Biomedical subjects

I Mark Olfert

Publications and source records attributed to I Mark Olfert.

8 recordsLinked to original sources

PubMed2007

Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise.

Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid-base status during cycle exercise at approximately 30, 50 and 90% VO2max in normoxia (F(IO2) = 0.2093) and acute hypoxia (F(IO2) = 0.125). In a double-blind, order-balanced, crossover design, six healthy, trained men (normoxic VO2max= 59 ml kg(-1) min(-1)) exercised at both F(IO2) values after ACZ (3 doses of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated using the other drug (placebo or ACZ). We measured cardiac output (QT), leg blood flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple inert gas elimination technique. ACZ did not significantly affect VO2, QT, LBF or muscle gas exchange. As expected, ACZ led to lower arterial and venous blood [HCO3-], pH and lactate levels (P < 0.05), and increased ventilation (P < 0.05). In both normoxia and hypoxia, ACZ resulted in higher arterial P(O2) and saturation and a lower alveolar-arterial P(O2) difference (AaD(O2)) due to both less VA/Q mismatch and less diffusion limitation (P < 0.05). In summary, ACZ improved arterial oxygenation during exercise, due to both greater ventilation and more efficient pulmonary gas exchange. However, muscle gas exchange was unaffected.

Acetazolamide↗

PubMed2006

The effect of incomplete acetylene washout on cardiac output measurement using open circuit acetylene uptake.

The open circuit acetylene uptake method is a useful non-invasive means of measuring cardiac output. However, because of accumulation of inhaled acetylene in tissues, the cardiac output uptake is underestimated, if residual acetylene is not allowed to wash out completely in between measurements. We determined the effect of applying a correction factor that estimates mixed venous acetylene concentration from endtidal values to the calculation of cardiac output. This accounts for mixed venous acetylene present during measurements made before complete washout. Six healthy subjects performed steady-state exercise at approximately 30% and 60% of V(O2 max). Cardiac output measurements were made at each exercise intensity using the open circuit acetylene uptake method (inspired [acetylene] approximately 1%), with the first and last measurements having no detectible levels of acetylene in expired gas (reference measurement). Data were also obtained with immediate pre-measurement endtidal concentrations ranging from 3% to 15% of the inspired [acetylene], in random order in between. Oxygen consumption, carbon dioxide production and heart rate did not change significantly during testing at each exercise intensity. Reference cardiac output also did not change significantly and averaged 11.1+/-0.8 L/min at 30% of V(O2 max) and 16.5+/-2.0 L/min at 60% of V(O2 max). Uncorrected cardiac output measurements progressively underestimated cardiac output by 15% at the 3% of inspired endtidal [acetylene] and by over 50% at 15% [acetylene] (p<0.0001). However, when corrected for residual endtidal [acetylene], cardiac outputs were not significantly different from the reference measurements. The results of this study suggest that by accounting for residual endtidal acetylene in mixed venous blood, cardiac output can be accurately measured even when washout of acetylene is incomplete, allowing measurements as often as every 10-15 s.

Acetylene↗

PubMed2006

Steep head-down tilt has persisting effects on the distribution of pulmonary blood flow.

Head-down tilt has been shown to increase lung water content in animals and alter the distribution of ventilation in humans; however, its effects on the distribution of pulmonary blood flow in humans are unknown. We hypothesized that head-down tilt would increase the heterogeneity of pulmonary blood flow in humans, an effect analogous to the changes seen in the distribution of ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the lung. To test this, we evaluated changes in the distribution of pulmonary blood flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt using the magnetic resonance imaging technique of arterial spin labeling. Data were acquired in triplicate before tilt and at 10-min intervals for 1 h after tilt. Pulmonary blood flow heterogeneity was quantified by the relative dispersion (standard deviation/mean) of signal intensity for all voxels within the right lung. Relative dispersion was significantly increased by 29% after tilt and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06 pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We speculate that the mechanism most likely responsible for our findings is that increased pulmonary capillary pressures and fluid efflux in the lung resulting from head-down tilt alters regional blood flow distribution.

Adult↗

PubMed2005

Muscle-targeted deletion of VEGF and exercise capacity in mice.

Methods to study exercise are evolving from classically integrative organ approaches towards the more fundamental cellular reactions. While in vitro cellular and molecular methods are well established, only recently has in vivo molecular manipulation been widely used. This review discusses two complementary methods for determining in vivo the significance of one gene thought important to exercise: vascular endothelial growth factor (VEGF). Because VEGF deletion is embryonically lethal, its study requires conditional and/or organ-targeted strategies. We inactivated the muscle VEGF gene in two ways:

Animals↗

PubMed2004

Loss of skeletal muscle HIF-1alpha results in altered exercise endurance.

The physiological flux of oxygen is extreme in exercising skeletal muscle. Hypoxia is thus a critical parameter in muscle function, influencing production of ATP, utilization of energy-producing substrates, and manufacture of exhaustion-inducing metabolites. Glycolysis is the central source of anaerobic energy in animals, and this metabolic pathway is regulated under low-oxygen conditions by the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha). To determine the role of HIF-1alpha in regulating skeletal muscle function, we tissue-specifically deleted the gene encoding the factor in skeletal muscle. Significant exercise-induced changes in expression of genes are decreased or absent in the skeletal-muscle HIF-1alpha knockout mice (HIF-1alpha KOs); changes in activities of glycolytic enzymes are seen as well. There is an increase in activity of rate-limiting enzymes of the mitochondria in the muscles of HIF-1alpha KOs, indicating that the citric acid cycle and increased fatty acid oxidation may be compensating for decreased flow through the glycolytic pathway. This is corroborated by a finding of no significant decreases in muscle ATP, but significantly decreased amounts of lactate in the serum of exercising HIF-1alpha KOs. This metabolic shift away from glycolysis and toward oxidation has the consequence of increasing exercise times in the HIF-1alpha KOs. However, repeated exercise trials give rise to extensive muscle damage in HIF-1alpha KOs, ultimately resulting in greatly reduced exercise times relative to wild-type animals. The muscle damage seen is similar to that detected in humans in diseases caused by deficiencies in skeletal muscle glycogenolysis and glycolysis. Thus, these results demonstrate an important role for the HIF-1 pathway in the metabolic control of muscle function.

Adenosine Triphosphate↗

PubMed2004

Effect of 60 degrees head-down tilt on peripheral gas mixing in the human lung.

The phase III slope of sulfur hexafluoride (SF6) in a single-breath washout (SBW) is greater than that of helium (He) under normal gravity (i.e., 1G), thus resulting in a positive SF6-He slope difference. In microgravity (microG), SF6-He slope difference is smaller because of a greater fall in the phase III slope of SF6 than He. We sought to determine whether increasing thoracic fluid volume using 60 degrees head-down tilt (HDT) in 1G would produce a similar effect to microG on phase III slopes of SF6 and He. Single-breath vital capacity (SBW) and multiple-breath washout (MBW) tests were performed before, during, and 60 min after 1 h of HDT. Compared with baseline (SF6 1.050 +/- 0.182%/l, He 0.670 +/- 0.172%/l), the SBW phase III slopes for both SF6 and He tended to decrease during HDT, reaching nadir at 30 min (SF6 0.609 +/- 0.211%/l, He 0.248 +/- 0.138%/l; P = 0.08 and P = 0.06, respectively). In contrast to microG, the magnitude of the phase III slope decrease was similar for both SF6 and He; therefore, no change in SF6-He slope difference was observed. MBW analysis revealed a decrease in normalized phase III slopes at all time points during HDT, for both SF6 (P < 0.01) and He (P < 0.01). This decrease was due to changes in the acinar, and not the conductive, component of the normalized phase III slope. These findings support the notion that changes in thoracic fluid volume alter ventilation distribution in the lung periphery but also demonstrate that the effect during HDT does not wholly mimic that observed in microG.

Adaptation, Physiological↗

PubMed2004

Does gender affect human pulmonary gas exchange during exercise?

Women may experience greater pulmonary gas exchange impairment during exercise than men. To test this we used the multiple inert gas elimination technique to study eight women and seven men matched for age, height and (O(2) max) ( approximately 48 ml x kg(-1) min(-1)) during normoxic and hypoxic (inspired P(O(2))= 95 Torr) cycle exercise. Resting lung function was similar between the sexes, except for a lower carbon monoxide diffusing capacity (DL(CO)) in women (P < 0.05). Arterial P(O(2)),P(CO(2)) and alveolar-arterial O(2) difference (A-aD(O(2))) were not significantly different in men and women. Despite a lower diffusing capacity for O(2) (DL(O(2))) in women, the ratio DL(O(2))/beta (which estimates pulmonary end-capillary diffusion equilibrium) was similar between men and women and estimates of diffusion limitation during hypoxic exercise were not different between the sexes. Ventilation-perfusion inequality (described by the second moment of the perfusion distribution, logSD increased during both normoxic and hypoxic exercise. Surprisingly, logSD values were slightly lower for women under all conditions (P < 0.05), but this did not significantly affect gas exchange. These data indicate that these active women, despite a lower DL(CO) and DL(O(2)), do not experience greater exercise-induced abnormalities in gas exchange than men matched for age, height, aerobic capacity and lung size. Possibly fitness level and lung size are more important in determining whether or not pulmonary gas exchange impairment occurs during exercise than sex per se.

Adult↗

PubMed2004

Oxygen consumption during maximal exercise in Fischer 344 x Brown Norway F1 hybrid rats.

We characterized O2 consumption (VO2) during treadmill exercise in 12-, 24-, and 35-month-old Fischer 344 x Brown Norway F1 hybrid (F344BNF1) rats. When accounting for differences in body mass (Mb), (O2)peak decreased by 10% and 33% in 24- and 35-month-old rats, respectively, compared with rats at 12 months (analysis of covariance, p < .01). O2 cost per unit work at VO2peak (i.e., VO2peak/work) was greater in 35-month-old rats compared with 12- and 24-month-old rats (p < .001). During submaximal exercise, the O2 cost was greater in 24- and 35-month-old than 12-month-old rats (p < .01). Analysis of covariance revealed similar patterns irrespective of differences in Mb or lean Mb as covariates. The underlying mechanism responsible for increasing O2 consumption in aged F344BNF1 rats during exercise, although partly explained by mechanical inefficiencies of locomotion, still remains to be determined.

Aging↗