Tim Holt, Colorado State University DVM and assistant professor of veterinary medicine and biomedical science, has studied brisket disease in cattle for more than 30 years. His work – looking for answers to what starts as a respiratory condition in some cattle at higher elevations and often ends in death – is taking on more importance as its incidence seems to be growing.

“Is what we consider ‘high elevation’ now becoming 3,000 ft., where we used to say it was 7,000 ft.? Today, we’re seeing brisket disease even in some Nebraska feedlots,” Holt says. “Is this related to genetics, disease or nutrition?”

Symptons of Brisket Disease

Cattle above 6,000 ft. are most at risk of brisket disease – also known as mountain sickness, pulmonary hypertension and dropsy – and incidence increases with increasing elevation. In Wyoming and Colorado, for instance, many cattle go to summer pasture at elevations above 9,000 ft.

The reduced amount of available oxygen at higher elevations can adversely affect the lungs and cause artery walls to thicken. The decrease in the arteries’ internal diameter, and subsequent pulmonary hypertension, make it difficult for the right side of the animal’s heart to pump blood into the lungs.

Thus, the heart’s right ventricle muscle enlarges from the extra effort needed to pump blood, eventually losing tone and its ability to contract. As blood pressure increases and starts to back up into the heart, it can blow out the valves of the right ventricle.

Some affected animals develop edema in the neck and brisket. Swelling may spread to the jaws, or along the belly. Often, you don’t see symptoms; you just find the animal dead.

Affected animals may develop problems early in life, or shortly after being brought to high elevation from lower altitudes, Holt says. Cattle with brisket disease are often lethargic, while other signs may include weakness, diarrhea, bulging eyes and difficult breathing. If cattle are trailed very far, those with brisket disease lag or lie down due to shortness of breath.

Feedlot incidence

Interestingly, the problem sometimes appears in feedlot cattle, even at low elevations, as they get heavier and closer to finish weight, because the heart must work harder.

“It may be a different mechanism, but it’s the same type of issue; they are dying of right-heart disease. We’re doing research now in feedlot cattle at 3,000 ft. elevation, because these cattle have the same clinical appearance,” Holt says.

Holt has tested cattle at elevations from sea level to 15,000 ft. (in Ethiopia) utilizing a test developed to measure pulmonary artery pressure (PAP) in humans. The PAP test helps determine which animals are most at risk for brisket disease and detects the early stages of the disease. The results, however, are only valid if cattle are tested at or above 6,500 ft. (see “Testing pulmonary arterial pressure in cattle”).

Holt says some people think European breeds, which originated in mountainous country, are less prone to brisket disease than British breeds, which originated at lower elevations. But there’s little evidence to support this. Holt adds though that some cattle appear less susceptible than others, if they’ve lived at high altitudes for many generations.

“When I went to Ethiopia, cattle grazing at 10,000-14,000 ft. had low PAP scores,” he says. He speculates that all the susceptible cattle had died off.

In North America, by contrast, Holt says, trait selection has concentrated on meat quality, feed efficiency, fertility, etc. Since brisket disease on this continent is limited to small geographic areas, little attention has been paid to how cattle function at high altitudes.

“Most cattle live at lower elevations, so there’s no natural selection to eliminate the problem,” he adds.

There are, however, some family lines within breeds that are more resistant than others, Holt says. Identifying these animals can aid ranchers at high elevations in selecting resistant animals for breeding stock.

Rich McCormick, a Univer-sity of Wyoming (UW) professor of muscle biology, says selective breeding of cattle in the Rocky Mountain West has reduced incidence of brisket disease to about 5%. “But this still has a significant impact on profitability,” he adds.

Seemingly “normal” cattle may have high PAP scores at high elevations, McCormick says. “But, once an animal comes to our area – 7,200-8,000 ft. elevation – I’m not sure you’ll find a truly normal individual. Of the animals we’ve PAP-tested at UW, we’ve never found one that tested below 40,” (see “PAP testing”).

Looking for markers

At UW, McCormick and Mark Stayton, professor and chair of UW’s Molecular Biology Department, are exploring the molecular biology of brisket disease, looking for better and cheaper diagnostic markers to identify early stages of the disease. “We’re trying to develop a blood-based diagnostic test based on gene expression,” he explains.

“Some animals are more susceptible, but we can currently only detect this after we bring them to higher elevation. If they are raised at low elevation, you might never know if they (or their offspring) would develop brisket disease.

“This is what limits the use of genetically superior sires at high elevations – sires that are superior in meat production and other desired traits. Sires untested for brisket disease may produce progeny that might develop brisket disease,” McCormick says.

McCormick says human patients have been identified with an inherited form of pulmonary hypertension, which shows similar symptoms to brisket disease in cattle. In humans, mutations in bone morphogenic protein receptor 2 (BMPR2) have been shown to be necessary for development of familial pulmonary hypertension, he explains.

“We set out to test the hypothesis that the BMPR2 signaling pathway is defective in cattle suffering from brisket disease and started looking at the gene in cattle. We haven’t yet identified any mutations in the bovine BMPR2 amino acid sequence that correlate with elevated PAP score, but we’ve found evidence that BMPR2 expression in cattle is reduced in lungs of animals with elevated PAP scores and brisket disease,” he says.

McCormick and Stayton are currently cloning BMPR2 from related ruminants that are altitude-resistant. “We’ll compare these sequences in an effort to identify genetic changes that correlate with altitude sensitivity. We’ve obtained blood samples from alpaca, elk, yak, and bighorn and domestic sheep, as well as cattle. Except for cattle, all these species are altitude-resistant. Any findings that link particular DNA sequences to disease susceptibility are potential diagnostic markers for brisket disease,” McCormick says.

“Of all mammals tested, cattle are the most susceptible to pulmonary hypertension, and if stressed, they become more susceptible. The only bovine I’m aware of that seems truly resistant is the yak. They do fine at 18,000 ft. or higher,” he says.

McCormick says that if the genetic basis to brisket disease can be determined, and a genetic marker highly correlated with development of brisket disease found, producers would have a way to evaluate an animal without bringing it to the high country for testing. “We have ideas for future research, but except for a few cattle producers in the West, no one is interested in funding this type of research,” McCormick says.

“The bovine genome is available, but we don’t know if it represents cattle that are free of genetic components responsible for brisket disease. Did it come from an animal that was resistant or susceptible? We don’t have a good baseline to compare brisket disease-susceptible animals to,” he says.

Other ongoing research is looking at the effect of nutrition in various areas across the country – and at various altitudes – to determine its effects on elevated PAP measurement. Some studies are looking at diet, to see if certain additives, carbohydrates or protein loads affect the pulmonary vascular system.

“We’re also looking at whether elevated PAP pressure can be related to fat (body condition). Cattle nearing finish weight, with more body mass, seem more at risk. We want to find out if the extra body mass is causing the hypoxia (shortage of oxygen) in tissues,” Holt says.

Sidebar: Testing pulmonary arterial pressure in cattle

The pulmonary arterial pressure (PAP) test measures blood pressure in the pulmonary artery and estimates the force required to push blood into the lungs. The higher the altitude, the more accurate the test.

Cattle tested at low elevations may have acceptably low scores, but test higher at higher elevations. The test must be done at elevations above 6,500 ft., and cattle must have been at that elevation for at least 3-6 weeks, says Tim Holt, Colorado State University DVM.

PAP test reliability is also better if the animal is at least one year old. Calves can be tested, but low scores don’t mean they won’t develop brisket disease later. The body is still growing and lung capacity hasn’t reached its limit, Holt adds.

To test an animal, a catheter is inserted into the jugular vein, threaded into the right ventricle of the heart and into the main pulmonary artery between the heart and lungs. Pressure in this artery is measured to determine blood pressure in the heart’s right side. The higher the blood pressure, the less capable the animal will be of living at that elevation.

In cattle older than 12 months and tested at or above 6,500 ft., a PAP score of 30-35 is considered excellent. Any score less than 41 is acceptable, but Holt says yearlings should measure less than that (depending on the altitude of the test).

Any animal with a score of 41 or higher should be retested prior to breeding. A PAP score of 41-45 is acceptable for animals more than 16 months old, while a score of 45-48 is acceptable only for older animals that have been at high elevation for a long time. Animals in this range are susceptible to environmental stresses leading to brisket disease and should be considered at risk. Animals scoring greater than 49 must always be considered high-risk for brisket disease, and their offspring as well.

Sidebar: Genetics of brisket disease in cattle

While brisket disease has a genetic component, little is understood about how it passes between generations, “and it seems to be able to skip generations,” says Rich McCormick, University of Wyoming professor of muscle biology. That’s one reason why you can’t entirely get rid of it by using the PAP test. “You’ll miss some animals that carry it and it may turn up in a later generation.”

McCormick says some producers report buying an untested bull that did fine at higher elevations and produced progeny free of brisket disease. However, later offspring developed brisket disease. Exactly how and why the condition expresses itself isn’t understood, he says. Even if you could estimate the percent of offspring of a certain animal that might inherit this susceptibility, you don’t know when it might occur.

Sidebar: It’s important to test for brisket disease in cattle

Most seedstock producers at low elevations don’t test animals they sell. Producers in Wyoming, Colorado and nearby states, however, generally use the PAP test to reassure customers that their animals are free of this problem.

It’s crucial for high-altitude producers to use tested seedstock, or death losses may become a huge issue, says Rich McCormick, University of Wyoming professor of muscle biology.

“In one instance, semen from an untested sire was used on 200 cows, and 75% of his progeny developed brisket disease,” he says. “For all his virtues, a great bull may not work at high elevation. If that sire has never been PAP-tested, you’re running a risk.”

Colorado State University DVM Tim Holt says a complicating factor is that testing has historically focused on the bull side, overlooking females. On some ranches, however, the females may be more indicative of the problem than the males, with some cows potentially being carriers (passing genetic susceptibility to their calves) without developing clinical signs themselves, he says.

Sidebar: Treatment of Brisket Disease in cattle

“The best treatment for an animal with brisket-disease symptoms is to immediately take it to lower elevation, or treat it in a hyperbaric chamber where oxygen concentration can be greatly increased, to simulate lower elevation,” says Tim Holt, Colorado State University DVM.

Other treatments that keep the animal from dying until it can be taken to lower elevation include diuretics to lower blood pressure and fluid volume.

“You treat these animals like you would a human patient with right-side congestive heart failure. You put them on Lasix (a diuretic), eliminate fluid and salt intake, and administer broad-spectrum antibiotics and a vitamin B complex. You can also drain the chest cavity, inserting a large-diameter needle through the chest wall, between the ribs,” he says.

Fluid observed on the outside (swelling in brisket and neck) is just a small part of the total. “There’s even more fluid inside the thoracic cavity – putting pressure on heart and lungs. Draining this can relieve the animal,” but you still must take it to lower elevation, Holt stresses.

A current study is looking at other treatments for acute cases – such as various medications to reverse the condition or treatment for the hypertension, he adds.

“But we’re still PAP-testing replacement heifers and bulls for use in high-altitude areas. Even though it’s not the greatest test, it’s still the best we have for determining which animals are at risk.”