Kumari 2019 Am J Physiol Heart Circ Physiol
|Kumari S, Braun RK, Tetri L, Barton GP, Hacker TA, Goss KN (2019) Bimodal right ventricular dysfunction after postnatal hyperoxia exposure: implications for the preterm heart. Am J Physiol Heart Circ Physiol [Epub ahead of print].|
Abstract: Rats exposed to postnatal hyperoxia develop right ventricular (RV) dysfunction, mild pulmonary hypertension, and dysregulated cardiac mitochondrial biogenesis when aged to 1 year, with the degree of cardiac dysfunction and pulmonary hypertension similar to that previously described in young adults born preterm. Here, we sought to understand the impact of postnatal hyperoxia exposure on RV hemodynamic and mitochondrial function across the lifespan.
Pups from timed-pregnant Sprague Dawley rats were randomized to normoxia or hyperoxia (FIO2 0.85) exposure for the first 14 days of life, a commonly used model of chronic lung disease of prematurity. RV hemodynamic and mitochondrial function were assessed by invasive measurement of RV pressure-volume loops and by high-resolution respirometry at postnatal day 21 (P21), P90, and P365.
At P21, hyperoxia-exposed rats demonstrated severe pulmonary hypertension and RV dysfunction, accompanied by depressed mitochondrial oxidative capacity. However, significant upregulation of mitochondrial biogenesis at P21 as well as improved afterload led to complete RV hemodynamic and mitochondrial recovery at P90. Mitochondrial DNA mutations were significantly higher by P90, and associated with significant late RV mitochondrial and hemodynamic dysfunction at P365.
There appears to be a "honeymoon period" where cardiac hemodynamic and mitochondrial function normalizes following postnatal hyperoxia exposure, only to decline again with ongoing aging. This finding may have significant implications if a long-term pulmonary vascular screening program were to be developed for children or adults with a history of severe prematurity. Further investigation into the mechanisms of recovery are warranted.
Labels: MiParea: Respiration, Developmental biology
Organism: Rat Tissue;cell: Heart Preparation: Permeabilized tissue
Regulation: Oxygen kinetics Coupling state: LEAK, OXPHOS, ET Pathway: N, S, CIV, ROX HRR: Oxygraph-2k