Triolein Infusion Research Articles

Triolein Emulsion Infusion Into the Carotid Artery Increases Brain Permeability to Anticancer Agents

Triolein emulsion infusion into the carotid artery has been reported to induce temporary and reversible opening of the blood-brain barrier by increasing vascular permeability. To evaluate the effect of triolein emulsion infusion on brain permeance by anticancer agents. In the doxorubicin study. 2.4 mg/kg doxorubicin was injected immediately after triolein emulsion (1%, 1.5%, and 2%) infusion into rabbit carotid arteries. Two hours later, bilateral hemispheres and eyeballs were harvested, and doxorubicin concentrations were measured fluorometrically. Doxorubicin ratios of ipsilateral/contralateral hemispheres were compared with those of doxorubicin controls by use of the Kruskal-Wallis test followed by the Dunn test. In the cisplatin study, 10 mg/kg cisplatin was injected immediately after 2% triolein emulsion infusion into rat carotid arteries. Ipsilateral hemispheres were harvested 2, 6, 12, 24, and 36 hours after treatment. Time-dependent cisplatin concentrations were determined by liquid chromatography/electrospray ionization-tandem mass spectrometry/mass spectrometry. Doxorubicin concentrations were significantly higher in ipsilateral hemispheres and eyeballs in all 3 triolein treatment groups than in doxorubicin controls. In the cisplatin study, cisplatin concentrations in the ipsilateral hemispheres peaked at 6 hours after infusion of cisplatin. Brain permeance to anticancer agents was increased by triolein emulsion infusion, which suggests that triolein infusion might be a useful adjuvant treatment for brain tumors.

Prominent hypointense veins on susceptibility weighted image in the cat brain with acute infarction: DWI, SWI, and PWI

The multiple prominent hypointense veins on susceptibility-weighted imaging (SWI) have been found in the ischemic territory of patients with acute ischemic stroke. Venous side is the unknown area in the hemodynamics of brain infarction. To evaluate the venous aspect in acute brain infarction through an animal study. The acute infarction in cat brains was induced with a bolus infusion of 0.25 mL of triolein through one side of the common carotid artery. The magnetic resonance (MR) images, including diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) map, SW, and perfusion-weighted (PWI) images, were obtained serially at 2 h (n = 17), 1 day (n = 11), and 4 days (n = 4) after triolein infusion. The obtained MR images were evaluated qualitatively and quantitatively. For qualitative assessment, the signal intensity of the serial MR images was evaluated. The presence or absence and the location with serial changes of infarction were identified on DWI and ADC map images. The presence or absence of prominent hypointense veins and the serial changes of cortical veins were also evaluated on SWI. Quantitative assessment was performed by comparing the relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit times (MTT) of the lesions with those of the contralateral normal side calculated on PWI. The serial changes of rCBV, rCBF, and MTT ratio were also evaluated. Acute infarction in the first and second medial gyrus of lesion hemisphere was found by qualitative evaluation of DWI and ADC map images. On the serial evaluation of SWI, the cortical veins of cat brain with infarction were obscured at 2 h and then re-appeared at 1 day. The hemorrhage transformation and prominent hypointense veins were seen at 4 days on SWI. The quantitative evaluation revealed increased MTT ratios and decreased rCBV and rCBF ratios on PWIs in the acute infarction of cat brain. The prominent hypointense veins on SWI were seen in the half of the acute infarction at 4 days. The prominent hypointense veins on SWI may have good agreement with the increased MTT ratio.

Hemorrhage in cerebral fat embolisms in a cat model using triolein dependent on the physical properties of triolein

Hemorrhage is a finding of clinical fat embolism syndrome. The purpose of the present study was to evaluate the occurrence of hemorrhage in the cat brain by SW MR imaging after infusion of triolein as a bolus or as an emulsion into the carotid artery. Twenty-two cats were divided into two groups according to the type of triolein infused: group 1 (n = 11) was infused with a 0.1 ml triolein bolus, group 2 (n = 11) with triolein emulsion containing 0.1 ml triolein in 20 ml saline. SW imaging was performed before and after triolein infusion (at 2 h, 1 and 4 days). After MR imaging on day 4, cats were sacrificed and brains were immediately excised. Hemorrhage was evaluated using H&E staining. Hemorrhage was observed in eight cats in group 1, in no cats in group 2. Hemorrhage on SW images was found to correspond with light microscopy. SW images revealed hemorrhage in lesion hemispheres infused with triolein bolus. However, there was no evidence of hemorrhage infused with emulsified triolein. Thus, the occurrence of hemorrhage in cerebral fat embolism may depend on fat status.

Intestinal synthesis and lymphatic secretion of apolipoprotein A-IV after cessation of duodenal fat infusion: mediation by bile

We tested whether secretion of apolipoprotein (apo) A-IV depends upon intestinal triglyceride (TG) transport by comparing output kinetics of TG and apo A-IV during and after duodenal lipid infusion in lymph-fistula rats. Lipid infusion (triolein, 40 μmol/h, 8 h) produced increases in lymphatic TG and apo A-IV output. After 8 h, triolein infusate was replaced with glucose–saline; TG output returned to basal levels 4–5 h later. However, apo A-IV output continued at significantly elevated levels until 20 h after the start of the experiment. Bile diversion blocked this continued output of A-IV during the post-lipid period, and resulted in basal TG output that was 75% lower than in bile-intact rats. Return of bile or low-dose triolein infusion (5 μmol/h) into the intestine reversed these effects. There were no differences in hepatic synthesis or filtration of plasma A-IV into lymph between bile-intact and bile-diverted groups. Intestinal A-IV synthesis was elevated in both groups even during the post-lipid period. The results support the hypothesis that intestinal triglyceride transport drives apo A-IV secretion, and suggest the existence of a bile-dependent, post-translational mechanism for the control of lymphatic apo A-IV output.

Synthesis and lymphatic transport of intestinal apolipoprotein A-IV in response to graded doses of triglyceride.

Factors regulating the intestinal synthesis and secretion of apoA-IV are incompletely understood. Although it is known that apoA-IV is stimulated by dietary lipid, it is not known whether graded doses of triglyceride elicit graded responses in apoA-IV synthesis and secretion. We used the chronic intestinal lymph-fistula rat to examine the effect of graded levels of intestinal triglyceride transport on secretion of apoA-IV into lymph and synthesis of apoA-IV in various regions of intestine. Rats were implanted with chronic duodenal and intestinal lymph duct cannulas and infused with lipid emulsions containing 5, 10, 20, 40, 80 mumol triolein (including [3H]triolein, 1.2 microCi), 8.7 mumol phosphatidylcholine, and 57 mumol sodium taurocholate in 3 ml phosphate-buffered saline (pH 6.4) at ml/h for 8 h. Lymph samples were collected for 1 h prior to and at 2, 4, 5, 6, 7, and 8 h after the start of lipid infusion. Lymphatic output of triglyceride, phospholipid, and apoA-IV was measured. Steady-state (8 h) content of radioactive lipid was also measured in the lumen and the wall of the gut. In separate studies rats were given infusions of either 5% glucose in saline ("fasting") or triolein emulsion (10, 20, 40, 80 mumol/h) for 8 h after which incorporation of [3H]leucine into apoA-IV in isolated, in situ loops of duodenum, proximal jejunum, mid-distal jejunum, and terminal ileum was measured. Lipid output increased dose-dependently in response to triolein infusion, with steady-state lipid transport achieved by 5 h after start of lipid infusion. Total recovery of 3H-labeled lipid was similar for all triolein doses. Increase in lymphatic apoA-IV output lagged that of triglyceride by 3-4 h, but by 8 h showed graded increases with triolein dose. ApoA-IV synthesis (apoA-IV radioactivity immunoprecipitated by an apoA-IV monospecific antibody and expressed as % of trichloroacetic acid-precipitable [3H]leucine radioactivity) in the duodenum and proximal jejunum showed a 2-fold increase (compared with fasting) in response to 10 mumol triolein/h, but no further increase at higher doses. However, apoA-IV synthesis in mid to distal jejunum increased dose-dependently.(ABSTRACT TRUNCATED AT 400 WORDS)

A re-examination of the fate of glyceride-glycerol in neutral lipid absorption and transport

Conventional ideas concerning the unidirectional movement of triacylglycerol from intestinal lumen to lymph with sn-2-monoacylglycerol being the major glyceride-glycerol precursor were challenged by our finding that steady state specific activities of radiolabeled triacylglycerol (glyceryl moiety) in the intestinal mucosa and lumen were greatly reduced as compared to the specific activity of intraduodenally infused triacylglycerol. Investigation of the point at which the radiolabel was diluted was performed in mesenteric lymph duct-cannulated rats with a duodenal cannula through which trioleoyl[3H]glycerol was constantly infused. Both within the bowel lumen and in the intestinal mucosa, monoacylglycerol, diacylglycerol, and triacylglycerol specific activities were 31% or less of the specific activity of the infusate; chylomicron triacylglycerol specific activity was 75%. Efflux of neutral lipid from the mucosa into the bowel lumen was directly demonstrated by finding that when 3H glucose was injected intraperitoneally during triolein infusion, luminal triacylglycerol had a higher specific activity than was present in the mucosa. We conclude that there are two pools of mucosal triacylglycerol. One is rapidly transported and derives most of its glyceride-glycerol from luminal monoacylglycerol. The second is slowly transported; it derives its glyceride-glycerol mainly from endogenous sources and may efflux back into the bowel lumen.

Intestinal lymph chylomicron cholesteryl ester during duodenal triolein infusion at increasing rate.

Chylomicron lipid composition in mesenteric lymph fistula rats was followed during duodenal triolein infusion at three rates. Esterified cholesterol decreased progressively in all groups as triglyceride transport continued, and the rate of decrease was reciprocally related to the triolein infusion rate. Suppression of cholesterol ester synthesis may spare unesterified cholesterol for chylomicron membrane formation. Ratios of triglyceride to phospholipid and to unesterified cholesterol increased with the duration of triglyceride secretion, while the chylomicron surface lipid composition remained constant over time. The rate of increase in the core:surface lipid ratios was the same irrespective of the triolein transport rate.

Effects and distribution of acute fat embolism in spontaneously breathing dogs using radioactive carbon triolein

The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause.

Resistance of intestinal triglyceride transport capacity in the rat to adaptation to altered luminal environment

Previous studies have shown that the transmucosal transport capacity for tiolein is slower in distal compared with proximal regions of rat small intestine. The effect of altered luminal conditions on the relative capacities for [14C]triolein transport through different regions of intestinal wall were examined by determining the net accumulation of 14C-lipid in the mucosa during maximal steady [14C]triolein absorption. The high 14C-lipid accumulation in distal mucosa was not reduced after direct distal infusion of oleic acid and monolein for 7 days before challenge (substrate induction). No decrease in distal intestinal lipid accumulation was found 1 month after removal of the proximal 40% of intestine beyond the duodenum. Conversely, alteration of the luminal environment in the proximal intestine by 3 days of starvation or by ileal resection did not increase the tissue 14C-lipid concentration in this region during maximal [14C]triolein challenge. When proximal and distal segments were exchanged without reduction in intestinal length, by jejunoileal transposition, major 14C-lipid accumulation still occurred in originally distal segments during 3 hr of [14C]triolein infusion 1 month later. Mucosal synthesis of triglyceride was equally efficient in jejunum and ileum, suggesting that the intrinsic differences in proximal and distal lipid accumulation during maximal rate transport were related to a relatively limited capacity for chylomicron synthesis or secretion in the distal intestine.

Intestinal lipid absorption: evidence for an intrinsic defect of chylomicron secretion by normal rat distal intestine.

Intracellular triglyceride accumulation and delayed chylomicron secretion were demonstrated in distal but not in proximal rat intestine following prolonged steady state fat absorption. After 1 and 4 hr of intraduodenal triolein infusion, the mucosal triglyceride content in distal intestinal segments was greatly increased compared with proximal segments. Electron microscopy at each time interval disclosed greater quantities of lipid droplets within the distal cells and these were much larger than the intracellular droplets in the proximal cells, some attaining an enormous size (9000 mum). When proximal and distal cells were compared at intervals after cessation of a 4 hr triolein infusion, the differences in intracellular lipid accumulation were also evident because, even after 6 hr the distal cells were still filled with large droplets, whereas the proximal cells were almost devoid of fat. These results indicate a basic cellular difference between proximal and distal intestine in the processing of fat and, in contrast to current concepts, suggest that defective chylomicron secretion is not necessarily associated with limited B-apoprotein availability.

Transmucosal triglyceride transport rates in proximal and distal rat intestine in vivo

Transmucosal transport rates for triolein in proximal and distal intestine were compared in unanesthetized rats. Emulsified [1-14-C] triolein together with bile and pancreatic juice from donor rats was infused for 6 hr into either the duodenum or the midpoint of the small intestine at such a rate that absorption was essentially complete in both regions of the intestine. Lymph was collected from the thoracic duct during triolein infusion and for an additional 6-hr period. The decrease in the rate of lymphatic output of labeled fat was found to follow a simple exponential function in all animals. This rate of decrease (decay rate) was used to calculate the half-times of lipid turnover through the intestinal wall and the fractional output rates. Distal intestine transported lipid 40% more slowly than proximal intestine, and the difference was associated with a greater accumulation of triglyceride in the distal intestinal wall. Chylomicron synthesis and/or release is the rate-limiting step for distal lymphatic fat transport in vivo, whereas fat uptake from the lumen is rate limiting for proximal intestine.