Universidad Nacional de La Plata, Argentina, 1962
Mechanisms of adaptation to hypoxia.
My research centers on the mechanisms of adaptation of intact organisms to alveolar hypoxia, a condition that occurs when environmental O2 levels are reduced, as in altitude, or in some types of pulmonary disease. One aspect of my research includes the effect of environmental hypoxia on the mechanisms of systemic O2 transport at rest and during exercise. A rat model developed in my laboratory allowed us to characterize the major steps in the O2 cascade from atmosphere to cells, at rest and during exercise. Using this approach, we have studied the mechanisms by which hypoxia influences maximal O2 uptake during exercise, and the roles played by aerobic training, changes in hemoglobin concentration and O2 affinity, and alterations in the autonomic nervous system on these mechanisms. Current research in this area involves the study of the determinants of maximal O2 uptake in rats artificially selected for running endurance.
Altitude hypoxia may result in acute illnesses such as acute mountain sickness( AMS) , high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE). Acclimatized individuals or persons indigenous to high altitude may develop chronic mountain sickness, or Monge's disease, which is characterized by excessive polycythemia. There is evidence that some of the acute altitude illnesses, specifically AMS and HACE, may have an inflammatory component. In collaboration with Dr John Wood's laboratory we have shown that alveolar hypoxia results in a rapid and widespread systemic inflammation. We have demonstrated that the inflammation is not triggered by a reduction in systemic tissue O2 levels, but rather by the release of a chemokyne, MCP-1 or CCL2, by the alveolar macrophages (AMO) activated by hypoxia. Circulating MCP-1 activates perivascular mast cells which release renin and activates the renin-angiotensin system to initiate the microvascular inflammation. Current work is directed to study the role of the inflammation as a possible trigger of the acclimatization process.
Norberto C. Gonzalez, M.D.
1006 Smith West
3901 Rainbow Blvd.
Kansas City, KS 66160
F: (913) 588-7430