Irish Setters UK & Ireland  
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 GASTRIC DILATION VOLVULUS (GDV) or BLOAT

Liverpool University

GDV Research

A Brief History

Gastric dilation volvulus (GDV), commonly known as bloat, is a life threatening condition which occurs most frequently in large, deep chested dogs. Although the incidence is relatively low it has a mortality rate of up to 60% and therefore remains a cause for concern to veterinary surgeons, breeders and owners.

In the initial stages of the syndrome dilation begins with the accumulation of gas in the stomach primarily through aerophagia and possibly fermentation. Fluid secretions also accumulate and the gastric content is prevented from leaving the stomach by failure of normal outflow mechanisms. The stomach then begins to rotate about it's oesophageal attachment in a clock or anti-clockwise direction. The region of the stomach called the pyloric antrum moves across the abdominal floor and comes to lie alongside the oesophagus on the left abdominal wall. The fundal region of the stomach moves to the right around the oesophageal axis and then ventrally. The spleen moves dorsally and to the right making contact with the liver or diaphragm. Venous return to the heart is then dramatically reduced as the result of torsion of the caudal vena cava and portal vein. Despite some progress on the treatment of GDV, its cause remains unknown.

Possible Causes

In 1984 Leib reported that gastrin, a gastric regulatory hormone, levels are significantly higher in dogs suffering from GDV during both the syndrome and the postoperative period. They proposed that the trophic effect of gastrin on the gastric mucosa could play a role in the development of GDV by delaying gastric emptying secondary to pyloric hypertrophy amd obstruction. They also believed that gastrin concentrations could directly delay gastric emptying and increase gastroesophageal sphincter pressure resulting in oesophageal spasm, aerophagia and decrease the possibility of vomiting thus leading to the onset of GDV. However, this hypothesis has been questioned because gastrin is eliminated through the kidneys, and, since renal blood flow is significantly reduced during GDV, this possibly accounts for the elevation. In 1989 a study by Hall found that gastroesophageal sphincter pressure and plasma gastrin concentrations in postoperative dogs treated for GDV were not significantly different from values of normal dogs. They also reported that the increase in gastroesophageal sphincter pressure in response to food-induced gastrin release was similar for dogs that had recovered from GDV and clinically normal dogs. The consensus of recent studies thus does not support a significant difference in regulatory hormone levels and gastroesophageal sphincter pressure in control dogs and those with GDV.

Diet and feeding patterns have also often been proposed as possible causes of GDV. Researchers have proposed that a once daily feeding of dry dog food could predispose a dog to the development of GDV by causing a heavy, chronically distended stomach that could easily undergo torsion. However, the same study found no significant difference in gastric motility and emptying patterns among dogs fed various diets. It has also been suggested that dry cereal or soy based foods could be a causative factor. It has been hypothesized that this food may take longer to empty due to it's physiochemical composition and perhaps thereby be predisposed to fermentation, resulting in a build up of gas that could lead to GDV. This is unlikely to be the cause since GDV develops in dogs subjected to a variety of feeding regimens, diets and has even been documented in hospitalised dogs that have fasted for over 24 hours. Research at the University of Florida and Colorado State University found no effect of diet on gastric function or the onset of GDV. No overall consensus has been established, but most suggest that small frequent meals are advisable for predisposed breeds.

A recent study, however, has shown a predilection of GDV for large and giant breeds of dogs. It was found that if small dogs (< 10 kg) were assigned a risk factor of 1, then medium dogs (11-39 kg) have a risk factor of 17, while large breeds (40-49 kg) had a risk factor of 23.5 and giant breeds (> 50 kg) 133.2. The study also found a predilection for pure bred dogs which have a 2.5 times higher risk of developing GDV than mongrels of similar size. There is also some evidence to support a familial susceptibility. Among colonies of dogs kept under identical conditions only certain lines had a tendency to develop GDV. The reason why large and giant breeds are predisposed to GDV is unclear. Perhaps gastric anatomy or function is different. If this is the case however, it is still not clear why pure bred dogs are at a much higher risk.

Our Work

The lack of progress on determining the cause of GDV suggests the need for a reassessment of research. Ultimately the activity of the stomach depends on smooth muscle and this can be influenced by intrinsic factors such as electrical activity, intracellular calcium and acidity levels, and extrinsic factors such as nerotransmitters. No previous work has systematically investigated the properties of gastric smooth muscle and its innervation in susceptible breeds before the onset of GDV. The aim of my work will be to characterise the stomach muscle from canine breeds that are susceptible to GDV and those which are not. I will measure contractile response, sensitivity to agonists, and control mechanisms for intracellular Ca2+ [Ca2+]i and intracellular pH (pHi). [Ca2+]i is known to be a critical determinant of smooth muscle function and pHi is also known to markedly alter mechanical activity of smooth muscle. This information will further elucidate the main factors responsible for gastric motility and promises to bring out the underlying differences that predispose some breeds to GDV. This forms the basis of my research.

The majority of our work has primarily focused on how acidity, i.e. internal pH (pHi) is regulated in gastric tissue. The proper functioning of the stomach depends on the mechanical activity of smooth muscle, which has been shown to be influenced by pH. Conditions in which the removal of metabolic waste products is hindered, as may be the case in GDV, will result in changes in both pHi and extracellular pH (pHo). Thus we have investigated the influence pHi and pHo have on gastric smooth muscle. Spontaneous and agonist induced contraction is simultaneously measured with the changes in pHi. Experimental work has concentrated on pH regulation in response to a pHi acid load, a pHi alkaline load and a decrease in external pH (pHo).

pHi has been altered with weak acids and bases and a control value for the regulation rate has been established. Different protocols have been used to investigate possible mechanisms of this pHi regulation rate. In order to exclude the buffering effects of bicarbonate, our initial work used the non-bicarbonate based buffer HEPES. Following an acid load, regulation may occur via protons being transported out of the cell in exchange for Na+ entry. Both amiloride and it's derivative EIPA are reported to block the activity of the sodium hydrogen exchange (NHE), thus they have been used to investigate it's role in pHi regulation. EIPA was used in initial experiments due to it's greater affinity for the NHE. It was able to completely block or significantly reduce any pHi regulation following an acid load. At this point, the protocol shifted to using amiloride. As with EIPA, amiloride also completely blocked or significantly reduced any pHi regulation following an acid load. Further investigations into the mechanisms of regulation are continuing using sodium free conditions. Studies have also suggested that the acid-extrusion system of regulation may be counterbalanced by a chloride dependent acid-loading system. Thus to gain a more thorough understanding of the entire process, we have begun examining the effects chloride exchange blockers have on acid loading. Another possible source of acid-loading that may operate in bicarbonate-free conditions could be a potassium dependent acid influx through a potassium hydrogen exchanger driven by the outward potassium gradient present within the cells. We thus have begun to investigate how the acid-loading system will be effected if external potassium levels are elevated to remove the gradient. The above experiments are also being performed in HCO3-/CO2 buffered solutions to examine its effects on the pHi regulation. We have also found that the changes in pHi produced by change of pHo to 6.4, was not affected by EIPA or amiloride, indicating no role for acid loading in this process. While studies of the role of pH in gastric smooth muscle function is still in progress, we have recently begun to investigate the role of intracellular calcium as well as how and if pH has an influence on its levels.

Comparative studies on the role of the interstitial cells of Cajal (ICC) in different areas of the stomach have also been conducted. The ICC’s were identified in the last century yet the mechanism of the activity and function remain unknown. They appear to be involved in the pacemaker activity of the mammalian gastrointestinal tract by initiating distally propagating phasic contractions, thus could play a role in the onset of GDV. ICC's are extensively connected to one another and smooth muscle cells through gap junctions. Thus, our initial work used an antibody developed against the gap junction protein connexin 43 to identify relative concentrations of ICC in different regions of the stomach. Recently, we have been attempting to use an antibody for the proto-oncogene product, c-kit, which has been shown to specifically label ICC in the mouse gastrointestinal tract. This technique would enable us to directly identify and quantify ICC densities thus provide more accurate data then the indirect measurements conducted with the connexin 43 antibody. Preliminary work has been promising and the innervation of the antrum in dogs that have suffered from GDV appears less extensive than that of the control group. However, due to an unfortunate freezer failure, we lost a large portion of our samples thus are desperate to obtain further tissue in order to pursue this possible area of interest.

The Future

Prior to this project, little progress had been made in establishing the aetiology and pathophysiology of GDV. As mentioned, we are currently working on the innervation pattern of the stomach and establishing the basic cellular physiology of contraction in relation to pH and Ca2+ in susceptible and non-susceptible breeds. We then hope to go on and compare their response to hormonal and neuronal stimuli and to hypoxia. In the immediate future we hope to then determine the following:

 

Does contractility differ in susceptible and non-susceptible breeds?

Are resting levels or the control of Ca2+ and pHi impaired in susceptible breeds?

Does hypoxia have greater effects in susceptible breeds?

Do abnormalities of the intrinsic or extrinsic innervation of the stomach predispose animals to develop impaired gastric function?

These experiments have and will continue to lead to a greater understanding of the normal physiology of gastric function and smooth muscle that will benefit all dogs but more importantly, could expose the cellular differences that predispose some breeds to GDV. The consequences of such differences can then be related to clinical cases, and preventative therapies explored. In the distant future, a genetic test could potentially be developed, thus a simple blood test could determine if a dog was susceptible to GDV. However, any such progress will only be achieved if we continue to receive tissue samples from susceptible breeds.

How You Can Help

In order to continue progressing with this research we need tissue samples from susceptible breeds that have and have not bloated. The areas of interest are the fundus, corpus and antrum all along the greater curvature of the stomach. We need full thickness biopsies, approximately 2 cm wide and 3-4 cm long cut parallel to the circular muscle. They should be stored in chilled saline and sent packed on ice or cool packs immediately to the address below. Obtaining these samples can be performed after an animal is put down. Due to legislation, samples can only be taken during surgery if the veterinary surgeon feels that doing so is for the benefit of that individual. Thus, in order for enough animals to be collected for statistical purposes, we desperately need your help.

We have an account with Parcel Force and it can be arranged for them to transport samples on our behalf. You must first contact me, Robert Duquette, during working hours at 0151-794-5312. I will need to know the exact location from which Parcel Force will be collecting the sample (most likely the vet clinic) and also a contact name and phone number. It is crucial that I know the sample is on the way in order for the appropriate preparations to be made to conduct the physiological work. If for some reason the sample couldn’t be sent immediately, please still contact me because it can be of use for the morphological aspects of the project. If a sample comes available and I can't be reached, Sandy Waterton, who has been cooperating with the project on behalf of the Irish Setter Breeders Club, has kindly allowed us to publish her home telephone number as an "after hours" contact. PLEASE, only contact her if you have a sample to send us and do not call her with any medical, first aid or general questions on bloat or the research project. She will then be able to contact me and provide the relevant information. Unfortunately, our delivery system with the University only operates during the week. We can still arrange for samples to be delivered over the weekend, but the cost is considerably higher. If anyone has any suggestions or connections with delivery services that could possibly help defray costs your advice would be appreciated.

Any occurrence of bloat will cause a stressful situation, thus I cannot emphasise enough the importance of discussing this matter with your vet prior to facing the emergency situation GDV can generate. Informing your vet can also benefit the project by ensuring that they have the ability to pass on any tissue samples removed in their practice.

Please send all samples marked URGENT to:

Professor S. Wray and R. Duquette

GDV Project

The Physiological Laboratories

Crown Street

University of Liverpool

Liverpool L69 3BX

Contact telephone numbers:

Robert Duquette  0151 794 5312 (work)

Sandy Waterton  01252 873895 (home)

If anyone would like a copy of the original newsletter containing a brief medical history of GDV research, recommendations to help avoid GDV and GDV phases, symptoms and recommended actions, please contact me, Robert Duquette, and I would gladly post it to you. Thanks again to everyone that has been helping and spreading the word.

Recommendations to help avoid GDV

1) Feed your dog two to three times daily, rather than once a day, and at times when someone can observe them after they have eaten.

2) Avoid rigorous exercise, excitement and stress one hour before and two hours after feeding. Walking is okay because it helps to stimulate normal gastrointestinal function.

3) Make diet changes gradually over a three to five day period. It has also been recommended to elevate both water and food dishes.

4) Ensure that water is always available but limit the amount immediately after feeding.

5) Watch for any actions or behaviour that may signal abdominal discomfort:

abdominal fullness

pacing

salivating

whining

getting up and lying down

stretching

looking at abdomen

anxiety

unsuccessful attempts to vomit

6) Establish a good relationship with your veterinarian.

GDV Phases, Symptoms and Recommended Actions

Phase 1 Symptoms:

Pacing, restlessness, panting and salivating

Unproductive attempts to vomit (every 10-20 minutes)

Abdomen exhibits fullness and beginning to enlarge

Phase 1 Actions:

Call vet to advise your suspicions.

Phase 2 Symptoms:

Very restless, whining, panting continuously, heavy salivating

Unproductive attempts to vomit (every 2-3 minutes)

Dark red gums

Elevated heart rate (80-100 bpm)

Abdomen is enlarged and tight. Emits a hollow sound when percussed.

Phase 2 Actions:

Call vet, your dog is likely to need urgent attention

Phase 3 Symptoms:

Gums are white or blue

Dog unable to stand or has spread-legged, shaky stance

Abdomen is very enlarged

Extremely elevated heart rate (+100 bpm) and weak pulse

Phase 3 Actions:

These symptoms indicate that death is likely to be imminent

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