Effects of Isoflurane on gastrointestinal motility after brief exposure in rats

Torjman, Marc C.; Joseph, Jeffrey I.; Munsick, Carey; Morishita, Mariko; Grunwald, Zvika

doi:10.1016/j.ijpharm.2004.12.028

Cited by 82 publications

(72 citation statements)

References 18 publications

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“…The contribution of GLUTs may facilitate the intestinal absorption of 2-FDG despite its very hydrophilic property. When rats were anesthetized with isoflurane or propofol, k GE was dramatically slowed (Table 1), corresponding well to the report that anesthesia significantly suppressed gastrointestinal peristaltic movement (25). In contrast, the effects of anesthesia on k IT were rather small.…”

Section: Discussionsupporting

confidence: 83%

PET Imaging of the Gastrointestinal Absorption of Orally Administered Drugs in Conscious and Anesthetized Rats

Yamashita¹,

Takashima²,

Kataoka³

et al. 2011

J Nucl Med

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This study assessed the process of gastrointestinal drug absorption in vivo using PET. Methods: 18 F-FDG was used as a model probe and was orally administered to rats as a solution. PET scans were obtained of the whole body and abdominal region under conscious and anesthetized conditions. Blood samples were routinely taken from the femoral vein during scanning. The rate of gastric emptying and intestinal absorption of 18 F-FDG was estimated from the time profiles of radioactivity in the stomach and small intestine. In addition, nonradiolabeled 2-fluoro-2-deoxy-D-glucose (2-FDG) was used in an intestinal closed-loop experiment to compare the intestinal permeability of 2-FDG with that of D-glucose. Results: In conscious rats, gastrointestinal absorption of 18 F-FDG was rate-limited by the process of intestinal membrane permeation, because the permeability of 2-FDG through the intestinal membrane was low compared with that of D-glucose. In anesthetized rats, the gastric emptying rate of 18 F-FDG decreased dramatically whereas the intestinal absorption rate constant was not significantly different from that in conscious rats. As a result, the rate-limiting step of gastrointestinal absorption of 18 F-FDG was shifted to the gastric emptying process by anesthesia. Conclusion: PET technology is a powerful tool for in vivo analysis of the gastrointestinal absorption of orally administered drugs. Gast rointestinal absorption of orally administered drugs involves many processes that occur in parallel or sequentially, starting with the disintegration and dissolution of drugs in the gastrointestinal fluid and continuing to the transit of drugs in the gastrointestinal tract, permeation of drug molecules through the intestinal membrane, and metabolism in the intestine or liver. The rate and amount of drug absorption into systemic circulation are defined as total outputs of these processes. Except for first-pass metabolism, the rate and amount of drug absorption are expressed by the following equations, Absorption rate 5 P eff · S · C E q : 1where P eff is an effective permeability of drugs, S is a surface area of the intestinal membrane, and C is the luminal concentration of drugs. AUC expresses the area under the drug concentration-time curve in the gastrointestinal tract during the intestinal transit time, t. To calculate the fraction of drugs absorbed in each segment of the gastrointestinal tract, these parameters in equations should be assessed. The P eff of drugs can be estimated by in vitro or in situ experiments (1,2). At pharmaceutical companies, in vitro permeation assays with cultured cell systems such as Caco2 or Madin-Darby canine kidney cell monolayers are widely used to determine drug permeability (3,4). Luminal concentration is affected by various factors, including drug solubility, dissolution rate, and the volume of gastrointestinal fluid. Among these factors, drug solubility and dissolution profiles can be evaluated by in vitro experiments. Recently, the use of simulated intestinal fluid under fasting or fed ...

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Section: Discussionsupporting

confidence: 83%

PET Imaging of the Gastrointestinal Absorption of Orally Administered Drugs in Conscious and Anesthetized Rats

Yamashita¹,

Takashima²,

Kataoka³

et al. 2011

J Nucl Med

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“…5) and revealed that sedating drugs inhibit digestion (Fig. 10), analogous to previous observations in rodents (38). The model is powerful in the controlled experimental conditions here (i.e., abundant food and known food deprivation times), but it may underrepresent other biological parameters.…”

Section: Discussionsupporting

confidence: 79%

A high-throughput assay for quantifying appetite and digestive dynamics

Jordi

Guggiana-Nilo

Soucy

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Jordi J, Guggiana-Nilo D, Soucy E, Song EY, Wee CL, Engert F. A high-throughput assay for quantifying appetite and digestive dynamics. Am J Physiol Regul Integr Comp Physiol 309: R345-R357, 2015. First published June 24, 2015 doi:10.1152/ajpregu.00225.2015.-Food intake and digestion are vital functions, and their dysregulation is fundamental for many human diseases. Current methods do not support their dynamic quantification on large scales in unrestrained vertebrates. Here, we combine an infrared macroscope with fluorescently labeled food to quantify feeding behavior and intestinal nutrient metabolism with high temporal resolution, sensitivity, and throughput in naturally behaving zebrafish larvae. Using this method and rate-based modeling, we demonstrate that zebrafish larvae match nutrient intake to their bodily demand and that larvae adjust their digestion rate, according to the ingested meal size. Such adaptive feedback mechanisms make this model system amenable to identify potential chemical modulators. As proof of concept, we demonstrate that nicotine, L-lysine, ghrelin, and insulin have analogous impact on food intake as in mammals. Consequently, the method presented here will promote large-scale translational research of food intake and digestive function in a naturally behaving vertebrate.appetite; hunger; satiation; satiety; DiR' dye FOOD INTAKE AND DIGESTION are key physiological processes that provide nutrients to drive all bodily functions. Nutrient intake is matched to nutritional needs by the brain-a process termed nutrient homeostasis-using an intertwined organism-wide array of extrinsic and intrinsic cues coding food availability and demand (2, 42). Dysfunction of feeding and digestive behavior is at the root of global health problems, such as obesity, malnutrition, and Type 2 diabetes, among many others, and, therefore, a deeper understanding of feeding and digestive behavior is of high importance (25).Drugs or genetic manipulations that alter food intake or digestion are highly desirable remedies for food-related disorders. To screen for genes or small molecules with clinically desirable impact, the technology of choice needs to support the analyses of hundreds to thousands of individual animals. Until now, large-scale studies of feeding behavior have solely been feasible in small invertebrates such as Drosophila, but were constrained to 20 -50 conditions in vertebrates, thereby making large-scale screens elusive (12,17,35). Technically, even more demanding than measuring food intake is the quantification of nutrient digestion, as there is no direct optical access to the gastrointestinal tract in most species. More specialized technologies, such as bioluminescence, MRI, or computed tomography, have been valuable to generate insights into in vivo dynamics of digestive function (10,18,19,31). However, all of these methods require immobilization of the experimental subject to reduce motion artifacts, thereby making concurrent behavioral observations impossible. Consequently, quantifying the dy...

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“…Overall outlines of the exteriorised intestines are displayed below each ST map and each ST map is 20 min long (vertical axis). reduced after the administration of anaesthetic (Ailiani et al, 2009;Torjman et al, 2005), whereas, in pigs, the frequency of slow waves varied depending on the type of anaesthetic used (Tachecí et al, 2013). MS222, the general anaesthetic used in this study, has been shown to impair cardiovascular performance in fish (Hill et al, 2002;Houston et al, 1971).…”

Section: Research Articlementioning

confidence: 76%

Effects of feeding on in vivo motility patterns in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius)

Brijs

Hennig

Axelsson

et al. 2014

Journal of Experimental Biology

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This is the first study to catalogue the diverse array of in vivo motility patterns in a teleost fish and how they are affected by feeding. Video recordings of exteriorised proximal intestine from fasted and fed shorthorn sculpin (Myoxocephalus scorpius) were used to generate spatio-temporal maps to portray and quantify motility patterns. Propagating and non-propagating contractions were observed to occur at different frequencies and durations. The most apparent difference between the feeding states was that bands of relatively high amplitude contractions propagating slowly in the anal direction were observed in all fasted fish (N=10) but in only 35% of fed fish (N=11). Additionally, fed fish displayed a reduced frequency (0.21±0.03 versus 0.32±0.06 contractions min −1 ) and rhythmicity of these contractions compared with fasted fish. Although the underlying mechanisms of these slow anally propagating contractions differ from those of mammalian migrating motor complexes, we believe that they may play a similar role in shorthorn sculpin during the interdigestive period, to potentially remove food remnants and prevent the establishment of pathogens. 'Ripples' were the most prevalent contraction type in shorthorn sculpin and may be important during mixing and absorption. The persistence of shallow ripples and pendular movements of longitudinal muscle after tetrodotoxin (1 μmol l −1 ) treatment suggests these contractions were myogenic in origin. The present study highlights both similarities and differences in motility patterns between shorthorn sculpin and other vertebrates, as well as providing a platform to examine other aspects of gastrointestinal functions in fish, including the impact of environmental changes.

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Effects of Isoflurane on gastrointestinal motility after brief exposure in rats

Cited by 82 publications

References 18 publications

PET Imaging of the Gastrointestinal Absorption of Orally Administered Drugs in Conscious and Anesthetized Rats

PET Imaging of the Gastrointestinal Absorption of Orally Administered Drugs in Conscious and Anesthetized Rats

A high-throughput assay for quantifying appetite and digestive dynamics

Effects of feeding on in vivo motility patterns in the proximal intestine of shorthorn sculpin (Myoxocephalus scorpius)

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