I. Definition and Overview

• A. Names and Classification

    ◦ Bovine High-Mountain Disease (BHMD).

    ◦ Also known as Brisket Disease or Hypoxia-Induced Bovine Pulmonary Hypertension.

• B. Cause and Location

    ◦ Occurs in cattle pastured at high altitude ($\geq 1,524$ meters [5,000 feet]).

    ◦ Caused by low environmental oxygen saturation (hypoxia).

    ◦ Most commonly and substantially affects cattle in the US in Colorado, Wyoming, New Mexico, and Utah.

    ◦ Also affects cattle globally in mountainous regions, predominantly at elevations $> 1,981$ meters [6,500 feet]) in western Canada and South America.

• C. Pathophysiological Summary

    ◦ Low environmental oxygen $\rightarrow$ pulmonary hypertension.

    ◦ Pulmonary hypertension $\rightarrow$ subsequent secondary right-sided heart failure (RV failure).

    ◦ RV failure $\rightarrow$ edema in ventral tissues of the chest and abdomen.

• D. Affected Populations and Incidence

    ◦ BHMD occurs in cattle of all ages and breeds.

    ◦ Most commonly affected animals are calves 6–8 months old.

    ◦ Average incidence on high-mountain pastures is 3%–5% (ranging from 0.5% to 10%).

    ◦ Incidence can be as high as 65% in genetically susceptible calves.

    ◦ A 25% rate of calf loss due to BHMD is not uncommon in high elevations in Colorado and Wyoming.

II. Etiology and Pathogenesis

• A. Primary Hypoxia-Induced Mechanism

    ◦ BHMD results from pulmonary arterial hypertension induced by pulmonary hypoxia.

    ◦ Hypoxia causes pulmonary arterial vasoconstriction and arterial hyperplasia.

    ◦ This decreases the diameter of the pulmonary arterioles.

    ◦ The result is pulmonary hypertension, leading to subsequent right ventricular (RV) hypertrophy.

    ◦ The disease progresses to RV congestive or dilatory failure if intervention does not lower hypoxia-induced pulmonary hypertension.

• B. Pulmonary Vascular Shunting

    ◦ Shunting is a normal physiological response to hypoxia.

    ◦ It occurs strongly in cattle and pigs, but less so in humans, dogs, guinea pigs, and llamas.

    ◦ The mechanism is intended to divert unoxygenated blood to oxygen-rich, dorsal pulmonary tissues.

    ◦ Cattle are uniquely susceptible due to exaggerated shunting, the anatomical pattern of the bovine lobulated lung, and the low ratio of lung size to body weight.

• C. Stages of Vascular Change

    ◦ Acute Hypoxia: Shunting is mediated through pulmonary arteriole constriction.

    ◦ Chronic Hypoxic Exposure (> 3 weeks): Leads to vascular remodeling (medial hypertrophy) and adventitial tissues.

    ◦ Narrowing of the luminal space increases pulmonary resistance and results in marked pulmonary hypertension.

• D. Contributing Factors

    ◦ Genetics: Supported by high familial incidence; marked variation in susceptibility between individual animals and breeds. Susceptibility to hypoxia-induced pulmonary hypertension is inherited.

    ◦ Stress: Occurs during high-stress periods like weaning or fall months (weather stress, extreme temperature variation). Severe cold, pregnancy, or change in nutrition can precipitate clinical signs.

    ◦ Plant Toxicosis: Locoweed (Oxytropis and Astragalus spp) is the only range plant experimentally shown to induce BHMD, contributing directly to increased pulmonary vascular resistance and hypertension, often affecting an entire herd within 1–2 weeks.

    ◦ Concurrent Illness: Acute viral or bacterial respiratory disease can exacerbate pulmonary hypoxia, leading to rapid RV failure. Any acute or chronic pulmonary disease that hinders function can result in a hypoxic condition similar to altitude-induced BHMD.

III. Clinical Findings and Lesions

• A. Clinical Signs of Heart Failure (CHF)

    ◦ Clinical changes usually develop slowly over several weeks, commonly within the first 3–4 weeks after moving from lower to higher elevations.

    ◦ Edema/Swelling: Subacute edema in the sternal region (parasternal muscles) extending cranially to the intermandibular space and caudally to the ventral abdominal wall.

    ◦ Vascular/Fluid: Distention and pulsation of jugular veins. Profound pleural effusion and ascites (ventral abdominal distention).

    ◦ Other Signs: Initial listlessness and reluctance to move. Labored respiration, cyanosis, decreased appetite. Profuse diarrhea resulting from intestinal venous hypertension.

    ◦ Progression: Affected cattle become reluctant to move, can become recumbent, and may collapse and die with forced exertion. Terminal stages involve anorexia and inability to rise.

• B. Pathology (Lesions)

    ◦ Edema: Generalized edema is especially severe in ventral subcutaneous tissues, skeletal musculature, perirenal tissues, mesentery, and GI tract wall.

    ◦ Fluid: Ascites, hydrothorax, and hydropericardium are consistent findings. Fluid characteristics are consistent with a transudate (low cellularity, low to normal protein) secondary to cardiac failure.

    ◦ Liver: Chronic passive congestion, varying from “nutmeg” appearance to severe lobular and vascular fibrosis.

    ◦ Lungs: May show atelectasis, interstitial emphysema, edema, and pneumonia.

    ◦ Heart: Marked RV hypertrophy and dilatation. Cardiac apex is displaced to the left, making the enlarged heart appear round. The right atrium is often two to three times larger than the left atrium and is flaccid.

    ◦ Vessels: Pulmonary arterial thrombosis is a common finding. Acute rupture of the pulmonary artery (aneurysm) secondary to severe pulmonary hypertension is often identified as a reason for acute death with no preceding clinical signs.

IV. Diagnosis

• A. Diagnostic Criteria

    ◦ Based on visible clinical signs of RV failure and/or pulmonary arterial pressure (PAP) measurement.

    ◦ A diagnosis is supported by PAP measurement > 50 mm Hg.

• B. Pulmonary Arterial Pressure (PAP) Testing

    ◦ Procedure: A flexible polyethylene catheter is passed through a large-bore needle inserted into the jugular vein, advanced through the right atrium and right ventricle, and into the pulmonary artery, where the pressure is taken.

    ◦ Normal Range: At 1,524–2,133 meters (5,000–7,000 feet), the normal mean PAP is 34–41 mm Hg (for animals $> 1$ year old).

    ◦ Range in Affected Cattle: PAP can range from 48 to 213 mm Hg.

    ◦ Risk Threshold: Any animal with PAP > 50 mm Hg is considered at risk of developing BHMD and a potential genetic carrier. Screening is required because not all animals with pulmonary hypertension display clinical signs.

    ◦ Timing: Cattle should remain at the new high elevation for $\geq 3$ weeks before PAP testing. Testing animals $\geq 16$ months old appears to be the most consistent and accurate approach.

    ◦ Variables Influencing PAP: Breed, gender, age, body condition, concurrent illness, environmental conditions, elevation, and genetics.

• C. Differential Diagnosis

    ◦ BHMD must be differentiated from other causes of CHF, including pericarditis, traumatic reticuloperitonitis (hardware disease), cardiac lymphosarcoma, valvular endocarditis, viral or bacterial myocarditis, cardiomyopathy, pulmonary arterial obstruction from embolic pneumonia, and chronic hypoxia/cor pulmonale due to other primary pulmonary disease.

    ◦ In peracute RV CHF, sternal edema may be absent, leading to misdiagnosis as acute viral or bacterial pneumonia.

V. Treatment and Control

• A. Treatment

    ◦ Relocation: Animals should be moved to a lower altitude with minimal restraint, stress, and excitement.

    ◦ Critical Intervention: Thoracocentesis is the treatment that most dramatically improves the survival rate.

    ◦ Stabilization/Supportive Care (Before Transport): Diuretics, thoracocentesis, prophylactic antimicrobials, and appetite stimulants (e.g., vitamin B complex).

    ◦ Advanced Treatments: Use of oxygen or a hyperbaric chamber can be considered for valuable animals at high elevations.

    ◦ Prognosis: Some animals recover and return to normal life after intervention and transport to lower elevations.

    ◦ Recurrence: Affected animals should not be returned to high altitudes, as BHMD can recur.

    ◦ Associated Diseases: Concurrent diseases (respiratory, cardiac, GI, parasitism, plant toxicosis) should be treated.

• B. Prevention (Preferred Method)

    ◦ Treatment can be expensive and unrewarding, making prevention preferable.

    ◦ Genetic Selection: Selective breeding for resistance to hypoxia is the more effective control method.

    ◦ Animals with PAP measurements $> 50$ mm Hg should be eliminated from the breeding pool.

    ◦ Affected cattle should not be retained for breeding.

    ◦ Locoweed Control: Minimize exposure; ensure animals have a good selection of forages, and move cattle to locoweed-free pastures immediately if poisoning is recognized.

VI. Related Conditions and Research

• A. Low-Elevation Heart Failure (Feedlots)

    ◦ A condition similar to BHMD has been observed in feedlots at low elevations ($\leq 1,219$ meters [4,000 feet]).

    ◦ Observed since approximately 2014, with an increased incidence of right-sided heart failure.

    ◦ Estimated to cause 4% of feedlot deaths, resulting in economic impact.

    ◦ Working theories suggest that cattle with an obese and/or over-muscled phenotype become hypoxic because their large body size exceeds their inherent cardiopulmonary capacity.

    ◦ Research is ongoing into this phenomenon.

• B. Cardiac Grading System (CGS)

    ◦ Developed due to concerns about heart failure in feedlots at low and moderate elevations (approximately 600–1,500 meters [2,000–5,000 feet]).

    ◦ Used at slaughter to identify the extent of heart remodeling and quantify the problem.

    ◦ Used by veterinarians for genetic selection of bulls due to a strong positive correlation between cardiac score and PAP measurement in sires.

    ◦ Grades 1 and 2 are normal or variants of normal. Grades 3–5 show marked anatomical changes, loss of function, and efficiency.

    ◦ Grade 3 Hearts: Moderate change; associated with the greatest gain and heaviest carcasses.

    ◦ Grade 4 Hearts: Severe anatomical changes; performance declines.

    ◦ Grade 5 Hearts: Severe changes, flaccid thin cardiac muscle, cardiac collapse. Animals with Grade 5 hearts usually die before slaughter.

• C. Ongoing Research

    ◦ Directed at pinpointing DNA markers to identify genetically susceptible animals.

    ◦ Investigating the relationship between absolute body condition (obesity) and the development of pulmonary hypertension and cardiac failure in cattle on low-elevation feedlots.

    ◦ Research shows a direct correlation between PAP score, cardiac grade, effect on carcass, and other traits