Carbon monoxide uptake kinetics of arterial, venous and capillary blood during CO rebreathing.

The uptake and distribution of CO throughout the circulatory system during two different methods of CO rebreathing (2 min 'Schmidt' and 40 min 'Burge' methods) were determined in nine healthy volunteers. Specifically, the impact of (i) differences in circulatory mixing time (t(mix)), (ii) CO diffusion to myoglobin (Mb) and (iii) CO wash-out was assessed on calculated haemoglobin mass (Hb(mass)). Arterial (a), muscle venous (vm) and capillary samples (c) were obtained simultaneously at 0, 1, 2, 3.5, 5, 7.5, 10, 12.5, 15, 20, 30 and 40 min for determination of carboxyhaemoglobin (HbCO). Carbon monoxide wash-out was measured from expired air following rebreathing. The rate of CO diffusion to Mb was calculated using the change in HbCO after t(mix), and the rate of CO wash-out. In both methods, HbCOa and HbCOc followed a near-identical time course, peaking within the first 2 min and decreasing thereafter. The HbCOvm increased slowly and was significantly lower at 1, 2 and 3.5 min in both methods (P < 0.01). The HbCOa peaked significantly higher in the Schmidt method (P = 0.03). Circulatory mixing had occurred by 10 min in most but not all subjects. The rate of CO wash-out was 0.25 ± 0.13 ml min⁻¹ in the Schmidt and 0.25 ± 0.16 ml min⁻¹ in the Burge method. The rate of CO diffusion to Mb was 0.22 ± 0.11 and 0.16 ± 0.13 ml min⁻¹ (P = 0.63) in Schmidt and Burge methods, respectively. Inhalation of a CO bolus during the Schmidt method results in faster HbCOa uptake but does not greatly shorten t(mix) or influence rates of CO wash-out and flux to Mb. The calculated Hb(mass) depends substantially on the plateau level of HbCO; therefore, it is paramount to ensure HbCO is mixed completely prior to blood sampling, as well as accounting for potential within-subject alterations of CO exhalation and CO flux to Mb.

Errors of measurement for blood volume parameters: a meta-analysis.

The volume of red blood cells (V(RBC)) is used routinely in the diagnostic workup of polycythemia, in assessing the efficacy of erythropoietin administration, and to study factors affecting oxygen transport. However, errors of various methods of measurement of V(RBC) and related parameters are not well characterized. We meta-analyzed 346 estimates of error of measurement of V(RBC) for techniques based on Evans blue (V(RBC,Evans)), 51chromium-labeled red blood cells (V(RBC,51Cr)), and carbon monoxide (CO) rebreathing (V(RBC,CO)), as well as hemoglobin mass with the carbon-monoxide method (M(Hb,CO)), in athletes and active and inactive subjects undergoing various experimental and control treatments lasting minutes to months. Subject characteristics and experimental treatments had little effect on error of measurement, but measures with the smallest error showed some increase in error with increasing time between trials. Adjusted to 1 day between trials and expressed as coefficients of variation, mean errors for M(Hb,CO) (2.2%; 90% confidence interval 1.4-3.5%) and V(RBC,51Cr) (2.8%; 2.4-3.2%) were much less than those for V(RBC,Evans) (6.7%; 4.9-9.4%) and V(RBC,CO) (6.7%; 3.4-14%). Most of the error of V(RBC,Evans) was due to error in measurement of volume of plasma via Evans blue dye (6.0%; 4.5-7.8%), which is the basis of V(RBC,Evans). Most of the error in V(RBC,CO) was due to estimates from laboratories with a relatively large error in M(Hb,CO), the basis of V(RBC,CO). V(RBC,51Cr) and M(Hb,CO) are the best measures for research on blood-related changes in oxygen transport. With care, V(RBC,Evans) is suitable for clinical applications of blood-volume measurement.

Standardising analysis of carbon monoxide rebreathing for application in anti-doping.

Determination of total haemoglobin mass (Hbmass) via carbon monoxide (CO) depends critically on repeatable measurement of percent carboxyhaemoglobin (%HbCO) in blood with a hemoximeter. The main aim of this study was to determine, for an OSM3 hemoximeter, the number of replicate measures as well as the theoretical change in percent carboxyhaemoglobin required to yield a random error of analysis (Analyser Error) of ≤1%. Before and after inhalation of CO, nine participants provided a total of 576 blood samples that were each analysed five times for percent carboxyhaemoglobin on one of three OSM3 hemoximeters; with approximately one-third of blood samples analysed on each OSM3. The Analyser Error was calculated for the first two (duplicate), first three (triplicate) and first four (quadruplicate) measures on each OSM3, as well as for all five measures (quintuplicates). Two methods of CO-rebreathing, a 2-min and 10-min procedure, were evaluated for Analyser Error. For duplicate analyses of blood, the Analyser Error for the 2-min method was 3.7, 4.0 and 5.0% for the three OSM3s when the percent carboxyhaemoglobin increased by two above resting values. With quintuplicate analyses of blood, the corresponding errors reduced to .8, .9 and 1.0% for the 2-min method when the percent carboxyhaemoglobin increased by 5.5 above resting values. In summary, to minimise the Analyser Error to ∼≤1% on an OSM3 hemoximeter, researchers should make ≥5 replicates of percent carboxyhaemoglobin and the volume of CO administered should be sufficient increase percent carboxyhaemoglobin by ≥5.5 above baseline levels.

Impaired K+ regulation contributes to exercise limitation in end-stage renal failure.

BACKGROUND: Patients with end-stage renal failure (ESRF) exhibit grossly impaired maximal exercise performance. This study investigated whether K+ regulation during exercise is impaired in ESRF and whether this is related to reduced exercise performance. METHODS: Nine stable hemodialysis patients and eight controls (CON) performed incremental cycling exercise to volitional fatigue, with measurement of peak oxygen consumption (VO2 peak). Arterial blood was sampled during and following exercise and analyzed for plasma [K+] (PK). RESULTS: The VO2 peak was approximately 44% less in ESRF than in CON (P < 0.001), whereas peak exercise PK was greater (7.23 +/- 0.38 vs. 6.23 +/- 0.14 mmol x L-1, respectively, P < 0.001). In ESRF, the rate of rise in PK during exercise was twofold greater (0.43 +/- 0.05 vs. 0.23 +/- 0.03 mmol. L-1x min-1, P < 0.005) and the ratio of rise in PK relative to work performed was 3.7-fold higher (90.1 +/- 13.5 vs. 24.7 +/- 3.3 nmol. L-1. J-1, P < 0.001). A strong inverse relationship was found between VO2 peak and the DeltaPK. work-1 ratio (r = -0.80, N = 17, P < 0.001). CONCLUSIONS: Patients with ESRF exhibit grossly impaired extrarenal K+ regulation during exercise, demonstrated by an excessive rise in PK relative to work performed. We further show that K+ regulation during exercise was correlated with aerobic exercise performance. These results suggest that disturbed K+ regulation in ESRF contributes to early muscle fatigue during exercise, thus causing reduced exercise performance.