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PubMed2001

Physiological levels and action of dehydroepiandrosterone in Yucatan miniature swine.

The biological role of dehydroepiandrosterone (DHEA) and its less active sulphated conjugate DHEAS was investigated in two experiments using Yucatan miniature swine. In experiment 1, plasma levels of both DHEA(S) among males were greater than female pigs that ranged in age from 0.3 to 84 mo old (P < 0.0001). In males, DHEA(S) were related inversely to serum triglycerides; DHEA was positively related to triglycerides in females (P < 0.01). In experiment 2, four 2-yr old male pigs, used as their own control, showed a 5% decrease in body weight, 11% increase in energy expenditure, 88% increase in lipid, and 100% decrease in glucose utilization (P < 0.0001) in response to DHEA vs. placebo treatments when adjusted for body weight. Plasma DHEA(S) were not different between treatment conditions. Glucose tolerance and plasma insulin levels were not different from controls. In vivo response to norepinephrine indicated beta-adrenergic sensitivity was altered by DHEA. Present findings suggest DHEA and/or its hormone products are important in modulating energy expenditure and lipid utilization for energy in male animals. The role of DHEA in energy metabolism and the difference between sexes warrant further investigation.

Adjuvants, Immunologic↗
PubMed1986

Hemodynamics of miniature swine during +Gz stress with and without anti-G support.

Nine unanesthetized, chronically instrumented, female miniature swine (MS) (avg wt, 39.7 kg) were exposed to head-to-tail inertial load (+Gz) levels of +3, +5, and +7 Gz for 60 s, with and without anti-G-suit inflation. Venous flow (VF) was measured by an electromagnetic flow sensor around the inferior thoracic vena cava at the diaphragm. Central venous pressure (CVP), abdominal venous pressure (AVP), eye-level blood pressure (ELBP), and esophageal pressure (EP) were also measured before, during, and after +Gz. There was a progressive significant decrease from control of both ELBP (P less than 0.001) and VF (P less than 0.05) during the three +Gz exposures, both with and without G-suit inflation. Without G-suit inflation, most of the MS were unable to tolerate +5 and +7 Gz. Although VF was significantly (P less than 0.02) improved by G-suit inflation during +Gz there was no significant difference in VF between the three +Gz levels, with or without G-suit inflation. The MS does a spontaneous straining maneuver (cyclic Valsalva) during +Gz with G-suit support. Using EP as a trigger, the data were grouped as strain or no strain (relaxation). A continuous AVP-to-CVP gradient existed during G-suit inflation, which increased dramatically during no strain with increasing +Gz, and was associated with an increase in VF. Thus, the majority of VF occurred during relaxation between strains, even though relaxation time was shortened as +Gz increased. Although ELBP is obviously dependent on cardiac output and venous return, the progressive reduction in ELBP with increased +Gz loads was not significantly related to changes in VF at the diaphragm which was maintained, although at a reduced rate, by the AVP-to-CVP gradient during G-suit inflation.

Acceleration↗
PubMed1988

Coronary blood flow reserve during +Gz stress and treadmill exercise in miniature swine.

The purpose of this study was to compare the coronary blood flow reserve (CBFR) that exists during maximal +Gz stress to the CBFR during maximal exercise stress. Maximal exercise stress was defined as an exercise intensity greater than or equal to that necessary to produce maximal levels of O2 consumption (VO2max). Coronary blood flows (CBF) were determined with the use of the microsphere technique in chronically instrumented conscious miniature swine during +Gz stress and exercise stress at 70 and 100% of maximal tolerance (for each stress) before and after maximal coronary vasodilation with 1-2 mg/kg dipyridamole. CBFR was measured as the amount of blood flow increase produced by maximal coronary vasodilation. During exercise at VO2max, dipyridamole produced 20-30% increases in CBF, whereas it induced no coronary vasodilation or changes in CBF during +Gz stress. Dipyridamole also produced decreases in the animals' tolerance to +Gz in that all five animals could maintain a steady state for 60 s at 7 +Gz before dipyridamole, whereas only two of these animals could maintain a steady state for 60 s at 7 +Gz after dipyridamole. These results confirm that CBFR exists during maximal exercise in normal mammals. However, this dose of dipyridamole produced no coronary vasodilation during either level of +Gz stress.

Animals↗
PubMed1989

Plateau in muscle blood flow during prolonged exercise in miniature swine.

Cardiovascular, metabolic, and thermoregulatory responses were studied in eight male miniature swine during a prolonged treadmill run. Each animal underwent 8-10 wk of exercise training, thoracic surgery, and 3 wk of retraining before the experimental run. This regimen enabled the animals to run at 65% of the heart rate range (210-220 beats/min) for approximately 100 min. Skin wetting and a fan were used to cool the pigs during the run. Regional blood flow was significantly altered with the onset of exercise; however, hindlimb muscle and total gastrointestinal blood flow were unchanged throughout the exercise period. Compared with 5-min values, heart rate and cardiac output were significantly elevated by 17 beats/min and 31 ml.min-1.kg-1 at 60 min and by 20 beats/min and 33 ml.min-1.kg-1 at end exercise, respectively. Core temperatures increased between 5 and 30 min of exercise (39.4 vs. 39.9 degrees C) but then remained unchanged to the end of exercise. Mean arterial pressure, O2 consumption, and blood lactate did not change during the exercise bout. These data indicate that limiting increases in core temperature during prolonged exercise was associated with a plateau in active muscle blood flow.

Animals↗
PubMed1991

Effects of feeding on muscle blood flow during prolonged exercise in miniature swine.

Eight exercise-trained miniature swine were studied during prolonged treadmill runs (100 min) under fasting and preexercise feeding conditions. Each animal ran at identical external work loads that corresponded to 65% of the heart rate reserve (210-220 beats/min) for the two exercise bouts. Cardiac outputs and stroke volumes were higher and heart rates lower for fed than for fasting runs (P less than 0.05). Preexercise feeding did not alter oxygen consumption, core temperature, mean arterial pressure, and arterial-mixed venous oxygen difference during prolonged exercise; however, mixed venous lactate concentration was lower at end exercise than during fasting conditions (1.2 vs. 2.6 mM, P less than 0.05). Microsphere measurements of regional blood flow revealed significantly higher total gastrointestinal flow (23%) for fed than for fasting conditions. Throughout the exercise bout, blood flow to the biceps femoris, semitendinosus, and tibialis anterior muscles was lower in fed than in fasted animals (P less than 0.05). Combined hindlimb muscle blood flow averaged 15 ml.min-1.100 g-1 (18%, P less than 0.05) lower under feeding than fasting run conditions. These findings provide further evidence that cardiovascular reflexes originate in the gut after feeding to increase cardiac output and redistribute a portion of the blood flow away from active muscle to the gastrointestinal tract during prolonged exercise.

Animals↗
PubMed2001

Gender influences coronary L-type Ca(2+) current and adaptation to exercise training in miniature swine.

Endurance exercise training increases smooth muscle L-type Ca(2+) current density in both resistance and proximal coronary arteries of female miniature swine. The purpose of the present study was to determine 1) whether gender differences exist in coronary smooth muscle (CSM) L-type Ca(2+) current density and 2) whether endurance training in males would demonstrate a similar adaptive response as females. Proximal, conduit (approximately 1.0 mm), and resistance [~200 microm (internal diameter)] coronary arteries were obtained from sedentary and treadmill-trained swine of both sexes. CSM were isolated by enzymatic digestion (collagenase plus elastase), and voltage-gated Ca(2+)-channel current (I(Ca)) was determined by using whole cell voltage clamp during superfusion with 75 mM tetraethylammonium chloride and 10 mM BaCl(2). Current-voltage relationships were obtained at test potentials from -60 to 70 mV from a holding potential of -80 mV, and I(Ca) was normalized to cell capacitance (pA/pF). Endurance treadmill training resulted in similar increases in heart weight-to-body weight ratio, endurance time, and skeletal muscle citrate synthase activity in male and female swine. I(Ca) density was significantly greater in males compared with females in both conduit (-7.57 +/- 0.58 vs. -4.14 +/- 0.47 pA/pF) and resistance arteries (-11.25 +/- 0.74 vs. -6.49 +/- 0.87 pA/pF, respectively). In addition, voltage-dependent activation of I(Ca) in resistance arteries was shifted to more negative membrane potentials in males. Exercise training significantly increased I(Ca) density in both conduit and resistance arteries in females (-7.01 +/- 0.47 and -9.73 +/- 1.13 pA/pF, respectively) but had no effect in males (-8.61 +/- 0.50 and -12.04 +/- 1.07 pA/pF, respectively). Thus gender plays a significant role in determining both the magnitude and voltage dependence of I(Ca) in CSM and the adaptive response of I(Ca) to endurance training.

Adaptation, Physiological↗
PubMed2005

Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording.

To study the neurophysiology of large-scale spatial cognition, we analyzed the neuronal activity of navigating homing pigeons. This is not possible using conventional radio-telemetry suitable for short distances only. Therefore we developed a miniaturized data logger ("neurologger") that can be carried by a homing pigeon on its back, in conjunction with a micro-global position system (GPS) logger recording the spatial position of the bird. In its present state, the neurologger permits recording from up to eight single-ended or differential electrodes in a walking or flying pigeon. Inputs from eight independent channels are preamplified, band-pass filtered, and directed to an eight-channel, 10-bit analog-digital converter of the microcontroller storing data on a "Multimedia" or "Secure Digital" card. For electroencephalography (EEG), the logger permits simultaneous recordings of up to eight channels during maximally 47 h, depending on memory, while single unit activity from two channels can be stored over 9 h. The logger permits single unit separation from recorded multiunit signals. The neurologger with GPS represents a better alternative to telemetry that will eventually permit to record neuronal activity during cognitive and innate behavior of many species moving freely in their habitats but will also permit automated high-throughput screening of EEG in the laboratory.

Action Potentials↗
PubMed1998

Effect of moderate exercise on blood flow in the gastrointestinal tract in trained conscious miniature swine.

AIM: To examine how moderate exercise affects the blood flow in the gastrointestinal tract. MATERIALS AND METHODS: Twelve miniature swine weighing 38-43 kg were used. All animals were trained on a cardiac exercise treadmill. Blood flow measurements were done on conscious animals using labeled microspheres with a diameter of 16.5 +/- 0.1 (SD) microm. The first flow was measured while the animal was awake and resting, the second flow after 15 min of exercise, the third flow after 30 min of rest. RESULTS: Flow in the oesophagus at rest was 19.5 +/- 1.3 (SEM) ml/min/100 g. During exercise the flow decreased to 13.3 +/- 1.2 (SEM) ml/min/100 g (ns). After 30 min of rest the flow was 9.9 +/- 1.2 (SEM) ml/min/100 g (p < 0.05 when comparing the flow before and after exercise). Flow in the cardia at rest was 23.1 +/- 1.3 (SEM) ml/min/100 g. During exercise the flow decreased to 14.0 +/- 1.2 (SEM) ml/min/100 g (p < 0.05). After 30 min of rest the flow was 15.0 +/- 1.2 (SEM) ml/min/100 g. Flow in the pylorus at rest was 38.9 +/- 1.1 (SEM) ml/min/100 g. During exercise the flow decreased to 24.6 +/- 1.1 (SEM) ml/min/100 g (p < 0.01). After 30 min of rest the flow was 26.9 +/- 1.2 (SEM) ml/min/100 g. Blood flow in the small and large intestine was mainly unaffected by moderate exercise. CONCLUSION: Under moderate exercise, blood flow in the upper part of the gastrointestinal tract declines while it is mainly unaffected in the duodenum, small and large intestine.

Analysis of Variance↗
PubMedDate not supplied

Comparative study of the efficacy of various moisturizers on the skin of the ASR miniature swine.

The skin of the back of the ASR hairless miniature swine shows a rough and scaly fissured appearance. Clinically it resembles that of ichthyosis vulgaris or senile xerosis in humans. By using the skin of this animal, we developed an assay system to evaluate the efficacy of different moisturizers. The study was carried out in winter months from January to March. To establish this system, we studied various topical agents including such ordinary emollients as petrolatum and 10% salicylic acid in petrolatum as well as those available as pseudodrugs from cosmetic companies or prescription drugs from pharmaceutical companies such as heparinoid- containing creams (w/o and o/w) and 10% urea creams. Applying 0.01 g of each agent to 7 randomly selected skin areas (2x2 cm(2)) on the back of a 6-month-old swine once daily for various periods of time, we measured high-frequency conductance, the parameter for the hydration state of the skin surface. As a result, we have established a simple assay system. It consists of applications of topical agents once daily for 5 days from Monday to Friday in the first week and of subsequent measurement of the skin surface hydration state once every week. Evaluation measurements were performed from day 14 to day 21 depending upon their moisturizing effects. We found that heparinoid-containing creams exerted highly effective moisturizing effects on the dry pig skin that lasted even over 3 weeks after discontinuation of the treatments that were carried out for the first 5 days.

Animals↗
PubMed2005

Effect of indomethacin on the hypercapnia-associated vasodilation of the optic nerve head vessels: an experimental study in miniature pigs.

PURPOSE: To evaluate whether prostaglandins are mediators of the hypercapnia-associated vasodilation of the optic nerve head vessels. METHODS: We measured the PO(2) at intervascular areas of the optic disc in 9 anaesthetized miniature pigs using oxygen-sensitive microelectrodes placed at <50 mum from the optic disc. PO(2) was measured continuously under normoxia, hyperoxia (breathing of 100% O(2)), carbogen breathing (95% O(2), 5% CO(2)), and hypercapnia (40% increase in inhaled CO(2)). Similar measurements under these conditions were also done after intravenous administration of the prostaglandin inhibitor indomethacin. RESULTS: Before the injection of indomethacin, we observed a slight increase in the optic disc PO(2) during hypercapnia (DeltaPO(2) = 2.0 +/- 1.7 mm Hg; p < 0.001; n = 18) or hyperoxia (DeltaPO(2) = 3.4 +/- 1.6 mm Hg; p < 0.001; n = 23), but a much more important increase during carbogen breathing (DeltaPO(2) = 12.0 +/- 5.1 mm Hg; p < 0.001; n = 23). After the injection of indomethacin, the increase in the optic disc PO(2) was similar during hyperoxia (DeltaPO(2) = 5.6 +/- 2.2 mm Hg; p < 0.001; n = 9) or carbogen breathing (DeltaPO(2) = 5.8 +/- 3.2 mm Hg; p < 0.001; n = 9), while in hypercapnia the variation of the optic disc PO(2) was minimal (DeltaPO(2) = 0.5 +/- 1.9 mm Hg; p > 0.1; n = 6). CONCLUSIONS: Indomethacin inhibits the vasodilatory effect of increased systemic PaCO(2) on the optic nerve head vessels, leading to a similar moderate increase in the optic disc PO(2) during carbogen breathing as in hyperoxia. Indomethacin also inhibits the increase in the optic disc PO(2) seen during hypercapnia. Those results indicate that prostaglandins are mediators of the hypercapnia-associated vasodilation of the optic nerve head vessels.

Animals↗
PubMed2005

Accuracy of customized miniature stereotactic platforms.

In this study, a new system was evaluated for implanting deep-brain stimulators based on a one-piece platform for each trajectory customized from a preoperative planning image. During surgery, the platform is attached to skull-implanted posts that extend through the scalp. The platform acts as a miniature stereotactic frame to provide guidance for parallel cannulas as they are advanced through a burr hole to the target. Accuracy is determined from a postoperative CT. For each implantation, the distance between the position observed in the postoperative image and the position calculated relative to the platform from the preoperative image is our measure of error. Because this measure incorporates the surgical error of electrode anchoring, brain shift between preoperative and postoperative scanning, and error in the measurement of the position of the electrode in CT, it will tend to overestimate the true error. The mean error was 2.8 mm for 20 implantations. These data reflect favorably the accuracy of this system when compared with others.

Artifacts↗
PubMed1986

Miniaturized eight-channel telemetry system for long-term EEG registration of humans and laboratory animals.

According to the increasing importance of telemetric EEG registration, a miniaturized telemetry system for AC and DC transmission has been developed. The basic model has been constructed for the demands of experiments with small rodents. The transmitter is 19 X 13 X 5 mm in size and weighs 5 g including two 1.5 V batteries. The transmission of AC or DC potentials can be chosen for each channel separately. In the case of eight-channel transmission, the bandwidth ranges from 0.8 to 100 Hz, and in the case of using only one channel, signals up to a frequency of 17 kHz may be registered. Semimicroelectrodes with an electrode impedance of about 10 M omega, as well as conventional surface electrodes can be applied. In case of long-term EEG registration of humans the total amplification at V = 1,000 has to be enlarged by using an extension module. This module consists of an additional amplification stage, a modified HF oscillator to enlarge the omnidirectional transmission sphere and external batteries to increase the operation time of the transmitter. Small dimensions, light weight and multifunctionality plead for the attractivity of this construction according to various clinical and experimental demands.

Animals↗
PubMed1995

Use of a bite-opening appliance in the miniature pig: modification of craniofacial growth.

The purpose of this study was to determine the growth response of pigs to a bite block, preparatory to investigating the functional correlates of altered growth. Three miniature pigs (Sus scrofa) wore bite-opening appliances, creating an anterior opening of 18-20 mm, for 42-67 days. Three untreated pigs served as controls. All animals received tantalum implants and tetracycline injections to track growth of the facial bones and sutures. Treatment caused relative intrusion of maxillary and mandibular posterior teeth, and supereruption and retroclination of anterior teeth. Vertical displacement of the premaxilla and maxilla of the experimental animals was altered significantly in the superior direction, as expected from previous studies on monkeys. Changes in condylar morphology were also found, and the jaw joint discs were remodeled. Contrary to primate findings, however, anterior growth of the premaxillary, maxillary and zygomatic bones was greatly reduced. This difference in response between monkeys and pigs may be due to the way the bite block altered the load on the zygomatico-maxillary suture.

Animals↗
PubMed1995

Effects of adaptation to dietary fat on fatty acid composition of serum and serum lipids in miniature swine.

The influence of dietary fat on the serum fatty acid composition and distribution in different serum lipids was studied in 24 miniature swine (Sus scrofa) divided into 4 groups. Three groups were fed a low-fat chow with different kind of fats added (sunflower oil, olive oil and bovine lard) and the other group was fed a control diet with no fat added. The animals were fed the four diets for an experimental period of 12 weeks. Afterwards blood samples were taken to obtain serum, and the serum lipids were separated into the following fractions: phospholipids, triglycerides, and esterified cholesterol. The fatty acid composition of the serum and fractions was analyzed by gas chromatography. Under our experimental conditions, the fatty acid composition of the diets was reflected in serum, but not in all cases. In the triglyceride fraction the fatty acid composition was more evident. Our results show the interaction of the fatty acids in the different series and even within a single series, along with the endogenous synthesis processes.

Animals↗
PubMed1992

Experience with the cochlear miniature speech processor in adults and children together with a comparison of unipolar and bipolar modes.

Following the experience with nearly 150 patients with the Nucleus cochlear implant, a more sophisticated and lighter speech processor was tested successfully in terms of better speech understanding. In order to prepare further miniaturization, the standard bipolar stimulation mode was compared with an unipolar mode. It was found that unipolar stimulation needs less energy, without decreasing speech understanding. Preconditions for supplying very young children with a cochlear implant were the use of electrically elicited stapedius reflex thresholds, obtained intraoperatively, for the fitting of the speech processor and the setup of a special rehabilitation center, where children together with their mothers could be trained in hearing and understanding by special teachers and engineers for 12 weeks, distributed over the 1st postoperative year.

Adult↗
PubMed1994

Inhibition of hepatic ACAT decreases ApoB secretion in miniature pigs fed a cholesterol-free diet.

To test the hypothesis that hepatic cholesteryl ester is involved in the regulation of apolipoprotein (apo) B secretion into plasma, apoB kinetic studies were performed in six control miniature pigs and in six pigs after a 21-day administration of the acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor DuP 128 (2.2 mg.kg-1.d-1 i.v.). Pigs were fed low-fat, cholesterol-free diets. Total plasma cholesterol, triglyceride, very-low-density lipoprotein (VLDL) triglyceride, and low-density lipoprotein (LDL) cholesterol decreased 18%, 29%, 40%, and 26% respectively (P < .03). 131I-VLDL and 125I-LDL were injected simultaneously into each animal, and apoB kinetics were analyzed by using multi-compartmental analysis (SAAM30). VLDL apoB pool size decreased significantly by 60% (0.32 versus 0.84 mg/kg), which was due to a 65% reduction in the VLDL apoB production or secretion rate (1.03 versus 2.94 mg.kg-1.h-1). The fractional catabolic rate was unchanged. LDL apoB pool size decreased nonsignificantly by 18% (5.61 versus 6.90 mg/kg) due entirely to a 24% decrease in production rate (0.26 versus 0.34 mg.kg-1.h-1). At necropsy, hepatic microsomal ACAT activity decreased by 68% (0.28 versus 0.88 nmol.min-1.mg-1; P < .0002). Although an increase in hepatic free cholesterol leading to a decreased LDL receptor expression might be expected, this did not occur. The concentration of hepatic cholesterol and the LDL apoB fractional catabolic rate were unaffected by DuP 128. In addition, the concentration of hepatic triglyceride and the activity of diacylglycerol acyltransferase were not altered by DuP 128, indicating a lack of effect of DuP 128 on hepatic triglyceride metabolism. We conclude that inhibition of hepatic cholesteryl ester synthesis in vivo decreases apoB secretion into plasma.

Animals↗
PubMed1997

Inhibition of HMG-CoA reductase by atorvastatin decreases both VLDL and LDL apolipoprotein B production in miniature pigs.

In the present studies, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin was used to test the hypothesis that inhibition of cholesterol biosynthesis in vivo with a consequent reduction in the availability of hepatic cholesterol for lipoprotein synthesis, would (1) reduce very low density lipoprotein (VLDL) apolipoprotein B (apoB) secretion into the plasma, (2) reduce the conversion of VLDL apoB to LDL apoB, and (3) reduce LDL apoB direct synthesis. ApoB kinetic studies were carried out in six control miniature pigs and in six animals after 21 days of administration of atorvastatin (3 mg/kg per day). Pigs were fed a fat- (34% of calories; polyunsaturated to monounsaturated to saturated ratio, 1:1:1) and cholesterol- (400 mg/d cholesterol; 0.1%; 0.2 mg/kcal) containing pig chow-based diet. Atorvastatin treatment significantly reduced plasma total cholesterol, LDL cholesterol, total triglyceride, and VLDL triglyceride concentrations by 16%, 31%, 19%, and 28%, respectively (P < .01). Autologous 131I-VLDL, 125I-LDL, and [3H]leucine were injected simultaneously into each pig, and apoB kinetic data were analyzed using multicompartmental analysis (SAAM II). The VLDL apoB pool size decreased by 29% (0.46 versus 0.65 mg/kg; P = .002), which was entirely due to a 34% reduction in the VLDL apoB production rate (PR) (1.43 versus 2.19 mg/kg per hour; P = .027). The fractional catabolic rate (FCR) was unchanged. The LDL apoB pool size decreased by 30% (4.74 versus 6.75 mg/kg; P = .0004), which was due to a 22% reduction in the LDL apoB PR (0.236 versus 0.301 mg/kg per hour; P = .004), since the FCR was unchanged. The reduction in LDL apoB PR was primarily due to a 34% decrease in conversion of VLDL apoB to LDL apoB; however, this reduction was not statistically significant (P = .114). Hepatic apoB mRNA abundance quantitated by RNase protection assay was decreased by 13% in the atorvastatin-treated animals (P = .003). Hepatic and intestinal LDL receptor mRNA abundances were not affected. We conclude that inhibition of hepatic HMG-CoA reductase by atorvastatin reduces both VLDL and LDL apoB concentrations, primarily by decreasing apoB secretion into the plasma and not by an increase in hepatic LDL receptor expression. This decrease in apoB secretion may, in part, be due to a reduction in apoB mRNA abundance.

Animals↗
PubMed1998

The HMG-CoA reductase inhibitor atorvastatin increases the fractional clearance rate of postprandial triglyceride-rich lipoproteins in miniature pigs.

We have previously shown in vivo that the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin decreases hepatic apolipoprotein B (apoB) secretion into plasma. To test the hypothesis that atorvastatin modulates exogenous triglyceride-rich lipoprotein (TRL) metabolism in vivo, an oral fat load (2 g fat/kg body wt) containing retinol (50 000 IU) was given to 6 control miniature pigs and to 6 animals after 28 days of treatment with atorvastatin 3 mg. kg-1. d-1. A multicompartmental model was developed by use of SAAM II and kinetic analysis performed on the plasma retinyl palmitate (RP) data. Peak TRL (d<1.006 g/mL; Sf>20) triglyceride concentrations were decreased 29% by atorvastatin, and the time to achieve this peak was delayed (5.2 versus 2.3 hours; P<0.01). The TRL triglyceride 0- to 12-hour area under the curve was decreased by 24%. In contrast, atorvastatin treatment had no effect on peak TRL RP concentrations, time to peak, or its rate of appearance into plasma; however, the TRL RP 0- to 12-hour area under the curve was decreased by 20%. Analysis of the RP kinetic parameters revealed that the TRL fractional clearance rate was increased significantly, 1.4-fold (3.093 versus 2.276 pools/h; P=0.012), with atorvastatin treatment. The percent conversion of TRL RP from the rapid-turnover to the slow-turnover compartment was decreased by 47% with atorvastatin treatment. The TRL RP fractional clearance rate was negatively correlated with very low density lipoprotein apoB production rate measured in the fasting state (r=-0.49). Thus, although atorvastatin had no effect on intestinal TRL assembly and secretion, plasma TRL clearance was significantly increased, an effect that may relate to a decreased competition for removal processes by hepatic very low density lipoprotein.

Animals↗