Role of airway resistance in the control of ventilation during exercise

To analyze the interdependence of respiratory drive, ventilation and airway resistance during exercise, mouth occlusion pressure (P_0.1), minute ventilation (V) and mean inspiratory flow (V_T/T_I) were studied in eight normal subjects performing cycle-ergometer exercise at loads ranging from 0 W to 200 W under two different ambient conditions: 1) during oxygen breathing at 1.3 ATA, and 2) during air breathing at 6 ATA (Po₂= 1–3 ATA). Comparison of measurements at 6 ATA with those at 1.3 ATA indicated that a 4.2-fold increase in respired gas density (D) had little or no influence on the V? and V_T/T_I responses whereas P_0.1 at any given V_T/T_I was increased by a factor of 1.9. In both conditions, P_0.1 increased at a faster rate than V_T/T_I as the work load increased. At loads higher than 40 W, the relationship between P_0.1, D and V_T/T_I was found to approximate the equation P_0.1=K·D^0.5(V_T/T_I)^1,4 where K is a constant that varies among subjects. The results indicate that the ratio P_0.1/(V_T/T_I), an estimate of respiratory impedance, increased with both D and V_T/T_I. Evidence is presented that the respiratory drive was reflexly enhanced in response to loading as airway resistance increased with D and/or V_T/T_I. We conclude that neural mechanisms compensating for internal flow-resistive loading play an important role in the control of ventilation during exercise, both at normal and at raised air pressures.     

The importance of nervous and humoral factors in the control of vascular resistance, blood flow distribution and net fluid absorption in the cat small intestine during hemorrhage

The influence of preganglionic (splanchnic) and postganglionic (periarterial) denervation of the cat small intestine on the changes in blood flow and net fluid absorption elicited by hemorrhage was investigated. The compiled data from a previous report indicate that hemorrhage induces a vasoconstriction and a redistribution of blood flow towards the absorptive part of the mucosa. The vasoconstriction was unaffected by a total postganglionic denervation whereas after a preganglionic denervation both the vasoconstriction and the redistribution of blood flow were abolished. We have also shown earlier that hemorrhage induced an increase in net fluid absorption as long as no ischemic mucosal lesions developed. This increase was reduced by postganglionic denervation, and was reversed into a small decrease after preganglionic denervation. On the basis of these findings it is proposed that the increase in vascular resistance, the redistribution of blood flow towards the absorptive part of the mucosa as well as the increase in net fluid absorption observed after hemorrhage all are effects mainly mediated via the splanchnic nerves. Furthermore, humoral factors are of major importance for the increase in vascular resistance observed after hemorrhage. The increase in net fluid absorption was shown to be induced both by direct nervous and by humoral factors.     

Metabolic control of large-bore arterial resistance vessels,arterioles, and veins in cat skeletal muscle during exercise

The metabolic control of the vascular bed in cat gastrocnemius muscle during exercise was studied with a new technique (Björnberg et al. 1988) permitting continuous and simultaneous recordings of arteriolar and capillary pressures, and of resistances in the following consecutive vascular section: proximal arterial resistance vessels > 25 μm, arterioles < 25 μm, and on the venous side. The study thereby provided quantitative data for resistance and active intrinsic tone in these vascular segments at rest, during graded exercise vasodilatation, and in the post-exercise period. Slight activation of the metabolic control system by low-frequency somatomotor nerve stimulation (light exercise') caused inhibition of intrinsic tone and decreased vascular resistance selectively in the arteriolar section. At increasing workloads, arteriolar resistance was further decreased, but resistance and tone in the proximal arterial resistance vessels and the veins then became clearly reduced as well. This difference in effectiveness of the metabolic control system on the different segments of the vascular bed was expressed quantitatively in terms of a ‘metabolic vasodilator index’. Graded activation of the metabolic control system led to a marked segmental redistribution of intrinsic vascular tone, in turn resulting in an increased pressure drop across the proximal arterial vessels and the veins and a decreased pressure drop over the arterioles. The observed decrease in the pre- to post-capillary resistance ratio caused, at a constant arterial pressure of 100 mmHg, a graded increase in capillary pressure with increasing workloads, at maximum vasodilatation by an average value of 14 mmHg above the resting control value of 15.4 ± 0.6 mmHg. In the post-exercise period, recovery of vascular tone to control was more rapid in the proximal arterial resistance vessels and the veins than in the arteriolar segment.     

Self-biofeedback control of heart rate during exercise.

To improve cardiac adjustment to exercise, we developed a new self-biofeedback heart rate (HR) controller. Using this device, we analyzed time courses of HR, running speed (RS), stride length (ST) and pitch of gait (PI) in response to various preset HR levels in 7 normal human subjects. When HR was preset at 80 bpm, HR increased rapidly in response to exercise and exceeded the preset level at 12. 1 s with overshoot. At the preset HRs of 100, 120, 140 and 160 bpm, the HRs increased to each preset level at 39.2, 64.5, 58.5 and 83.0 s after the onset of exercise, respectively, and the HRs were adjusted with a range of +/- 4%. For all preset HRs, RS, ST and PI increased more rapidly than the HR and reached the maximum values within 30 s. During exercise, RS, ST and PI remained constant within 1.5-5.5 min. HR, RS, ST and PI increased in proportion to the preset HR. The increases in PI against HR (DeltaPI/DeltaHR) decreased with the higher HR level, and at HRs of 160-170 bpm, HR and PI showed identical rhythm. The increases in RS were produced by 18-59% increases in PI and by 12-44% increases in ST. We concluded that, using our newly developed self-biofeedback HR control system, we could control HR to a given preset value by a change in RS due to PI and ST.     

Acute exercise improves endothelial function despite increasing vascular resistance during stress in smokers and nonsmokers

The present study examined the effect of acute exercise on flow mediated dilation (FMD) and reactivity to neurovascular challenges among female smokers and nonsmokers. FMD was determined by arterial diameter, velocity, and blood flow measured by Doppler ultrasonography after forearm occlusion. Those measures and blood pressure and heart rate were also assessed in response to forehead cold and the Stroop Color‐Word Conflict Test (CWT) before and after 30 min of rest or an acute bout of cycling exercise (～50% VO₂peak). Baseline FMD and stress responses were not different between smokers and nonsmokers. Compared to passive rest, exercise increased FMD and decreased arterial velocity and blood flow responses during the Stroop CWT and forehead cold in both groups. Overall, acute exercise improved endothelial function among smokers and nonsmokers despite increasing vascular resistance and reducing limb blood flow during neurovascular stress.     

Hemodynamic and metabolic adjustments during exercise and shock avoidance in dogs.

The purpose of this study was to examine whether the hemodynamic and metabolic consequences of a physical (treadmill excercise) and behavioral (signaled shock-avoidance) stressor could be differentiated. To do this, direct continuous recordings of cardiac output, systolic and diastolic blood pressure, and discrete determinations of the arterial-mixed venous oxygen ((a-v)O2) content difference were analyzed in six dogs during exposure to three grades of treadmill exercise and when working on a shock-avoidance task. The results indicated that in five animals the relationship between cardiac output and the (a-v)O2 difference during shock-avoidance conditioning was significantly different from the corresponding pattern observed during exercise. In four animals the data suggested that avoidance conditioning, relative to exercise stress, elicited overperfusion. Behavioral stress also produced reliable elevations in diastolic and systolic blood pressure. These results suggest that, when compared to physical stress, behavioral stress can produce a dissociation of cardiovascular and metabolic processes in the presence of acute pressor responses.     

Gender differences in temperature and vascular characteristics during exercise recovery.

Temperature and vascular responses during exercise recovery were examined in men and women of similar age and fitness status (VO2max: 76 +/- 5 vs 73 +/- 5 mL O2 / kg Fat Free Mass x min). Forearm blood flow (venous occlusion plethysmography; FBF), rectal (Trectal) and forearm skin (Tskin) temperatures (degree C) were measured before and every 15 min up to 105 min (t105) during recovery from a 45-min run at 75% of VO2max. Results indicate Trectal decreased to pre-exercise levels within 25 min in men but reached and remained at values lower than baseline between 60 and 105 min of recovery in women. From 90 to 105 min of recovery, Tskin was lower in women than men (t105 : 29.0 +/- 1.3 vs 30.7 +/- 1.5; p <.05). Recovery FBF (mL/100mL x min) was higher in men than women from the start (6.2 +/- 1.9 vs 4.9 +/- 1.9) to the end of recovery (t105 = 1.7 +/- 0.6 vs 2.6 +/- 1.1) (p <.05). Heat flux calculated at the forearm was higher in women and increased throughout the last hour of recovery (p <.05). Further investigations are needed to examine mechanisms underlying failure of post-exercise core and skin temperatures in women to stabilize at pre-exercise levels.     

Altered metabolic response of iron-deficient women during graded,maximal exercise

Summary Metabolic responses during a standardized, progressive, maximal work capacity test on a cycle ergometer were studied in 11 women, mean age 28 (SEM 2) years, at admission to the study, after their body iron stores were depleted by diet, phlebotomy and menstruation for about 80 days and after iron repletion by diet for about 100 days, including daily iron supplementation (0.9 mmol iron as ferrous sulfate) for the last 14 days of repletion. Iron depletion was characterized by a decline (P<0.05) in hemoglobin, ferritin and body iron balance. Iron repletion, including supplementation, increased (P<0.05) hemoglobin, ferritin and iron balance. No changes were observed in cardiovascular and ventilatory responses or peak oxygen uptake. Iron depletion was associated with a reduced (P<0.05) rate of oxygen utilization, total oxygen uptake and aerobic energy expenditure, and elevated (P<0.05) peak respiratory exchange ratio and post-exercise concentration of lactate. Reduction of body iron stores without overt anemia affects exercise metabolism by reducing total aerobic energy production and increasing glycolytic metabolism.     

Effect of order of exercise intensity upon cardiorespiratory,metabolic, and perceptual responses during exercise of mixed intensity

Exercise of mixed intensities can be of benefit in many different ways. However, whether physiological interaction exists between exercises of different intensity is questionable. As such, the primary aim of this study was to examine the effect of order of exercise intensity upon cardiorespiratory, metabolic, and perceptual responses during exercise of mixed intensity. Eight males and four females volunteered to serve as subjects for the study. They were informed of the purpose of the experiment and gave their written consent to participate. Each subject completed a peak oxygen uptake (O_2peak) test and two submaximal exercises of mixed intensity on three separate laboratory visits. During each submaximal exercise trial, subjects performed a 15-min (high intensity) exercise at 70%O_2peak that was followed by another 15-min (low intensity) exercise at 50%O_2peak (high/low, H/L), or a 15-min exercise at 50%O_2peak that was followed by another 15-min exercise at 70%O_2peak (low/high, L/H). Oxygen uptake (O₂), respiratory exchange ratio (R), expired ventilation (_E), heart rate (HR) and ratings of perceived exertion (RPE) were measured every 5 min throughout exercise. Energy expenditure and carbohydrate and fat oxidation were calculated from O₂ adjusted for substrate metabolism using R and then accumulated for each phase of exercise intensity as well as for the entire exercise session. O₂ and HR were higher (P<0.05), while R was lower (P<0.05) at the lower intensity in H/L than in L/H. _E and RPE were lower (P<0.05) at the higher intensity in H/L than in L/H. While no differences in caloric expenditure and carbohydrate oxidation between the two trials were observed, fat oxidation was higher (P<0.05) both at the lower intensity and for the entire trial in H/L than in L/H. It appears that during exercise of mixed intensity, placing some periods of moderate intensity exercise prior to a milder one is a more favorable sequence in that it can elicit a greater fat oxidation while being felt less stressful.     

Effect of multiple set on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction

Our previous study reported that intramuscular metabolic stress during low-intensity resistance exercise was significantly enhanced by combining blood flow restriction (BFR); however, they did not reach the levels achieved during high-intensity resistance exercise. That study was performed using a single set of exercise; however, usual resistance exercise consists of multiple sets with rest intervals. Therefore, we investigated the intramuscular metabolic stress during multiple-set BFR exercises, and compared the results with those during multiple-set high-intensity resistance exercise. Twelve healthy young subjects performed 3 sets of 1-min unilateral plantar flexion (30 repetitions) with 1-min intervals under 4 different conditions: low intensity (L, 20 % 1 RM) and high intensity (H, 65 % 1 RM) without BFR, and L with intermittent BFR (IBFR, only during exercise) and with continuous BFR (CBFR, during rest intervals as well as exercise). Intramuscular metabolic stress, defined as intramuscular metabolites and pH, and muscle fiber recruitment were evaluated by ³¹P-magnetic resonance spectroscopy. The changes of intramuscular metabolites and pH during IBFR were significantly greater than those in L but significantly lower than those in H. By contrast, those changes in CBFR were similar to those in H. Moreover, the fast-twitch fiber recruitment, evaluating by a splitting Pi peak, showed a similar level to H. In conclusion, the multiple sets of low-intensity resistance exercise with continuous BFR could achieve with the same metabolic stress as multiple sets of high-intensity resistance exercise.     

Regulation of coronary blood flow during exercise

Exercise is the most important physiological stimulus for increased myocardial oxygen demand. The requirement of exercising muscle for increased blood flow necessitates an increase in cardiac output that results in increases in the three main determinants of myocardial oxygen demand: heart rate, myocardial contractility, and ventricular work. The approximately sixfold increase in oxygen demands of the left ventricle during heavy exercise is met principally by augmenting coronary blood flow (~5-fold), as hemoglobin concentration and oxygen extraction (which is already 70-80% at rest) increase only modestly in most species. In contrast, in the right ventricle, oxygen extraction is lower at rest and increases substantially during exercise, similar to skeletal muscle, suggesting fundamental differences in blood flow regulation between these two cardiac chambers. The increase in heart rate also increases the relative time spent in systole, thereby increasing the net extravascular compressive forces acting on the microvasculature within the wall of the left ventricle, in particular in its subendocardial layers. Hence, appropriate adjustment of coronary vascular resistance is critical for the cardiac response to exercise. Coronary resistance vessel tone results from the culmination of myriad vasodilator and vasoconstrictors influences, including neurohormones and endothelial and myocardial factors. Unraveling of the integrative mechanisms controlling coronary vasodilation in response to exercise has been difficult, in part due to the redundancies in coronary vasomotor control and differences between animal species. Exercise training is associated with adaptations in the coronary microvasculature including increased arteriolar densities and/or diameters, which provide a morphometric basis for the observed increase in peak coronary blood flow rates in exercise-trained animals. In larger animals trained by treadmill exercise, the formation of new capillaries maintains capillary density at a level commensurate with the degree of exercise-induced physiological myocardial hypertrophy. Nevertheless, training alters the distribution of coronary vascular resistance so that more capillaries are recruited, resulting in an increase in the permeability-surface area product without a change in capillary numerical density. Maintenance of alpha- and ss-adrenergic tone in the presence of lower circulating catecholamine levels appears to be due to increased receptor responsiveness to adrenergic stimulation. Exercise training also alters local control of coronary resistance vessels. Thus arterioles exhibit increased myogenic tone, likely due to a calcium-dependent protein kinase C signaling-mediated alteration in voltage-gated calcium channel activity in response to stretch. Conversely, training augments endothelium-dependent vasodilation throughout the coronary microcirculation. This enhanced responsiveness appears to result principally from an increased expression of nitric oxide (NO) synthase. Finally, physical conditioning decreases extravascular compressive forces at rest and at comparable levels of exercise, mainly because of a decrease in heart rate. Impedance to coronary inflow due to an epicardial coronary artery stenosis results in marked redistribution of myocardial blood flow during exercise away from the subendocardium towards the subepicardium. However, in contrast to the traditional view that myocardial ischemia causes maximal microvascular dilation, more recent studies have shown that the coronary microvessels retain some degree of vasodilator reserve during exercise-induced ischemia and remain responsive to vasoconstrictor stimuli. These observations have required reassessment of the principal sites of resistance to blood flow in the microcirculation. A significant fraction of resistance is located in small arteries that are outside the metabolic control of the myocardium but are sensitive to shear and nitrovasodilators. The coronary collateral system embodies a dynamic network of interarterial vessels that can undergo both long- and short-term adjustments that can modulate blood flow to the dependent myocardium. Long-term adjustments including recruitment and growth of collateral vessels in response to arterial occlusion are time dependent and determine the maximum blood flow rates available to the collateral-dependent vascular bed during exercise. Rapid short-term adjustments result from active vasomotor activity of the collateral vessels. Mature coronary collateral vessels are responsive to vasodilators such as nitroglycerin and atrial natriuretic peptide, and to vasoconstrictors such as vasopressin, angiotensin II, and the platelet products serotonin and thromboxane A(2). During exercise, ss-adrenergic activity and endothelium-derived NO and prostanoids exert vasodilator influences on coronary collateral vessels. Importantly, alterations in collateral vasomotor tone, e.g., by exogenous vasopressin, inhibition of endogenous NO or prostanoid production, or increasing local adenosine production can modify collateral conductance, thereby influencing the blood supply to the dependent myocardium. In addition, vasomotor activity in the resistance vessels of the collateral perfused vascular bed can influence the volume and distribution of blood flow within the collateral zone. Finally, there is evidence that vasomotor control of resistance vessels in the normally perfused regions of collateralized hearts is altered, indicating that the vascular adaptations in hearts with a flow-limiting coronary obstruction occur at a global as well as a regional level. Exercise training does not stimulate growth of coronary collateral vessels in the normal heart. However, if exercise produces ischemia, which would be absent or minimal under resting conditions, there is evidence that collateral growth can be enhanced. In addition to ischemia, the pressure gradient between vascular beds, which is a determinant of the flow rate and therefore the shear stress on the collateral vessel endothelium, may also be important in stimulating growth of collateral vessels.