Effect of Pharmaceuticals on Radiographic Appearance of Selected Examinations of the Abdomen and Thorax

CLINICAL RADIOLOGY

0195-5616/00 $15.00 + .00

EFFECT OF PHARMACEUTICALS ON RADIOGRAPHIC APPEARANCE OF SELECTED EXAMINATIONS OF THE ABDOMEN AND THORAX Jean A. Hall, DVM, PhD, and Barbara J. Watrous, DVM

Many pitfalls are encountered when interpreting radiographs of the thorax and abdomen. For example, intrathoracic disease may be mimicked by disease or anatomic variation of superimposed bony and soft tissues, by inappropriate phase of respiration, or by other artifacts. 26 Previous experience, attitude of the observer, and even the way that visual signals are perceived by the brain are integral in radiographic interpretation. 69 Iatrogenic therapy as a cause of image artifact or drugrelated pathologic change is yet another variable to consider before making a diagnosis of intrinsic disease or dysfunction. This article provides an overview of selected organ systems of the abdomen and thorax and the pharmaceuticals that most commonly affect their radiographic images. Consideration of previous drug therapy should be part of the routine in the seven-step approach to studying radiographs19 :

Funding for data on radiopacity of oral pharmaceuticals was provided by the Rockland Kennel Club, New York.

From the Department of Biomedical Sciences (JAH), and Department of Large Animal Clinical Sciences, Veterinary Teaching Hospital (BJW), College of Veterinary Medicine, Oregon State University, Corvallis, Oregon

VETERINARY CLINICS OF NORTH AMERICA: SMALL ANIMAL PRACTICE VOLUME 30 • NUMBER 2 • MARCH 2000

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1. Identify the artifacts of radiographic technique, positioning, and processing as well as the normal variants. 2. Identify the patient's species, age, breed, gender, and previous drug therapy. 3. Locate any radiographic abnormalities. 4. Describe the lesions (radiographic signs). 5. Make a radiographic diagnosis (radiographic pattern). 6. Construct and rank a list of diagnostic differentials. 7. Choose the most likely diagnosis based on history, clinical findings, and ancillary tests. The correct interpretation of radiographic findings caused by underlying drug therapy may save the owners of dogs and cats unnecessary worry and expense or resolve a diagnostic or therapeutic dilemma. GASTROINTESTINAL SYSTEM

Esophagus The esophagus is not normally visualized on survey thoracic radiographs unless air is present within the lumen. Occasionall)" a small amount of gas can be seen within the esophageal lumen because of aerophagia associated with swallowing, struggling or increased respiratory effort, or light sedation. Small amounts of gas related to normal swallowing are most often visible in the cranial cervical or cranial thoracic region of the esophagus and do not persist from one radiograph to the next. Large amounts of air may be present within a grossly dilated esophagus when general anesthesia or heavy sedation is used for restraint (Fig. 1). Differential considerations for abnormal gas include megaesophagus, esophagitis, foreign bod)" tumor, granuloma or abscess, stricture, vascular ring anomalies, gastroesophageal intussusception, and hiatal hernia. 68 Sedation and general anesthesia can enlarge the radiographic appearance of the esophagus because of centrally mediated skeletal muscle relaxation and can predispose the patient to gastric reflux and aspiration. Therefore, it is preferable to perform esophagraphy on the awake animal. 80, 95 High doses of acepromazine (0.2-0.4 mg/kg) affect the canine gastroesophageal region and are not recommended for esophagraphy in dogs, 24 although low doses may be acceptable in the dog and cat. Diazepam, fentanyl-droperidol, oxymorphone, and other drugs similarly decrease resting gastroesophageal sphincter pressure. 34, 84

Stomach Sedatives for Chemical Restraint

Methods that are available for evaluating gastric emptying include radioisotopic scanning, serial sampling of gastric contents by intubation,

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Figure 1. Lateral radiograph of an 8·year·old Brittany under general anesthesia for dentistry. Films were obtained immediately after positive end-expiratory pressure ventilation. The dog had been induced with ketamine and diazapam and was then intubated and given 3% isoflurane because of concern for shallow, rapid respirations. An air-filled dilated esophagus has occurred as a result of the general anesthesia.

ultrasonography, computed tomograph~ radiographic monitoring of radiopaque nondigestible liquids or particles, electrophysiology, and manometry.30 Radiographic techniques are the most readily available means for diagnosing gastric motility disorders in veterinary practice. The rate of gastric emptying during an upper gastrointestinal contrast study can be altered by some medications (e.g., sedatives, atropine) and by the type (barium- versus iodine-containing compounds), temperature, and consistency (liquid, particle, or solid food as well as its protein, fiber, and fat composition) of the contrast medium. 68 In general, sedation is not recommended for contrast radiography of the upper gastrointestinal tract because it alters contractility and muscle tone, prolongs emptying times, and increases the risk of aspiration of the contrast medium.80• 97 Xylazine produces generalized bowel distention consistent with gastric dilatation and adynamic ileus (Fig. 2).2 Gastrointestinal contractions are also inhibited for several hours. Parasympatholytic drugs (e.g., atropine) produce gastrointestinal atony.80 Barbiturates and opioids prolong gastric emptying time and are not recommended.80 If sedation is required, acepromazine (0.02-0.10 mg/kg administered subcutaneously, intramuscularly, or intravenously; maximum dose of 3 mg per dog or cat) is recommended followed by butorphanol if necessary (0.05 mg/kg administered subcutaneously, intramuscularly, or intravenously; maximum dose of 4.5 mg per dog or cat). This combination depresses gastrointestinal motility and thus increases transit time (Fig. 3) but allows for exami-

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Figure 2. Lateral survey abdominal radiograph of a 6-year-old mixed large breed dog that was presented for acute hind limb paresis. A combination of xylazine and ketamine was administered intravenously to restrain the dog for spinal survey radiographs. Gastric dilatation occurred as a result of the xylazine.

nation of mechanical causes of obstruction over a 2- to 5-hour period. Higher doses of butorphanol adversely affect gastrointestinal motility and emptying times.80 In cats, ketamine (2.7 mg/kg) plus acepromazine (0.05 mg/kg) administered intramuscularly or ketamine (5.5 mg/kg) administered intramuscularly is recommended for sedation during contrast studies.39 Gastric emptying is almost twice as fast in sedated cats as in cats without sedation. If a functional motility problem is suspected, ketamine (2.7 mg/kg) and diazepam (0.1 mg/kg) administered intramuscularly are recommended by some authors to chemically restrain cats even though motility is affected. 39 Pharmaceuticals That Delay Gastric Emptying

A considerable number of drugs, including anticholinergics, betaadrenergic agonists, opiate analgesics, enkephalins and levodopa (Ldopa), delay gastric emptying.30 Prolonged use of anticholinergic agents results in severe gastric atony and delayed gastric emptying accompanied by persistent vorniting. 29• 30• 90 Synthetic opiates are used for their potent antisecretory properties in the small intestine; these properties account for the long-standing use of these agents as antidiarrheal compounds. In addition to their effects on secretion, opioid peptides also influence gut motility by direct effects on smooth muscle and indirect effects on enteric neurons.l5 Gut motility can be further modified b y opioid actions in the central nervous system and in prevertebral ganglia.

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Figure 3. Two lateral upper gastrointestinal contrast radiographs of the same, healthy 2year-old spayed female Setter cross. A. Obtained 15 minutes after administration of barium contrast medium with the dog sedated with 0.2 mg/kg acepromazine IM. The barium has passed through most of the distal jejunum. 8 , Obtained 30 minutes after administration of barium contrast medium with the dog sedated with 0.1 mg/kg acepromazine and 0.2 mg/ kg butorphanol IM. Only a small amount of barium has exited the stomach, and it is at the transition between the ascending duodenum and proximal jejunum.

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In guinea pig ileum, opioid peptides inhibit the release of acetylcholine and substance P via mu receptors on myenteric neurons. 15 In canine intestine, the main action of opioid peptides seems to be inhibition of the release of inhibitory transmitters such as vasoactive intestinal polypeptide. 3 The pyloric sphincter in the cat has a rich enkephalinergic innervation, and there is evidence for a direct excitatory .effect on smooth muscleP Vagal stimulation, duodenal acidification, and intraluminal amino acids cause pyloric contraction; these effects are naloxone sensitive, suggesting opioid control of gastric emptying. Thus, the net effect of opioid peptides on gastrointestinal motility can be either stimulatory or inhibitory depending on the species and the region of the gut. Their impact on contrast medium-based motility studies of the gastrointestinal tract may be negligible or may affect motility regionally. Transit times for each region may selectively increase and disorganize the movement of contrast, resulting in segmentation of the contrast column (Fig. 4). With acute stress, the increased sympathetic nervous activity that would occur with excitement or trauma decreases or abolishes contractions by decreasing both amplitude and duration of the plateau potential in gastric smooth muscle cells. 89 Circulating beta-endorphin may mediate the inhibitory effect of stress on gastric motility.74 The delay in gastric emptying caused by enkephalin may be the result of interaction with central dopaminergic Drreceptors. 85 L-dopa is thought to inhibit gastric emptying by stimulating dopamine receptors in the stomach. 59 Dopamine is an inhibitory neurotransmitter involved in gastric relaxation? Caution should be exercised in the interpretation of radiographic studies when these or similar drugs have been administered, as delayed gastric emptying may be related to the drug therapy rather than to the underlying condition. If gastrointestinal disturbances occur with chemotherapeutic agents, they are usually mild and transient. The spectrum of gastrointestinal toxicities includes emesis, diarrhea, and anorexia. 61 Diarrhea is usually caused by nonspecific epithelial cell damage to the intestine that results in malabsorption. Emesis associated with chemotherapy is usually the result of either gastric epithelial cell damage, damage to the intestinal epithelial cell surfaces that induces vomiting via stimulation of intestinal afferent input to the vomiting center in the brain, or direct stimulation of the vomiting center. Pharmaceuticals That Induce Gastrointestinal Ulceration

Delayed gastric emptying has been reported in animals with an experimental gastric ulcer. 22' 53 The most common causes of gastric ulceration in dogs and cats include drugs (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs], corticosteroids), neoplasia, liver disease, and shock. 29 Drugs, especially NSAIDs, are more commonly ulcerative than erosive. The mechanism by which NSAIDs cause gastric ulcer or erosion formation is probably multifactorial, but inhibition of prostaglandin synthesis seems to be important. Different NSAIDs have differing abilities to inhibit cyclooxygenase (the source of prostaglandins) and

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Figure 4. Ventrodorsal upper gastrointestinal contrast radiograph of a 10-year-old neutered male Collie given butorphanol for musculoskeletal pain for the past 4 days. An upper gastrointestinal contrast examination was performed to confirm clinical suspicion of a splenic mass. This film was obtained 2.5 hours after administration of barium sulfate contrast medium. The contrast column is highly segmented, with contrast medium in the pylorus and duodenum, none in the remainder of the small intestine, and contrast filling the cecum and proximal large Intestine. Segmentation of the contrast column is a radiographic sign that indicates disturbed motility from inflammation (a functional abnonmality) or partial obstruction (a mechanical abnormality). It was caused by prior butorphanol administration in this dog.

5-lipoxygenase (the source of leukotrienes), which may explain the various ulcerogenic potentials of these drugs. Gastric prostaglandins (especially prostaglandin E2) serve as cytoprotective agents by inhibiting gastric acid secretion, enhancing mucosal blood flow, and promoting secretion of mucus. Local irritation from mucosal contact allows backdiffusion of acid into the gastric mucosa and induces tissue damage. Oral administration, especially of aspirin, seems to cause gastric ulcer or erosion formation more commonly, although parenteral or suppository administration of many NSA!Ds also produces gastric ulcers or erosions. Buffered aspirin and enteric-coated products are sometimes helpful in reducing the gastric side effects. Risk factors for NSAID-induced gastric

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ulcers or erosions include higher doses, longer administration times, increased gastric acidity, and coadministration of another NSAID or a corticosteroid. Dogs seem to be especially prone to NSAID-induced lesions, probably because these drugs often have a longer serum halflife in dogs than in people, resulting in the accumulation of high concentrations of the drug. There is also marked individual variation regarding sensitivity to NSAIDs. Some dogs develop life-threatening upper gastrointestinal hemorrhage after receiving relatively small doses of aspirin. Absence of clinical signs, however, does not imply lack of lesions. Indomethacin, naproxen, piroxicam, flunixin meglumine, and ibuprofen are particularly toxic for dogs. This correlates with these NSAIDs being potent inhibitors of prostaglandin synthesis and having relatively longer half-lives. Naproxen also undergoes enterohepatic cycling, which allows the intestines to be exposed several times. Newer NSAIDs may offer anti-inflammatory activity with less gastrointestinal toxicity. Prednisone at commonly administered doses usually does not cause gastric ulcer or erosion formation, although coadministration of corticosteroids with NSAIDs appears to increase the risk in dogs significantly. Administration of large dexamethasone dosages (e.g., 2.2 mg/kg every 12 hours) has been associated with gastric ulcer or erosion formation, but such dosages are seldom used, except in neurosurgery patients.29 Ulcers occur most commonly in the gastric antrum and duodenum. 10 Diagnosis can be difficult, however, because survey radiographs are often normal. Ulcer perforation often produces pneumoperitoneum or pneumohydroperitoneum. Solitary ulcers may not be recognized on upper gastrointestinal contrast examination if they are small and unless they are projected tangentially to the X-ray beam. Double-contrast gastrography is more sensitive for detecting gastric ulcers. 68 Duodenal ulcers must be differentiated from pseudoulcers and generalized inflammatory bowel disease associated with other causes. Pharmaceuticals That Accelerate Gastric Transit

Prokinetic drug therapy may result in accelerated gastric emptying. Effective gastroprokinetic agents stimulate contractions in the gastropyloroduodenal area and accelerate gastric emptying. Stimulation of contractions alone is not enough to accelerate gastric emptying as demonstrated by bethanechol chloride. 56 Bethanechol stimulates gastric contractions yet has no significant effect on the rate of gastric emptying. Thus, an effective gastric prokinetic agent must also stimulate other parameters that influence gastric emptying, for example, the percentage of contractions that propagate in the stomach, the percentage of contractions that propagate from the antrum or pylorus to the duodenum, or the percentage of contractions that propagate in the duodenum. 66 Cisapride, recommended as the initial gastric prokinetic agent of choice,92' 94 is representative of a group of serotonergic or 5-hydroxytryptamine (5-HT) drugs that bind 5-HT4 receptors on enteric postganglionic cholinergic neurons and stimulate contraction of gastrointestinal smooth

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muscle. Cisapride also has 5-HT1 and 5-HT3 antagonistic effects on enteric cholinergic neurons and non-5-HT effects on canine antral cholinergic neurons. Cisapride accelerates gastric emptying in dogs by stimulating pyloric and duodenal motor activity, by enhancing antropyloroduodenal coordination, and by increasing the mean propagation distance · of duodenal contractions. In this regard, cisapride appears to be superior to metoclopramide and domperidone in stimulating gastric emptying and thus may have a greater impact on radiographic examinations of gastric emptying. Metoclopramide works as a gastric prokinetic and antiemetic agent32 through antagonism of dopaminergic D2 receptors and agonism of serotonergic 5-HT4 receptors, respectively. It increases the amplitude and frequency of antral contractions; inhibits fundic receptive relaxation; and coordinates gastric, pyloric, and duodenal motility. All of these actions result in accelerated gastric emptying. In normal dogs, however, gastric emptying time is not significantly shortened by metoclopramide. 66 Neither does metoclopramide change gastric myoelectric and motor activities in a way that would promote increased gastric emptying in dogs with gastric dilatation-volvulus. 35 Whereas cisapride stimulates most parameters of gastropyloroduodenal contractions that accelerate gastric emptying, metoclopramide enhances mainly the antropyloroduodenal coordination. 66 Any prokinetic effect of metoclopramide may be limited to the emptying of liquids. In one study, using a double-radioisotopic technique to assess simultaneous gastric emptying of solids and liquids, metoclopramide was shown to increase the gastric emptying time of the liquid phase at 1 hour postprandially but to have no effect on the gastric emptying time of the solid phase.27 In another study, metoclopramide was shown to speed gastric emptying of liquids but to slow the emptying rate of digestible solids.38 Thus, the usefulness of metoclopramide as a gastroprokinetic drug to improve gastric emptying of solids is limited, and it would similarly have a limited impact on gastric emptying studies using solid food. Erythromycin may be used as a prokinetic drug in some patients if cisapride fails to improve gastric emptying.33 Erythromycin at low microbially ineffective doses accelerates gastric emptying by inducing antral contractions that are similar but not identical to those associated with phase III of the migrating motility complex. Phase III contractions, which usually occur only during the fasting state, empty the stomach of indigestible solids. Erythromycin accelerates gastric emptying of solids during the fed state, which would decrease the gastric emptying time during a contrast-impregnated food examination. Ranitidine is a competitive, reversible, histaminergic H 2-receptor antagonist that was developed to inhibit gastric acid secretion.31• 60 Ranitidine also stimulates gastrointestinal motility by inhibiting acetylcholinesterase activity, thereby increasing the amount of acetylcholine available to bind smooth muscle muscarinic cholinergic receptors. Ranitidine may be used in the treatment of gastric emptying disorders as well as in the treatment of gastric ulcers. Indeed, delayed gastric emptying is a

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consequence of gastric ulcer disease in the dog. Treatment with ranitidine would promote gastric emptying. Nizatidine acts in a manner similar to cimetidine, ranitidine, and famotidine as a reversible competitive Hz-receptor antagonist with gastric antisecretory properties. 31• 91 Nizatidine also stimulates gastric contractions and accelerates gastric emptying at gastric antisecretory doses. Like ranitidine, nizatidine may have clinical applications (i.e., gastrointestinal prokinetic therapy) that are not found with cimetidine or famotidine. Nizatidine stimulates gastric motor activity and accelerates gastric emptying in a manner comparable to cisapride. Rapid gastric emptying during an upper gastrointestinal study is not commonly encountered. Vomiting of gastric contents before obtaining radiographs early in the contrast examination may mimic rapid emptying. Infiltrative gastric diseases that prevent mural stretching when contrast medium is administered per os (e.g., chronic fibrosing gastritis, scirrous adenocarcinoma) may induce vomiting or cause rapid transit of contrast medium such that initial radiographs show barium well into the small intestine and a small contrast medium-filled gastric lumen. Pharmaceuticals that accelerate gastric transit may mimic this finding. Oral Pharmaceuticals That Increase Radiopacity of Gastrointestinal Contents

Frequently, the presence of radiopaque "debris" is encountered on survey abdominal radiographs (Fig. 5). The animal's diet may account for some of the density seen; sources include bones or high fish byproduct- and bonemeal-containing foods. Clays used in kitty litter and sand or small gravel used in runs may produce focal mineral opacities dispersed through the gastrointestinal tract contents in an abdominal radiograph. Specific formulations for pet vitamin and mineral supplements add mineral density to the diet because of calcium, manganese, and iron (Fig. 6). Oral pharmaceuticals may also produce increased radiopacity of the contents of the gastrointestinal tract as a result of the active ingredients in the pharmaceutical itself or because of the inactive ingredients used in the formulation process. Gastrointestinal medications include antacids (e.g., Maalox [Novartis Consumer Health, Summit, NJ], Mylanta [Johnson and JohnsonMerck Consumer Pharmaceuticals Co., Ft. Washington, PA], Turns [SmithKline Beecham Consumer Healthcare, L.P., Pittsburgh, PA]), enteric-coating agents, and antidiarrheal medications (e.g., Pepto-Bismol [Procter and Gamble, Cincinnati, OH], Amforol [Fort Dodge Animal Health, Overland Park, KS]). They may be in suspension, liquid, or tablet form. Common active ingredients that impart radiopacity include calcium, magnesium, aluminum, bismuth, and silicate (Figs. 7 and 8). 14 The manufacturing process of oral medications may require the addition of inactive ingredients as fillers or diluents, binders, disintegrants, or lubricants. Common components of these additives that impart radiopacity include aluminum, calcium, magnesium, silica, and zinc (Fig. 9). 5 Diluents increase bulk for easier administration of an active ingredi-

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Figure 5. Lateral survey abdominal radiograph of a healthy, approximately 6-month·old Beagle puppy 24 hours after administration of amforol. Fragments of the tablet can be seen as radiopaque debris throughout the gastrointestinal tract. (Courtesy of Victor T. Rendano, Jr, VMD, MS, Cornell University, Ithaca, NY.)

ent and are chosen for drug compatibility, nonreactivity with the active drug, chemical stability, physical stability, physiologic inertness, and no adverse effect on the active drug bioavailability. Good low-cost diluents include insoluble calcium salts. These are often used for vitamins, steroids, and other water-sensitive drugs.14 Binders and adhesives maintain the physical stability of compressed tablets and include nonradiopaque components such as cellulose and starch paste. Disintegrants serve to counteract the process of compression and the binders added in the tabulation process. They are added to break up tablets in the stomach and work based on the principle of absorbing water and swelling with hydration. Cornstarch, microcrystalline cellulose, and the radiopaque mineral clay powders (bentonite and veegum) are common disintegrants. Absorbents are occasionally used to sorb small amounts of a liquid such as the oily free-base form of a drug. Light magnesium oxide and magnesium carbonate bentonite are examples of absorbents. Lubricants are used to eject tablets from the die by reducing adhesion or friction between the tablet and die. Magnesium and calcium stearate are examples of lubricants used. They are coated or layered on the tablet. Antiadherents such as talc and cornstarch are also used to reduce sticking and adhesion. Cosmetic-grade talc (magnesium silicate) can be used as a filler to keep tablets from sticking to the molds, pw1ches, and dies. 81 Colloidal silicas are sometimes used as glidants to reduce interparticle friction and promote granular flow.5 To finish a tablet, several steps may be needed. Dyes for coloration

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Figure 6. Lateral survey abdominal radiograph of a healthy 5-year-old neutered male Basset Hound that recently ingested several PetTabs (Pfizer Animal Health, Exton, PA), which the owner fed as doggie treats for reward. The variable density of the tablets is a result of (1) variable and partial dissolution, and (2) beam angle relative to tablet geometry.

of tablets may be adsorbed on the alumina and aluminum hydroxide layer. Coating agents are added to control the site of drug release, provide continuous release, protect the physical or chemical integrity of the drug, or produce a pharmaceutically better product. A common coating agent is sugar, which essentially shellacs the tablet to protect it from water. Shellacing may delay drug release; thus, an annealing agent such as calcium carbonate is used to enhance dissolution in gastric acid. Finally, the tablet is rounded using a smoothing syrup containing calcium carbonate or a coating powder (e.g., precipitated chalk, powdered calcium carbonate, talc). Radiopacity and dissolution characteristics of commonly used pharmaceuticals were studied at Cornell University (V. T. Rendano and B. J. Watrous, unpublished observations, 1981 ). Besides gastrointestinal medications, several other drugs imparted some degree of radiopacity to gastrointestinal contents. Examples include ampicillin, chloramphenicol

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Figure 7. Lateral survey abdominal radiograph of a healthy, approximately 6-month-old Beagle puppy immediately after administration of a Pepto·Bismol tablet (Procter and Gamble, Cincinnati, OH). The shape and clarity of the tablet are consistent with recent administration. (Courtesy of Victor T. Rendano Jr, VMD, MS, Cornell University, Ithaca, NY.)

Figure 8. Lateral survey abdominal radiograph of a 7-year-old female German Shepherd dog presented to a veterinarian for acute abdominal distention. Initial intubation with an orogastric tube for gastric decompression was only partially successful. This radiograph was obtained after referral to an emergency facility for further work-up and treatment. There is pneumohydroperitoneum resulting from gastric rupture. Multiple mineral foci represent several tablets of an enteric coating agent administered earlier by the owner for gastric discomfort. (Courtesy of the University of California, Davis.)

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Figure 9. Radiographs obtained of several tablets, caplets, and capsules representative of medicinal drugs commonly found in a veterinary practice. A, Drugs are radiographed in air. Although all the drugs appear relatively radiopaque, the larger two on the right would be radiopaque in water and the others would be isodense and not visible. 8 , Drugs are radiographed immediately after being submerged in water. There are six tablets submerged, but only two are sufficiently radiopaque to be seen, a resu lt of fillers used in their tablet formulation. (Courtesy of Victor T. Rendano, Jr, VMD, MS, Cornell University, Ithaca, NY.)

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capsules, diltiazem hydrochloride, aminophylline, DL-methionine, Liothyronine, strongid, and sucralfate (see Fig. 9). Small Intestine D 2-dopaminergic antagonists (e.g., metoclopramide), 5-HT4 serotonergic agonists (e.g., cisapride}, and motilin-like drugs (e.g., erythromycin) have been recommended in the therapy of small intestinal motility disorders. 32' 33' 94 The 5-HT4 serotonergic agonists seem to have distinct advantages over the other two drug classifications in the treatment of small intestinal motility disorders. Cisapride, for example, stimulates jejunal spike burst migration, 86 jejunal propulsive motility/7 and antropyloroduodenal coordination16 following intestinal lipid infusion in the dog. Thus, cisapride, which seems to have a rational place in the treatment of postoperative ileus and intestinal pseudo-obstruction, may mask some of the motility disturbances in a small intestinal contrast examination.

Large Intestine

Radiographic evaluation of the large intestine is primarily a static anatomic study rather than a functional study. For a complete barium enema examination, heavy sedation or general anesthesia is necessary to adequately relax and distend the colon. Narcotic premedication should be avoided because of its spasmogenic properties, which are similar to the spasms induced by a luminal balloon catheter used for contrast enema examination. 64 The normal diameter of the colon is no more than three times the diameter of the small intestine and less than the measured length of the seventh lumbar vertebra. 68 Colonic dilatation results in disruption of the coordinated motility patterns of the distal colon and rectum. These patterns are responsible for the receptive relaxation associated with fecal storage and the giant migrating contractions associated with the defecation reflex. Abnormal colonic dilatation leads to constipation, obstipation, and idiopathic megacolon. Several authors have emphasized the importance of considering an extensive list of differential diagnoses (e.g., neuromuscular, mechanical, inflammatory, metabolic or endocrine, pharmacologic, environmental, behavioral causes) for the obstipated cat. A recent review/3 however, suggests that 96% of cases of obstipation are accounted for by idiopathic megacolon (62%), pelvic canal stenosis (23%}, nerve injury (6%}, or Manx sacral spinal cord deformity (5%). A smaller number of cases are accounted for by complications of colopexy (1%) and colonic neoplasia (1% ). Colonic hypo- or aganglionosis was suspected but not proven in another 2% of cases. Pharmacologic, inflammatory, and environmental or behavioral causes were not cited as predisposing factors in any of the original case reports. Endocrine factors

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(obesity [n = 5], hypothyroidism [n 1]) were cited in several cases but were not necessarily implicated as part of the pathogenesis of megacolon. Thus, although it is important to consider an extensive list of differential diagnoses in an individual animal, it should be kept in mind that most cases are idiopathic, orthopedic, or neurologic and not pharmacologic in origin. 93 Patients may be treated with emollient laxatives (e.g., dioctylsodium sulfosuccinate), stimulant laxatives (e.g., phenolphthalein), lubricant laxatives (e.g., petrolatum), saline laxatives (e.g., magnesium citrate), hyperosmotic agents (e.g., lactulose), or motility agents. 93 Cats treated with liquid suppository agents usually show replacement of the normal heterogenous colonic fecal pattern with a fluid pattern on survey radiographs. Those treated with heavy metal ingredients (magnesium citrate) may present with an increased radiopacity of the luminal contents. SPLEEN

Splenic masses are more common than diffuse splenomegaly in dogs, whereas diffuse splenomegaly is more common in cats. In dogs, neoplastic splenic masses include mainly hemangiomas and hemangiosarcomas. Non-neoplastic splenic masses include primarily hematomas and abscesses. 11 Differential diagnoses for diffuse splenomegaly can be assigned to four major categories with respect to the pathogenesis: lymphoreticular hyperplasia, inflammatory changes, infiltration with abnormal cells or substances (e.g., amyloidosis), or congestion.U· 62• 68 Hyperplastic splenomegaly is common in dogs with subacute bacterial endocarditis, systemic lupus erythematosus, or chronic bacterernic disorders. Certain hemolytic disorders, including immune hemolytic anemia and hemobartonellosis, result in red blood cell phagocytosis by the splenic mononuclear phagocytic system, which leads to hyperplasia of this cell population and splenomegaly. Inflammatory changes (splenitis) can be classified as suppurative (e.g., bacterial endocarditis, toxoplasmosis, acute infectious canine hepatitis, mycobacteriosis), granulomatous (e.g., histoplasmosis, mycobacteriosis), pyogranulomatous (e.g., blastomycosis, feline infectious peritonitis), eosinophilic (e.g., hypereosinophilic syndrome), necrotizing (e.g., in association with splenic torsion or neoplasia), and lymphoplasmacytic (e.g., chronic ehrlichiosis, hemobartonellosis, brucellosis). Infiltrative (neoplastic) splenomegalies are also common (e.g., acute and chronic leukemias, systemic mastocytosis, malignant histiocytosis, lymphoma, multiple myeloma). Non-neoplastic causes of infiltrative splenomegaly are uncommon, with the exception of extramedullary hematopoiesis in dogs. Congestive splenomegaly may be a physiologic response to some drugs. It may also result from portal hypertension (e.g., right congestive heart failure) or splenic torsion (e.g., isolated or in association with gastric dilatation and volvulus). Congestive splenomegaly develops if venous drainage from the spleen is impaired or obstructed. The canine and feline spleens have a

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Figure 10. Lateral abdominal radiograph of a healthy 2-year-old male Rhodesian Ridgeback cross sedated with 0.4 mg/kg acepromazine administered half IV and half SC. Generalized splenomegaly is identified. The body of the spleen extends the length of the ventral abdomen and the tail (T) lies below the apex of the urinary bladder. The head of the spleen is superimposed on the shadow of the right kidney, filling the space immediately caudal to the dorsal extent of the gastric fundus (·).

great capacity to store blood and may contain 10% to 20% of the total blood volume. Phenothiazine tranquilizers and barbiturates increase blood pooling in the spleen as a result of smooth muscle relaxation of the splenic capsule, leading to congestive splenomegaly (Fig. 10).11• 62 Pooling of blood in an enlarged spleen can account for up to 30% of the total blood volume. Anesthetics such as halothane are also associated with splenomegaly as a result of the same mechanism. u

LIVER

The liver has a dual blood supply. The hepatic artery supplies 20% of the total blood volume, and the portal vein supplies the remaining 80%. Portal vein blood is derived from the stomach, small intestine, colon, pancreas, and spleen but not from the rectum and anus. The hepatic artery and portal vein each provide approximately 50% of the hepatic oxygen supply. In the dog but not the cat, central and interlobular veins contain muscular sphincters that adjust blood flow within the liver and portal vascular bed. Several compounds are known to significantly decrease hepatic vein outflow by causing constriction of these venous sphincters (e.g., digitalis, morphine, histamine, and endo-

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toxins }.73 These compounds result in significant venous congestion within the liver and portal vein. Generalized hepatomegaly is characterized radiographically by displacement of the stomach shadow and increased visibility of the hepatic margin beyond the costal margin. Caudal displacement of the stomach axis is present on the lateral radiograph. This may be accompanied by elevation of the gastric body and pyloric canal. The ventral margin or hepatic angle extends caudally beyond the costal arch and may become rounded. On the ventrodorsal view, the stomach axis may be caudally displaced along with the head of the spleen, the small intestine, and the right kidney. The pylorus may angle caudally or may be displaced leftward toward midline, and the fundus may be displaced rightward toward midline. The right or left hepatic angle may extend beyond the costal arch and may be rounded. 68 The most common causes of hepatomegaly are vascular congestion (e.g., right-sided conge~tive heart failure), infiltration of inflammatory cells or hepatocyte inflammation (e.g., canine infectious hepatitis), primary neoplasia (e.g., hepatocellular carcinoma, bile duct carcinoma), metastatic neoplasia (e.g., sarcoma, carcinoma, lymphoma), chronic hepatitis with nodular hyperplasia, excessive storage of lipid or glycogen (e.g., hepatic lipidosis, steroid hepatopathy), and Kupffer cell hyperplasia (e.g., systemic mycosis). 50 Abdominal enlargement secondary to hepatomegaly, abdominal wall muscle weakness, and increased abdominal fat accumulation occur in approximately 60% to 80% of dogs with hyperadrenocorticism. 51 The associated hepatomegaly is characterized histologically by diffuse vacuolation of hepatocytes and intracytoplasmic glycogen accumulation. 1 Iatrogenic Cushing's syndrome occurring after systemic corticosteroid use has been documented. 12' 46, 47' ss, 78' 79 For example, a single intramuscular dose of glucocorticoid (methyprednisolone acetate) for pruritus in a dog caused iatrogenic steroid hepatopathy with generalized hepatomegaly identified on abdominal radiographs. 58 High-dose chronic corticosteroid therapy (1 mg I lb of prednisone daily for 5 years) administered to a dog also caused Cushing's syndrome with hepatomegaly and a pendulous abdomenP Various glucocorticoids at varying dosages can cause the syndrome. 58 Topical skin and ophthalmic corticosteroids also have the potential to cause adrenocortical suppression and hepatic metabolic changes. 75, 96 Cats do not seem to develop the marked hepatic pathologic changes characteristic of glucocorticoid "hepatopathy" in the dog, 72' 79 but mild hepatomegaly may be recognized (Fig. 11). Because of their slight androgenic effect, which inhibits luteinizing hormone release and in turn ovulation, progestagens have been used to prevent estrus. Moderate to severe acromegaly resulting from reversible growth hormone overproduction has been reported in female dogs treated with progestagens (medroxyprogesterone acetate) for estrus control,18 Along with other findings of acromegaly (e.g., inspiratory stridor resulting from diffuse soft tissue excess in the orolingual or oropharyngeal region, excessive skin fold formation, polyuria or polydipsia, hyper-

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Figure 11. Lateral survey abdominal radiographs of a 12-year-old male domestic shorthair cat with clinical signs of feline asthma. A, Obtained prior to therapy. 8, Obtained 1 month after beginning corticosteroid therapy and demonstrates mild hepatomegaly.

glycemia, fatigue, enlargement of the interdental spaces), abdominal enlargement was noted.I8 Although not commonly used for estrus control, progestagens are nonetheless prescribed. Medroxyprogesterone acetate and megestrol acetate are frequently used in behavioral medicine because of their calming effects and their suppressant effects on male stereotypic behavior.67 In human patients with cancer, megestrol acetate has been shown to result in substantial weight gain. It is now being recommended as a chemica] stimulant to encourage food consumption in dogs and cats with cancer cachexia.65 PANCREAS

Pancreatitis associated with drug administration in dogs is rare but has primarily been linked with the use of L-asparagi.nase, azathioprine, and prednisone.61 A retrospective study of 101 cases of acute pancreatitis in dogs showed that anticancer drug administration was a risk factor in 5 dogs and that corticosteroid administration was a risk factor in 18 dogs.8 Other cytotoxic drugs that have been associated with pancreatitis in dogs include cisplatin and methotrexate.61 Because of concurrent

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myelosuppression, pancreatitis associated with chemotherapy often lacks some of its typical hallmarks such as neutrophilia and fever. Thus, diagnosis can be difficult. In addition, vomiting caused by pancreatitis may be indistinguishable from vomiting caused by chemotherapeutic agents alone. 61 Abdominal radiographic changes suggestive of pancreatitis include a mass effect between the pyloric antrum and proximal descending duodenum, gas retention and mild to moderate distention of the descending duodenum, a fixed abaxial location of the descending duodenum, caudal displacement of the transverse colon, spastic contraction of the transverse colon, and a hazy right cranial abdomen with poor to no serosal detail, suggesting fluid or cellular accumulation. 64

UROGENITAL SYSTEM

Several disorders may cause mild, reversible, bilateral renomegaly. Although best detected with ultrasonography, 6 the attentive examiner may observe mild renal enlargement on radiographs with endocrinopathies such as acromegaly (growth hormone excess), 13 hyperadrenocorticism, and diabetes mellitus (T. R. O'Brien, personal communication, 1999). Exogenous progestagen therapy may similarly cause mild enlargement via excess growth hormone. Administration of intravenous contrast media, 83 diuretics, or intravenous fluids that cause diuresis may also increase renal size. 6 Normal renal length in the dog is 3.0 ± 0.25 times the length of L2 (renal length ratio), and normal renal width is 2.0 ± 0.2 times L2.21 In the cat, renal length is dependent on reproductive status. The renal length ratio for neutered cats is 2.22 ± 0.14. In intact cats, the renal length ratio for the left kidney is 2.60 ± 0.19 and that for the right kidney is 2.65 ± 0.24. 83 The renal width is 3.0 to 3.5 cm. 21 Complications of chemotherapy affecting the urinary tract are usually related to the use of cyclophosphamide, cisplatin, and corticosteroids.61 Hemorrhagic cystitis may develop in animals treated with cyclophosphamide. It is most commonly noted in female dogs, followed in frequency of occurrence by that in neutered male dogs, intact male dogs, and intact and neutered cats in about equal frequency. Cystitis is attributed to the irritating effects of acroelin (one of the drug's metabolites) on the bladder mucosa. Cystitis usually occurs after prolonged use, although it has been reported in dogs following a single intravenous dose. 71 Cyclophosphamide is a known carcinogen. Transitional cell carcinoma of the urinary bladder has been reported in dogs previously treated with cyclophosphamide,52 but this side effect is rare. 61 Corticosteroid use, in addition to causing diuresis, may also be associated with cystitis. 51 Urinary tract infections are often found in dogs with prolonged glucocorticoid administration secondary to urine retention in the bladder coupled with the immunosuppressive effects of chronic hypercortisolism.51

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LUNGS

Prolonged lateral recumbency results in hypostatic congestion of the dependent lung. 25 this occurs almost immediately after animals are placed under general anesthesia and results in the appearance of a generalized unstructured interstitial or alveolar pattern that is more severe in the dependent lung (Fig. 12). The changes progress as the time under anesthesia increases. In addition to creating what seems to be pathologic changes, the increased opacity in the lung may mask actual pathologic changes. Thus, sedation is generally preferable to general anesthesia for thoracic radiographs in animals. If in doubt about whether dependent lung opacity is caused by anesthesia, the veterinarian should recover the patient from anesthesia and repeat the radiographic procedure or, alternatively, provide positive-pressure ventilation to reinflate the atelectatic alveoli and resolve the congestion over a few minutes and then reradiograph the patient in a ventrodorsal view to verify improved lung aeration.25 Atelectasis and gas exchange impairment during enflurane and nitrous oxide anesthesia was studied in 16 lung-healthy patients.28 After 10 minutes of anesthesia, 14 of 16 subjects had developed atelectasis. After 30 minutes of anesthesia, all patients had developed atelectasis, and a further increase to approximately 5% of the intrathoracic area was observed after 90 minutes. The findings suggested that besides prompt

Figure 12. Serial ventrodorsal thoracic radiographs of the same dog as in Figure 1. A, Obtained immediately after induction of general anesthesia and acquisition of the left lateral recumbent radiograph. The alveolar pattern in most of the left lung is the result of hypostatic congestion caused by general anesthesia. 8 , Obtained after a short period of positive endexpiratory pressure to reinflate the left lung. The alveolar pattern has resolved, although minor opacity of an interstitial nature still exists when one compares the density of the left lung to that of the right.

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collapse of lung tissue during induction of anesthesia, absorption of gas from closed-off or poorly ventilated regions takes place and further increases the atelectatic area. In another study of 24 adult patients, the lungs were ventilated with 30% oxygen in nitrogen during anesthesia induction in 12 patients; in the other 12 patients, 100% oxygen during induction and 40% oxygen in nitrogen for maintenance (a conventional protocol) were used?6 There was a significantly greater amount of atelectasis in the 100% oxygen group. Researchers suggested that the composition of inspired gas is important in atelectasis formation during general anesthesia and that the use of a lower oxygen concentration than is now standard practice might prevent the early formation of atelectasis. In children undergoing general anesthesia, it was shown that with an intraoperative inspired oxygen fraction of 0.4, densities in dependent regions of both lungs were observed in all children 5 minutes after induction. After ventilation with a positive end-expiratory pressure (PEEP) of 5 em of water, all the observed densities disappeared. Thus, a PEEP of 5 em of water is able to recruit all the available alveolar units and to induce the disappearance of atelectasis in dependent lung regions. 82 Similarly, a PEEP of 10 em of water was shown to prevent atelectasis during general anesthesia in adult patients even in the presence of 100% inspired oxygen.63 Thus, if general anesthesia is used during thoracic radiography in animals, it would be prudent to minimize the time between induction and the radiographic procedure and to inflate the lungs several times before exposures are obtained. Antineoplastic agents have been shown to cause pulmonary toxicity, producing pulmonary lesions that resemble metastatic nodules to the lungs. 4 In cats, the use of cisplatin at standard doses (60-70 mg/m2 ) causes acute pulmonary disease and death, resulting from severe hydrothorax and pulmonary and mediastinal edema. 61 Microangiopathologic changes in alveolar capillaries are likely responsible for fluid shifts into the lungs and pleural space. 49 To avoid pulmonary toxicity, a safe alternative in cats is the analog drug carboplatin. 61 Pulmonary complications of high-dose chronic corticosteroid therapy have also been reportedP Although the mechanism of mineralization is not known, elevated glucocorticoid levels may alter proteins such as collagen and elastin to produce a calcifiable matrix. 48 A dog treated with 1 mg I lb of prednisone daily for 5 years was presented with iatrogenic Cushing's syndrome. The thoracic radiographic findings were consistent with alveolar lung disease with prominent air bronchograms. Although reported radiographic changes associated with Cushing's syndrome include increased interstitial lung densities and mineralization of the trachea and mainstem bronchi, 40 at the postmortem examination, this dog had extensive interstitial mineralization. Thus, extensive interstitial pulmonary disease may appear as an alveolar pattern radiographically, and pulmonary edema might erroneously be considered as the underlying cause of the radiographic pattern. Respiratory distress is more likely the result of extensive metastatic mineralization in the pulmonary parenchyma, which explains the clinical lack of response to furosemide. 12' 48

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Changes in breathing pattern, dynamic lung compliance, and gas exchange seem to be related directly to the degree of pulmonary fibrosis and septa] mineralization. 48 Parenchymal mineralization presenting in regional, multifocal, and generalized rustributions has been seen in cats treated with long-term corticosteroid therapy for asthma. Dystrophic mineralization secondary to inflammation likely accounts for focal changes in the cat. Diffuse mineralization occurs rarely, but may be seen in cats with lifelong asthma and clinical signs responsive to chronic corticosteroid therapy (Fig. 13). Other complications of high-dose chronic corticosteroid therapy indude pulmonary thromboembolism. 48 Thromboembolic complications are a recognized sequela in human patients with Cushing's rusease and have been documented in dogs with hyperadrenocorticism. Thromboembolic events present problems in ruagnosis and treatment and should be considered in the evaluation of patients with this disease, particularly if overt signs of respiratory distress are present. Thoracic radiographs are often normal; however, changes may include one or more of the following: enlarged truncated pulmonary arteries, regional peripheral arterial hypovascularity (oligemia), mild right heart enlargement, enlarged pulmonary artery segment, enlarged caudal vena cava, and mild to moderate pleural effusion.87

Figure 13. Lateral thoracic radiograph of a 12-year-old neutered male domestic shorthair cat with a life-long history of feline asthma. Corticosteroid therapy had been administered long term to control clinical signs. Radiographically, there is diffuse mineralization of the parenchyma and bronchioles, with mineralization following the secondary and tertiary bronchovascular structures. Histologic examination revealed alveolar calcipherytes or the presence of pulmonary microlithiasis. (Courtesy of Patrick Long, DVM, Corvallis, OR.)

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HEART Malposition of the heart is an important modifying factor in the evaluation of cardiac size and shape. Malposition of the cardiac apex to the right of midline instead of to the left is the most common positional abnormality in dogs. Although it may be associated with thoracic conformation (e.g., wide shallow thorax) or cardiomegaly, it may also result from physical displacement induced by uneven lung inflation. 88 Thus, the pharmacologic manipulations (e.g., general anesthesia) and prolonged lateral recumbency that affect lung inflation may secondarily cause malposition of the heart. A reduction in cardiac size (microcardia) is an uncommon result of cardiac disease. An increased overinflated thorax often conveys the erroneous impression of a reduced heart size. Hypovolemia (or the lack of pharmacologic fluid therapy intervention), severe dehydration, shock, tension pneumothorax, and severe weight loss with chronic disease and malnutrition are more common conditions that may cause a reduction in heart size. 88 Overuse of diuretics may deplete blood volume sufficiently to cause a reduction in heart size. Secondary (iatrogenic) hypoadrenocorticism from abruptly discontinued exogenous corticosteroid therapy may produce microcardia and a reduction in pulmonary artery or caudal vena cava size similar to naturally occurring primary hypoadrenocorticism in the dog. 57 Anesthesia can influence heart rate, peripheral circulatory hemodynamics, and myocardial contractility. Presumably, the effects of anesthesia can also alter cardiac dimensions and function. 45 Short radiographic exposure times, especially in large-breed dogs, may catch the normal heart in end systole, producing a relatively small heart size, or in end diastole, maximizing heart size. 88 Drugs that increase heart rate may increase the incidence of exposure coincident with systole, and drugs that decrease heart rate may lead to an increased incidence of radiographic exposure timed with diastole. Ketamine anesthesia in cats can cause substantial increases in heart rate and alters peripheral circulatory hemodynamics, thereby affecting cardiac dimensions and functional indices.44 Diazepam does not induce significant cardiopulmonary effects, except for an increase in heart rate, and it blunts the cardiovascular changes and enhances the respiratory changes induced by ketamine. 36 Phenothiazine tranquilizers uniformly decrease arterial blood pressure, which has been attributed to peripheral alpha-receptor adrenergic blockade and to inhibition of centrally mediated pressor reflexes. 20 Myocardial depression may be contributory. The reported decrease in left ventricular work and left ventricular stroke volume caused by acepromazine was attributed to a decrease in blood pressure and cardiac output-2° The cardiopulmonary consequences of intravenously administered xylazine in dogs include significant decreases in heart rate, cardiac output, and left ventricular work. 37 Preanesthetic treatment of cats with xylazine has a profound influence on cardiac function and regional blood flow in various tissues. This clearly complicates the interpretation of diagnostic

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studies of the cardiovascular system if xylazine has been used. Bradycardia, decreased cardiac contractility, decreased cardiac output, and increased left ventricular end-diastolic pressure are hemodynamic changes consistent with a state of compensated cardiac failure. 23 Thus, the cardiopulmonary effects of anesthetic pharmaceuticals depend on the particular drug administered, whether combinations of drugs are used, the dosages and times after administration before cardiac evaluation, and concurrent variables (e.g., hypovolemia). 9• 41-43, 70 Chemotherapeutic agents with adverse effects on the heart include doxorubicin and epirubicin.61 The time interval from the onset of treatment with doxorubicin to detectable cardiac abnormalities is from 1 to approximately 270 days. 54 Cardiotoxicity may culminate in cardiomyopathy or sudden death from a fatal arrhythmia. Early hypertrophic change with mild left atrial enlargement and left and right ventricular enlargement has been reported in cats treated with doxorubicin. 55 References 1. Badylak SF, Van Vleet JF: Sequential morphologic and clinicopathologic alterations in dogs with experimentally induced glucocorticoid hepatopathy. Am J Vet Res 42:13101318, 1981 2. Bargai U: The effect of xylazine hydrochloride on the radiographic appearance of the stomach and intestine in the dog. Vet Radio! 23:60-63, 1982 3. Bauer AJ, Szurszewski JH: Effect of opioid peptides on circular muscle of canine duodenum. J Physiol (Lond) 434:409-422, 1991 4. Ben Arush MW, Roguin A, Zamir E, et al: Bleomycin and cyclophosphamide toxicity simulating metastatic nodules to the lungs in childhood cancer. Pediatr Hematol Oncol 14:381-386, 1997 5. Brown JL: Incomplete labeling of pharmaceuticals: A list of "inactive" ingredients [letter]. N Engl J Med 309:439-441, 1983 6. Burk RL, AckermanN: The abdomen. In Small Animal Radiology and Ultrasonography. A Diagnostic Atlas and Text, ed 2. Philadelphia, WB Saunders, 1996, pp 215-426 7. Camilleri M, Malagelada JR: Gastric motility in disease. In Akkermans LMA, Johnson AG, Read NW (eds): Gastric and Gastroduodenal Motility. New York, Praeger, 1984, pp 201-232 8. Cook AK, Breitschwerdt EB, Levine JF, et al: Risk factors associated with acute pancreatitis in dogs: 101 cases (1985-1990). JAVMA 203:673-679, 1993 9. Copland VS, Haskins SC, Patz JD: Oxymorphone: Cardiovascular, pulmonary, and behavioral effects in dogs. Am J Vet Res 48:1626-1630, 1987 10. Couto CG: Disorders of the stomach. In Nelson RW, Couto CG (eds): Small Animal Internal Medicine, ed 2. St Louis, Mosby, 1998, pp 420-432 11. Couto CG: Lymphadenopathy and splenomegaly. In Nelson RW, Couto CG (eds): Essentials of Small Animal Internal Medicine. St Louis, Mosby-Year Book, 1992, pp 941-951 12. Crawford MA, Robertson S, Miller R: Pulmonary complications of Cushing's syndrome: Metastatic mineralization in a dog with high-dose chronic corticosteroid therapy. JAm Anim Hosp Assoc 23:85-87, 1987 13. Cuypers MD, Grooters AM, Williams J, et al: Renomegaly in dogs and cats. Part I. Differential diagnoses. Compend Contin Educ Pract Vet 19:1019-1032, 1997 14. Dittert LW: Sprowls' American Pharmacy. An Introduction to Pharmaceutical Techniques and Dosage Forms, ed 7. Philadelphia, JB Lippincott, 1974 15. Dockray GJ: Physiology of enteric neuropeptides. In Johnson LR (ed): Physiology of the Gastrointestinal Tract, ed 3. New York, Raven Press, 1994, pp 169-209

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16. Edelbroek M, Schuurkes J, De Ridder W, et al: Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal region during intraduodenallipid and antral tachygastria in conscious dog. Dig Dis Sci 40:901-911, 1995 17. Edin R, Lundberg J, Terenius L, et al: Evidence for vagal enkephalinergic neural control of the feline pylorus and stomach. Gastroenterology 78:492--497, 1980 18. Eigenmann JE, Venker-van Haagen AJ: Progestagen-induced and spontaneous canine acromegaly due to reversible growth hormone overproduction: Clinical picture and pathogenesis. JAm Anim Hosp Assoc 17:813-822, 1981 19. Evans SM: An approach to interpretation of radiographs. Compend Contin Educ Pract Vet 11:825-829, 1989 20. Farver TB, Haskins SC, Patz JD: Cardiopulmonary effects of acepromazine and of the subsequent administration of ketamine in the dog. Am JVet Res 47:631-635, 1986 21. Feeney DA, Johnston GR: The kidneys and ureters. In Thrall DE (ed): Textbook of Veterinary Diagnostic Radiology, ed 3. Philadelphia, WB Saunders, 1998, pp 466--478 22. Fioramonti J, Bueno L: Gastrointestinal myoelectric activity disturbances in gastric ulcer disease in rats and dogs. Dig Dis Sci 25:575-580, 1980 23. Fosse RT, Grong K, Stangeland L, et al: Anesthetic interaction in cardiovascular research models: Effects of xylazine and pentobarbital in cats. Am J Vet Res 48:211218, 1987 24. Gaynor F, Hoffer RE, Nichols MF, et al: Physiologic features of the canine esophagus: Effects of tranquilization on esophageal motility. Am J Vet Res 41:727-732, 1980 25. Godshalk CP: Common pitfalls in radiographic interpretation of the thorax. Compend Contin Educ Pract Vet 16:731-751, 1994 26. Gronner AT, Ominsky SH: Plain film radiography of the chest: Findings that simulate pulmonary disease. AJR Am J Roentgenol163:1343-1348, 1994 27. Gue M, Fioramonti J, Bueno L: A simple double radiolabeled technique to evaluate gastric emptying of canned food meal in dogs. Application to pharmacological tests. Gastroenterol Clin Bioi 12:425--430, 1988 28. Gunnarsson L, Strandberg A, Brismar B, et a!: Atelectasis and gas exchange impairment during enflurane/nitrous oxide anaesthesia. Acta Anaesthesia! Scand 33:629-637, 1989 29. Hall JA: Diseases of the stomach. In Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 5. Philadelphia, WB Saunders, 1999, pp 1154-1182 30. Hall JA, Washabau RJ: Diagnosis and treatment of gastric motility disorders. Vet Clin North Am Small Anim Pract 29:377-395, 1999 31. Hall JA, Washabau RJ: Gastrointestinal prokinetic therapy: Acetylcholinesterase drugs. Compend Contin Educ Pract Vet 19:615-621, 1997 32. Hall JA, Washabau RJ: Gastrointestinal prokinetic therapy: Dopaminergic antagonist drugs. Compend Contin Educ Pract Vet 19:214-221, 1997 33. Hall JA, Washabau RJ: Gastrointestinal prokinetic therapy: Motilin-like drugs. Compend Contin Educ Pract Vet 19:281-288, 1997 34. Hall JA, Magne ML, Twedt DC: Effect of acepromazine, diazepam, fentanyl-droperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs. Am J Vet Res 48:556-557, 1987 35. Hall JA, Solie TN, Seim HBD, et al: Gastric myoelectric and motor activity in dogs with gastric dilatation-volvulus. Am J Physiol 265(suppl):G646-653, 1993 36. Haskins SC, Farver TB, Patz JD: Cardiovascular changes in dogs given diazepam and diazepam-ketarnine. Am JVet Res 47:795-798, 1986 37. Haskins SC, Patz JD, Farver TB: Xylazine and xylazine-ketarnine in dogs. Am J Vet Res 47:636-641, 1986 38. Hinder RA, San-Garde BA: Gastroduodenal motility-a comparison between domperidone and metoclopramide. S Afr Med J 63:270-273, 1983 39. Hogan PM, Aronson E: Effect of sedation on transit time of feline gastrointestinal contrast studies. Vet Radio! 29:85-88, 1988 40. Huntley K, Frazer J, Gibbs C, et al: The radiological features of canine Cushing's syndrome: A review of forty-eight cases. J Small Anim Pract 23:369-380, 1982 41. Ilkiw JE, Haskins SC, Patz JD: Cardiovascular and respiratory effects of thiopental administration in hypovolemic dogs. Am J Vet Res 52:576-580, 1991

EFFECT OF PHARMACEUTICALS ON RADIOGRAPHS OF ABDOMEN AND THORAX

375

42. Ilkiw JE, Pascoe PJ, Haskins SC, et a!: Cardiovascular and respiratory effects of propofol administration in hypovolemic dogs. Am J Vet Res 53:2323-2327, 1992 43. Ilkiw JE, Pascoe PJ, Haskins SC, et a!: The cardiovascular sparing effect of fentanyl

44. 45.

46. 47.

48.

49. 50. 51. 52. 53. 54. 55.

56.

57. 58.

59. 60.

61.

62. 63.

64.

and atropine, administered to enflurane anesthetized dogs [published erratum appears in Can J Vet Res 59:25, 1995]. Can J Vet Res 58:248-253, 1994 Jacobs G, Knight DH: Change in M-mode echocardiographic values in cats given ketamine. Am JVet Res 46:1712-1713, 1985 Jacobs G, Knight DH: M-mode echocardiographic measurements in nonanesthetized healthy cats: Effects of body weight, heart rate, and other variables. Am J Vet Res 46:1705-1711, 1985 Kemppainen RJ, Lorenz MD, Thompson FN: Adrenocortical suppression in the dog after a single dose of methylprednisolone acetate. Am JVet Res 42:822-824, 1981 Kemppainen RJ, Lorenz MD, Thompson FN: Adrenocortical suppression in the dog given a single intramuscular dose of prednisone or triamcinolone acetonide. Am J Vet Res 43:204-206, 1982 King RR, Mauderly JL, Hahn FF, et a!: Pulmonary function studies in a dog with pulmonary thromboembolism associated with Cushing's disease. J Am Anim Hosp Assoc 21:555-562, 1985 Knapp DW, Richardson RC, DeNicola DB, eta!: Cisplatin toxicity in cats. J Vet Intern Med 1:29-35, 1987 Lieb MS: Hepatobiliary diseases. In Leib MS, Monroe WE (eds): Practical Small Animal Internal Medicine. Philadelphia, WB Saunders, 1997, pp 775-825 Mack RE, Wilson SM, Feldman EC: Diagnosis of hyperadrenocorticism in dogs. Compend Cantin Educ Pract Vet 16:311-329, 1994 Macy DW, Withrow SJ, Hoopes J: Transitional cell carcinoma of the bladder associated with cyclophosphamide administration. JAm Anim Hosp Assoc 19:965-969, 1982 Malbert CH, Hara S, Ruckebusch Y: Early myoelectrical activity changes during gastric or duodenal ulceration in dogs. Dig Dis Sci 32:737-742, 1987 Mauldin GE, Fox PR, Patnaik AK, et a!: Doxorubicin-induced cardiotoxicosis. Clinical features in 32 dogs. J Vet Intern Med 6:82-88, 1992 Mauldin GN, Matus RE, Patnaik AK, et a!: Efficacy and toxicity of doxorubicin and cyclophosphamide used in the treatment of selected malignant tumors in 23 cats. J Vet Intern Med 2:60-65, 1988 McCallum RW, Fink SM, Lerner E, et a!: Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients. Gastroenterology 84:1573-1577, 1983 Melian C, Stefanacci J, Peterson ME, et a!: Radiographic findings in dogs with naturally-occurring primary hypoadrenocorticism. JAm Anim Hosp Assoc 35:208-212, 1999 Meyer DJ: Prolonged liver test abnormalities and adrenocortical suppression in a dog following a single intramuscular glucocorticoid dose. J Am Anirn Hosp Assoc 18:725-727, 1982 Minami H, McCallum RW: The physiology and pathophysiology of gastric emptying in humans. Gastroenterology 86:1592-1610, 1984 Mizumoto A, Fujimura M, Iwanaga Y, et a!: Anticholinesterase activity of histamine H,-receptor antagonists in the dog: Their possible role in gastric motor activity. Journal of Gastrointestinal Motility 2:273-280, 1990 Morrison WB: Principles of treating chemotherapy complications. In Cancer in Dogs and Cats: Medical and Surgical Management. Baltimore, Williams & Wilkins, 1998, pp 387-397 Neer TM: Clinical approach to splenomegaly in dogs and cats. Compend Cantin Educ Pract Vet 18:35-49, 1996 Neumann P, Rothen HU, Berglund JE, et a!: Positive end-expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration. Acta Anaesthesia! Scand 43:295-301, 1999 O'Brien TR: Liver, spleen, and pancreas. In Radiographic Diagnosis of Abdominal Disorders in the Dog and Cat: Radiographic Interpretation. Clinical Signs. Pathophysiology. Philadelphia, WB Saunders, 1978, pp 463-468

376

HALL & WATROUS

65. Ogilvie GK, Moore AS: Nutritional support. In Managing the Veterinary Cancer Patient: A Practice Manual. Trenton, NJ, Veterinary Learning Systems, 1995, pp 124-136 66. Orihata M, Sarna SK: Contractile mechanisms of action of gastroprokinetic agents: Cisapride, metoclopramide, and domperidone. Am J Physiol 266(suppl):G665-676, 1994 67. Overall KL: Behavioral pharmacology. In Clinical Behavioral Medicine for Small Animals. StLouis, Mosby-Year Book, 1997, pp 293-322 68. Owens JM, Biery DN: Gastrointestinal system. In Radiographic Interpretation for the Small Animal Clinician, ed 2. Baltimore, Williams & Wilkins, 1998, pp 223-260 69. Papageorges M: Visual perception and radiographic interpretation. Compend Contin Educ Pract Vet 20:1215-1223, 1998 70. Pascoe PJ, Ilkiw JE, Haskins SC, et a!: Cardiopulmonary effects of etomidate in hypovolemic dogs. Am J Vet Res 53:2178-2182, 1992 71. Peterson JL, Couto CG, Hammer AS, et a!: Acute sterile hemorrhagic cystitis after a single intravenous administration of cyclophosphamide in three dogs [comments]. JAVMA 201:1572-1574, 1992 72. Peterson ME, Steele P: Pituitary-dependent hyperadrenocorticism in a cat. JAVMA 189:680-683, 1986 73. Raffe MR, Hardy R: Anesthetic management of the hepatic patient. Compend Contin Educ Pract Vet 4:841-851, 1982 74. Rees MR, Clark RA, Holdsworth CD, et al: The effect of beta-adrenoceptor agonists and antagonists on gastric emptying in man. Br J Clin Pharmacol 10:551-554, 1980 75. Roberts SM, Lavach JD, Macy DW, et al: Effect of ophthalmic prednisolone acetate on the canine adrenal gland and hepatic function. Am J Vet Res 45:1711-1714, 1984 76. Rothen HU, Sporre B, Engberg G, et a!: Prevention of atelectasis during general anaesthesia [comments]. Lancet 345:1387-1391, 1995 77. Schemann M, Ehrlein HJ: 5-Hydroxytryptophan and cisapride stimulate propulsive jejunal motility and transit of chyme in dogs. Digestion 34:229-235, 1986 78. Scott DW, Greene CE: Iatrogenic secondary adrenocortical insufficiency in dogs. J Am Anim Hosp Assoc 10:555-564, 1974 79. Scott DW, Manning TO, Reimers TJ: Iatrogenic Cushing's syndrome in the cat. Feline Pract 12:30-36, 1982 80. Scrivani PV, Bednarski RM, Myer CW, et a!: Restraint methods for radiography in dogs and cats. Compend Contin Educ Pract Vet 18:899-917, 1996 81. Scully RE, Mark EJ, McNeely BU: Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 35-1982. N Eng! J Med 307:605-614, 1982 82. Serafini G, Cornara G, Cavalloro F, et a!: Pulmonary atelectasis during paediatric anaesthesia: CT scan evaluation and effect of positive end-expiratory pressure (PEEP). Paediatr Anaesth 9:225-228, 1999 83. Shiroma JT, Gabriel JK, Carter RL, et a!: Effect of reproductive status on feline renal size. Vet Radio! Ultrasound 40:242-245, 1999 84. Strombeck DR, Harrold D: Effect of gastrin, histamine, serotonin, and adrenergic amines on gastroesophageal sphincter pressure in the dog. Am J Vet Res 46:16841690, 1985 85. Sullivan SN, Lamki L, Corcoran P: Inhibition of gastric emptying by enkephalin analogue [letter]. Lancet 2:86-87, 1981 86. Summers RW, Flatt AJ: A comparative study of the effects of four motor-stimulating agents on canine jejunal spike bursts. The use of a computer program to analyze spike burst spread. Scand J Gastroenterol 23:1173-1181, 1988 87. Suter PF: Lower airway and pulmonary parenchymal diseases. In Thoracic Radiography. A Text Atlas of Thoracic Diseases of the Dog and Cat. Wettswil, Switzerland, PF Suter, 1984, pp 517-682 88. Suter PF: The radiographic diagnosis of canine and feline heart disease. Compend Contin Educ Pract Vet 3:441-454, 1981 89. Szurszewski JH: Electrical basis for gastrointestinal motility. In Johnson LR (ed): Physiology of the Gastrointestinal Tract. New York, Raven Press, 1981, pp 1435-1466 90. Twedt DC: Disorders of gastric retention. In Kirk RW (ed): Current Veterinary Therapy. VIII. Small Animal Practice. Philadelphia, WB Saunders, 1983, pp 761-765

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91. Ueki S, Seiki M, Yoneta T, et al: Gastroprokinetic activity of nizatidine, a new H 2receptor antagonist, and its possible mechanism of action in dogs and rats. J Pharmacal Exp Ther 264:152-157, 1993 92. Washabau RJ, Hall JA: Cisapride. JAVMA 207:1285-1288, 1995 93. Washabau RJ, Hasler AH: Constipation, obstipation, and megacolon. In August JR (ed): Consultations in Feline Internal Medicine. Philadelphia, WB Saunders, 1996, pp 104--113 94. Washabau RJ, Hall JA: Gastrointestinal prokinetic therapy: Serotonergic drugs. Compend Contin Educ Pract Vet 19:473-480, 1997 95. Watrous BJ, Suter PF: Normal swallowing in the dog: A cineradiographic study. Vet Radiol 20:99-109, 1979 96. Zenoble RD, Kemppainen RJ: Adrenocortical suppression by topically applied corticosteroids in healthy dogs. JAVMA 191:685-688, 1987 97. Zontine WJ: Effect of chemical restraint drugs on the passage of barium sulfate through the stomach and duodenum of dogs. JAVMA 162:878-884, 1973

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