Effects of erythropoietin on muscle O2 transport during exercise in patients with chronic renal failure.

Abstract

Erythropoietin (rHuEPO) has proven to be effective in the treatment of anemia of chronic renal failure (CRF). Despite improving the quality of life, peak oxygen uptake after rHuEPO therapy is not improved as much as the increase in hemoglobin concentration ([Hb]) would predict. We hypothesized that this discrepancy is due to failure of O 2 transport rates to rise in a manner proportional to [Hb]. To test this, eight patients with CRF undergoing regular hemodialysis were studied pre-and post-rHuEPO ([Hb] ϭ 7.5 Ϯ 1.0 vs. 12.5 Ϯ 1.0 g · dl Ϫ 1 ) using a standard incremental cycle exercise protocol. A group of 12 healthy sedentary subjects of similar age and anthropometric characteristics served as controls. Arterial and femoral venous blood gas data were obtained and coupled with simultaneous measurements of femoral venous blood flow ( leg) by thermodilution to obtain O 2 delivery and oxygen uptake ( O 2 ). Despite a 69% increase in [Hb], peak O 2 increased by only 33%. This could be explained largely by reduced peak leg blood flow, limiting the gain in O 2 delivery to 37%. At peak O 2 , after rHuEPO, O 2 supply limitation of maximal O 2 was found to occur, permitting the calculation of a value for muscle O 2 conductance from capillary to mitochondria (DO 2 ). While DO 2 was slightly improved after rHuEPO, it was only 67% of that of sedentary control subjects. This kept maximal oxygen extraction at only 70%. Two important conclusions can be reached from this study. First, the increase in

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

“…In a previous study with CRF patients (10), O 2 supply dependency of O 2 max was demonstrated. This indicates that peak O 2 is not determined by mitochondrial oxidative limits.…”

“…This returns elevated muscle blood flow ( ) to values similar to levels seen in matched control subjects during peak exercise and partially offsets the effect of the rise in arterial O 2 content on O 2 delivery. Second, O 2 conductance from muscle microcirculation to mitochondria is particularly low in CRF patients (10) and after rHuEPO therapy still remains at ‫ف‬ 70% of that seen in control subjects. The structural basis of this abnormal O 2 transport conductance is likely microvascular rarification and capillarymyofiber dissociation provoked by a uremic myopathy (11)(12)(13).…”

“…The structural basis of this abnormal O 2 transport conductance is likely microvascular rarification and capillarymyofiber dissociation provoked by a uremic myopathy (11)(12)(13). As a result of these changes, the ratio of muscle diffusive to perfusive conductance as defined by Piiper et al (14)(15)(16) may either not vary (10) or even fall after rHuEPO. Since this Q .…”

Efeitos negativos da insuficiência renal crônica sobre a função pulmonar e a capacidade funcional

“…Other complications in lung tissue are found in patients with CKF, such as pulmonary edema, pleural effusion (mainly in terminal patients with CKF), pulmonary and pleural fibrosis and calcification, pulmonary hypertension, decreased pulmonary capillary blood flow and hypoxemia 13,14 . There are also deficits in oxygen supply to the muscles as a result of decreased peripheral microcirculation, decreased muscle ATP synthesis due to deficiencies in the use of carbohydrates, signs of insulin resistance and changes to glycolytic enzymes, and decreased oxidation of fatty acids [15][16][17] .…”

Optimal health and function among the elderly: lessening severity of ADL disability

“…Consequently, maximal oxygen uptake (VO 2 max), the best single indicator of physical working capacity, is decreased. In older adults, a strong inverse association between physical activity and functional decline has been consistently observed [42,57,64,68]. Accordingly, one may expect maximal cardiac output to decrease with aging irrespective of lifestyle due to genetic factors.…”