ABSTRACT
BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major cause of morbidity and mortality in premature infants exposed to high levels of oxygen. This is mainly attributed to increased oxidative stress and angiogenesis defects impacting lung alveolarization. METHODS: Here we use optical imaging to investigate the role of Bcl-2 in modulation of oxidative stress and angiogenesis and pathogenesis of BPD. Cryoimaging of the mitochondrial redox state of mouse lungs was applied to determine the metabolic state of the lungs from Bcl-2 +/+ (control), Bcl-2-deleted in the endothelium (Bcl-2 VE-cad) and Bcl-2-deficient (Bcl-2 -/-; global null) using mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide), and FADH2 (Flavin Adenine Dinucleotide) as the primary electron carriers in oxidative phosphorylation. RESULTS: We observed a 47% and 26% decrease in the NADH redox in Bcl-2 deficient lungs, Bcl-2 -/- and Bcl-2 VE-cad, respectively. CONCLUSIONS: Thus, Bcl-2 deficiency is associated with a significant increase in oxidative stress contributing to reduced angiogenesis and enhanced pathogenesis of BPD.
ABSTRACT
The oxygenation level of a tissue is an important marker of the health of the tissue and has a direct effect on performance. It has been shown that the blood flow to the paretic muscles of hemiparetic post-stroke patients is significantly reduced compared to non-paretic muscles. It is hypothesized that hemodynamic activity in paretic muscles is suppressed as compared to non-paretic muscles, and that oximetry can be used to measure this disparity in real-time. In order to test this hypothesis, a custom-made oximetry device was used to measure hemodynamic activity in the forearm extensor muscles in post-stroke patients' paretic and non-paretic sides and in a control population during three exercise levels calibrated to the subject's maximum effort. The change in oxygenation (ΔOxy) and blood volume (ΔBV) were calculated and displayed in real-time. Results show no apparent difference in either ΔOxy or ΔBV between control subjects' dominant and non-dominant muscles. However, the results show a significant difference in ΔOxy between paretic and non-paretic muscles, as well as a significant difference between normalized post-stroke and control data. Further work will be necessary to determine if the observed difference between the paretic and non-paretic muscles changes over the course of physical therapy and can be correlated with functional improvements.
