Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber (FiO2=0.1), while controls stayed in normoxia. We compared NO production in expired air, plasma and perfusate drained from isolated rat lungs and measured superoxide concentration in the perfusate. We also detected the presence of superoxide products (hydrogen peroxide and peroxynitrite) and the level of ROS-induced damage expressed as the concentration of lipid peroxydation end products. We found that the production and release of ROS and NO during early phase of chronic hypoxia has specific timing and differs in various compartments, suggesting the crucial role of ROS interaction for development of hypoxic pulmonary hypertension.
- MeSH
- arteria pulmonalis metabolismus MeSH
- hypoxie komplikace metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina peroxydusitá metabolismus MeSH
- oxid dusnatý biosyntéza krev MeSH
- peroxid vodíku metabolismus MeSH
- plicní hypertenze etiologie MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Lungs retrieved from non-heart-beating donors (NHBDs) may alleviate the shortage of suitable organs for transplantation. The critical point is the preservation of lungs during warm ischemia, when severe damage is caused by free radicals. We investigated the effect of ventilation, pre-arrest administration of heparin, and the cell-permeable free radical scavenger, tempol, on the function of NHBD grafts. METHODS: Six experimental and two control groups (n = 6 per group) were established. All experimental groups underwent a protocol of NHBD lung harvesting, which included 1 hour of warm ischemia after pentobarbital euthanasia followed by 90 minutes of cold ischemia. The groups were constructed as follows: Group An-non-ventilated during warm ischemia, no heparin; Group Av-room-air ventilated during warm ischemia, no heparin; Group Hn-non-ventilated, heparin added pre-arrest; Group Hv-ventilated, heparin; Group Tn-non-ventilated, heparin and tempol added pre-arrest; Group Tv-ventilated, tempol, heparin; Group Ac-control group, no warm and cold ischemia, lungs harvested immediately after euthanasia; and Group Tc-controls with tempol added pre-arrest. The lungs were then perfused ex vivo and the perfusion pressure, lung weight and arteriovenous difference in oxygen partial pressure were measured. RESULTS: We found that room-air ventilation during warm ischemia caused severe pulmonary edema during reperfusion. Heparinization prevented an increase in perfusion pressure and ameliorated the oxygen transport ability. Pre-arrest administration of tempol prevented edema formation after ventilation during warm ischemia and had a positive effect on the oxygen transport ability of the lungs. CONCLUSIONS: The free radical scavenger tempol, which has a very good ability to permeate biologic membranes, contributes to better preservation of lungs retrieved from NHBDs.
- MeSH
- antikoagulancia farmakologie MeSH
- časové faktory MeSH
- cyklické N-oxidy farmakologie MeSH
- dárci tkání MeSH
- financování organizované MeSH
- heparin MeSH
- krysa rodu rattus MeSH
- plíce fyziologie účinky léků MeSH
- plicní ventilace MeSH
- reperfuzní poškození prevence a kontrola MeSH
- scavengery volných radikálů farmakologie MeSH
- spinové značení MeSH
- srdeční zástava MeSH
- teplá ischemie škodlivé účinky MeSH
- transplantace plic MeSH
- uchovávání orgánů metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Hypoxic pulmonary vasoconstriction (HPV), an important physiological mechanism, is regulated by changes in the production of and interactions among reactive oxygen species (ROS). There is controversy, however, over whether HPV is mediated by an increase or a decrease in ROS production. Also, the role of NO in HPV remains unclear. The aim of this study was to investigate whether the inhibition of HPV by the antioxidant tempol was dependent on the concentration of NO, and how its effect was influenced by increased basal pulmonary vascular tone. In isolated rat lungs, we measured vasoconstrictor responses to acute ventilatory hypoxia before and after administration of tempol during perfusion with or without L-NAME. We found that tempol abolished HPV independently of NO production. When we increased basal vascular tone by K(+)-induced depolarization, we also found that tempol completely inhibited HPV. Our results indicate that inhibition of HPV by the superoxide dismutase mimetic tempol does not depend on either NO production or a decrease in basal vascular tone.
- MeSH
- antioxidancia farmakologie MeSH
- cyklické N-oxidy farmakologie MeSH
- financování organizované MeSH
- hypoxie farmakoterapie metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- krysa rodu rattus MeSH
- NG-nitroargininmethylester farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- plicní oběh fyziologie účinky léků MeSH
- reaktivní formy kyslíku metabolismus MeSH
- spinové značení MeSH
- superoxiddismutasa metabolismus MeSH
- vazokonstrikce fyziologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- dárci tkání MeSH
- heparin MeSH
- ischemie MeSH
- modely u zvířat * MeSH
- mozková smrt MeSH
- potkani Wistar MeSH
- srdeční zástava MeSH
- transplantace plic * MeSH
- umělé dýchání MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
