Static and dynamic components of right ventricular afterload are negatively associated with calf survival at high altitude1

Abstract

The purposes of this study were to evaluate mean, systolic, and diastolic pulmonary arterial pressures; pulmonary arterial pulse pressures; and systemic oxygen extraction fraction as risk factors for the survival of suckling calves on one ranch located at an altitude of ≥ 2,730 m in Colorado, USA. A prospective cohort study of 58 calves was performed. Pulmonary arterial pressures and systemic oxygen extraction were measured when calves were approximately 3 mo (86 ± 7 d) and 7 mo (197 ± 6 d) of age. Seven of the 58 calves (12%), 4 steers and 3 heifers, were unaccounted for and presumed dead between 3 and 7 mo of age. Calves presumed to have died between 3 and 7 mo of age had significantly greater mean ( = 0.005) and systolic ( = 0.001) pulmonary arterial pressures and greater pulse pressures ( = 0.03) at 3 mo of age than calves that survived to 7 mo. Calves presumed to have died tended to have greater systemic oxygen extraction fractions at 3 mo of age than calves that survived ( = 0.13). Diastolic pressure was not associated with survival ( = 0.27). Mean pulmonary arterial pressure is predominantly determined by static resistance attributable to distal pulmonary arterial remodeling. Pulse pressure and systolic pulmonary arterial pressure represents the dynamic or oscillatory resistance and is determined by the characteristics of ventricular ejection and proximal arterial stiffness. These findings indicate that it may be beneficial to include pressure measurements indicative of both static and dynamic pulmonary arterial resistance in the selection of breeding stock at high altitude.

Brief Report: Case Comparison of Therapy With the Histone Deacetylase Inhibitor Vorinostat in a Neonatal Calf Model of Pulmonary Hypertension

“…In their study using hypoxic rats with sustained HDAC inhibitor dosing (21 days), Cavasin et al reported significantly lowered mPAP with reduced PA medial hypertrophy and stiffening, together with evidence of direct beneficial actions on RV remodeling. Studies in beef cattle raised at high altitude showed that increased mean, systolic, and PA pulse pressures, independently predicted increased risk of mortality due to right heart failure ( Neary et al, 2016 ). Taken together, we hypothesize that the beneficial actions of vorinostat on pulmonary vascular stiffening in our study lead to the observed improvements in cardiac morphology and performance, and molecular markers of pathologic remodeling.…”

Hypoxia induces an increase in intestinal permeability and pulmonary arterial pressures in neonatal Holstein calves despite feeding the flavonoid rutin

“…Hypoxia, however, significantly increased both mPAP and intestinal permeability. Hypoxia-induced pulmonary hypertension in bovine calves has been well documented (Stenmark et al, 1987;Neary et al, 2013Neary et al, , 2016b, but hypoxia-induced gastrointestinal permeability has not. However, numerous studies in rodent models demonstrate the deleterious effect of hypoxia on intestinal permeability (Fisher et al, 2013;Novosad et al, 2013).…”

Successful treatment of suckling Red Angus calves for bovine respiratory disease is not associated with increased mean pulmonary arterial pressures at weaning

“…Furthermore, the mPAP levels reported in this study were considerably greater than mPAP reported in other mammalian species and even similarly aged calves located at a higher altitude. These findings are much more than a physiological curiosity; pulmonary hypertension is deleterious to the health and survival of cattle ( Neary et al, 2016b ).…”