RESUMO
KEY POINTS: Precapillary gas exchange for oxygen has been documented in both humans and animals. It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET). We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1 cm proximal to the wedge position) and systemic artery. Some 12-19% of pulmonary gas exchange occurred within small (1.7 mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane. Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. ABSTRACT: Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1 cm proximal to the wedge position (using a 5-F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F = (P - D)/(P - A). The lowest solubility inert gases, sulphur hexafluoride (SF6 ) and ethane were used because, with higher solubility gases, the P-A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n = 12) with oxygen (O2 ) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P = 88.6 ± 18.1%; P = 0.03) and ethane (D/P = 90.6 ± 16.0%; P = 0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1 ± 6.8% vs. 69.0 ± 4.9%; P = 0.03). Fractional precapillary gas exchange was similar for SF6 , ethane and O2 (0.12 ± 0.19, 0.12 ± 0.20 and 0.19 ± 0.26, respectively; P = 0.54). Under these experimental conditions, 12-19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases.
Assuntos
Pulmão/metabolismo , Pulmão/fisiologia , Gases Nobres/metabolismo , Oxigênio/metabolismo , Troca Gasosa Pulmonar/fisiologia , Animais , Cães , Circulação Pulmonar/fisiologiaRESUMO
In chronic mountain sickness (CMS), increased blood oxygen (O2)-carrying capacity due to excessive erythrocytosis (EE, [Hb] ≥ 21 g/dL) could be offset, especially during exercise by both impaired cardiac output (QÌt) and O2 diffusion limitation in lungs and muscle. We hypothesized that EE results in reduced peak VÌo2 despite increased blood O2-carrying capacity, and that isovolumic hemodilution (IVHD) improves exercise capacity. In 14 male residents of Cerro de Pasco, Peru (4,340 m), six with and eight without EE, we measured peak cycle-exercise capacity, VÌo2, QÌt, arterial blood gas parameters, and (resting) blood volume. This was repeated for participants with EE after IVHD, reducing hematocrit by 20% (from 67% to 53%). From these data, we quantified the major O2 transport pathway components (ventilation, pulmonary alveolar-capillary diffusion, QÌt, and blood-muscle mitochondria diffusion). Participants with EE had similar peak VÌo2, systemic O2 delivery, and O2 extraction as non-EE controls, however, with lower QÌt and higher arterial [O2]. After IVHD, peak VÌo2 was preserved (but not enhanced), with lower O2 delivery (despite higher QÌt) balanced by greater O2 extraction. The considerable variance in exercise capacity across the 14 individuals was explained essentially completely by differences in both pulmonary and muscle O2 diffusional conductances and not by any differences in ventilation, [Hb], nor QÌt. In conclusion, EE does not result in lower peak VÌo2 in Andean males, and IVHD maintains, but does not enhance, exercise capacity.NEW & NOTEWORTHY Male Andean highlanders with and without excessive erythrocytosis (EE) have similar peak VÌo2 at 4,340 m, with higher arterial [O2] in EE and lower cardiac output (QÌt), thus maintaining similar O2 delivery. Peak VÌo2 in participants with EE was unaffected by isovolumic hemodilution (hematocrit reduced from 67% to 53%), with lower O2 delivery balanced by slightly increased QÌt and greater O2 extraction. Differences in lung and muscle diffusing capacity, and not hematocrit variation, accounted for essentially all interindividual variance in peak VÌo2.
Assuntos
Doença da Altitude , Policitemia , Humanos , Masculino , Altitude , Tolerância ao Exercício , Hemodiluição , Oxigênio/metabolismo , Consumo de OxigênioAssuntos
Altitude , Hipóxia/sangue , Consumo de Oxigênio/fisiologia , Oxigênio/sangue , Humanos , MasculinoRESUMO
Previous work has shown remarkable differences in the pressure-flow relations of the pulmonary circulation between birds and mammals. For example several studies suggest that the avian pulmonary blood vessels behave like rigid tubes, very different from the situation in mammalian lung. We therefore speculated that birds would develop high pulmonary artery pressures when the cardiac output was substantially increased during heavy exercise, for example during flight. However because of the technical difficulties of measuring pulmonary artery pressures in flight, the metabolic rate and cardiac output in anesthetized chickens were increased by infusing 2,4 Dinitrophenol (DNP) and the mean pressure was measured by means of a catheter in the pulmonary artery. Although the pulmonary artery pressure rose steadily as cardiac output increased, it remained below the high levels predicted from the previous studies for similar changes in pulmonary blood flow. Furthermore the increase in pressure was less than in mammals where recruitment and distension of pulmonary capillaries are known to occur. The reasons for this unexpected result are not clear.
Assuntos
Pressão Sanguínea/fisiologia , Débito Cardíaco/fisiologia , Galinhas/fisiologia , Artéria Pulmonar/fisiologia , Animais , Consumo de Oxigênio/fisiologia , Condicionamento Físico Animal/fisiologia , Circulação Pulmonar/fisiologiaRESUMO
Untrained rats selectively bred for either high (HCR) or low (LCR) treadmill running capacity previously demonstrated divergent physiological traits as early as the seventh generation (G7). We asked whether continued selective breeding to generation 15 (G15) would further increase the divergence in skeletal muscle capillarity, morphometry, and oxidative capacity seen previously at G7. At G15, mean body weight was significantly lower (P < 0.001) in the HCR rats (n = 11; 194 +/- 3 g) than in LCR (n = 12; 259 +/- 9 g) while relative medial gastrocnemius muscle mass was not different (0.23 +/- 0.01 vs. 0.22 +/- 0.01% total body weight). Normoxic (Fi(O(2)) = 0.21) Vo(2max) was 50% greater (P < 0.001) in HCR despite the lower absolute muscle mass, and skeletal muscle O(2) conductance (measured in hypoxia; Fi(O(2)) = 0.10) was 49% higher in HCR (P < 0.001). Muscle oxidative enzyme activities were significantly higher in HCR (citrate synthase: 16.4 +/- 0.4 vs. 14.0 +/- 0.6; beta-hydroxyacyl-CoA dehydrogenase: 5.2 +/- 0.2 vs. 4.2 +/- 0.2 mmol.kg(-1).min(-1)). HCR rats had approximately 36% more total muscle fibers and also 36% more capillaries in the medial gastrocnemius. Because average muscle fiber area was 35% smaller, capillary density was 36% higher in HCR, but capillary-to-fiber ratio was the same. Compared with G7, G15 HCR animals showed 38% greater total fiber number with an additional 25% decrease in mean fiber area. These data suggest that many of the skeletal muscle structural and functional adaptations enabling greater O(2) utilization in HCR at G7 continue to progress following additional selective breeding for endurance capacity. However, the largest changes at G15 relate to O(2) delivery to skeletal muscle and not to the capacity of skeletal muscle to use O(2).
Assuntos
Tolerância ao Exercício/genética , Consumo de Oxigênio/genética , Oxigênio/metabolismo , Corrida/fisiologia , Seleção Genética , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Adaptação Fisiológica , Animais , Transporte Biológico/genética , Peso Corporal/genética , Cruzamento , Capilares/anatomia & histologia , Teste de Esforço , Feminino , Hipóxia/sangue , Modelos Genéticos , Fibras Musculares Esqueléticas/citologia , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/enzimologia , Tamanho do Órgão/genética , RatosRESUMO
Previous studies found that selection for endurance running in untrained rats produced distinct high (HCR) and low (LCR) capacity runners. Furthermore, despite weighing 14% less, 7th generation HCR rats achieved the same absolute maximal oxygen consumption (Vo(2max)) as LCR due to muscle adaptations that improved oxygen extraction and use. However, there were no differences in cardiopulmonary function after seven generations of selection. If selection for increased endurance capacity continued, we hypothesized that due to the serial nature of oxygen delivery enhanced cardiopulmonary function would be required. In the present study, generation 15 rats selected for high and low endurance running capacity showed differences in pulmonary function. HCR, now 25% lighter than LCR, reached a 12% higher absolute Vo(2max) than LCR, P < 0.05 (49% higher Vo(2max)/kg). Despite the 25% difference in body size, both lung volume (at 20 cmH(2)O airway pressure) and exercise diffusing capacity were similar in HCR and LCR. Lung volume of LCR lay on published mammalian allometrical relationships while that of HCR lay above that line. Alveolar ventilation at Vo(2max) was 30% higher, P < 0.05 (78% higher, per kg), arterial Pco(2) was 4.5 mmHg (17%) lower, P < 0.05, while total pulmonary vascular resistance was (insignificantly) 5% lower (30% lower, per kg) in HCR. The smaller mass of HCR animals was due mostly to a smaller body frame rather than to a lower fat mass. These findings show that by generation 15, lung size in smaller HCR rats is not reduced in concert with their smaller body size, but has remained similar to that of LCR, supporting the hypothesis that continued selection for increased endurance capacity requires relatively larger lungs, supporting greater ventilation, gas exchange, and pulmonary vascular conductance.
Assuntos
Tolerância ao Exercício/genética , Pulmão/fisiologia , Consumo de Oxigênio/genética , Troca Gasosa Pulmonar/genética , Corrida/fisiologia , Seleção Genética , Animais , Cruzamento , Teste de Esforço , Feminino , Pulmão/anatomia & histologia , Masculino , Modelos Genéticos , Músculo Esquelético/metabolismo , Tamanho do Órgão/genética , Oxigênio/metabolismo , RatosRESUMO
Although lung diffusing capacity for carbon monoxide (DL(CO)) is a widely used test of diffusive O2 transfer, few studies have directly related DL(CO) to O2-diffusing capacity (DL(O2)); none has used the components of Dl(CO), i.e., conductance of alveolar membrane and capillary blood, to predict DL(O2) from rest to exercise. To understand the relationship between DL(CO) and DL(O2) at matched levels of cardiac output, we analyzed cumulative data from rest to heavy exercise in 43 adult dogs, with normal lungs or reduced lung capacity following lung resection, that were studied by two techniques. 1) A rebreathing (RB) technique was used to measure Dl(CO) and pulmonary blood flow at two O2 tensions, independent of O2 exchange. DL(CO) was partitioned into CO-diffusing capacity of alveolar membrane and pulmonary capillary blood volume using the Roughton-Forster equation and converted into an equivalent DL(O2), [DL(O2)(RB)]. 2) A multiple inert-gas elimination technique (MIGET) was used to measure ventilation-perfusion distributions, O2 and CO2 exchange under hypoxia, to derive DL(O2) [DL(O2)(MIGET)] by the Lilienthal-Riley technique and Bohr integration. For direct comparisons, DL(O2)(RB) was interpolated to the cardiac output measured by the Fick principle corresponding to DL(O2)(MIGET). The DL(O2)-to-DL(CO) ratio averaged 1.61. Correlation between DL(O2)(RB) and DL(O2)(MIGET) was similar in normal and post-resection groups. Overall, DL(O2)(MIGET) = 0.975 DL(O2)(RB); mean difference between the two techniques was under 5% for both animal groups. We conclude that, despite various uncertainties inherent in these two disparate methods, the Roughton-Forster equation adequately predicts diffusive O2 transfer from rest to heavy exercise in canines with normal, as well as reduced, lung capacities.
Assuntos
Oxigênio/metabolismo , Esforço Físico , Alvéolos Pulmonares/metabolismo , Capacidade de Difusão Pulmonar , Animais , Dióxido de Carbono/sangue , Dióxido de Carbono/metabolismo , Débito Cardíaco , Cães , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Microcirculação , Modelos Biológicos , Oxigênio/sangue , Pneumonectomia , Alvéolos Pulmonares/irrigação sanguínea , Alvéolos Pulmonares/cirurgia , Circulação Pulmonar , Reprodutibilidade dos TestesRESUMO
We previously found that, following surgical resection of approximately 58% of lung units by right pneumonectomy (PNX) in adult canines, oxygen-diffusing capacity (Dl(O(2))) fell sufficiently to become a major factor limiting exercise capacity, although the decline was mitigated by recruitment, remodeling, and growth of the remaining lung units. To determine whether an upper limit of compensation is reached following the loss of even more lung units, we measured pulmonary gas exchange, hemodynamics, and ventilatory power requirements in adult canines during treadmill exercise following two-stage resection of approximately 70% of lung units in the presence or absence of mediastinal distortion. Results were compared with that in control animals following right PNX or thoracotomy without resection (Sham). Following 70% lung resection, peak O(2) uptake was 45% below normal. Ventilation-perfusion mismatch developed, and pulmonary arterial pressure and ventilatory power requirements became markedly elevated. In contrast, the relationship of Dl(O(2)) to cardiac output remained normal, indicating preservation of Dl(O(2))-to-cardiac output ratio and alveolar-capillary recruitment up to peak exercise. The impairment in airway and vascular function exceeded the impairment in gas exchange and imposed the major limitation to exercise following 70% resection. Mediastinal distortion further reduced air and blood flow conductance, resulting in CO(2) retention. Results suggest that adaptation of extra-acinar airways and blood vessels lagged behind that of acinar tissue. As more lung units were lost, functional compensation became limited by the disproportionately reduced convective conductance rather than by alveolar diffusion disequilibrium.
Assuntos
Pulmão/fisiologia , Pulmão/cirurgia , Pneumonectomia/efeitos adversos , Testes de Função Respiratória , Limiar Anaeróbio , Animais , Capilares/fisiologia , Débito Cardíaco/fisiologia , Artérias Carótidas/fisiologia , Difusão , Cães , Gases Nobres , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Condicionamento Físico Animal/fisiologia , Alvéolos Pulmonares/fisiologia , Circulação Pulmonar/fisiologia , Capacidade de Difusão Pulmonar/fisiologia , Troca Gasosa Pulmonar/fisiologia , Pressão Propulsora Pulmonar/fisiologia , Músculos Respiratórios/fisiologia , Tomografia Computadorizada por Raios X , Trabalho Respiratório/fisiologiaRESUMO
Measurement of respiratory muscle blood flow (RMBF) in humans has important implications for understanding patterns of blood flow distribution during exercise in healthy individuals and those with chronic disease. Previous studies examining RMBF in humans have required invasive methods on anesthetized subjects. To assess RMBF in awake subjects, we applied an indicator-dilution method using near-infrared spectroscopy (NIRS) and the light-absorbing tracer indocyanine green dye (ICG). NIRS optodes were placed on the left seventh intercostal space at the apposition of the costal diaphragm and on an inactive control muscle (vastus lateralis). The primary respiratory muscles within view of the NIRS optodes include the internal and external intercostals. Intravenous bolus injection of ICG allowed for cardiac output (by the conventional dye-dilution method with arterial sampling), RMBF, and vastus lateralis blood flow to be quantified simultaneously. Esophageal and gastric pressures were also measured to calculate the work of breathing and transdiaphragmatic pressure. Measurements were obtained in five conscious humans during both resting breathing and three separate 5-min bouts of constant isocapnic hyperpnea at 27.1 +/- 3.2, 56.0 +/- 6.1, and 75.9 +/- 5.7% of maximum minute ventilation as determined on a previous maximal exercise test. RMBF progressively increased (9.9 +/- 0.6, 14.8 +/- 2.7, 29.9 +/- 5.8, and 50.1 +/- 12.5 ml 100 ml(-1) min(-1), respectively) with increasing levels of ventilation while blood flow to the inactive control muscle remained constant (10.4 +/- 1.4, 8.7 +/- 0.7, 12.9 +/- 1.7, and 12.2 +/- 1.8 ml 100 ml(-1) min(-1), respectively). As ventilation rose, RMBF was closely and significantly correlated with 1) cardiac output (r = 0.994, P = 0.006), 2) the work of breathing (r = 0.995, P = 0.005), and 3) transdiaphragmatic pressure (r = 0.998, P = 0.002). These data suggest that the NIRS-ICG technique provides a feasible and sensitive index of RMBF at different levels of ventilation in humans.
Assuntos
Músculos Respiratórios/irrigação sanguínea , Adulto , Limiar Anaeróbio/fisiologia , Ciclismo/fisiologia , Gasometria , Débito Cardíaco/fisiologia , Corantes , Diafragma/fisiologia , Eletromiografia , Humanos , Verde de Indocianina , Músculos Intercostais/irrigação sanguínea , Masculino , Consumo de Oxigênio/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Mecânica Respiratória/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho , Trabalho Respiratório/fisiologiaRESUMO
Mammals native to high altitude (HA) exhibit larger lung volumes than their lowland counterparts. To test the hypothesis that adaptation induced by HA residence during somatic maturation improves pulmonary gas exchange in adulthood, male foxhounds born at sea level (SL) were raised at HA (3,800 m) from 2.5 to 7.5 mo of age and then returned to SL prior to somatic maturity while their littermates were simultaneously raised at SL. Following return to SL, all animals were trained to run on a treadmill; gas exchange and hemodynamics were measured 2.5 years later at rest and during exercise while breathing 21% and 13% O(2). The multiple inert gas elimination technique was employed to estimate ventilation-perfusion (Va/Q) distributions and lung diffusing capacity for O(2) (Dl(O(2))). There were no significant intergroup differences during exercise breathing 21% O(2). During exercise breathing 13% O(2), peak O(2) uptake and Va/Q distributions were similar between groups but arterial pH, base excess, and O(2) saturation were higher while peak lactate concentration was lower in animals raised at HA than at SL. At a given exercise intensity, alveolar-arterial O(2) tension gradient (A-aDo(2)) attributable to diffusion limitation was lower while Dlo(2) was 12-25% higher in HA-raised animals. Mean systemic arterial blood pressure was also lower in HA-raised animals; mean pulmonary arterial pressures were similar. We conclude that 5 mo of HA residence during maturation enhances long-term gas exchange efficiency and Dl(O(2)) without impacting Va/Q inequality during hypoxic exercise at SL.
Assuntos
Aclimatação/fisiologia , Altitude , Cães/fisiologia , Pulmão/fisiologia , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Troca Gasosa Pulmonar/fisiologia , Animais , Masculino , Fatores de TempoRESUMO
In athletic animals the spleen induces acute polycythemia by dynamic contraction that releases red blood cells into the circulation in response to increased O(2) demand and metabolic stress; when energy demand is relieved, the polycythemia is rapidly reversed by splenic relaxation. We have shown in adult foxhounds that splenectomy eliminates exercise-induced polycythemia, thereby reducing peak O(2) uptake and lung diffusing capacity for carbon monoxide (DL(CO)) as well as exaggerating preexisting DL(CO) impairment imposed by pneumonectomy (Dane DM, Hsia CC, Wu EY, Hogg RT, Hogg DC, Estrera AS, Johnson RL Jr. J Appl Physiol 101: 289-297, 2006). To examine whether the postsplenectomy reduction in DL(CO) leads to abnormalities in O(2) diffusion, ventilation-perfusion inequality, or hemodynamic function, we studied these animals via the multiple inert gas elimination technique at rest and during exercise at a constant workload equivalent to 50% or 80% of peak O(2) uptake while breathing 21% and 14% O(2) in balanced order. From rest to exercise after splenectomy, minute ventilation was significantly elevated with respect to O(2) uptake compared with exercise before splenectomy; cardiac output, O(2) delivery, and mean pulmonary and systemic arterial blood pressures were 10-20% lower, while O(2) extraction was elevated with respect to O(2) uptake. Ventilation-perfusion inequality was unchanged, but O(2) diffusing capacities of lung (DL(O2)) and peripheral tissue during exercise were lower with respect to cardiac output postsplenectomy by 32% and 25%, respectively. The relationship between DL(O2) and DL(CO) was unchanged by splenectomy. We conclude that the canine spleen regulates both convective and diffusive O(2) transport during exercise to increase maximal O(2) uptake.
Assuntos
Hemodinâmica , Pulmão/metabolismo , Oxigênio/metabolismo , Esforço Físico/fisiologia , Troca Gasosa Pulmonar , Baço/fisiologia , Esplenectomia , Animais , Pressão Sanguínea , Volume Sanguíneo , Dióxido de Carbono/metabolismo , Monóxido de Carbono/metabolismo , Débito Cardíaco , Difusão , Cães , Volume de Eritrócitos , Hematócrito , Hemoglobinas/metabolismo , Concentração de Íons de Hidrogênio , Masculino , Oxigênio/sangue , Consumo de Oxigênio , Capacidade de Difusão Pulmonar , Baço/cirurgia , Resistência VascularRESUMO
The amount of O(2) available to tissues is essentially the product of cardiac output, [Hb], and O(2) saturation. Saturation depends on P(O2) and the O(2)Hb dissociation curve. With altitude, increased [2,3-DPG] shifts the dissociation curve rightward, but hypocapnia and alkalosis move it leftward. We determined both standard and in vivo P(50) in 5 fit subjects decompressed over 42 days in an altitude chamber to the equivalent of the Mt. Everest summit (Operation Everest II). Arterial and venous blood was sampled at five "altitudes " (P(B) = 760, 429, 347, 282, 253 mmHg), and P(O2), P(CO2), pH, O(2) saturation, [Hb] and [2,3-DPG] were measured. As reported previously, 2,3-DPG levels increased from 1.7 (P(B) = 760) to 3.8 mmol/L (P(B) = 282). Standard P(50) also increased (from 28.2 mmHg at sea level to 33.1 on the summit, p<0.001). Alone, this would have lowered saturation by 12 percentage points at a summit arterial P(O2) of approximately 30 mmHg. However, in vivo P(50) remained between 26 and 27 mmHg throughout due to progressive hypocapnia and alkalosis. Calculations suggest that the increase in standard P(50) did not affect summit V(O2 MAX)), alveolar, arterial and venous P(O2)'s, but reduced arterial and venous O(2) saturations by 8.4 and 17.4 points, respectively, and increased O(2) extraction by 7.9 percentage points. Reduced saturation was balanced by increased extraction, resulting in no significant overall O(2) transport benefit, thus leaving unanswered the question of the purpose of increased [2,3-DPG] concentrations at altitude.
Assuntos
2,3-Difosfoglicerato/sangue , Doença da Altitude/sangue , Altitude , Hemoglobinas/metabolismo , Montanhismo/fisiologia , Oxigênio/sangue , Adaptação Fisiológica , Adulto , Câmaras de Exposição Atmosférica , Gasometria/métodos , Simulação por Computador , Humanos , Hipóxia/sangue , Masculino , Consumo de Oxigênio/fisiologia , Valores de Referência , Testes de Função RespiratóriaRESUMO
We previously showed that after seven generations of artificial selection of rats for running capacity, maximal O2 uptake (VO2max) was 12% greater in high-capacity (HCR) than in low-capacity runners (LCR). This difference was due exclusively to a greater O2 uptake and utilization by skeletal muscle of HCR, without differences between lines in convective O2 delivery to muscle by the cardiopulmonary system (QO2max). The present study in generation 15 (G15) female rats tested the hypothesis that continuing improvement in skeletal muscle O2 transfer must be accompanied by augmentation in QO2max to support VO2max of HCR. Systemic O2 transport was studied during maximal normoxic and hypoxic exercise (inspired PO2 approximately 70 Torr). VO2max divergence between lines increased because of both improvement in HCR and deterioration in LCR: normoxic VO2max was 50% higher in HCR than LCR. The greater VO2max in HCR was accompanied by a 41% increase in QO2max: 96.1 +/- 4.0 in HCR vs. 68.1 +/- 2.5 ml stpd O2 x min(-1) x kg(-1) in LCR (P < 0.01) during normoxia. The greater G15 QO2max of HCR was due to a 48% greater stroke volume than LCR. Although tissue O2 diffusive conductance continued to increase in HCR, tissue O2 extraction was not significantly different from LCR at G15, because of the offsetting effect of greater HCR blood flow on tissue O2 extraction. These results indicate that continuing divergence in VO2max between lines occurs largely as a consequence of changes in the capacity to deliver O2 to the exercising muscle.
Assuntos
Tolerância ao Exercício/genética , Consumo de Oxigênio/fisiologia , Oxigênio/sangue , Esforço Físico/fisiologia , Corrida , Seleção Genética , Animais , Transporte Biológico , Cruzamento , Feminino , Masculino , Modelos Animais , Ratos , Corrida/fisiologiaRESUMO
The relative contribution of genetic and environmental influences to individual exercise capacity is difficult to determine. Accordingly, animal models in which these influences are carefully controlled are highly useful to understand the determinants of intrinsic exercise capacity. Studies of systemic O(2) transport during maximal treadmill exercise in two diverging lines of rats artificially selected for endurance capacity showed that, at generation 7, whole body maximal O(2) uptake ((.)V(O(2)(max)) was 12% higher in high capacity (HCR) than in low capacity runners (LCR) during normoxic exercise. The difference in (.)V(O(2)(max) between HCR and LCR was larger during hypoxic exercise. Analysis of the linked O(2) conductances of the O(2) transport system showed that the higher (.)V(O(2)(max) was not due to a higher ventilatory response, a more effective pulmonary gas exchange, or an increased rate of O(2) delivery to the tissue by blood. The main reason for the higher (.)V(O(2)(max) of HCR was an increased tissue O(2) extraction, due largely to a higher tissue diffusive O(2) conductance. The enhanced tissue O(2) diffusing capacity was paralleled by an increased capillary density of a representative locomotory skeletal muscle, the gastrocnemius, in HCR. Activities of skeletal muscle oxidative enzymes citrate synthase and beta-HAD were also higher in HCR than LCR. Thus, the functional characteristics observed during exercise are consistent with the structural and biochemical changes observed in skeletal muscle that imply an enhanced capacity for muscle O(2) uptake and utilization in HCR. The results indicate that the improved (.)V(O(2)(max) is solely due to enhanced muscle O(2) extraction and utilization. However, the question arises as to whether it is possible to maintain a continually expanding capacity for O(2) extraction at the tissue level with successive generations, without a parallel improvement in the capacity to deliver O(2) to the exercising muscles.
Assuntos
Cruzamento , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Resistência Física/fisiologia , Corrida , Animais , Transporte Biológico/fisiologia , Hipóxia/sangue , Modelos Animais , Fibras Musculares Esqueléticas/fisiologia , Oxigênio/sangue , Condicionamento Físico Animal , RatosRESUMO
To attempt to explain the difference in intrinsic (untrained) endurance running capacity in rats selectively bred over seven generations for either low (LCR) or high running capacity (HCR), the relationship among skeletal muscle capillarity, fiber composition, enzyme activity, and O(2) transport was studied. Ten females from each group [body wt: 228 g (HCR), 247 g (LCR); P = 0.03] were studied at 25 wk of age. Peak normoxic maximum O(2) consumption and muscle O(2) conductance were previously reported to be 12 and 33% higher, respectively, in HCR, despite similar ventilation, arterial O(2) saturation, and a cardiac output that was <10% greater in HCR compared with LCR. Total capillary and fiber number in the medial gastrocnemius were similar in HCR and LCR, but, because fiber area was 37% lower in HCR, the number of capillaries per unit area (or mass) of muscle was higher in HCR by 32% (P < 0.001). A positive correlation (r = 0.92) was seen between capillary density and muscle O(2) conductance. Skeletal muscle enzymes citrate synthase and beta-hydroxyacyl-CoA dehydrogenase were both approximately 40% higher (P < 0.001) in HCR (12.4 +/- 0.7 vs. 8.7 +/- 0.4 and 3.4 +/- 0.2 vs. 2.4 +/- 0.2 mmol. kg(-1). min(-1), respectively), whereas phosphofructokinase was significantly (P = 0.02) lower in HCR (27.8 +/- 1.2 vs. 35.2 +/- 2.5 mmol. kg(-1). min(-1)) and hexokinase was the same (0.65 +/- 0.04 vs. 0.65 +/- 0.03 mmol. kg(-1). min(-1)). Resting muscle ATP, phosphocreatine, and glycogen contents were not different between groups. Taken together, these data suggest that, in rats selectively bred for high-endurance exercise capacity, most of the adaptations for improved O(2) utilization occur peripherally in the skeletal muscles and not in differences at the level of the heart or lung.