Darren S. DeLorey

Fat Distribution and End-Expiratory Lung Volume in Lean and Obese Men and Women

BACKGROUND Although obesity significantly reduces end-expiratory lung volume (EELV), the relationship between EELV and detailed measures of fat distribution has not been studied in obese men and women. To investigate, EELV and chest wall fat distribution (ie, rib cage, anterior subcutaneous abdominal fat, posterior subcutaneous fat, and visceral fat) were measured in lean men and women (ie, < 25% body fat) and obese men and women (ie, > 30% body fat). METHODS All subjects underwent pulmonary function testing, hydrostatic weighing, and MRI scans. Data were analyzed for the men and women separately by independent t test, and the relationships between variables were determined by regression analysis. RESULTS All body composition measurements were significantly different among the lean and obese men and women (p < 0.001). However, with only a few exceptions, fat distribution was similar among the lean and obese men and women (p > 0.05). The mean EELV was significantly lower in the obese men (39 +/- 6% vs 46 +/- 4% total lung capacity [TLC], respectively; p < 0.0005) and women (40 +/- 4% vs 53 +/- 4% TLC, respectively; p < 0.0001) compared with lean control subjects. Many estimates of body fat were significantly correlated with EELV for both men and women. CONCLUSIONS In both men and women, the decrease in EELV with obesity appears to be related to the cumulative effect of increased chest wall fat rather than to any specific regional chest wall fat distribution. Also, with only a few exceptions, relative fat distribution is markedly similar between lean and obese subjects.

Effects of ageing on muscle O2 utilization and muscle oxygenation during the transition to moderate-intensity exercise.

At the onset of exercise, an increase in muscle and pulmonary O2 consumption is met by increases in muscle O2 delivery and muscle O2 extraction. Thus, the study of pulmonary O2 uptake kinetics reflects the integrated response between the convective and diffusive O2 delivery systems and the muscle metabolic machinery (i.e., mitochondrial enzyme activation and provision of acetyl groups to the tricarboxcylic acid cycle) to increase muscle O2 consumption. Pulmonary O2 uptake kinetics are slowed in older adults compared with young adults and previous studies suggest that the slower O2 uptake kinetics may be the result of an age-associated decline in the ability of older adults to increase O2 delivery to active muscles. However, an inherent limitation to understanding the control of and limitations to pulmonary O2 uptake kinetics is that it is methodologically difficult to examine the adaptation of muscle perfusion and O2 delivery and muscle O2 utilization in the muscle microcirculation of active muscles in the dynamically exercising human. In this review, we provide an overview of the effect of ageing on pulmonary O2 uptake kinetics (reflecting the activation of muscle O2 consumption) during the transition to moderate-intensity exercise. Age-related changes in O2 delivery systems and muscle oxidative capacity are examined as potential limitations to pulmonary O2 uptake kinetics. We then review recent studies from our laboratory that have investigated the control of pulmonary O2 uptake kinetics at the level of the muscle microcirculation by examining the adaptation of muscle O2 delivery and muscle O2 utilization using near-infrared spectroscopy during the transition to exercise in healthy young and older adults.

Increased left ventricular twist, untwisting rates, and suction maintain global diastolic function during passive heat stress in humans

Left ventricular (LV) systolic function increases with passive heat stress (HS); however, less is known about diastolic function. Eight healthy subjects (24.0 +/- 2.0 yr of age) underwent whole body passive heating approximately 1 degrees C above baseline (BL). Cardiac magnetic resonance imaging was used to measure biventricular volumes, function, filling velocities, volumetric flow rates, and LV twist and strain at BL and after 45 min of HS. Passive heating reduced left atrial volume (-17.6 +/- 11.7 ml, P < 0.05), right and LV end-diastolic volumes (-22.7 +/- 11.0 and -25.7 +/- 24.9 ml, respectively; P < 0.05), and LV stroke volume (-6.7 +/- 6.8 ml, P < 0.05) from BL. LV ejection fraction (EF), end-systolic elastance, septal and lateral mitral annular systolic velocities, circumferential strain, and peak LV twist increased with HS (P < 0.05). Right ventricular stroke volume, EF, and systolic tissue velocities were unchanged with HS (P > 0.05). Early LV diastolic tissue and blood velocities and strain rates were maintained with HS, whereas untwisting rate increased significantly from 166.4 +/- 46.9 to 268.7 +/- 76.8 degrees /s (P < 0.05). The major novel finding of this study was that, secondary to an increase in peak LV twist and untwisting rate, early diastolic blood and tissue velocities and strain rates are maintained despite a reduction in filling pressure.

Cerebral and muscle tissue oxygenation in acute hypoxic ventilatory response test

Eight men were exposed to progressive isocapnic hypoxia for 10 min to test the hypothesis that (i) cerebral and muscle tissue would follow similar deoxygenation profiles during an acute hypoxic ventilatory response (AHVR) test; and (ii) strong cerebrovascular responsiveness to hypoxia would be related to attenuated cerebral deoxygenation. End-tidal O(2) concentration was reduced from normoxia (approximately 102 mmHg) to approximately 45 mmHg while arterial oxygen saturation (SpO2 %) declined from 98+/-1% to 77+/-7% (P<0.001). Near-infrared spectroscopy (NIRS)-derived local cerebral tissue (frontal lobe) deoxyhemoglobin increased 5.55+/-2.22 microM, while oxyhemoglobin and tissue oxygenation index decreased 2.57+/-1.99 microM and 6.2+/-3.4%, respectively (all P<0.001). In muscle (m. vastus lateralis) the NIRS changes from the initial normoxic level were non-significant. Cerebral blood velocity (V(mean), transcranial Doppler) in the middle cerebral artery increased from 53.4+/-10.4 to 60.6+/-11.6 cms(-1) (P<0.001). In relation to the decline in SpO2 % the mean rate of increase of V(mean) and AHVR were 0.33+/-0.19 cms(-1)%(-1) and 0.52+/-0.20l min(-1)%(-1), respectively. We conclude that cerebral, but not muscle, tissue shows changes reflecting a greater deoxygenation during acute hypoxia. However, the changes in NIRS parameters were not related to cerebrovascular responsiveness or ventilatory chemosensitivity during graded hypoxia.

Cerebral and muscle deoxygenation, hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness during incremental exercise.

To examine if cerebral (frontal cortex) and skeletal muscle (m. vastus lateralis) deoxygenation and cerebral blood flow velocity (V(mean)) in the middle cerebral artery differentiated between normoxic and hypoxic (end-tidal P(O)(2) 71 mmHg) conditions, and if they were associated with hypoxic ventilatory chemosensitivity and cerebrovascular responsiveness, 8 men performed incremental cycling trials (30W/min ramp) under normoxic (T1-N) and hypoxic (T1-H) conditions until volitional fatigue, or until arterial O2 saturation decreased below 80%. The tests were repeated (T2-N; T2-H) on another day with supplemental O2 (Sup-O2) at the end of exercise. The V(mean) response was similar in normoxia and hypoxia. In hypoxia compared to normoxia, cerebral deoxygenation ( upward arrow deoxyhemoglobin concentration (Delta[HHb]) and downward arrow tissue oxygenation index (TOI)) was greater at a given work rate. A strong hypoxic ventilatory chemosensitivity was associated with a rapid reduction of cerebral TOI (r=0.94, P<0.001). Muscle deoxygenation was similar in normoxia and hypoxia suggesting greater muscle blood flow in hypoxia compared to normoxia and thus the existence of control features that match muscle perfusion and O2 delivery tightly with O2 demand during exercise. Sup-O2 reduced both cerebral and muscle deoxygenation, at least transiently.

Short-term exercise training enhances functional sympatholysis through a nitric oxide-dependent mechanism.

Sympathetic nervous system activity causes tonic vasoconstriction in resting and contracting skeletal muscle. Vasoactive molecules released from the active skeletal muscle and/or endothelium have been shown to inhibit sympathetic vasoconstriction, a phenomenon defined as functional sympatholysis. A definitive mechanism responsible for functional sympatholysis has yet to be identified; however, nitric oxide (NO) appears to be involved. It is unknown whether exercise training alters the inhibition of sympathetic vasoconstriction and NO‐mediated sympatholysis in resting and contracting skeletal muscle. The present findings demonstrate that short‐term exercise training augments functional sympatholysis in a training‐intensity‐dependent manner through a NO‐dependent mechanism. These novel findings advance our understanding of the effects of exercise training on the regulation of sympathetic vasoconstriction in resting and contracting skeletal muscle.

Weight Loss via Diet and Exercise Improves Exercise Breathing Mechanics in Obese Men

BACKGROUND Obesity alters breathing mechanics during exercise. Weight loss improves lung function at rest, but the effect of weight loss, especially regional fat loss, on exercise breathing mechanics is unclear. We hypothesized that weight loss, especially a decrease in abdominal fat, would improve breathing mechanics during exercise because of an increase in end-expiratory lung volume (EELV). METHODS Nine obese men were studied before and after weight loss (13% ± 8% of total fat weight, mean ± SD). Subjects underwent pulmonary function testing, underwater weighing, fat distribution estimates (MRI), and graded cycle ergometry before and after a 12-week diet and exercise program. In seven men, esophageal and gastric pressures were measured. The effects of weight loss were analyzed at rest, at ventilatory threshold (VTh), and during peak exercise by dependent Student t test, and the relationship among variables was determined by correlation analysis. RESULTS Subjects lost 7.4 ± 4.2 kg of body weight (P < .001), but the distribution of fat remained unchanged. After weight loss, lung volume subdivisions at rest were increased (P < .05) and were moderately associated (P < .05) with changes in chest, waist, and hip circumferences. At VTh, EELV increased, and gastric pressure decreased significantly (P < .05). The changes in waist circumference, hip circumference, BMI, and sum of chest, waist, and hip circumferences were also consistently and significantly correlated (P < .05) with changes in gastric pressure during exercise at VTh. CONCLUSIONS Modest weight loss improves breathing mechanics during submaximal exercise in otherwise healthy obese men, which is clinically encouraging. Improvement appears to be related to the cumulative loss of chest wall fat.

Short-term exercise training augments sympathetic vasoconstrictor responsiveness and endothelium-dependent vasodilation in resting skeletal muscle

We tested the hypotheses that 4 wk of exercise training would diminish the magnitude of vasoconstriction in response to sympathetic nerve stimulation and augment endothelium-dependent vasodilation (EDD) in resting skeletal muscle in a training intensity-dependent manner. Sprague-Dawley rats were randomly assigned to sedentary time-control (S), mild- (M; 20 m/min, 5% grade), or heavy-intensity (H; 40 m/min, 5% grade) treadmill exercise groups. Animals trained 5 days/wk for 4 wk with training volume matched between groups. Rats were anesthetized and instrumented for study 24 h after the last training session. Arterial pressure and femoral artery blood flow were measured, and femoral vascular conductance (FVC) was calculated. Lumbar sympathetic chain stimulation was delivered continuously at 2 Hz and in patterns at 20 and 40 Hz. EDD was assessed by the vascular response to intra-arterial bolus injections of ACh. The response (% change FVC) to sympathetic stimulation increased (P < 0.05) in a training intensity-dependent manner at 2 Hz (S: -20.2 ± 9.8%, M: -34.0 ± 6.7%, and H: -44.9 ± 2.0%), 20 Hz (S: -22.0 ± 10.6%, M: -31.2 ± 8.4%, and H: -42.8 ± 5.9%), and 40 Hz (S: H -24.5 ± 8.5%, M: -35.1 ± 8.9%, H: -44.9 ± 6.5%). The magnitude of EDD also increased in a training intensity-dependent manner (P < 0.05). These data demonstrate that short-term exercise training augments the magnitude of vasoconstriction in response to sympathetic stimulation and EDD in resting skeletal muscle in a training intensity-dependent manner.

Left ventricular systolic and diastolic function during tilt-table positioning and passive heat stress in humans

The ventricular response to passive heat stress has predominantly been studied in the supine position. It is presently unclear how acute changes in venous return influence ventricular function during heat stress. To address this question, left ventricular (LV) systolic and diastolic function were studied in 17 healthy men (24.3 ± 4.0 yr; mean ± SD), using two-dimensional transthoracic echocardiography with Doppler ultrasound, during tilt-table positioning (supine, 30° head-up tilt, and 30° head-down tilt), under normothermic and passive heat stress (core temperature 0.8 ± 0.1°C above baseline) conditions. The supine heat stress LV volumetric and functional response was consistent with previous reports. Combining head-up tilt with heat stress reduced end-diastolic (25.2 ± 4.1%) and end-systolic (65.4 ± 10.5%) volume from baseline, whereas heart rate (37.7 ± 2.0%), ejection fraction (9.4 ± 2.4%), and LV elastance (37.7 ± 3.6%) increased, and stroke volume (-28.6 ± 9.4%) and early diastolic inflow (-17.5 ± 6.5%) and annular tissue (-35.6 ± 7.0%) velocities were reduced. Combining head-down tilt with heat stress restored end-diastolic volume, whereas LV elastance (16.8 ± 3.2%), ejection fraction (7.2 ± 2.1%), and systolic annular tissue velocities (22.4 ± 5.0%) remained elevated above baseline, and end-systolic volume was reduced (-15.3 ± 3.9%). Stroke volume and the early and late diastolic inflow and annular tissue velocities were unchanged from baseline. This investigation extends previous work by demonstrating increased LV systolic function with heat stress, under varied levels of venous return, and highlights the preload dependency of early diastolic function during passive heat stress.

Role of neuronal nitric oxide in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats.

Isoform-specific nitric oxide (NO) synthase (NOS) contributions to NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle are incompletely understood. The purpose of the present study was to investigate the role of neuronal NOS (nNOS) in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats. We hypothesized that acute pharmacological inhibition of nNOS would augment sympathetic vasoconstriction in resting and contracting skeletal muscle, demonstrating that nNOS is primarily responsible for NO-mediated inhibition of sympathetic vasoconstriction. Sprague-Dawley rats (n = 13) were anesthetized and instrumented with an indwelling brachial artery catheter, femoral artery flow probe, and lumbar sympathetic chain stimulating electrodes. Triceps surae muscles were stimulated to contract rhythmically at 60% of maximal contractile force. In series 1 (n = 9), the percent change in femoral vascular conductance (%FVC) in response to sympathetic stimulations delivered at 2 and 5 Hz was determined at rest and during muscle contraction before and after selective nNOS blockade with S-methyl-l-thiocitrulline (SMTC, 0.6 mg/kg iv) and subsequent nonselective NOS blockade with N(ω)-nitro-l-arginine methyl ester (l-NAME, 5 mg/kg iv). In series 2 (n = 4), l-NAME was injected first, and then SMTC was injected to determine if the effect of l-NAME on constrictor responses was influenced by selective nNOS inhibition. Sympathetic stimulation decreased FVC at rest (-25 ± 7 and -44 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (-7 ± 3 and -19 ± 5%FVC at 2 and 5 Hz, respectively). The decrease in FVC in response to sympathetic stimulation was greater in the presence of SMTC at rest (-32 ± 6 and -49 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (-21 ± 4 and -28 ± 4%FVC at 2 and 5 Hz, respectively). l-NAME further increased (P < 0.05) the sympathetic vasoconstrictor response at rest (-47 ± 4 and -60 ± 6%FVC at 2 and 5 Hz, respectively) and during muscle contraction (-33 ± 3 and -40 ± 6%FVC at 2 and 5 Hz, respectively). The effect of l-NAME was not altered by the order of nNOS inhibition. These data demonstrate that NO derived from nNOS and endothelial NOS contribute to the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle.