Oxygen therapy may worsen the survival rate in rats with monocrotaline-induced pulmonary arterial hypertension

Abstract

Although oxygen therapy rapidly improves arterial oxygen saturation in idiopathic pulmonary arterial hypertension, the effects of chronic administration of oxygen are unknown. The purpose of the present study was to investigate the effects of chronic oxygen therapy on the histological changes and survival rate in rats with idiopathic pulmonary arterial hypertension. Idiopathic pulmonary arterial hypertension was induced by monocrotaline injection. The rats were then randomly assigned to receive or not receive oxygen therapy (O2 group and non-O2 group, respectively). The rats in the O2 group were exposed to a high (90%) oxygen environment from day 17 following injection of monocrotaline, when hypoxemia was first observed. The pulmonary arteriole walls were significantly thicker in monocrotaline-injected rats than in saline-injected rats as vehicle on day 19 and were significantly thicker in the rats that received oxygen therapy than in the rats that did not. Right ventricular inflammations were significantly higher in monocrotaline-injected rats than in saline-injected rats on day 19 and were significantly higher in the rats that received oxygen therapy than in the rats that did not. By day 20 after injection of monocrotaline, the survival rate was significantly lower in the rats that received oxygen therapy than in those that did not. Superoxide dismutase activity in the lungs was higher in monocrotaline-injected rats than in saline-injected rats on day 19 after monocrotaline injection and was also higher in the saline-injected rats that received oxygen therapy than in the saline-injected rats that did not. No interaction was detected between monocrotaline injection and oxygen therapy. These results suggest that chronic oxygen therapy worsens the histological changes and survival rate in idiopathic pulmonary arterial hypertension. The fact that degradation of the histological changes and survival rate was accompanied by increase in superoxide dismutase activity suggests that antioxidant capacity may contribute to the degradation.

Oxidative Stress and Its Implications in the Right Ventricular Remodeling Secondary to Pulmonary Hypertension

“…Rats that received MCT and oxygen therapy recruited leukocytes that promoted RV inflammation and failure. And despite increases in SOD activity, antioxidants were not able to sufficiently counteract the oxidative stress caused by the combination of MCT and chronic oxygen therapy (Fujita et al, 2018).…”

Glucose loading for heart failure protects the myocardium and improves physical function

“…Our results also confirmed that administration of MCT induced heart failure, increased HIF-1 alpha (a marker of hypoxia), increased lactate, and enhanced the glycolytic system. Recent reports showed that excessive utilization of mitochondrial metabolism in the pathogenesis of heart failure induces higher than normal oxidative stress (ROS) and apoptosis 5 ) . Furthermore, normalized oxygen administration for acute heart failure can increase myocardial necrosis 21 ) .…”

“…However, oxygen administration for heart failure has recently been reported to cause myocardial damage. Fujita et al reported that overexploitation of fatty acid metabolism during heart failure causes more oxidative stress (reactive oxygen species [ROS]) in mitochondria than usual, leading to myocardial injury 5 ) . Glucose loading, which increases glucose metabolism in heart failure, may suppress fatty acid metabolism in mitochondria and exert a protective effect on the myocardium.Therefore, in this study we generated rat models of heart failure to examine the effects of forced turnover of glycolytic metabolism on the myocardium and physical functions.…”

Effects of nasal high flow on sympathovagal balance, sleep, and sleep-related breathing in patients with precapillary pulmonary hypertension

“…During the day, NHF20 increased mean SpO 2 from approximately 91 to 93%, while at nighttime, where hypoxia has previously been described to be more severe [ 8 , 10 ], mean oxygen saturation was approximately 88% in the same patients. Faster and greater increases in oxygen saturation have been shown to be associated with increased levels of oxygen radicals, which in turn are associated with poor functional status in patients with heart failure [ 43 , 45 – 47 ]. It appears that differences in the effects of NHF20 on oxygen saturation also account for the unwanted increase in sympathetic drive during daytime and a beneficial reduction in sympathetic drive at night in the present study.…”