Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

PERSPECTIVESAlthough it has been over 100 years since Claude Bernard first reported the use of the isolated perfused rat liver (IPRL) (l), this model is still a valuable and commonly used tool for exploring the physiology and pathophysiology of the liver. Indeed, the IPRL remains an important experimental model despite the availability of newer techniques (e.g., liver slices, isolated and cultured cells, and isolated organelles) for evaluating hepatic function. This popularity is due to the fact that, in contrast to in uiuo models, such as the bile fistula rat, the IPRL allows repeated sampling of the perfusate, permits easy exposure of the liver to different concentrations of test substances and is amenable to alterations in temperature that would not be tolerated in uiuo. Furthermore, experiments can be done independent of the influence of other organ systems, plasma constituents and neural-hormonal effects. In contrast to other in uitro models, such as isoiated and cultured hepatocytes and isolated organelles, hepatic architecture, cell polarity and bile flow are preserved in the IPRL.Given these considerations, it seems timely to update and, in a selective manner, to review the IPRL, especially as it relates to the study of hepatic function, the advantages and disadvantages of different technical aspects of the model and the problem of reliably assessing organ viability. This manuscript is intended not only to help the reader establish this model, but also to allow him to choose those conditions which best fit his particular needs. In addition, it will provide sufficient conceptual information to permit the reader to critically evaluate work with the IPRL. However, the manuscript is not meant to be a comprehensive technical review, as these are readily available (2). Rather, it is a highly selective update focusing on concepts, practical considerations and applications. EXPERIMENTAL TECHNIQUEAlthough this review concerns itself with the IPRL, other animals such as the monkey, hamster, guinea pig, cat, rabbit, dog, sheep, calf and pig have all been used as liver donors. However, the rat is most commonly used because it is of convenient size and is relatively inexpensive to purchase and maintain; also, a large data base exists from studies using rat livers for comparison of observations.The rat liver may be isolated and perfused in situ or ex situ (i.e., attached to or removed from the animal carcass). In the in situ preparation, it may be difficult to maintain the carcass at a constant temperature, although a method for maintaining physiologic temperatures has recently been described (3). In contrast, ex situ perfusion in a temperature-controlled cabinet (2) allows for easy temperature control. The basic perfusion apparatus has three parts in series: a reservoir, a pump and an oxygenator. Peristaltic or pulsating perfusion pumps are generally used. While the peristaltic pump works well, the pulsating pump minimizes hemolysis in red blood cell-containing perfusates.Two types of oxygenators have been described ...

Gastric emptying of solids is used to screen for gastric motor disorders. Two parameters that are clinically useful are t 1/2 and the proportion emptied at four hours [1][2][3] ; these reflect overall emptying functions. The time for the first 10% to empty (or lag time 1 ) is a marker for the ability of the stomach to triturate solid food to a particle size that can be emptied (<2 mm 4 ). These measurements (t LAG , t 1/2 ) are best estimated by scintigraphy and the state of the art analysis uses a power exponential or a nonlinear model. [1][2][3][4][5] Stable isotope breath tests were recently introduced to measure gastric emptying of solids because of their potential advantages [6][7][8][9] which include performance of the test at the bedside or in the community; remote laboratory automated analysis; application at sites where gamma camera facilities are not available; and avoidance of radiation, facilitating research studies in children and pregnant women.The lack of validity for interindividual comparisons is a significant pitfall 10 ; inaccuracies of the test may result partly from the nonlinear models used to fit the cumulative breath 13 CO 2 recoveries. In the breath test, the total gastric residual is unknown and is estimated by a formula where time is infinite and 13 CO 2 excretion is assumed to have reached a steady state. Estimates of gastric half-emptying time (t 1/2 ) and lag phase duration (t LAG ) using nonlinear models are determined by the shape of the curve and are independent of endogenous CO 2 production. The results, however, are strongly associated with the estimated parameter "m" or estimated gastric residual.11 In contrast, scintigraphy can be used to follow complete emptying of the stomach, an unequivocal end point. In our previous studies 10 12 using the conventional nonlinear model, we determined that accurate determination of the parameter "m" in healthy subjects (that is a steady 13 CO 2 excretion state) required at least six hours of breath collection. We anticipated that patients with impaired gastric emptying may require an even longer sampling time, suggesting the breath test may become impractical.From a review of simultaneous scintigraphic and 13 CO 2 cumulative excretion curves performed in nearly 70 healthy volunteers in our laboratory, we noted that the "tail" of the cumulative excretion curve often did not reach steady state conditions; moreover, this portion of the curve corresponded to a time when all of the 99m Tc isotope had emptied from the stomach. Thus optimizing the curve fit might represent a futile exercise unrelated to the process of emptying.In the present study we aimed to develop a new mathematical model for breath data analysis that was independent of the parameter "m" and would oVer accuracy with shorter (three hours or less) sampling times. This new mathematical model was developed while assessing the accuracy of a breath test using a 13 C substrate consisting predominantly of the protein [ 13 C]Spirulina platensis (described below). Subsequently, the model...

We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk.

alpha2-adrenergic mechanisms modulate colorectal sensations and motility; at doses as low as 0.05 mg, clonidine reduced colorectal sensation while the tone response to feeding was preserved. These studies provide insight into the potential use of alpha2 agents in disease states.