MEGAESOPHAGUS - GREAT DANEUpdate - A Top Health Concern in Great Danes - Purina Pro Club
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GREAT DANE Update
A NESTLÉ PURINA PUBLICATION DEDICATED TO GREAT DANE ENTHUSIASTS VOLUME 19 | FALL 2021
MEGAESOPHAGUS
A Top Health Concern in Great Danes
FALL 2021
GREAT DANE PUPPIES WITH
MEGAESOPHAGUS
MAY BENEFIT FROM NEW TREATMENT
It had been 33 years since Sterling should, and there was an odd slosh-
Moffat had produced a puppy with ing or clicking sound in his throat.”
megaesophagus. Not a condition Megaesophagus is one of the top
easily forgotten, she recognized health concerns in Great Danes, says
the clinical signs right away in a Neil O’Sullivan, PhD, co-chair of the
5-week-old blue male puppy from Health and Research Committee of
her 2018 litter. the Great Dane Club of America.
“He regurgitated his food and had Although no statistics are available,
“As with any heritable a bullfrog throat,” says Moffat of Lyme, Great Danes are cited in a survey of
New Hampshire, who has bred Great owners conducted from December
trait in a breed with a lot Danes under the Sterling prefix since 2014 to May 2015 as one of the breeds
1973. “Milk came out of his nose as he most often affected by congenital
of genetic diversity, some nursed. He was not thriving as puppies megaesophagus.
lines see megaesophagus
very frequently and others
never report seeing it.”
Neil O’Sullivan, PhD, co-chair of the
Health and Research Committee of
the Great Dane Club of America
“Wabi-Sabi” at 6 weeks of age had just begun showing clinical signs of congenital
idiopathic megaesophagus.
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GREAT DANE Update
“As with any heritable trait in a breed
with a lot of genetic diversity, some LEARN MORE AT CANINE UPRIGHT BRIGADE
lines see megaesophagus very
frequently and others never report The homepage of the Canine Upright Brigade website promises that
seeing it. It is a serious challenge in megaesophagus is not a death sentence and things will get better.
the breed, and since the affected A comprehensive resource for owners of dogs with megaesophagus
puppies are typically diagnosed at due to various conditions, Canine Upright Brigade offers information,
3 to 5 weeks of age, the burden inspiration and provides support including assistance with veterinary
has been heavy for breeders,” Dr. expenses and supplies such as a Bailey chair to qualified dog owners.
O’Sullivan says. A private Facebook group with over 9,000 members offers real-time
Congenital idiopathic megaesoph- mentorship and opportunities to share experiences.
agus, which is usually diagnosed
around weaning, literally means “a
huge esophagus.” The esophagus is whom she named “Wabi-Sabi” after
a long, slender muscular tube that the Japanese philosophy of finding
carries food from the mouth to the beauty in imperfection, was malnour-
stomach, but in puppies with megae- ished and smaller than his littermates.
sophagus the enlarged tube fails to Moffat took Wabi-Sabi to the veter-
contract normally thus hindering the inarian, who took barium radiographs
transit of food. Swallowing depends of the esophagus. Liquid barium, a
on the synchronized constriction of metallic compound that shows up
the esophagus with the opening and on radiographs, appears as a bright
closing of the lower esophageal ball in the stomach of normal puppies.
sphincter (LES) that separates the In puppies with megaesophagus, the
esophagus from the stomach. barium may pool and balloon at the
“The LES in a normal dog relaxes LES. In some affected puppies, the
and opens in response to swallow- barium stops midway down the
ing, which increases pressure in the esophagus due to a constricting
esophagus,” explains Jillian Haines, ring anomaly of the blood vessels
DVM, MS, DACVIM, associate profes- of the heart known as persistent
sor in small animal internal medicine right aortic arch. These cases re-
at Washington State University. “In quire surgical treatment.
dogs with megaesophagus, the LES The radiographs taken of Wabi-Sabi’s
does not open appropriately to allow esophagus showed the barium stopping
the passage of food out of the at the LES, confirming a diagnosis
esophagus and into the stomach.” of megaesophagus. Left untreated,
As a result, food is trapped in the puppies like Wabi-Sabi often die from
esophagus until it is regurgitated. malnutrition or pneumonia second-
Unlike vomiting, regurgitation happens ary to aspirating regurgitated food.
suddenly and effortlessly. Regurgitation Prognosis for resolution of congenital
usually occurs soon after a puppy megaesophagus in puppies tradition-
eats but can also happen hours later. ally is 20 to 40 percent. If puppies
Regurgitated food does not contain receive proper nutrition and care,
stomach bile, though it may be partially some outgrow the condition.
digested from salivary enzymes.
Puppies with megaesophagus may NOVEL TREATMENT FOR
cry from pain as the esophagus MEGAESOPHAGUS
stretches when food is trapped. They Medical management of megae-
also may cry from being hungry due sophagus is challenging. Medications
to most of the food they eat never that are effective in stimulating
reaching the stomach. Moffat’s puppy, esophageal movement in humans
3
FALL 2021
A GENETIC STUDY OF MEGAESOPHAGUS IN GREAT DANES
The genetic cause(s) of congenital idiopathic megae- Dr. Clark is generating genetic profiles from Great
sophagus (CIM) likely varies on a breed-by-breed basis. Danes using a new genetic processing technology called
Geneticist Leigh Anne Clark, PhD, associate professor low-pass whole genome sequencing (LP-WGS). The
at Clemson University, has been studying the disorder three-step process starts with LP-WGS followed by
in Great Danes and German Shepherd Dogs. imputing missing data and then conducting genome-wide
“The genetic complexity of megaesophagus relates to association analyses with millions of genetic variants.
some risk factors that may be shared across breeds and “We’ve performed the low-pass sequencing on 83
other factors may be unique to a breed,” Dr. Clark says. Great Danes,” she says. “This process produces a large
Dr. Clark is the lead investigator of research to identify amount of data that will take us closer to the causal
genetic risk factors contributing to gastrointestinal mutation.”
motility disorders in Great Danes. The two-year study, The findings in Great Dane also are being compared
funded by the AKC Canine Health Foundation and with Dr. Clark’s earlier work in German Shepherd Dogs
sponsored by the Great Dane Club of America Charitable showing an association between megaesophagus and
Trust, aims to determine if there is a genetic link between a region of chromosome 12.
CIM and gastric dilatation-volvulus (GDV), or bloat. Great Dane breeders and owners are encouraged to
Based on her earlier work in Great Danes, Dr. Clark help advance the research. For more information about
is studying a narrow region of chromosome 6 that was participating in the study, contact Sarah Murphy at Clemson
shown to be a risk factor for CIM. Meanwhile, she is University. Note that DNA samples are needed from:
searching for additional genomic regions that contribute • Dogs greater than 5 years of age with no history of
to CIM to determine if there is an association between megaesophagus or bloat, as well as no known relatives
CIM and GDV due to shared genetic risk factors impacting (parents, littermates or offspring) diagnosed with
gastrointestinal motility. megaesophagus or bloat. Priority is given to dogs
CIM is an esophageal disorder in which poor contrac- that have not had prophylactic gastropexy.
tility causes enlargement of the esophagus. GDV is • Dogs that have survived a bloat episode.
characterized by gas filling the stomach like a balloon • Dogs that have been diagnosed with idiopathic
— gastric dilatation — and then twisting 180 degrees megaesophagus, not due to persistent right aortic
clockwise cutting off an escape for the gas through the arch (PRAA), as a puppy via a barium radiograph
esophagus or duodenum — gastric dilatation-volvulus. or other X-ray method.
are not effective in dogs because Haines explains. “Even with upright
the canine esophagus is made of feedings, food is retained within the
striated muscle rather than smooth esophagus that is later regurgitated.”
muscle as in humans. Similarly, med- Breeders may choose to euthanize
ications used to treat acid reflux or affected puppies rather than face an
vomiting are not effective as they uncertain survival. That’s what Moffat
stimulate the LES to remain closed. did 33 years ago. “I had a necropsy
Owners of affected puppies turn to done on an affected puppy,” she says.
feeding their dog in an upright posi- “His esophagus looked like a bag full
tion so gravity can help push the food of food that took up his entire chest.”
downward. Special feeding chairs, Moffat had hope that a new treat-
called Bailey chairs, can be fitted to ment could potentially help Wabi-Sabi.
an individual dog. After completing “I had heard there was a new treatment
a meal, a dog stays in the chair for and told my veterinarian I wanted to
about 10 to 20 minutes, though try using sildenafil (Viagra®),” she says.
sometimes even this doesn’t work. “She looked at me like I had two
“In many dogs with megaesoph- heads. I went home and forwarded
agus, the LES does not open at the the research article to her. After looking
appropriate time or sufficiency,” Dr. into it, she agreed we should try it.”
4
GREAT DANE Update
Published in Veterinary Record in “Fortunately, all the enrolled puppies
April 2017, a clinical trial performed by fully recovered after the end of the
researchers at the University of Parma clinical trial and no longer needed
in Italy showed successful treatment any further treatment,” Dr. Menozzi
of puppies with oral sildenafil citrate. says. “Thirty days after the conclusion
Their study included 21 puppies, the of the trial those in the sildenafil
majority of which were Great Danes, group had only sporadic regurgitation
with congenital megaesophagus. episodes, and after two to three
Ranging from 22 to 45 days of months, they were completely healthy.
age, the puppies were randomly “Congenital idiopathic megaesoph-
assigned to a group that received agus is probably related to delayed
two times a day a sildenafil liquid development of neurons controlling
mixture at a rate of 1 milligram per the motility of the esophagus, thus
kilogram (0.45 milligram per pound) affected puppies have a good chance
or a placebo. All puppies were held to fully recover over time. Sildenafil
in an upright position for 10 minutes treatment has the goal of improving
following each feeding. the clinical signs and hastening the
“We thought that sildenafil might recovery. It also minimizes the risk
be effective by relaxing the lower of aspiration pneumonia, the main
esophageal sphincter smooth muscle,” cause of death in these puppies
explains lead researcher Alessandro together with euthanasia.”
Menozzi, DVM, PhD, associate pro-
fessor of veterinary pharmacology NEW OUTLOOK FOR
and toxicology at the University AFFECTED PUPPIES
of Parma. “This could facilitate the Unlike the reduced episodes of
passage of food into the stomach regurgitation seen immediately in the
and relieve the pressure on the treated puppies at the University of
esophageal wall.” Parma, Moffat did not see quick results
The results were immediate. “The
number of regurgitation episodes
were notably decreased in puppies of
the sildenafil treatment group after
the first dose,” Dr. Menozzi says.
“Regurgitation episodes ceased
almost completely after 10 days of
sildenafil administration, and no
relapses were observed up to one
month after the end of the treatment.
The puppies without sildenafil contin-
ued to regurgitate, though the rate of
regurgitation gradually decreased.”
The puppies receiving sildenafil
also gained significantly more weight.
Radiographs of their esophagus
taken at the start and finish of the
study showed that the esophageal
diameter had narrowed significantly;
in contrast, the esophageal diam-
eter had grown even larger in the
placebo group puppies. No side At 10 months of age, Wabi-Sabi, right, had caught up in size to his littermates,
effects of sildenafil were noted. including his sister, “Phaedra.”
5
FALL 2021
with Wabi-Sabi. “This may have to allow the meal through. Once the
been because he was treated with sildenafil is in the stomach, it can
a tablet form of sildenafil,” she says. begin working to relax the LES.”
“The biggest variable affecting the Dr. Haines speculates that the timing
success of sildenafil is its ability to of dosing is linked to success. The Ital-
get the drug into the stomach for ian study used twice-daily dosing
absorption,” explains Dr. Haines. based on published studies in humans
“Just like food and water can get and cats. “Dogs with megaesopha-
retained in the esophagus, so can gus may eat many meals a day,” she
the medication.” says. “The sildenafil would therefore
A recent study at Washington only be effective for two of the meals.”
State (see Abstract G104) found After changing to a liquid mixture
short-term success giving dogs with of sildenafil and giving it three times a
LOOKING TO REPRINT?
megaesophagus liquid sildenafil. “We day right before meals, Moffat began
found that giving liquid sildenafil to see improvement in Wabi-Sabi.
Great Dane Update articles may
diluted to a 5-milliliter volume in an “The nighttime regurgitation con-
be reprinted provided the article is
upright position followed by a meal tinued for a few weeks before it
used in its entirety and in a pos-
resulted in good delivery of the drug resolved, but the daytime regurgi-
itive manner. To request permis-
into the stomach,” Dr. Haines says. tation pretty much stopped,” she
sion to reprint this article, please
“The liquid sildenafil moved to just says. “He began to gain weight, and
contact the editor at: Barbara.
above the LES or directly into the by 8 1/2 weeks of age, he was almost
Fawver@purina.nestle.com. Re-
stomach in a small number of dogs. caught up to his littermates.”
prints should include the following
When a meal was given, the LES At age 4 months, Wabi Sabi was
attribution: Used with permission
relaxed to move the liquid through doing well. “When I was sure he was
from the Great Dane Update,
to the stomach though not enough stable, I let him go to a home,” Moffat
Nestlé Purina PetCare.
As an adult dog, Wabi-Sabi, renamed “Cos” by his new owner, no longer needs
medications or special feeding accomodations for megaesophagus.
6
GREAT DANE Update
says. “At that time, he was still get-
ting sildenafil and was eating from
an elevated feeder.”
Wabi Sabi — now called “Cos”
(Sterling’s Wabi-Sabi v. Bgdawgs)
— appears healthy. “His new owner
had him radiographed at 7 months
of age and his esophagus was normal
so she weaned him off the sildenafil,”
says Moffat. “At 1 year, he was radio-
graphed because he ate a sock and
was still normal. He is now 3 years
old and lives a normal life with no
medications or special feeding
accommodations.”
Although sildenafil is still in the
early stages of research, it may not
be a cure-all for congenital megae-
sophagus. “Sildenafil is likely most
effective in dogs with moderate
disease severity and less retention
of food material,” Dr. Haines says.
“Dogs that have severe disease are
often retaining a lot of food and liq-
uid in the esophagus. This material
blocks the sildenafil from reaching
the stomach to be effective. How- agus as a death sentence. I figured I
ever, I have still seen improvement was giving her a loving home for the
in these dogs with longer term use.” last few months of her life. However,
Dr. Haines became interested in that was not Cake’s plan. She was a
megaesophagus as a veterinary fighter, so I decided to fight with her.
resident when she adopted a mixed- The entire hospital rallied around us,
breed dog with the condition. “Every and Cake thrived,” she says. “Cake
dog with this disease is different,” lived eight great years with the dis-
she says. “What works for one dog ease before passing away in 2020
may not work at all for another. from cancer.”
Owners should work with their vet- Although there is much to learn
erinarian to find the best treatment about effective treatments for dogs
for their dog.” with congenital megaesophagus,
She also advocates optimism. “Many sildenafil provides a promising
dogs recover and go on to live full possibility. n
lives with megaesophagus. During an
initial diagnosis, dogs may be feel-
ing their worst and likely a feeding Purina appreciates the support of
plan has not yet been developed. I the Great Dane Club of America,
encourage owners to stay positive particularly Dr. Daryl Pitts and
during this first phase. With some Dr. Neil O’Sullivan, co-chairs of
time and consistent care, dogs will the GDCA Health and Research
hopefully improve.” Committee, in helping to identify
Dr. Haines should know. “When I got topics for the Great Dane Update.
‘Cake,’ we still thought of megaesoph-
7
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