SUMMARY1. We determined the incidence of exercise-induced arterial hypoxaemia and its determinants in sixteen highly trained, healthy runners who were capable of achieving and sustaining very high metabolic rates (maximal 02 uptake = 72 + 2 ml kg-' min-or 4-81 + 0-131 min'). Arterial blood gases and acidbase status were determined at each load of a progressive short-term exercise test and repeatedly during constant-load treadmill running while breathing air and during inhalation of mildly hypoxic, hyperoxic, and helium-enriched gases.2. 5. In view of the correction of hypoxaemia with mild hyperoxia and the very high ratios of alveolar ventilation to pulmonary blood flow (PA/C = 4-6) achieved during heavy exercise, we think it unlikely that non-uniformity of the VA/QC distribution or veno-arterial shunt could explain the hypoxaemia observed in most of our subjects. By exclusion, we suggest that hypoxaemia may be attributed to a diffusion limitation secondary to very short red cell transit times in at least a portion of the pulmonary circulation. These excessively short transit times may occur at high metabolic rates 6 PHY 355 J. A. DEMPSEY, P. G. HANSON AND K. S. HENDERSON if pulmonary capillary blood volume has achieved its maximum expansion at a time when pulmonary blood flow continues to increase.6. Considerable individual variations were present in the hyperventilatory response to heavy work. These variations were inconsistently related to corresponding levels of metabolic acidosis and in many cases a compensatory hyperventilation was minimal or absent in the face of substantial acidosis and hypoxaemia. The findings that tidal breaths during heavy exercise often exceeded the maximum flow-volume curve and that hyperventilation was consistently obtained with helium inhalation, suggest that the hyperventilatory response to heavy work is determined to a significant extent by the mechanical load imposed on the chest wall secondary to increased pulmonary impedance.

We have recently demonstrated that changes in the work of breathing during maximal exercise affect leg blood flow and leg vascular conductance (C. A. Harms, M. A. Babcock, S. R. McClaran, D. F. Pegelow, G. A. Nickele, W. B. Nelson, and J. A. Dempsey. J. Appl. Physiol. 82: 1573-1583, 1997). Our present study examined the effects of changes in the work of breathing on cardiac output (CO) during maximal exercise. Eight male cyclists [maximal O2 consumption (VO2 max): 62 +/- 5 ml . kg-1 . min-1] performed repeated 2.5-min bouts of cycle exercise at VO2 max. Inspiratory muscle work was either 1) at control levels [inspiratory esophageal pressure (Pes): -27.8 +/- 0.6 cmH2O], 2) reduced via a proportional-assist ventilator (Pes: -16.3 +/- 0.5 cmH2O), or 3) increased via resistive loads (Pes: -35.6 +/- 0.8 cmH2O). O2 contents measured in arterial and mixed venous blood were used to calculate CO via the direct Fick method. Stroke volume, CO, and pulmonary O2 consumption (VO2) were not different (P > 0.05) between control and loaded trials at VO2 max but were lower (-8, -9, and -7%, respectively) than control with inspiratory muscle unloading at VO2 max. The arterial-mixed venous O2 difference was unchanged with unloading or loading. We combined these findings with our recent study to show that the respiratory muscle work normally expended during maximal exercise has two significant effects on the cardiovascular system: 1) up to 14-16% of the CO is directed to the respiratory muscles; and 2) local reflex vasoconstriction significantly compromises blood flow to leg locomotor muscles.

Cyclosporine-induced hypertension is associated with sympathetic neural activation, which may be accentuated by the cardiac denervation that results from heart transplantation.

Eighteen hemodialysis, 12 chronic ambulatory peritoneal dialysis (CAPD), and 20 renal transplant patients performed maximal treadmill exercise tests. Heart rates and blood pressures were determined every minute and maximal oxygen consumption was measured directly. Exercise capacity as measured by VO₂ max is low in dialysis patients and similar to sedentary normal individuals in renal transplant patients. Maximal heart rates were significantly lower in hemodialysis patients than transplant recipients. The lower exercise tolerance in end-stage renal disease indicates that most patients regardless of the treatment mode could benefit from attempts through exercise training to increase physical working capacity.