Laminitis

Laminitis is a disease that affects the feet of ungulates. It is best known in horses and cattle. Clinical signs include lameness, inflammation, and increased temperature in the hooves. Laminitis is characterized by inflammation of the digital laminae of the hoof, and severe cases with outwardly visibly clinical signs are known by the colloquial term founder.

Laminae

The digital laminae are responsible for suspension of the axial skeleton of the animal within the hooves of ungulates, and act as shock absorbers during locomotion. In Horses there are about 600 pairs of interleaved laminae: the epidermal laminae attached to the hoof wall and the dermal laminae attached to the coffin bone (a.k.a. PIII, P3, the third phalanx, pedal bone, or distal phalanx).^[1]

Pathology

Laminitis literally means inflammation of the laminae, and while it remains controversial whether this is the primary mechanism of disease, evidence of inflammation occurs very early in some instances of the disease.^[2]

Laminitis is characterized by a 'compromise in the interaction' of the Laminae between the hoof wall and the coffin bone, the mechanism of which remains unclear and is currently the subject of much research.

Laminitis can be either mechanical or systemic.

Mechanical laminitis

Mechanical laminitis starts when the hoof wall is pulled away from the bone or lost, as a result of external influences. Mechanical laminitis can occur when a horse habitually paws, is ridden or driven on hard surfaces (or loses laminar function, due to an injury or pathologies affecting the hoof wall).

Systemic laminitis

Systemic laminitis is usually bilateral (on two feet) and though it can affect any number of feet, it is most common in the front feet.

At present there are three primary hypotheses for the mechanism that results in laminar failure.

Classical inflammation, which includes infiltration of potentially destructive white blood cells.^{[citation needed]}
Ischemia-reperfusion injury. Researchers have observed both decreased and increased blood flow to the laminae. As ischemia-reperfusion injury reconciles both observations, it has received much attention in past years.^{[citation needed]}
Metabolic derangements that lead to impaired cell function and proteolytic enzyme activation.^{[citation needed]}

Systemic Laminitis can lead to rotation or sinking and this in turn may lead to abscesses, within the hoof capsule, that can be severe and very painful.

Rotation, sinking, and founder

Depending upon the severity at the onset of the pathology, there may be no movement of the coffin bone, rotation only, sinking only or a combination of both rotation and sinking, to varying extents.

Normally, the front of the third phalanx is parallel to the hoof wall and its lower surface should be roughly parallel to the ground surface. A single severe laminitic episode or repeated less severe episodes can, depending upon the degree of separation of dermal and epidermal laminae, lead to either Rotation or Sinking of the pedal bone, both of which result in anatomical changes in the position of the coffin bone with visible separation of the laminae colloquially known as founder.

Rotation occurs when the damage to the laminae is less severe and it will show up mainly in the toe area of the foot. The degree of rotation may be determined by severity of the initial attack or by how soon laminitis is detected and how soon actions are taken to treat the horse. A combination of forces (e.g., the tension of the deep digital flexor tendon and the weight of the horse) result in the deep digital flexor tendon, literally pulling the dorsal face of the coffin bone away from the inside of the hoofwall, which allows the coffin bone to rotate. There are also ligaments attaching the collateral cartilages to the digit, primarily in the palmar portion of the foot, possibly contributing to a difference in support from front to back. It is also theorized that the body weight of the animal contributes to rotation of the coffin bone. Rotation results in an obvious misalignment between PII (the short pastern bone) and PIII (the coffin bone). If rotation of the third phalanx continues, its tip can eventually penetrate the sole of the foot.

Sinking is less common and much more severe. It results when there is a significant failure of the interdigitation between the sensitive and insensitive laminae around the entire perimeter of the hoof. The destruction of the sensitive laminae results in the hoof wall becoming separated from the rest of the hoof. Pus may leak out at the white line or at the coronary band. In extreme cases this event allows the tip to eventually penetrate the sole of the foot. Penetration of the sole is not inherently fatal; many horses have been returned to service by aggressive treatment by a veterinarian and farrier, but the treatment is time-consuming, difficult and expensive. It is generally agreed that a severe "sinker" warrants the gravest prognosis and may, depending upon many factors, including the quality of after care, age of the horse, diet and nutrition, skill, knowledge and ability of the attending veterinarian and farrier(s), lead to euthanasia of the patient.

Causes

Laminitis has multiple causes, some of which commonly co-occur. These causes can be grouped into broad categories.

Endotoxins

Carbohydrate overload: One of the more common causes. Current theory states that if a horse is given grain in excess or eats grass that is under stress and has accumulated excess non-structural carbohydrates (NSC, i.e. sugars, starch or fructan), it may be unable to digest all of the carbohydrate in the foregut. The excess then moves on to the hindgut and ferments in the cecum. The presence of this fermenting carbohydrate in the cecum causes proliferation of lactic acid bacteria and an increase in acidity. This process kills beneficial bacteria, which ferment fiber. The endotoxins and exotoxins may then be absorbed into the bloodstream, due to increased gut permeability, caused by irritation of the gut lining by increased acidity. The result is body-wide inflammation, but particularly in the lamina of the feet, where swelling tissues have no place to expand without injury to other structures. This results in laminitis.

Nitrogen compound overload: Herbivores are equipped to deal with a normal level of potentially toxic non-protein nitrogen (NPN) compounds in their forage. If, for any reason, there is rapid upward fluctuation in levels of these compounds, for instance in lush spring growth on artificially fertilized lowland pasture, the natural metabolic processes can become overloaded, resulting in liver disturbance and toxic imbalance. For this reason, many avoid using artificial nitrogen fertilizer on horse pasture. If clover (or any legume) is allowed to dominate the pasture, this may also allow excess nitrogen to accumulate in forage, under stressful conditions such as frost or drought. Many weeds eaten by horses are nitrate accumulators. Direct ingestion of nitrate fertilizer material can also trigger laminitis, via a similar mechanism.

Colic: Laminitis can sometimes develop after a serious case of colic, due to the release of endotoxins into the blood stream.

Lush pastures: When releasing horses back into a pasture after being kept inside (typically during the transition from winter stabling to spring outdoor keeping), the excess fructan of fresh spring grass can lead to a bout of laminitis. Ponies and other easy keepers are much more susceptible to this form of laminitis than are larger horses.

Frosted grass: Freezing temperatures in the fall also coincide with outbreaks of laminitis in horses at pasture. Cold temperatures cause growth to cease so that sugar in pasture grasses cannot be utilized by the plant as fast as it is produced and thus they accumulate in the forage. Cool season grasses form fructan, and warm season grasses form starch.^[3] Sugars cause increase in insulin levels, which is known to trigger laminitis. Fructan is theorized to cause laminitis by causing an imbalance of the normal bowel flora leading to endotoxin production. These endotoxins may exacerbate insulin resistance, or the damage to the lining of the gut may release other as yet unidentified trigger factors in to the blood stream. For horses prone to laminitis, restrict or avoid grazing when night temperatures are below 40 °F (5 °C) followed by sunny days. When growth resumes during warmer weather, sugar will be used to form protein and fiber and will not accumulate.

Untreated infections: Systemic infections, particularly where caused by bacteria, can cause release of endotoxins into the blood stream. A retained placenta in a mare (see below) is a notorious cause of laminitis and founder.

Insulin resistance: Laminitis can also be caused by insulin resistance in the horse. Insulin resistant horses tend to become obese very easily and, even when starved down, may have abnormal fat deposits in the neck, shoulders, loin, above the eyes and around the tail head, even when the rest of the body appears to be in normal condition. The mechanism by which laminitis associated with insulin resistance occurs is not understood but may be triggered by sugar and starch in the diet of susceptible individuals. Ponies and breeds that evolved in relatively harsh environments, with only sparse grass, tend to be more insulin resistant, possibly as a survival mechanism. Insulin resistant animals may become laminitic from only very small amounts of grain or "high sugar" grass. Slow adaptation to pasture is not effective, as it is with laminitis caused by microbial population upsets. Insulin resistant horses with laminitis must be removed from all green grass and be fed only hay that is tested for Non Structural Carbohydrates (sugar, starch and fructan) and found to be below 11% NSC on a dry matter basis.

Vasoactive amines

The inflammatory molecule histamine has also been hypothesized as a causative agent of laminitis.^[4]^[5] However, contradictory evidence has demonstrated that the role of histamine in laminitis has not been conclusively established.^[6]

Mechanical separation

Commonly known as road founder, this occurs when horses with long toes are worked extensively on hard ground. The long toes and hard ground together contribute to delayed breakover and hence mechanical separation of the laminae at the toe. Historically this was seen in carriage horses. These horses were bred for heavy bodies and long slim legs with relatively small hooves; their hooves were trimmed for long toes (to make them lift their feet higher, enhancing their stylish "action"); and they were worked at speed on hard roads. Road founder is also seen in overweight animals, particularly when hooves are allowed to grow long: classic examples are ponies on pasture board in spring, and pregnant mares.^[7]

Poor blood circulation

Normal blood circulation in the lower limbs of a horse depends in part on the horse moving about. Lack of sufficient movement, alone or in combination with other factors, can cause stagnant anoxia, which in turn can cause laminitis.^[7]

A horse favoring an injured leg will both severely limit its movement and place greater weight on the other legs. This sometimes leads to static laminitis, particularly if the animal is confined in a stall.^[7] A notable example is the 2006 Kentucky Derby winner Barbaro.^[8]

Transport laminitis sometimes occurs in horses confined in a trailer or other transportation for long periods of time. Historically, the most extreme instances were of horses shipped overseas on sailing ships. However, there is some evidence that the continual shifting of weight required to balance in a moving vehicle enhances blood circulation.^{[citation needed]} For this reason, some horsemen recommend trailering as an initial step in rehabilitation of a horse after long confinement.^{[citation needed]}

Laminitis has been observed following an equine standing in extreme conditions of cold, especially if there is a depth of snow.^{[citation needed]} Laminitis has also followed prolonged heating such as may be experienced from prolonged contact with extremely hot soil or from incorrectly applied hot-shoeing.^{[citation needed]}

Complex causes

Pituitary pars intermedia dysfunction:Pituitary pars intermedia dysfunction (PPID), or Cushing's disease, is common in older horses and ponies and causes an increased predisposition to laminitis.

Equine Metabolic Syndrome: is an area of much new research and is increasingly believed to have a major role in laminitis. It involves many factors such as cortisol metabolism and insulin resistance. It has some similarities to type II diabetes in humans (see also insulin resistance, described above). In this syndrome, peripheral adipocytes (fat cells) synthesise adipokines which are analogous to cortisol, resulting in Cushings-like symptoms.

Retained placenta: If the entire placenta is not passed after the birth of a foal, mares that retain all or some of the afterbirth can founder, whether through toxicity, bacterial fever or both.

Drug reactions: Anecdotally there have been reports of laminitis following the administration of drugs, especially in the case of corticosteroids. The reaction may be an expression of idiosyncrasy in a particular patient as many horses receive high dose glucocorticoid into their joints without showing any evidence of clinical laminitis.

Exposure to agrichemicals: Even horses not considered to be susceptible to laminitis can become laminitic when exposed to certain agrichemicals. The most commonly experienced examples are certain herbicides and synthesized nitrate fertilizer.

Diagnosis

Early diagnosis is essential to effective treatment. However, early outward signs may be fairly non-specific. Careful physical examination typically is diagnostic, but radiographs are also very useful.

Signs

Increased temperature of the wall, sole and/or coronary band of the foot.
A pounding pulse in the digital palmar artery. (The pulse is very faint or undetectable in a cold horse, readily evident after hard exercise.)
Anxiety
Visible trembling
Increased vital signs and body temperature
Sweating
Flared Nostrils
Walking very tenderly, as if walking on egg shells
Repeated "easing" of affected feet
Lameness
The horse standing in a "founder stance" (the horse will attempt to decrease the load on the affected feet). If it has laminitis in the front hooves, it will bring its hindlegs underneath its body and put its forelegs out in front called "pointing"
Tendency to lie down, whenever possible or, if extreme, to remain lying down.

Radiographs

A lateral-medial radiograph gives useful information regarding the degree of rotation, the sole thickness, measurement of the dorsal hoof wall thickness, and vertical deviation. It is critical to be consistent in hoof positioning and focal distance in order to make objective comparisons. Digital radiography often provides built-in digital calibration and measurement tools that can be used to provide angle and distance data. Abscesses are sometimes visible as gas pockets. Repeat radiographs can be used to monitor progression of the condition.^[9]

The use of venograms can help to add prognostic information, particularly in horses where the degree of pain does not match the radiographic changes. In venography, a contrast agent which is visible on radiographs is injected into a blood vessel in the foot, delineating the vasculature of the foot. The venogram can assess the severity and location of tissue compromise and monitor effectiveness of the current therapy.^[9]

Other diagnostics

Other imaging tools to show mechanical deviations which have been used in laminitis cases are computed tomography as well as MRI which also provides some physiologic information.^{[citation needed]} Nuclear scintigraphy may also be useful in certain situations. Ultrasonography has been explored as a way to quantify changes in bloodflow to the foot.^[10]

Prognosis

The sooner the diagnosis is made the faster the treatment and the recovery process can begin. Rapid diagnosis of laminitis is often difficult since the general problem often starts somewhere else in the horses body. With modern therapies, most laminitics will be able to bear a rider or completely recover, if treated quickly, and if the laminitis was not severe or complicated (e.g. by Equine Metabolic Syndrome or Cushing's disease). Even in these cases, a clinical cure can often be achieved. Endotoxic laminitis (e.g. after foaling) tends to be more difficult to treat. Successful treatment requires a competent farrier and veterinarian and success is not guaranteed. A horse can live with laminitis for many years, and although a single episode of laminitis predisposes to further episodes, with good management and prompt treatment it is by no means the catastrophe sometimes supposed: most horses suffering an acute episode without pedal bone displacement make a complete functional recovery.^[11] Discovery of laminitis, either active or relatively stabilized, on an equine prepurchase exam typically downgrades the horse's value, as the possibility of recurrence is a significant risk factor for the future performance of the horse.

Several radiographic abnormalities can be judged to correlate with a worsened prognosis:

Increased degree of rotation of P3 relative to the dorsal hoof wall
Increased founder distance, the vertical distance from the coronary band (seen with a radiopaque marker) to the dorso-proximal aspect of P3
Decreased sole depth
Solar penetration by P3

Treatment

In laminitis cases, a clear distinction must be made between the acute situation, starting at the onset of a laminitis attack and a chronic situation. A chronic situation can be either stable or unstable. The difference between acute, chronic, stable and unstable is of vital importance, when choosing a treatment protocol.

There is no cure for a laminitic episode and many go undetected. Initial treatment with cryotherapy and anti-inflammatory drugs may prevent mechanical breakdown if instituted immediately, but many cases are only detected after the initial microscopic damage has been done.^{[citation needed]}

Medical therapies

Cryotherapy

Cooling of the hoof in the developmental stages of laminitis has been shown to have a protective effect when horses are experimentally exposed to carbohydrate overload. Feet placed in ice slurries were less likely to experience laminitis than "un-iced" feet.^[12]

Pain management

Non-steroidal anti-inflammatory medications (NSAIDS) are the main drug type used for analgesia as well as control of any ongoing inflammation. Phenylbutazone (bute) is commonly used for its strong effect and relatively low cost. Flunixin (Banamine), ketofen, and others are also used. While 'stacking' NSAIDS may provide some analgesic benefit, this considerably increases the risk associated with this type of drug, including gastric ulcers, kidney disease, and colitis.^{[citation needed]} Newer non-specific NSAIDS such as suxibuzone may be somewhat safer than bute.^[13] Cox-2 specific drugs are now labeled for use in horses, such as firocoxib and diclofenac, which are much safer than non-selective NSAIDS.^{[citation needed]} Pentoxifylline and isoxsuprine both have anti-inflammatory effects, and may help improve circulation by improving deformability of red blood cells.^{[citation needed]}

Other analgesics currently in less widespread use, but with good potential benefit include opioids, gabapentin, and many others.^{[citation needed]}

Vasodilators;

Vasodilators are often used with the goal of improving laminar blood flow. However, during the develomental phases of laminitis, vasodilation is contraindicated, either through hot water or vasodilatory drugs.^[14] Systemic acepromazine as a vasodilator with the fringe benefit of mild sedation which reduces the horse/pony's movements and thus reduces concussion on the hooves, may be beneficial after lamellar damage has occurred, although no effects on laminar blood flow with this medication have been shown.^[15] Nitroglycerine has also been applied topically in an attempt to increase blood flow, but this treatment does not appear to be an effective way to increase bloodflow in the equine digit.^[16]

Mechanical treatments

Besides pain management and control of any predisposing factors, mechanical stabilization is a primary treatment goal once the initial inflammatory/metabolic issues have resolved. No approach has been shown to be effective in all situations, and there is ongoing debate over the merits and faults of the numerous techniques.

Once the distal phalanx rotates, it is essential to de-rotate and re-establish proper spatial orientation of P3 within the hoof capsule, to ensure the best long-term prospects for the horse. With correct trimming and, as necessary, the application of orthotics, one can effect this re-orientation. However, this attempt at re-orientation is not always completely effective.

Successful treatment for any type of founder must necessarily involve stabilization of the bony column by some means. Stabilization can take many forms but most include trimming the hoof to facilitate "break over" and trimming the heels to ensure frog pressure. While some horses stabilize if left barefooted, some veterinarians believe that the most successful methods of treating founder involve positive stabilisation of the distal phalanx, by mechanical means, e.g., shoes, pads, polymeric support, etc.

Steps taken to stabilize the bony column gain maximum effect when combined with steps that will reduce the pulling force of the deep digital flexor tendon on the coffin bone.

The application of external orthotic devices to the foot in a horse with non-displaced laminitis and once displacement has occurred is widespread. Most approaches attempt to shift weight away from the laminae and onto secondary weight-bearing structures, while sparing the sole

3M support foam
Heart bar shoes
Lily pad
Nolan hoof plate
Ultimate Wedge

Medical approaches

Dorsal hoof wall resection

A dorsal hoof wall resection may help in certain conditions after consultation with an experienced veterinarian and farrier team. If decreased bloodflow distal to the coronary plexus is seen on a venogram, or when a laminar wedge forms between P3 and the hoof wall, preventing the proper re-attachment (interdigitation) of the laminae, this procedure may be beneficial. When the coffin bone is pulled away from the hoofwall, the remaining laminae will tear. This may lead to abscesses within the hoof capsule that can be severe and very painful, as well as a mass of disorganized tissue called a laminar (or lamellar) wedge.^[17]

Deep Digital flexor tenotomy

Because the rotation of P3 is exacerbated by continued pull on the deep digital flexor tendon, one approach to therapy has been to cut this tendon, either in the cannon region or in the pastern region. While this technique has been criticized as being unsuccessful and invasive, its advocates claim that it is too often used in cases which are too far advanced. Advocates claim that by cutting the tendon at the right time, mechanical de-rotation of P3 is possible, which can allow time for the new laminar attachments to form.^[18]

Botulinum toxin infusion

As an alternative to the deep digital flexor tenotomy, Botulinum type A toxin has been infused into the body of the deep digital flexor muscle. This theoretically allows for the same de-rotation as the tenotomy procedure, but without the potential for scarring or contracture associated with that procedure. A recent study used this technique in seven laminitic horses. There was significant improvement in six of the horses, and moderate improvement in the seventh.^[19]

Informal use of the word founder

Informally, particularly in the United States, "founder" has come to mean any chronic changes in the structure of the foot that can be linked to laminitis. In some texts, the term "founder" is even used synonymously with laminitis, though such usage is technically incorrect. Put simply, not all horses that experience laminitis will founder but all horses that founder will first experience laminitis.

References

^ Pollitt (1995). Color Atlas of the Horse's Foot. Mosby. ISBN 0-7234-1765-2.
^ Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK (2007). "Early laminar events involving endothelial activation in horses with black walnut- induced laminitis". Am. J. Vet. Res. 68 (11): 1205–11. doi:10.2460/ajvr.68.11.1205. PMID 17975975.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ http://www.safergrass.org/pdf/CTEPforagelaminitis.pdf
^ Nilsson, S. A. 1963. "Clinical, morphological and experimental studies of laminitis in cattle". Acta Vet. Scand. 4(Suppl. 1):188–222.
^ Takahashi, K., and B. A. Young. 1981. "Effects of grain overfeeding and histamine injection on physiological responses related to acute bovine laminitis". Jpn. J. Vet. Sci. 43:375–385.
^ Thoefner, M.B., C.C. Pollitt, A.W. van Eps, G.J. Milinovich, D.J. Trott, O. Wattle and P.H. Andersen. 2004. "Acute bovine laminitis: A new induction model using alimentary oligofructose overload". J. Dairy Sci. 87:2932–2940.
^ ^a ^b ^c Nonclassical laminitis, James Rooney, DVM
^ "Transcript of Press Conference on the condition of Barbaro" (PDF). University of Pennsylvania School of Veterinary Medicine. 13 July 2006.
^ ^a ^b Ramey, Taylor (2011). Care and Rehabilitation of the Equine Foot. Hoof Rehabilitation Publisher. pp. 234–253. ISBN 978-0-615-52453-5.
^ Wongaumnuaykul, Santi (2006). "Doppler Sonograpohic Evaluation of the Digital Blood Flow in Horses with Laminitis or Septic Pododermatitis" (abstract). Veterinary Radiology & Ultrasound. 47 (2): pp. 199–205. doi:10.1111/j.1740-8261.2006.00128.x. Retrieved 2008-04-19. {{cite journal}}: |pages= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
^ Colahan, Patrick (1998). Equine Medicine and Surgery (Fifth Edition ed.). Mosby. p. 408. ISBN 978-0-8151-1743-8. {{cite book}}: |edition= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
^ Pollitt, Christopher (2003). "Equine Laminitis" (PDF). Proceedings of the AAEP. 49. Retrieved 2008-04-19. {{cite journal}}: Unknown parameter |month= ignored (help)
^ Sabaté, David (2005). "Suxibuzone as a Therapeutical Alternative to Phenylbutazone in the Treatment of Lameness in Horses" (PDF). XIV. Retrieved 2008-04-19. {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Pollitt, Christopher C. (2003). "Medical Therapy of Laminitis". In Ross MW, Dyson SJ (ed.). Diagnosis and Management of Lameness in the Horse. St. Louis, MO: Saunders. p. 330. ISBN 0-7216-8342-8. {{cite book}}: |access-date= requires |url= (help)
^ Adair, HS (1997). "Effects of acepromazine maleate, isoxsuprine hydrochloride and prazosin hydrochloride on laminar blood flow in healthy horses". Journal of Equine Veterinary Science. 17: 599. doi:10.1016/S0737-0806(97)80186-4. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Belknap, JK (2005). "Review of the Pathophysiology of the Developmental Stages of Equine Laminitis". Proceedings American Association of Equine Practitioners. 51. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Eustace (1996). Explaining Laminitis and its Prevention. E.F.S. pp. 29–31. ISBN 0-9518974-0-3.
^ Eastman, TG (1998). "Deep Digital Flexor Tenotomy as a Treatment for Chronic Laminitis in Horses: 37 Cases" (PDF). Proceedings of the American Association of Equine Practitioners. 44. Retrieved 2008-04-19. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Carter, D (2009). "A Novel Approach to the Treatment and Prevention of Laminitis: Botulinum Toxin Type A for the Treatment of Laminitis". Journal of Equine Veterinary Science. 29. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

External links

[1] Pollitt (1995). Color Atlas of the Horse's Foot. Mosby. ISBN 0-7234-1765-2.

[2] Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK (2007). "Early laminar events involving endothelial activation in horses with black walnut- induced laminitis". Am. J. Vet. Res. 68 (11): 1205–11. doi:10.2460/ajvr.68.11.1205. PMID 17975975.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[3] ttp://www.safergrass.org/pdf/CTEPforagelaminitis.pdf

[4] Nilsson, S. A. 1963. "Clinical, morphological and experimental studies of laminitis in cattle". Acta Vet. Scand. 4(Suppl. 1):188–222.

[5] Takahashi, K., and B. A. Young. 1981. "Effects of grain overfeeding and histamine injection on physiological responses related to acute bovine laminitis". Jpn. J. Vet. Sci. 43:375–385.

[6] Thoefner, M.B., C.C. Pollitt, A.W. van Eps, G.J. Milinovich, D.J. Trott, O. Wattle and P.H. Andersen. 2004. "Acute bovine laminitis: A new induction model using alimentary oligofructose overload". J. Dairy Sci. 87:2932–2940.

[RooneyNL-7] Nonclassical laminitis, James Rooney, DVM

[8] "Transcript of Press Conference on the condition of Barbaro" (PDF). University of Pennsylvania School of Veterinary Medicine. 13 July 2006.

[Ramey-9] Ramey, Taylor (2011). Care and Rehabilitation of the Equine Foot. Hoof Rehabilitation Publisher. pp. 234–253. ISBN 978-0-615-52453-5.

[10] Wongaumnuaykul, Santi (2006). "Doppler Sonograpohic Evaluation of the Digital Blood Flow in Horses with Laminitis or Septic Pododermatitis" (abstract). Veterinary Radiology & Ultrasound. 47 (2): pp. 199–205. doi:10.1111/j.1740-8261.2006.00128.x. Retrieved 2008-04-19. {{cite journal}}: |pages= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

[11] Colahan, Patrick (1998). Equine Medicine and Surgery (Fifth Edition ed.). Mosby. p. 408. ISBN 978-0-8151-1743-8. {{cite book}}: |edition= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

[Pollitt_2003-12] Pollitt, Christopher (2003). "Equine Laminitis" (PDF). Proceedings of the AAEP. 49. Retrieved 2008-04-19. {{cite journal}}: Unknown parameter |month= ignored (help)

[13] Sabaté, David (2005). "Suxibuzone as a Therapeutical Alternative to Phenylbutazone in the Treatment of Lameness in Horses" (PDF). XIV. Retrieved 2008-04-19. {{cite journal}}: Cite journal requires |journal= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[14] Pollitt, Christopher C. (2003). "Medical Therapy of Laminitis". In Ross MW, Dyson SJ (ed.). Diagnosis and Management of Lameness in the Horse. St. Louis, MO: Saunders. p. 330. ISBN 0-7216-8342-8. {{cite book}}: |access-date= requires |url= (help)

[15] Adair, HS (1997). "Effects of acepromazine maleate, isoxsuprine hydrochloride and prazosin hydrochloride on laminar blood flow in healthy horses". Journal of Equine Veterinary Science. 17: 599. doi:10.1016/S0737-0806(97)80186-4. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[16] Belknap, JK (2005). "Review of the Pathophysiology of the Developmental Stages of Equine Laminitis". Proceedings American Association of Equine Practitioners. 51. {{cite journal}}: |access-date= requires |url= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[17] Eustace (1996). Explaining Laminitis and its Prevention. E.F.S. pp. 29–31. ISBN 0-9518974-0-3.

[18] Eastman, TG (1998). "Deep Digital Flexor Tenotomy as a Treatment for Chronic Laminitis in Horses: 37 Cases" (PDF). Proceedings of the American Association of Equine Practitioners. 44. Retrieved 2008-04-19. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[19] Carter, D (2009). "A Novel Approach to the Treatment and Prevention of Laminitis: Botulinum Toxin Type A for the Treatment of Laminitis". Journal of Equine Veterinary Science. 29. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

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