Biomedical subjects
Publications and source records attributed to Robert F Grover.
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John T. (Jack) Reeves' science is reviewed across the 37 years of his research career at the University of Colorado Health Sciences Center, a period which occupied approximately half his remarkable life. His contributions centered on understanding the inter-relatedness as well as the underlying mechanisms controlling the various components of the O(2) transport system. We review here his studies on exercise performance; these encompassed about half his scientific output with the other half being devoted to the study of hypoxic pulmonary hypertension. Early studies concerned cardiac output, showing how it was a balance between O(2) uptake and O(2) extraction, and that cardiac output during exercise at high altitude was reduced, most likely because of decreased plasma volume and left ventricular filling. Jack's many studies addressed virtually every aspect of the O(2) transport system -- adding significantly to our understanding of the syndromes of altitude illness, the mechanisms by which ventilatory sensitivity to hypoxia and hypercapnia influenced ventilatory acclimatization, and the contributions of the various limbs of the autonomic nervous system on systemic blood pressure, vascular resistance and substrate utilization. His scientific career ended abruptly in 2004 when struck by a car while biking to work, but his legacy remains in his more than 385+ research articles or chapters, the 40+ fellows he trained, and the countless number of younger (and older) scientists for whom he served as a role model for learning how to scrutinize their data and present their findings in clear and sometimes bold prose. An integral man, he is sorely missed.
Pulmonary hypertension had long been suspected in high-altitude natives of the Andes. However, it remained for a team of Peruvian scientists led by Dante Penaloza to provide not only the first clear evidence that humans living at high altitude did indeed have chronic, and occasionally severe, pulmonary hypertension, but more importantly, that this was a consequence of structural changes in the pulmonary vascular bed. Novel histological findings by one of the team, Javier Arias-Stella, indicated that hypoxia-induced thickening of the pulmonary arteriolar walls was the primary cause of the elevated pressure. Because the hypertension was not promptly reversed by vasodilators (oxygen inhalation or acetylcholine infusion), they found it differed from acute hypoxic pulmonary vasoconstriction. The team's other novel findings included a delay in the normal fall in pulmonary vascular resistance after birth and, in adults, a lack of vasodilation with muscular exercise. Furthermore, the altitude-related pulmonary hypertension resolved over time at sea level.
In Andean natives (NAT), the ventilatory response to hypoxia is blunted at rest but potential interaction with exercise has been little studied. Therefore, during three levels of submaximal exercise, 13 NAT were compared with 6 sojourners (SOJ) acclimatized at 4,360 m for an average of 7 months. Exercise ventilation was measured first breathing oxygen (PI(O(2)) 410 Torr) and then ambient air (PI(O(2)) 86 Torr). In SOJ ventilation was increased by hypoxia at all three exercise levels including the mildest. In NAT, however, the threshold for hypoxic sensitivity was displaced, but during exercise above this threshold hypoxia increased ventilation at a rate similar to that seen in SOJ. At the heaviest workload, ventilation was increased by hypoxia 18% in NAT compared with 30% in SOJ. Thus, during exercise Andean NAT do exhibit a ventilatory sensitivity to hypoxia, the magnitude of which is dependent upon exercise intensity.