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USING SILDENAFIL TO TREAT A DOG WITH IDIOPATHIC MEGAESOPHAGUS

Article  in  Taiwan Veterinary Journal · April 2020

DOI: 10.1142/S1682648520720014

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 Taiwan Veterinary Journal, Vol. 46, No. 1 (2020) 1–6
DOI: 10.1142/S1682648520720014
by NATIONAL PINGTUNG UNIVERSITY OF SCIENCE & TECHNOLOGY on 05/17/20. Re-use and distribution is strictly not permitted, except for Open Access articles.

USING SILDENAFIL TO TREAT A DOG WITH

IDIOPATHIC MEGAESOPHAGUS

Yi-Ju Tu*, Cheng-Shu Chung† and Lee-Shuan Lin*,‡

*Laboratory of Veterinary Diagnostic Imaging
Department of Veterinary Medicine
College of Veterinary Medicine
National Pingtung University of Science and Technology
Pingtung, Taiwan
†
Laboratory of Veterinary Surgery
Department of Veterinary Medicine
College of Veterinary Medicine
Taiwan Vet J Downloaded from www.worldscientific.com

National Pingtung University of Science and Technology

Pingtung, Taiwan

Received 21 January 2020

Accepted 9 February 2020
Published 30 April 2020

ABSTRACT
A 4-month old, male intact, mixed-breed dog was referred for sudden onset of regurgitation for
two weeks. Thoracic radiographs revealed severe dilatation of esophagus with barium aspi-
ration pneumonia. Idiopathic megaesophagus (IME) was diagnosed after serial laboratory,
endoscopic and computed tomographic examinations. Symptomatic treatment including
medication for pneumonia, feeding through percutaneous endoscopic gastrostomy (PEG) tube
with upright feeding position was performed at ¯rst, but regurgitation persisted. Sildena¯l
(1 mg/kg, PO, BID) was then administrated for two weeks and regurgitation remitted one day
after. Sildena¯l was then tapered to half dose (0.5 mg/kg, PO, BID) for another two weeks.
During following-up thoracic radiography on 10 days after sildena¯l administration, the degree
of esophagus dilation signi¯cantly reduced. The clinical sign was completely resolved without
relapse for more than 300 days. Sildena¯l was reported having inhibitory e®ect of canine
gastric contraction without a®ecting gastric emptying time. This e®ect could ameliorate per-
sisting regurgitation after using PEG feeding directly into the stomach while bypassing the
esophagus.

Keywords: Dog; Idiopathic megaesophagus; Sildena¯l.

‡Corresponding author: Lee-Shuan Lin, Laboratory of Veterinary Diagnostic Imaging, Department of Veterinary Medicine,
College of Veterinary Medicine, National Pingtung University of Science and Technology, No. 1, Shefu Road, Neipu, Pingtung
91201, Taiwan. E-mail: [email protected]

1
 2 Y.-J. Tu, C.-S. Chung & L.-S. Lin

INTRODUCTION was accidentally aspirated during contrast

esophagography. In addition, the result of esophageal
Megaesophagus is a disorder characterized by reduced or
mucosal biopsy showed infectious esophagitis and
absent esophageal peristalsis, which results in regurgi-
the antibiotics treatment was given for 10 days by
by NATIONAL PINGTUNG UNIVERSITY OF SCIENCE & TECHNOLOGY on 05/17/20. Re-use and distribution is strictly not permitted, except for Open Access articles.

tation after food ingestion, and sometimes described as

the referral veterinarian. The respiratory discomfort of
vomit by the owner. Esophageal dilatation is often seen
the dog recovered after treatment but regurgitation
on survey or contrast radiographs. Secondary mega-
persisted.
esophagus is a sequela to di®erent diseases, including
myasthenia gravis, neoplasia, hypoadrenocorticism,
dysautonomia, polyradiculoneuritis, leiomyoma, and
hypothyroidism.1–5 Idiopathic megaesophagus (IME) is Clinical and Diagnostic Findings
often diagnosed by exclusion of the underlying causes. The patient was emaciated (BW: 4.65 kg, body condi-
Treatments for secondary megaesophagus generally tion score: 2/9) on the ¯rst day presented. Harsh lung
focus on correcting the primary causes, whereas IME has sounds and moderately loss of skin elasticity due to de-
no curative treatment. Treatments for IME are usually hydration were noted upon physical examination. Tho-
symptomatic such as upright feeding position, and racic radiographs revealed severe dilatation of esophagus
treating or preventing aspiration pneumonia.6 Surgical causing ventral displacement of the trachea and heart.
or endoscopic placement of gastrostomy feeding tube The severity of esophageal dilation was determined by
Taiwan Vet J Downloaded from www.worldscientific.com

can be considered to bypass the esophagus if regurgita- relative esophageal diameter (RED) to minimize the
tion remains after symptomatic treatment.7 However, di®erences in fast growing puppy as described in the
many dogs still have regurgitation even though all previous study.13 The esophageal diameter (ED) was
nutritional needs are given through a gastrostomy tube, measured in each radiograph at its widest point, per-
and eventually develops aspiration pneumonia. The pendicularly to the esophageal longitudinal axis, at the
prognosis of IME is guarded to poor, with median sur- level of its luminal surface. The thoracic inlet (TI) was
vival time of 90 days and 16 days if complicated with also measured in the same radiograph, from the mid-
aspiration pneumonia.8 point of ventral aspect of the 7th cervical vertebrae to
Sildena¯l is a selective phosphodiesterase-type 5 in- the inner aspect of the manubrium at the point of nar-
hibitor that reduces the intracellular cyclic guanosine rowest diameter of the TI. The RED, calculated by ED/
monophosphate (cGMP) degradation and indirectly TI ratio, was 1.11 at the ¯rst presentation (Fig. 1(A)).
potentiates the action of nitric oxide (NO). NO is a Barium aspiration pneumonia was also con¯rmed by the
neurotransmitter that plays an important role of smooth interstitial to patchy alveolar pattern in the left lung
muscle relaxation at vessel and gastrointestinal (GI)
lobes, and amorphous mineral opacity materials dis-
tract.9,10 Sildena¯l has inhibitory e®ects on lower
tributing along the bronchi and bronchioles of all lung
esophageal sphincter and gastric slow wave amplitude,
lobes and mediastinal/tracheobronchial lymph nodes
fundic tone and antral motility, thus facilitates the
(Fig. 2(A)). Although additional diagnostic to deter-
emptying of esophagus and reducing gastric contraction,
mine the primary causes was recommended, yet it was
resulting in reducing regurgitation and relieving mega-
declined by the owner. Conservative treatments in-
esophagus.11,12 Here, we report a dog with IME and
cluding oral medication such as proton-pump inhibitors
successfully treated by combination of sildena¯l with
and antibiotics with upright standing feeding position
supportive treatment and gastrostomy tube feeding.
were prescribed.
Two days later, the patient was presented again
without improvement in clinical signs. Severe leukocy-
CASE PRESENTATION tosis (79,770/l; reference interval 5050–16,760/l) with
worsen aspiration pneumonia were noted (Fig. 2(B)).
Case History Computed tomography (CT) scan and esophagogas-
A four-month old, male intact, mix breed dog was pre- troduodenoscopy that were performed on the same day
sented to Veterinary Medical Teaching Hospital of Na- revealed extensive dilation of the esophagus from TI to
tional Pingtung University of Science and Technology the level of gastroesophageal junction, and excluded
for sudden onset of regurgitation for two weeks. Barium neoplasia, anatomical diseases and severe esophagitis
esophagography, esophagogastroduodenoscopy with (Fig. 3). Other primary causes of megaesophagus, such
esophageal mucosal biopsy, and thyroid screening test as neuromuscular diseases, endocrine disorders and
were performed by the referral veterinarian. The barium toxicosis were excluded by the patient's clinical signs
 Sildena¯l to Treat a Dog with Idiopathic Megaesophagus 3
by NATIONAL PINGTUNG UNIVERSITY OF SCIENCE & TECHNOLOGY on 05/17/20. Re-use and distribution is strictly not permitted, except for Open Access articles.
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Fig. 1 Lateral projection of thoracic radiographs from day 1 to 56. The ED was measured in each radiograph at its widest point,
perpendicularly to the esophageal longitudinal axis, at the level of its luminal surface. The TI was also measured on the same
radiograph, from the mid-point of ventral aspect of the 7th cervical vertebrae to the inner aspect of the manubrium at the point of
narrowest diameter of the TI. The relative ED (RED) was calculated, using the ED/TI ratio. Radiograph on day 1 (A) and day 9
(B) revealed moderate amount of barium distributed along the bronchi and bronchioles and severe dilation of esophagus (between
white arrows) with 1.11 RED and 1.07 RED, respectively. (C) Contrast esophagogram on day 25. ED (between white arrows)
decreased to 0.58 RED. (D) No signs of esophageal dilation and the amount of barium decreased and mostly migrated to regional
lymph nodes on day 56.

Fig. 2 Ventrodorsal projection of thoracic radiographs of day 1 (A), day 3 (B) and day 56 (C). (A) On day 1, interstitial to
patchy alveolar pattern of the left lung lobes, with moderate amount of amorphous mineral opacity materials distributed along the
bronchi and bronchioles in all lung lobes and mediastinal/tracheobronchial lymph nodes, indicating barium aspiration pneumonia.
The alveolar pattern increased signi¯cantly in the left lung lobes on day 3 (B). The amount of amorphous mineral opacity
materials decreased with time compared from day 1 to 56. On day 56 (C), no alveolar pattern was noted, while mild interstitial
pattern still noted in the left lung lobes.
 4 Y.-J. Tu, C.-S. Chung & L.-S. Lin

during this period. Although the respiratory discomfort

was not noted, the thoracic radiography still revealed a
persisted pneumonia. On the postoperative day 3, dry
food powder mixed with liquid diet were fed through
by NATIONAL PINGTUNG UNIVERSITY OF SCIENCE & TECHNOLOGY on 05/17/20. Re-use and distribution is strictly not permitted, except for Open Access articles.

PEG tube (total dry food powder 42 g with liquid diet

48 ml, 6 times/day), however, 5 times of regurgitation
were noted on that day. On postoperative day 4, sil-
dena¯l (1 mg/kg, PEG feeding, BID) was prescribed
with the same supportive treatment. The regurgitation
was decreased to four times on the same day, and no
regurgitation noted on day 5. On postoperative day 6,
Fig. 3 CT of sagittal plane reconstruction of thoracic cavity.
the RED reduced to 1.07 and the patient was dis-
The image reveals dilated esophagus (asterisk) from TI to
charged. The sildena¯l (1 mg/kg, PEG feeding, BID)
gastroesophageal junction without signs of congenital or neo-
was continued after getting discharged, and the patient
plastic obstructive disease, the barium accumulation at the
area dorsal to the heart base and caudal to the trachea carina is was fed half of the diet through the mouth and the other
noted. half through the PEG tube. Regurgitation did not re-
lapse after discharge and the patient returned to normal
feeding position a week later.
Taiwan Vet J Downloaded from www.worldscientific.com

and history, therefore the diagnosis of idiopathic mega- Follow-up contrast esophagography was taken two
esophagus was made.
weeks (day 25) after discharge, the RED signi¯cantly
decreased to 0.58. Sildena¯l was tapered then, from
1 mg/kg BID to 0.5 mg/kg BID for two weeks, before
Treatments and Outcome withdrawal. On day 56, the dog weighted 10 kg equiv-
Enteral hyperalimentation was done via placing percu- alent to 215% body weight gain compared with the ¯rst
taneous endoscopic gastrostomy (PEG) feeding tube visit. Thoracic radiographs revealed no signs of esoph-
during esophagogastroduodenoscopy. On the ¯rst two ageal dilation and RED could not be calculated
days, postoperative, liquid diet (Recovery Liquid, Royal (Fig. 1). Also, the amount of amorphous mineral
Canin, France) was given through PEG tube (total opacity materials distributed along the bronchi and
72 ml approximately 15 Kcal/kg, 8 times/day) and bronchioles decreased to a minimum and now mostly
maintained 30 minutes postprandial upright feeding presented in regional lymph nodes, with no respiratory
position. Moreover, symptomatic therapy (Table 1) by signs (Fig. 2). The PEG tube was removed since day 56,
omeprazole (0.5 mg/kg, PEG feeding, SID), amoxicillin/ without disease relapse noticed for the following 11
clavulanate (15 mg/kg, IV, BID) and ranitidine (1 mg/ months. The major events of this case are shown in
kg, IV, BID) was given. Regurgitation was noted once timeline (Fig. 4).

Table 1. Therapy Protocol for the Canine Idiopathic Megaesophagus During Hospitalization.

Agents Dose Route Day of Administration

Medications
Omeprazole 0.5 mg/kg SID PEG tube 1–6
Amoxicillin/Clavulanic acid 15 mg/kg BID IV 1–6
Ranitidine 1 mg/kg BID IV 1–6
Sildena¯l 1 mg/kg BID PEG 4–6
Calorie supplement
Liquid diet 0.5 RER/day Q2h PEG tube 1–2
Mixture of liquid diet and dry food 0.75–1.5 RER/day Q3h* PEG tube 3–6

Notes: *0.75 RER per day gradually increased to 1.5 RER per day in four days, and diet intake frequency
gradually decreased from 8 to 4 times per day.
SID, once per day, BID, twice per day, PEG, giving through percutaneous endoscopic gastrostomy feeding tube,
IV, intravenous, RER and resting energy requirement.
 Sildena¯l to Treat a Dog with Idiopathic Megaesophagus 5
by NATIONAL PINGTUNG UNIVERSITY OF SCIENCE & TECHNOLOGY on 05/17/20. Re-use and distribution is strictly not permitted, except for Open Access articles.

Fig. 4 A brief timeline of the case treatment. Regurgitation presented in the ¯rst attendance remitted after sildena¯l was
prescribed for 1 day. Gray bar stands for conservative treatments for megaesophagus. No relapse of clinical signs was noted after all
treatments stopped for two weeks. The PEG feeding tube was removed at the last visit (day 56).

DISCUSSION could increase the risk of gastro-esophageal re°ux. Un-

like humans and cats, the dogs' esophagus are mainly
A recent study demonstrated that sildena¯l could add in
composed of striated muscle,20 thus sildena¯l should not
the clinical treatment of congenital IME in dogs.12 They
Taiwan Vet J Downloaded from www.worldscientific.com

reduce esophageal peristaltic contractions in dogs,

treated the dogs with sildena¯l 1 mg/kg, BID, for two
rather could reduce lower esophageal sphincter tone and
weeks in combination with upright feeding position,
facilitate the emptying of the esophagus.12 Therefore,
with signi¯cantly increased weight gain and reduced
the previous report12 suggested to remain upright feed-
regurgitation episodes.12 In this case, the clinical signs
ing position for longer duration to prevent the regurgi-
and radiographic features were similarly improved since
tation from the dilated lower esophageal sphincter.
sildena¯l was prescribed 1 mg/kg, BID. Although the
However, in this case, the dog returned to normal oral
dog was capable of eating with normal feeding position
feeding position within a week after discharge without
after two weeks without regurgitation, the esophagus
relapse of regurgitation, suggesting yet unknown mech-
was still dilated. As a result, the sildena¯l was tapered
anism of sildena¯l for improving canine IME clinical
for another two weeks before withdrawal which was
signs.
di®erent from that of the previous study.12 Finally, the
Instead of a®ecting the lower esophageal sphincter,
esophagus returned to normal without relapsing. Our
sildena¯l inhibits the gastric motility.11 Gastric myo-
results indicate that sildena¯l is e®ective to treat IME
electrical activity consists of two components: slow
and extend the medication period may improve the
waves and spike potentials. The interstitial cells of Cajal
outcome.
in the GI system generate slow waves potential that
Sildena¯l is a vasodilator mainly used to treat pul-
leads to contraction of smooth muscles.21 Sildena¯l sig-
monary hypertension in humans and dogs,14,15 as well as
in cats.16 Sildena¯l also induces smooth muscle relaxa- ni¯cantly reduces the amplitude of gastric slow waves,
tion of the GI system.9,17–19 The esophageal walls of fundic tone and antral contractions but does not
humans and cats are similar, i.e. the proximal one-third increases gastric emptying time. As a result, sildena¯l
is striated muscle and transits into smooth muscle till induces gastric relaxation in the fasting state but does
the lower esophageal sphincter.17,20 Therefore, the not enhance the relaxation in the postprandial state.11
smooth muscular relaxation e®ect of sildena¯l acts on By reducing the contraction of stomach without a®ect-
not only lower esophageal sphincter, but also on the ing gastric emptying time, sildena¯l may ameliorate re-
distal two-third esophagus of humans and cats. In pre- gurgitation secondary to IME. This may explain how
vious studies, sildena¯l signi¯cantly reduced the ampli- sildena¯l e®ects in this case, especially when foods al-
tude of peristaltic contractions of the esophageal ready bypassed the esophagus and lower esophageal
body,17,18 and could be useful in treating di®use esoph- sphincter through PEG tube feeding. Moreover, the ra-
ageal spasm and segmental aperistalsis of humans and diographic features of dilated esophagus were signi¯-
cats. However, this mechanism may sometimes be det- cantly improved both in the previous report12 using
rimental to treat regurgitation in megaesophagus cases sildena¯l and in our case despite the slightly longer pe-
because, while reducing muscle tone of lower esophageal riod of treatments. However, the mechanism of how the
sphincter results in easier transit of food into stomach, it degree of esophageal distension alters remains uncertain.
 6 Y.-J. Tu, C.-S. Chung & L.-S. Lin

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by NATIONAL PINGTUNG UNIVERSITY OF SCIENCE & TECHNOLOGY on 05/17/20. Re-use and distribution is strictly not permitted, except for Open Access articles.

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