Even before the very beginning of human<unk>  exploration, serious and reasonable concerns were expressed about exposure of humans to the microgravity of<unk>  due to the potential systemic<unk>  on terrestrially-evolved life forms adapted to Earth gravity. Unloading of skeletal muscle, both on Earth via bed-rest experiments and during<unk> flight, result in remodeling of muscle (atrophic response). As a result, decrements occur in skeletal muscle strength, fatigue resistance, motor performance, and connective tissue integrity. In addition, there are cardiopulmonary and vascular changes, including a significant decrease in red blood cell mass, that affect skeletal muscle function. This normal adaptive response to the microgravity environment may become a liability resulting in increased risk of an inability or decreased efficiency in crewmember performance of physically demanding tasks during extravehicular activity (EVA) or upon return to Earth. In the US human<unk>  program, the only in-flight countermeasure to skeletal muscle functional deficits that has been utilized thus far is physical exercise. In-flight exercise hardware and protocols have varied from mission to mission, somewhat dependent on mission duration and the volume of the<unk> craft available. Collective knowledge gained from these mission has aided in the evolution of exercise hardware and protocols designed to minimize muscle atrophy and the concomitant deficits in skeletal muscle function. Russian scientists have utilized a variety of exercise hardware and in-flight exercise protocols during long-duration<unk> flight (up to and beyond one year) aboard the Mir<unk>  station. On the International<unk>  Station (ISS), a combination of resistive and aerobic exercise has been used. Outcomes have been acceptable according to current expectations for crewmember performance on return to Earth. However, for missions to the Moon, establishment of a lunar base, and interplanetary travel to Mars, the functional requirements for human performance during each specific phase of these missions have not been sufficiently defined to determine whether currently developed countermeasures are adequate to meet physical performance requirements. Research access to human crewmembers during<unk>  flight is limited. Earth-bound physiologic models have been developed and findings reviewed. Models include horizontal or head-down bed rest, dry immersion bed rest, limb immobilization, and unilateral lower-limb suspension. While none of these ground-based analogs provides a perfect simulation of human microgravity exposure during<unk> flight, each is useful for study of particular aspects of muscle unloading as well as for investigation of sensorimotor alterations. Development, evaluation and validation of new countermeasures to the<unk>  of skeletal muscle unloading will likely employ variations of these same basic ground-based models. Prospective countermeasures may include pharmacologic and/or dietary interventions, innovative exercise hardware providing improved loading modalities, locomotor training devices, passive exercise devices, and artificial gravity either as an integral component of the<unk> craft or as a discrete device contained within it. With respect to the latter, the hemodynamic and metabolic responses to increased loading provided by a human-powered centrifuge have been described recently.
Physiological effects in space
Adequate stimulus
Route of administration
Pain tolerance
Modes of toxic action
Neural binding
Theories of general anaesthetic action
Mechanical properties of biomaterials