To determine whether delivery of compounded liquid sildenafil directly to the stomach of dogs with megaesophagus (ME) would affect esophageal clearance, regurgitation frequency, body weight, or quality of life.
10 client-owned otherwise healthy dogs with stable ME.
A randomized crossover study was performed. Dogs received either sildenafil (1 mg/kg, PO, q 12 h) or a placebo for 14 days, followed by a 7-day washout period, then the opposite treatment for 14 days. Esophageal clearance time was assessed by means of videofluoroscopy prior to treatment and on day 1 of each treatment period. Owners maintained logs of regurgitation episodes and quality of life.
Compounded liquid sildenafil moved into the stomach during 21 of 30 (70%) videofluoroscopy sessions. Sildenafil resulted in a significant reduction in the number of regurgitation episodes (median, 3.5 episodes/wk; range, 0 to 14.5 episodes/wk), compared with baseline (median, 6.5 episodes/wk; range, 1.5 to 19.5 episodes/wk) and the placebo (median, 4 episodes/wk; range, 0 to 28 episodes/wk), and a significant increase in body weight (median, 22.05 kg; range, 6 to 26.3 kg), compared with baseline (median, 21.55 kg; range, 5.1 to 26.2 kg) and the placebo (median, 22.9 kg; range, 5.8 to 25.9 kg). There were no differences in esophageal clearance times or quality-of life-scores between sildenafil and placebo.
Although significant differences with placebo administration were identified, clinically relevant improvements were not seen with the use of compounded liquid sildenafil in dogs with ME.
To compare the volume of saline (0.9% NaCl) solution required to reach a maximum intraluminal peristaltic pressure of 25 mm Hg in dogs of various sizes.
25 grossly normal jejunal segments from 6 canine cadavers < 20 kg (small dogs) and 25 segments from 5 cadavers ≥ 20 kg (large dogs).
Jejunal specimens were obtained within 1.5 hours after euthanasia. Harvested tissue was transected into 12-cm-long segments, mesentery was trimmed, and each segment was measured from the antimesenteric to mesenteric serosal edges. A 10-cm segment was isolated with Doyen forceps, securing a pressure sleeve within the lumen. Intraluminal saline was infused, and the volume was recorded when a pressure of > 25 mm Hg was achieved. Data were analyzed only from specimens in which the pressure remained between 24 and 26 mm Hg for > 5 seconds.
Mean ± SD intestinal measurement for large dogs (17.82 ± 1.44 mm) was greater than that for small dogs (12.38 ± 1.38 mm) as was the volume of saline solution infused (17.56 ± 7.17 mL vs 3.28 ± 1.41 mL, respectively). The volume infused increased by 1.31 mL (95% CI, 1.08 to 1.18) for every 1-mm increase in intestinal measurement and by 1.06 mL (95% CI, 1.052 to 1.068) for every 1-kg increase in body weight.
CONCLUSIONS AND CLINICAL RELEVANCE
The volume of saline solution used for intestinal leak testing should be determined on the basis of patient intestinal measurement or body weight. In vivo studies are necessary to establish the optimal volume for intestinal leak testing.
To determine the feasibility of sidestream dark field (SDF) video microscopy for the evaluation of the jejunal microvasculature of healthy dogs.
30 healthy sexually intact female shelter dogs anesthetized for ovariohysterectomy.
Preoperative physical and clinicopathologic assessments were performed to confirm health status. Then healthy dogs were anesthetized, and the abdomen was incised at the ventral midline for ovariohysterectomy and jejunal microvasculature evaluation. An SDF video microscope imaged the microvasculature of 2 sites of a portion of the jejunum, and recorded videos were analyzed with software capable of quantitating parameters of microvascular health. Macrovascular parameters (heart rate, respiratory rate, and hemoglobin oxygen saturation) were also recorded during anesthesia.
Quantified jejunal microvascular parameters included valid microvascular density (mean ± SD, 251.72 ± 97.10 μm/mm), RBC-filling percentage (66.96 ± 8.00%), RBC column width (7.11 ± 0.72 μm), and perfused boundary region (2.17 ± 0.42 μm). The perfused boundary region and RBC-filling percentage had a significant negative correlation. Strong to weak positive correlations were noted among the perfused boundary regions of small-, medium-, and large-sized microvessels. No significant correlations were identified between microvascular parameters and age, body weight, preoperative clinicopathologic results, or macrovascular parameters.
CONCLUSIONS AND CLINICAL RELEVANCE
Interrogation of the jejunal microvasculature of healthy dogs with SDF video microscopy was feasible. Results of this study indicated that SDF video microscopy is worth additional investigation, including interrogation of diseased small intestine in dogs.
Objective—To describe the in vitro effects of bethanechol on contractility of smooth muscle preparations from the small intestines of healthy cows and define the muscarinic receptor subtypes involved in mediating contraction.
Sample Population—Tissue samples from the duodenum and jejunum collected immediately after slaughter of 40 healthy cows.
Procedures—Cumulative concentration-response curves were determined for the muscarinic receptor agonist bethanechol with or without prior incubation with subtype-specific receptor antagonists in an organ bath. Effects of bethanechol and antagonists and the influence of intestinal location on basal tone, maximal amplitude (Amax), and area under the curve (AUC) were evaluated.
Results—Bethanechol induced a significant, concentration-dependent increase in all preparations and variables. The effect of bethanechol was more pronounced in jejunal than in duodenal samples and in circular than in longitudinal preparations. Significant inhibition of the effects of bethanechol was observed after prior incubation with muscarinic receptor subtype M3 antagonists (more commonly for basal tone than for Amax and AUC). The M2 receptor antagonists partly inhibited the response to bethanechol, especially for basal tone. The M3 receptor antagonists were generally more potent than the M2 receptor antagonists. In a protection experiment, an M3 receptor antagonist was less potent than when used in combination with an M2 receptor antagonist. Receptor antagonists for M1 and M4 did not affect contractility variables.
Conclusions and Clinical Relevance—Bethanechol acting on muscarinic receptor sub-types M2 and M3 may be of clinical use as a prokinetic drug for motility disorders of the duodenum and jejunum in dairy cows.
Objective—To determine effects of reactive oxygen metabolites (ROMs), with and without flunixin meglumine, on equine right ventral colon (RVC) in vitro.
Animals—18 healthy horses and ponies.
Procedures—In 3 groups of 6 animals each, short-circuit current and conductance were measured in RVC mucosa in Ussing chambers. The 3 groups received physiologic saline (0.9% NaCl) solution, IV, 10 minutes before euthanasia and tissue incubation in Krebs-Ringer-bicarbonate (KRB) solution; flunixin meglumine (1.1 mg/kg, IV) 10 minutes before euthanasia and tissue incubation in KRB solution; or physiologic saline solution, IV, 10 minutes before euthanasia and incubation in KRB solution with 2.7 × 10−5M flunixin meglumine. Incubation conditions included control (no addition) and ROM systems, including addition of 1mM xanthine and 80 mU of xanthine oxidase (to produce the superoxide radical), 1mM H2O2, and 1mM H2O2 and 0.5mM ferrous sulfate (to produce the hydroxyl radical).
Results—All ROMs that were added or generated significantly increased the short-circuit current except in tissues coincubated with flunixin meglumine, and they induced mild epithelial vacuolation and apoptosis, but did not disrupt the epithelium nor change conductance, lactate dehydrogenase release, or [3H]mannitol flux.
Conclusions and Clinical Relevance—Responses to ROMs could be attributed to increased chloride secretion and inhibited neutral NaCl absorption in equine RVC, possibly by stimulating prostaglandin production. The ROMs examined under conditions of this study could play a role in prostaglandin-mediated colonic secretion in horses with enterocolitis without causing direct mucosal injury.