jugular infusion rate. Journal of Endocrinology (1994) 141, 353–358


2006 ◽  
Vol 20 (2) ◽  
pp. 81-87
Author(s):  
Pedro Eduardo Fröehlich ◽  
Raquel Borges Pinto ◽  
André Castagna Wortmann ◽  
Richard Borba Magalhães ◽  
Ana Cláudia Reis Schneider ◽  
...  

The objective of this work was to develop and fully validate an analytical assay to quantify zinc in hepatic tissue. The procedure should be as simple and fast as possible in order to avoid sample contamination. The amount of sample used should also reflect the sample size usually obtained in clinical biopsies, which are about 3–4 mg at most. The validation protocol is in accordance to international guidelines, such as ICH and FDA. The parameters evaluated were precision, accuracy, range, limit of detection and limit of quantification. The method was evaluated in the 2.0–32.0 parts per billion (μg/l) range. Under the described conditions intra and inter day precision of the three levels of quality controls were lower than 9.06 and 5.27, respectively, expressed as relative standard deviation (RSD). The accuracy ranged from 86.35 to 114.71%. Limit of detection and limit of quantification were 0.60 and 2.0 μg/l, respectively. Fresh bovine liver samples were used in order to evaluate the clinical procedure used to collect biopsies. According to the results and experimental protocol, the method is fully validated and ready to use in clinical trials involving zinc quantitation using hepatic samples as small as 2.00 mg of dry tissue.


Author(s):  
Miranda K Stotz ◽  
Darren D Henry ◽  
Whitney L Crossland

Abstract Bacteriological characterization of bovine liver abscesses has been accomplished by cultural methods but DNA methods are still needed, as many bacteria are not conducive to laboratory culture. In addition to this gap in research, there have been no studies which identify the bacterial presence within healthy, non-abscessed liver tissue. The objective of this study was to compare the bacteriome of both abscessed and non-abscessed bovine livers in an observational case-control study design. Fifty-six livers, obtained from Holstein steers, were scored according to a modified Elanco liver abscess score description where A- was partitioned into active abscesses or scarred where only scars were present. Parenchyma tissue was collected from non-abscessed livers (n=22), and scarred livers (n=7), and purulent material was collected from abscessed livers (n=24), and DNA was extracted for 16s rRNA gene sequence-based bacterial analysis. Across liver samples, 21 total phyla were identified with a mean of 14. Predominant phyla, accounting for > 98% of reads, were Fusobacteria (51.7%), Bacteroidetes (26.9%), Proteobacteria (8.03%), Firmicutes (5.39%), Cyanobacteria (3.85 %) and Actinobacteria (2.21%). Proteobacteria, Cyanobacteria and Firmicutes were greater in non-abscessed and scarred livers, whereas Fusobacteria and Bacteroidetes prevailed in abscessed livers. Non-abscessed livers shared 3,059 operational taxonomic units (OTU) with abscessed livers (total OTU of all livers= 4,167), but non-abscessed livers had greater richness and evenness whereas abscessed livers had greater dominance (P ≤ 0.0014). Liver score affected the relative abundance of OTU (R = 0.463; P = 0.001) but abscessed livers shared ≥ 40% similarity and were not different from each other (P ≥ 0.370). Of the predominant OTU (top 10 as a % of reads), three OTU (Fusobacteria necrophorum, Bacteroides spp., and Trueperella pyogenes) were shared across both abscessed and non-abscessed livers. Fusobacterium necrophorum was the dominant OTU regardless of liver score, and the single most abundant OTU, even among non-abscessed livers. We describe bacterial DNA detected in non-abscessed bovine liver tissue for the first time, which indicates possible presence of viable bacteria with pathogenic potential in apparently healthy liver tissue.


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