This presentation describes various aspects of the regulation of tissue oxygenation, including the roles of the circulatory system, respiratory system, and blood, the carrier of oxygen within these components of the cardiorespiratory system. The respiratory system takes oxygen from the atmosphere and transports it by diffusion from the air in the alveoli to the blood flowing through the pulmonary capillaries. The cardiovascular system then moves the oxygenated blood from the heart to the microcirculation of the various organs by convection, where oxygen is released from hemoglobin in the red blood cells and moves to the parenchymal cells of each tissue by diffusion. Oxygen that has diffused into cells is then utilized in the mitochondria to produce adenosine triphosphate (ATP), the energy currency of all cells. The mitochondria are able to produce ATP until the oxygen tension or PO2 on the cell surface falls to a critical level of about 4–5 mm Hg. Thus, in order to meet the energetic needs of cells, it is important to maintain a continuous supply of oxygen to the mitochondria at or above the critical PO2 . In order to accomplish this desired outcome, the cardiorespiratory system, including the blood, must be capable of regulation to ensure survival of all tissues under a wide range of circumstances. The purpose of this presentation is to provide basic information about the operation and regulation of the cardiovascular and respiratory systems, as well as the properties of the blood and parenchymal cells, so that a fundamental understanding of the regulation of tissue oxygenation is achieved.

High altitude physiology and medicine has again become important. The excep tional achievements of mountaineers who have climbed nearly all peaks over 8,000 m without breathing equipment raise the question of maximal adaptation ca pacity of man to low oxygen pressures. More importantly, the increase in tourism in the Andes and the Himalayas brings over 10,000 people to sites at altitudes above 4,000 and 5,000 m each year. At such heights several kinds of high alti tude diseases are likely to occur, and these complications require detailed medical investigations. Medical authorities need to inform both mountaineers and tourists as to how great a physical burden can be taken in the mountain environment without risk to health. Physicians need to know what kind of prophylaxis is to be employed at high altitudes to prevent the development of diseases and what therapeutic measures should be used once high altitude diseases have occurred. Moreover, the physical condition of the indigenous population living at higher altitudes such as the Andes and the Himalayas, who are exposed continuously to the stress of high altitude, requires our attention. We have become familiar with symptoms characteristic of chronic high-altitude disease: under special conditions this popu lation has a tendency to develop pulmonary hypertension, which is associated with pulmonary edema, pulmonary congestion, and right heart failure.

The ability of cells to sense and respond to changes in oxygenation underlies a multitude of developmental, physiological, and pathological processes. This volume provides a comprehensive compendium of experimental approaches to the study of oxygen sensing in 48 chapters that are written by leaders in their fields.

The appearance of photosynthetic organisms about 3 billion years ago increased the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation. Hypoxia is commonly defined as the reduced availability of oxygen in the tissues produced by different causes, which include reduction of atmospheric PO2 as in high altitude, and secondary to pathological conditions such as sleep breathing and pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays, it has been shown that hypoxia plays an important role in the genesis of several human pathologies including cardiovascular, renal, myocardial and cerebral diseases in fetal, young and adult life. Several mechanisms have evolved to maintain oxygen homeostasis. Certainly, all cells respond and adapt to hypoxia, but only a few of them can detect hypoxia and initiate a cascade of signals intended to produce a functional systemic response. In mammals, oxygen detection mechanisms have been extensively studied in erythropoietin-producing cells, chromaffin cells, bulbar and cortical neurons, pulmonary neuroepithelial cells, smooth muscle cells of pulmonary arteries, and chemoreceptor cells. While the precise mechanism underpinning oxygen, sensing is not completely known several molecular entities have been proposed as possible oxygen sensors (i.e. Hem proteins, ion channels, NADPH oxidase, mitochondrial cytochrome oxidase). Remarkably, cellular adaptation to hypoxia is mediated by the master oxygen-sensitive transcription factor, hypoxia-inducible factor-1, which can induce up-regulation of different genes to cope the cellular effects related to a decrease in oxygen levels. Short-term responses to hypoxia included mainly chemoreceptor-mediated reflex ventilatory and hemodynamic adaptations to manage the low oxygen concentration while more prolonged exposures to hypoxia can elicit more sustained physiological responses including switch from aerobic to anaerobic metabolism, vascularization, and enhancement of blood O2 carrying capacity. The focus of this research topic is to provide an up-to-date vision on the current knowledge on oxygen sensing mechanism, physiological responses to acute or chronic hypoxia and cellular/tissue/organ adaptations to hypoxic environment.

Molecular oxygen deficiency leads to altered cellular metabolism and can dramatically reduce crop productivity. Nearly all crops are negatively affected by a lack of oxygen (hypoxia) due to adverse environmental conditions such as excessive rain and soil waterlogging. Extensive efforts to fully understand how plants sense oxygen deficiency and their ability to respond using different strategies are crucial to increase hypoxia tolerance. Progress in our understanding has been significant in recent years. This topic certainly deserves more attention from the academic community; therefore, we have compiled a series of articles reflecting the advancements made thus far.

The activities of the Food and Nutrition Board's Committee on Military Nutrition Research (CMNR, the committee) have been supported since 1994 by grant DAMD17-94-J-4046 from the U.S. Army Medical Research and Materiel Command (USAMRMC). This report fulfills the final reporting requirement of the grant, and presents a summary of activities for the grant period from December 1, 1994 through May 31, 1999. During this grant period, the CMNR has met from three to six times each year in response to issues that are brought to the committee through the Military Nutrition and Biochemistry Division of the U.S. Army Research Institute of Environmental Medicine at Natick, Massachusetts, and the Military Operational Medicine Program of USAMRMC at Fort Detrick, Maryland. The CMNR has submitted five workshop reports (plus two preliminary reports), including one that is a joint project with the Subcommittee on Body Composition, Nutrition, and Health of Military Women; three letter reports, and one brief report, all with recommendations, to the Commander, U.S. Army Medical Research and Materiel Command, since September 1995 and has a brief report currently in preparation. These reports are summarized in the following activity report with synopses of additional topics for which reports were deferred pending completion of military research in progress. This activity report includes as appendixes the conclusions and recommendations from the nine reports and has been prepared in a fashion to allow rapid access to committee recommendations on the topics covered over the time period.