Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity‐associated pulmonary hypertension with left heart disease

Abstract

The obesity epidemic in developed societies has led to increased cardiovascular diseases including pulmonary hypertension associated with left heart disease (PH-LHD), the largest and fastest-growing class of PH. Similar to obese humans, PH and heart failure (HF) are increasingly recognized in North American fattened beef cattle. We hypothesized that PH and HF in fattened beef cattle are novel, phenotypically distinct manifestations of bovine PH arising from left ventricular (LV) dysfunction similar to obesity-related PH-LHD in humans. We conducted a semi-quantitative histopathological assessment of cardiopulmonary tissues obtained from fattened beef cattle suffering end-stage HF compared to asymptomatic cattle of equivalent age undergoing the same fattening regimens. In HF animals we observed significant LV fibrosis, abundant cardiac adipose depots, coronary artery injury, and pulmonary venous remodeling recapitulating human obesity-related PH-LHD. Additionally, striking muscularization, medial hypertrophy, adventitial fibrosis, and vasa vasorum hyperplasia in the pulmonary arterial circulation were associated with sequela of pathologic right ventricular (RV) remodeling suggesting combined pulmonary venous and arterial hypertension. The association between obesity, pathologic cardiopulmonary remodeling, and HF in fattened beef cattle appears to recapitulate the complex pathophysiology of obesity-associated PH-LHD in humans. This novel, naturally occurring, and large animal model may provide mechanistic and translational insights into human disease.Keywords bronchopulmonary anastomoses, cardiac adiposity and fibrosis, obesity, pulmonary venous and arterial remodeling, small vessel disease Date

Investigation of congestive heart failure in beef cattle in a feedyard at a moderate altitude in western Nebraska

“…In that same study, localized hypoxia resulting from respiratory disease was a risk factor, given that cattle treated for respiratory disease were 2-3 times more likely to die of RHF than cattle not treated for respiratory disease. 21 Although high altitude is a well-established factor, previous studies 15,20,21 indicate that obesity and potentially coronary artery disease and left-heart dysfunction are likely major contributing factors to pulmonary hypertension and right-sided heart failure, and may have played a role in disease in the cattle in our study. Cattle are now fed to heavier finishing weights, with abdominal fat accumulation causing hypoxia through hypoventilation.…”

“…These changes likely preceded "muscularization, medial hypertrophy, adventitial fibrosis, and vasa vasorum hyperplasia of the pulmonary" arteries and, in turn, was "associated with the sequela of right ventricular remodeling." 15 Although coronary artery remodeling is thought to play a role in the pathogenesis of obesity-related congestive heart failure in feedyard cattle, 15 interestingly, intramural coronary arteriosclerosis is now recognized to commonly occur subclinically in slaughtered veal calves and beef cattle. 4 Notably, 1 of 3 controls in our study had coronary arteriosclerosis.…”

“…The severity of perivascular, interstitial, and replacement fibrosis 3,10,15,26 in the right and left ventricular myocardium was assessed on sections stained with Masson trichrome using a semiquantitative scoring scheme: 0, no detectable lesions; 1-3 represented increasing amounts and distribution of collagen deposition in perivascular and interstitial locations of the myocardium. Replacement fibrosis was identified as foci of collagen deposition associated with confluent loss of cardiac myocytes (scars), with scores of 1-3 representing increasing sizes and numbers of foci.…”

Evaluation of EPAS1 variants for association with bovine congestive heart failure

“…Since the 1970’s, bovine congestive heart failure (BCHF) has become increasingly common in feedlot cattle maintained at the low to moderate altitudes of the North American Plains (800 to 1,600 m) 5 . However, it is uncertain whether hypobaric hypoxia is the underlying cause of BCHF in these cattle, and evidence suggests that left heart dysfunction may initiate BCHF 6 . Histopathological assessment of cardiopulmonary tissues obtained from affected cattle fattened at 544-1,420 m revealed significant ventricular fibrosis, abundant cardiac adipose depots, coronary artery injury, and pulmonary venous remodeling 6 .…”

Characterizing the impact of altitude and finishing system on mean pulmonary arterial pressure and carcass characteristics in Angus cattle

“…However, it is speculated that the conditions reflect distinct etiologies owing to the differing management practices that exist between ranches and feedlots. Krafsur et al, (2019) found that the physiology of FHD is characterized as significant pathophysiologic remodeling of the left ventricle and pulmonary venous circulation accompanying right heart and pulmonary arterial remodeling. Conversely, HMD has been characterized as pulmonary hypertension and right ventricular dysfunction ( Rhodes, 2005 ).…”