Parabiotic model for differentiating local and systemic effects of continuous and intermittent hypoxia.
Hypoxia can be damaging either because cells are directly sensitive to low oxygen pressure in their local microenvironment and/or because they are exposed to circulating factors systemically secreted in response to hypoxia. The conventional hypoxia model, breathing hypoxic air, does not allow one to distinguish between these local and systemic effects. Here we propose and validate a model for differentially applying local and systemic hypoxic challenges in an animal. We used parabiosis, two mice sharing circulation by surgical union through the skin, and tested the hypothesis that when one of the parabionts breathes room air and the other one is subjected to hypoxic air, both mice share systemic circulation but remain normoxic and hypoxic, respectively. We tested two common hypoxic paradigms in 10 parabiotic pairs: continuous hypoxia (10% O2) mimicking chronic lung diseases, and intermittent hypoxia (40 s, 21% O2; 20 s, 5% O2) simulating sleep apnea. Arterial oxygen saturation and oxygen partial pressure at muscle tissue were measured in both parabionts. Effective cross-circulation was assessed by intraperitoneally injecting a dye in one of the parabionts and measuring blood dye concentration in both animals after 2 h. The results confirmed the hypothesis that tissues of the parabiont under room air were perfused with normally oxygenated blood and, at the same time, were exposed to all of the systemic mediators secreted by the other parabiont actually subjected to hypoxia. In conclusion, combination of parabiosis and hypoxic/normoxic air breathing is a novel approach to investigate the effects of local and systemic hypoxia in respiratory diseases.
CIBER de Enfermedades Respiratorias, Bunyola, Spain; Sleep Laboratory, Hospital Clinic, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain;
Marta
M
Torres
Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
Mauricio
M
Rojas
CIBER de Enfermedades Respiratorias, Bunyola, Spain; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain;
Noelia
N
Campillo
Dorothy P. & Richard P. Simmons Center for Interstitial Lung Disease, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
Nayra
N
Cardenes
CIBER de Enfermedades Respiratorias, Bunyola, Spain; Sleep Laboratory, Hospital Clinic, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Institut Investigacions Biomediques August Pi Sunyer, Barcelona, Spain; and.
Josep M
JM
Montserrat
CIBER de Enfermedades Respiratorias, Bunyola, Spain; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Institut de Bioenginyeria de Catalunya, Barcelona, Spain.
Daniel
D
Navajas
CIBER de Enfermedades Respiratorias, Bunyola, Spain; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain; Institut Investigacions Biomediques August Pi Sunyer, Barcelona, Spain; and rfarre@ub.edu.
Ramon
R
Farré
D000818:Animals; D004195:Disease Models, Animal; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D051379:Mice; D010100:Oxygen / Q000097:blood*; D010227:Parabiosis; D012119:Respiration
D010100:Oxygen
animal model; local hypoxia; parabiosis; systemic hypoxia