Age alters the cardiovascular response to direct passive heating

During direct passive heating in young men, a dramatic increase in skin blood flow is achieved by a rise in cardiac output (Qc) and redistribution of flow from the splanchnic and renal vascular beds. To examine the effect of age on these responses, seven young (Y; 23 +/- 1 yr) and seven older (O; 70 +/- 3 yr) men were passively heated with water-perfused suits to their individual limit of thermal tolerance. Measurements included heart rate (HR), Qc (by acetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (by p-aminohippurate clearance), and esophageal and mean skin temperatures. Qc was significantly lower in the older than in the young men (11.1 +/- 0.7 and 7.4 +/- 0.2 l/min in Y and O, respectively, at the limit of thermal tolerance; P < 0. 05), despite similar increases in esophageal and mean skin temperatures and time to reach the limit of thermal tolerance. A lower stroke volume (99 +/- 7 and 68 +/- 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to an attenuated increase in inotropic function during heating, was the primary factor for the lower Qc observed in the older men. Increases in HR were similar in the young and older men; however, when expressed as a percentage of maximal HR, the older men relied on a greater proportion of their chronotropic reserve to obtain the same HR response (62 +/- 3 and 75 +/- 4% maximal HR in Y and O, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from the combined splanchnic and renal circulations at the limit of thermal tolerance (960 +/- 80 and 720 +/- 100 ml/min in Y and O, respectively, P < 0. 05). As a result of these combined attenuated responses, the older men had a significantly lower increase in total blood flow directed to the skin.     

Kinetics of oxygen uptake at the onset of exercise in boys and men

The objective of this study was to compare the O2 uptake (VO2) kinetics at the onset of heavy exercise in boys and men. Nine boys, aged 9-12 yr, and 8 men, aged 19-27 yr, performed a continuous incremental cycling task to determine peak VO2 (VO2 peak). On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice by cycling at 50% VO2 peak for 3.5 min, once by cycling at 100% VO2 peak for 2 min, and once by cycling at 130% VO2 peak for 75 s. O2 deficit was not significantly different between boys and men (respectively, 50% VO2 peak task: 6.6 +/- 11.1 vs. 5.5 +/- 7.3 ml . min-1 . kg-1; 100% VO2 peak task: 28.5 +/- 8.1 vs. 31.8 +/- 6.3 ml . min-1 . kg-1; and 130% VO2 peak task: 30.1 +/- 5.7 vs. 35.8 +/- 5.3 ml . min-1 . kg-1). To assess the kinetics, phase I was excluded from analysis. Phase II VO2 kinetics could be described in all cases by a monoexponential function. ANOVA revealed no differences in time constants between boys and men (respectively, 50% VO2 peak task: 22. 8 +/- 5.1 vs. 26.4 +/- 4.1 s; 100% VO2 peak task: 28.0 +/- 6.0 vs. 28.1 +/- 4.4 s; and 130% VO2 peak task: 19.8 +/- 4.1 vs. 20.7 +/- 5. 7 s). In conclusion, O2 deficit and fast-component VO2 on-transients are similar in boys and men, even at high exercise intensities, which is in contrast to the findings of other studies employing simpler methods of analysis. The previous interpretation that children rely less on nonoxidative energy pathways at the onset of heavy exercise is not supported by our findings.     

Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise

The rates of increase in O2 uptake (VO2) after step changes in work rate from 25 W to 60% of pretraining peak VO2 (VO2 peak) were measured at various times during an endurance training program (2 h/day at 60% pretraining VO2 peak). Seven untrained males [23 +/- 1 (SE) yr] performed a series of repeated step changes in work rate before training (PRE) and after 4 days (4D), 9 days (9D), and 30 days (30D) of training. VO2 kinetic responses were determined from breath-by-breath data averaged across four repetitions and analyzed using a two-component exponential model. Mean response time (time taken to reach 63% of steady-state VO2) was faster (P < 0.01) than PRE (38.1 +/- 2.6 s) at both 4D (34.9 +/- 2.4 s) and 9D (32.5 +/- 1.8 s) and was faster (P < 0.01) at 30D than at all other times (28.3 +/- 1.0 s). Blood lactate concentrations (after 6 min of cycling) were also lower at 4D and 9D than PRE (P < 0.01) and were lower at 30D than at all other times (P < 0.01). VO2 peak was unchanged from PRE (3.52 +/- 0.20 l/min) at 8D (3.55 +/- 0.20 l/min) but was increased (P < 0.01) at 30D (3.89 +/- 0.18 l/min). Muscle oxidative capacity (maximal citrate synthase activity) was not significantly increased until 30D (P < 0.01). It is concluded that at least part of the acceleration of whole body VO2 kinetics with endurance training is a rapid phenomenon, occurring before changes in VO2 peak and/or muscle oxidative potential.     

Post-exercise changes in blood pressure, heart rate and rate pressure product at different exercise intensities in normotensive humans

To evaluate the effect of exercise intensity on post-exercise cardiovascular responses, 12 young normotensive subjects performed in a randomized order three cycle ergometer exercise bouts of 45 min at 30, 50 and 80% of VO2peak, and 12 subjects rested for 45 min in a non-exercise control trial. Blood pressure (BP) and heart rate (HR) were measured for 20 min prior to exercise (baseline) and at intervals of 5 to 30 (R5-30), 35 to 60 (R35-60) and 65 to 90 (R65-90) min after exercise. Systolic, mean, and diastolic BP after exercise were significantly lower than baseline, and there was no difference between the three exercise intensities. After exercise at 30% of VO2peak, HR was significantly decreased at R35-60 and R65-90. In contrast, after exercise at 50 and 80% of VO2peak, HR was significantly increased at R5-30 and R35-60, respectively. Exercise at 30% of VO2peak significantly decreased rate pressure (RP) product (RP = HR x systolic BP) during the entire recovery period (baseline = 7930 +/- 314 vs R5-30 = 7150 +/- 326, R35-60 = 6794 +/- 349, and R65-90 = 6628 +/- 311, P < 0.05), while exercise at 50% of VO2peak caused no change, and exercise at 80% of VO2peak produced a significant increase at R5-30 (7468 +/- 267 vs 9818 +/- 366, P < 0.05) and no change at R35-60 or R65-90. Cardiovascular responses were not altered during the control trial. In conclusion, varying exercise intensity from 30 to 80% of VO2peak in young normotensive humans did not influence the magnitude of post-exercise hypotension. However, in contrast to exercise at 50 and 80% of VO2peak, exercise at 30% of VO2peak decreased post-exercise HR and RP.     

Dependence of muscle VO2 on blood flow dynamics at onset of forearm exercise

The hypothesis that the rate of increase in muscle O2 uptake (VO2mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of approximately 2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase in VO2mus and blood flow was assessed from the mean response time (MRT), which is the time to achieve approximately 63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow and VO2mus both increased, with a MRT of approximately 30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 +/- 15.7 (SE)s] and VO2mus (50.2 +/- 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting valued in the above heart position (2.8 +/- 0.4 mmol/l) than in the below heart position (0.9 +/- mmol/l). At the lower power, both blood flow and VO2mus also increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2 transport.     

Intracellular application of calmidazolium increases Ca2+ current through activation of protein kinase A in cultured vascular smooth muscle cells

This study compared markers of the metabolic processes occurring in male and female adolescent triathletes from two age groups (over 15 years of age [O15] and under 15 years of age [U15]) during a laboratory based duathlon. Participants were tested on three separate occasions; two peak VO2 tests on a treadmill and cycle ergometer, and a third session involved a simulated duathlon (2 km run, 12 km ride and 4 km run for the O15 group or 1 km run, 8 km ride and 2 km run for the U15). Data collection included performance speed, cardiorespiratory responses and blood borne markers of exercise metabolism. The performance speeds selected by the two age groups did not differ. The mean relative percentage of VO2peak at which subjects participated were 79+/-3, 77+/-4%, for the O15 males and females, and 71+/-5 and 82+/-2%, for the U15 males and females, respectively. While the plasma metabolites of ammonia [NH3] and lactate [La] were not different between age groups and sex (p>0.05) there were however, higher concentrations recorded during the cycling phase when compared with the running phases (p < 0.05). The respective mean concentrations for NH3 and La were 80.5+/-5.6 microM, and 4.9+/-0.3 microM for cycling, and 56.3+/-2.7 microM, and 2.7+/-0.2 microM for the combined running phases.     

Hepatic blood flow and splanchnic oxygen consumption in patients with liver failure. Effect of high-volume plasmapheresis

Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more. Measurements were repeated after high-volume plasmapheresis (HVP) with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant infusion of D-sorbitol and calculated according to Fick's principle from peripheral artery and hepatic vein concentrations. In 14 patients with acute liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min) were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3 mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36 L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32 to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2 L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm-5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD, neither systemic nor splanchnic vascular resistance was affected by HVP, but as cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more blood was directed to the splanchnic region. In all liver failure patients treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP. Changes of ET-1 were positively correlated with changes in HBF (P <.005) and VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and oxygenation. ET-3 was negatively correlated with systemic vascular resistance index before HVP (P <.05) but changes during HVP did not correlate. Our data suggest that liver failure is associated with increased HBF and VO2, sp. HVP further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that splanchnic hypoxia was not present.     

Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists: observations from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction 9 Study

We evaluated the hypotheses that endurance training increases relative lipid oxidation over a wide range of relative exercise intensities in fed and fasted states and that carbohydrate nutrition causes carbohydrate-derived fuels to predominate as energy sources during exercise. Pulmonary respiratory gas-exchange ratios [(RER) = CO2 production/O2 consumption (VO2)] were determined during four relative, graded exercise intensities in both fed and fasted states. Seven untrained (UT) men and seven category 2 and 3 US Cycling Federation cyclists (T) exercised in the morning in random order, with target power outputs of 20 and 40% peak VO2 (VO2 peak) for 2 h, 60% VO2 peak for 1.5 h, and 80% VO2 peak for a minimum of 30 min after either a 12-h overnight fast or 3 h after a standardized breakfast. Actual metabolic responses were 22 +/- 0.33, 40 +/- 0.31, 59 +/- 0.32, and 75 +/- 0.39% VO2 peak. T subjects showed significantly (P < 0.05) decreased RER compared with UT subjects at absolute workloads when fed and fasted. Fasting significantly decreased RER values compared with the fed state at 22, 40, and 59% VO2 peak in T and at 40 and 59% VO2 peak in UT subjects. Training decreased (P < 0.05) mean RER values compared with UT subjects at 22% VO2 peak when they fasted, and at 40% VO2 peak when fed or fasted, but not at higher relative exercise intensities in either nutritional state. Our results support the hypothesis that endurance training enhances lipid oxidation in men after a 12-h overnight fast at low relative exercise intensities (22 and 40% VO2 peak). However, a training effect on RER was not apparent at high relative exercise intensities (59 and 75% VO2 peak). Because most athletes train and compete at exercise intensities >40% maximal VO2, they will not oxidize a greater proportion of lipids compared with untrained subjects, regardless of nutritional state.     

Alteration of peripheral vasodilatory reserve capacity after cardioversion of atrial fibrillation

In atrial fibrillation, exercise capacity is often reduced. This is usually ascribed to a decreased cardiac output as compared with sinus rhythm. Very few studies, however, have focused on changes in the peripheral blood flow during atrial fibrillation as a potential mechanism for exercise limitation. The aim of the present study was to determine the effect of conversion of atrial fibrillation to sinus rhythm on peripheral blood flow. Calf blood flow, using an electrocardiogram-triggered venous occlusion plethysmograph, and peak oxygen consumption (peak VO2), using treadmill exercise testing, were studied in 28 patients with chronic atrial fibrillation eligible for electrical cardioversion. Measurements were performed before cardioversion, and repeated 1 day and 1 month thereafter. Calf blood flow at rest, maximal calf blood flow, and minimal calf vascular resistance during the hyperaemic response immediately following 700 J of calf exercise were determined plethysmographically. One day and 1 month after cardioversion, 23 and 14 patients were still in sinus rhythm, respectively. In patients who still had sinus rhythm after 1 month, maximal calf blood flow increased from 33.7 +/- 12 to 40.0 +/- 13 ml. 100 ml-1.min-1 (P < 0.01) and minimal calf vascular resistance fell from 3.2 +/- 0.9 to 2.7 +/- 0.7 mmHg. ml-1. 100 ml-1. min-1 (P < 0.01); peak VO2 increased from 21.3 +/- 4 to 24.2 +/- 5 ml. min-1. kg-1 (P < 0.001). Calf blood flow at rest did not improve. In contrast, no significant changes in maximal calf blood flow, minimal calf vascular resistance and peak VO2 occurred in patients who had atrial fibrillation 1 month after cardioversion. A significant correlation was found between changes in maximal calf blood flow and peak VO2 1 month after cardioversion (r = 0.53, P < 0.01). One day after cardioversion, no changes in calf blood flow or peak VO2 were found, either in patients with sinus rhythm or atrial fibrillation. In conclusion, transition from chronic atrial fibrillation to sinus rhythm is associated with a (delayed) improvement in maximal calf blood flow, minimal calf vascular resistance, and peak VO2. Our findings suggest that increase in vasodilatory reserve capacity may contribute to the improvement of exercise capacity after cardioversion of atrial fibrillation.     

Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans

Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2 and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res. Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin. Physiol. (Colch.) 13: 653-662, 1993), the same increase in mean arterial blood pressure (4%), decreases in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 +/- 3 vs. 23 +/- 2%, P < 0.02), with a total reduction corresponding to 43 +/- 3% (P < 0.01 vs. 23 +/- 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.     

Effects of sensor selection on exercise stroke volume in pacemaker dependent patients

The effects of sensor selection and sensor blending on the cardiovascular response to graded exercise was evaluated in 10 patients (age 74 +/- 2 yrs; 7 men and 3 women) implanted with a dual sensor rate adaptive VVIR pacemaker (Vitatron Topaz model 515). Patients underwent three graded exercise tests (GXT) with sensor programming randomly assigned. For a given graded exercise text the pacemaker was programmed into activity sensing (ACT), QT sensing, or dual sensing (ACT = QT). Data were recorded at rest and during each stage of the graded exercise text. Oxygen uptake (VO2) was measured continuously using a Q Plex I system. Heart rate (HR), stroke volume (SV), and cardiac output (Qc) were measured by impedance cardiography. Systolic time intervals were calculated from simultaneous recordings of the ECG, phonocardiogram, and the impedance cardiogram. In response to the GXT no differences in peak VO2 were observed across the three sensor settings. Regardless of the sensor setting Qc increased linearly with each increment in VO2. The HR response to ACT only pacing was significantly higher than in the other two pacing conditions. During ACT only pacing SV failed to rise in response to exercise. The increased exercise Qc during QT and ACT = QT pacing were mediated by significant increases in both HR and SV. The QT and dual pacing conditions were also associated with longer diastolic filling times. The data indicate that the mechanisms responsible for the increase Qc during exercise were different for ACT versus ACT = QT or QT sensor-driven pacing.     

Blood flow distribution in working in situ canine muscle during blood flow reduction

The purpose of this study was to determine whether reduction in apparent muscle O2 diffusing capacity (Dmo2) calculated during reduced blood flow conditions in maximally working muscle is a reflection of alterations in blood flow distribution. Isolated dog gastrocnemius muscle (n = 6) was stimulated for 3 min to achieve peak O2 uptake (VO2) at two levels of blood flow (controlled by pump perfusion): control (C) conditions at normal perfusion pressure (blood flow = 111 +/- 10 ml.100 g-1.min-1) and reduced blood flow treatment [ischemia (I); 52 +/- 6 ml.100 g-1.min-1]. In addition, maximal vasodilation was achieved by adenosine (A) infusion (10(-2)M) at both levels of blood flow, so that each muscle was subjected randomly to a total of four conditions (C, CA, I, and IA; each separated by 45 min of rest). Muscle blood flow distribution was measured with 15-microns-diameter colored microspheres. A numerical integration technique was used to calculate Dmo2 for each treatment with use of a model that calculates O2 loss along a capillary on the basis of Fick's law of diffusion. Peak VO2 was reduced significantly (P < 0.01) with ischemia and was unchanged by adenosine infusion at either flow rate (10.6 +/- 0.9, 9.7 +/- 1.0, 6.7 +/- 0.2, and 5.9 +/- 0.8 ml.100 g-1.min-1 for C, CA, I, and IA, respectively). Dmo2 was significantly lower by 30-35% (P < 0.01) when flow was reduced (except for CA vs. I; 0.23 +/- 0.03, 0.20 +/- 0.02, 0.16 +/- 0.01, and 0.13 +/- 0.01 ml.100 g-1.min-1.Torr-1 for C, CA, I, and IA, respectively). As expressed by the coefficient of variation (0.45 +/- 0.04, 0.47 +/- 0.04, 0.55 +/- 0.03, and 0.53 +/- 0.04 for C, CA, I, and IA, respectively), blood flow heterogeneity per se was not significantly different among the four conditions when examined by analysis of variance. However, there was a strong negative correlation (r = 0.89, P < 0.05) between Dmo2 and blood flow heterogeneity among the four conditions, suggesting that blood flow redistribution (likely a result of a decrease in the number of perfused capillaries) becomes an increasingly important factor in the determination of Dmo2 as blood flow is diminished.     

Bioenergetics of contracting skeletal muscle after partial reduction of blood flow

The purpose of this study was to examine the bioenergetics and regulation of O2 uptake (VO2) and force production in contracting muscle when blood flow was moderately reduced during a steady-state contractile period. Canine gastrocnemius muscle (n = 5) was isolated, and 3-min stimulation periods of isometric, tetanic contractions were elicited sequentially at rates of 0.25, 0.33, and 0.5 contractions/s (Hz) immediately followed by a reduction of blood flow [ischemic (I) condition] to 46 +/- 3% of the value obtained at 0.5 Hz with normal blood flow. The VO2 of the contracting muscle was significantly (P < 0.05) reduced during the I condition [6.5 +/- 0.8 (SE) ml . 100 g-1 . min-1] compared with the same stimulation frequency with normal flow (11.2 +/- 1.5 ml . 100 g-1 . min-1), as was the tension-time index (79 +/- 12 vs. 123 +/- 22 N . g-1 . min-1, respectively). The ratio of VO2 to tension-time index remained constant throughout all contraction periods. Muscle phosphocreatine concentration, ATP concentration, and lactate efflux were not significantly different during the I condition compared with the 0. 5-Hz condition with normal blood flow. However, at comparable rates of VO2 and tension-time index, muscle phosphocreatine concentration and ATP concentration were significantly less during the I condition compared with normal-flow conditions. These results demonstrate that, in this highly oxidative muscle, the normal balance of O2 supply to force output was maintained during moderate ischemia by downregulation of force production. In addition, 1) the minimal disruption in intracellular homeostasis after the initiation of ischemia was likely a result of steady-state metabolic conditions having already been activated, and 2) the difference in intracellular conditions at comparable rates of VO2 and tension-time index between the normal flow and I condition may have been due to altered intracellular O2 tension.     

Analysis of impaired exercise capacity in patients with cirrhosis

Exercise limitation in cirrhosis is typically attributed to a cirrhotic myopathy (without impaired oxygen utilization) and/or a cardiac chronotropic dysfunction. We performed symptom-limited cardiopulmonary exercise testing in 19 cirrhotics without confounding variables (cardiopulmonary disease, beta blockade, anemia, smoking). Twelve concurrently exercised patients without cirrhosis and with normal resting pulmonary function were controls. Oxygen consumption (VO2) at peak exercise, at anaerobic threshold (VO2-AT), work rate (WR), and heart rate (HR) were measured. Cirrhotics had significantly lower peak WR (73+/-4 vs 107+/-7% predicted, p < 0.001), VO2 (72+/-4 vs 98+/-5% predicted, P < 0.001), VO2-AT (53+/-4 vs 71+/-5% predicted peak VO2, P < 0.01), HR (83+/-2 vs 91+/-2% predicted, P < 0.01) and were more likely to have chronotropic dysfunction (peak HR < 85% predicted). Six cirrhotics had normal aerobic capacity (peak VO2 > 80% predicted), while 13 were abnormal. The abnormals had an earlier AT (46+/-2 vs 67+/-3% predicted peak VO2, P < 0.05) but no difference in peak HR percent predicted was found. In conclusion, two thirds of cirrhotics, without confounding factors, have significantly reduced aerobic capacity. Cirrhotic myopathy (without impaired O2 utilization) and cardiac chronotropic dysfunction do not adequately account for the observed decrease in aerobic capacity.     

Muscle oxygenation kinetics measured by near-infrared spectroscopy during recovery from exercise in chronic heart failure

The aim of the present study was to determine the kinetics of recovery of muscle oxygenation (MO) from comparable levels of exercise in chronic heart failure (CHF) patients and normal subjects and to relate MO kinetics to the level of exercise intolerance. The rationale is based on the observation that the O2 debt is increased in patients with heart failure and repayment of the debt is relatively slow. Ten patients with stable CHF (mean age 47 +/- 10 years) and nine healthy control subjects (47 +/- 6 years) were studied. All patients had ischemic cardiomyopathy (ejection fraction 33 +/- 7%). On different days, all subjects performed an upright incremental cycle ergometer exercise test with gas-exchange analysis to determine peak VO2, and a 6-minute constant work-rate (CWR) protocol at 60% of peak VO2. Oxygenation of the vastus lateralis muscle was continuously monitored during exercise and recovery using near-infrared spectroscopy (NIRS). Both MO and VO2 responses to recovery were described by a monoexponential model with a time delay. The time constant and time delay were combined to calculate a mean response time (MRT). Recovery VO2 and MO MRTs for the incremental and constant work rate exercise test were longer in CHF patients than in control subjects (p < 0.05). Both VO2 and MO MRTs were inversely related to peak VO2 (r = -0.73 and -0.52, respectively; p < 0.05 for both). However, both kinetics were not significantly different within each group between the two exercise intensities. In conclusion, the greater the cardiac dysfunction, as assessed by peak VO2, the more the recovery of muscle and total body oxygenation from both maximal and submaximal exercise is delayed.     

Physiological and biomechanical responses during treadmill walking with graded loads

Eleven healthy men [mean (SD) for age, height, body mass and maximum oxygen consumption: 25.1 (3.0) years, 1.79 (0.06) m, 78.2 (10.5) kg and 56.9 (7.1) ml x kg(-1) x min(-1), respectively) completed two treadmill walking tests at their self-selected velocity while bilaterally carrying 15-kg and 20-kg loads (in a boxed container) for 4 min in front of the body. Each handle of the boxed container was fitted with a load cell so as to allow quantification of the load supported by each hand during load carriage. During the tests, oxygen uptake (VO2), heart rate (HR), and blood pressure (BP) were monitored using standardized procedures, and cardiac output (Qc) was measured using the carbon dioxide rebreathing method. Stroke volume (SV), arterio-venous oxygen difference (C(a-v)O2), rate pressure product (RPP) and total peripheral resistance (TPR) were calculated from the above measurements. The results showed that the two extremities sustained approximately 60% to 70% of the total load, with the balance being supported by the body. Significant increases (P < 0.05) in VO2, HR, Qc, and mean BP were observed during both of the load carriage walks compared to unloaded walking. However, SV, C(a-v)O2, RPP and TPR were unchanged (P > 0.05) during load carriage. Although VO2 was significantly higher during the 20-kg load carriage walk, no significant differences were observed between the two loads for any of the cardiovascular responses monitored. Contrary to our hypothesis, these results suggest that increasing the load from 15 kg to 20 kg during treadmill walking does not significantly increase the cardiovascular stress that occurs in healthy subjects.     

Faster adjustment of O2 delivery does not affect V(O2) on-kinetics in isolated in situ canine muscle

The mechanism(s) limiting muscle O2 uptake (VO2) kinetics was investigated in isolated canine gastrocnemius muscles (n = 7) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% of peak V(O2)). Two conditions were mainly compared: 1) spontaneous adjustment of blood flow (Q) [control, spontaneous Q (C Spont)]; and 2) pump-perfused Q, adjusted approximately 15 s before contractions at a constant level corresponding to the steady-state value during contractions in C Spont [faster adjustment of O2 delivery (Fast O2 Delivery)]. During Fast O2 Delivery, 1-2 ml/min of 10(-2) M adenosine were infused intra-arterially to prevent inordinate pressure increases with the elevated Q. The purpose of the study was to determine whether a faster adjustment of O2 delivery would affect V(O2) kinetics. Q was measured continuously; arterial (Ca(O2)) and popliteal venous (Cv(O2)) O2 contents were determined at rest and at 5- to 7-s intervals during contractions; O2 delivery was calculated as Q x Ca(O2), and V(O2) was calculated as Q x arteriovenous O2 content difference. Times to reach 63% of the difference between baseline and steady-state VO2 during contractions were 23.8 +/- 2.0 (SE) s in C Spont and 21.8 +/- 0.9 s in Fast O2 Delivery (not significant). In the present experimental model, elimination of any delay in O2 delivery during the rest-to-contraction transition did not affect muscle V(O2) kinetics, which suggests that this kinetics was mainly set by an intrinsic inertia of oxidative metabolism.     

VO2 kinetics in the horse during moderate and heavy exercise

The horse is a superb athlete, achieving a maximal O2 uptake (approximately 160 ml . min-1 . kg-1) approaching twice that of the fittest humans. Although equine O2 uptake (VO2) kinetics are reportedly fast, they have not been precisely characterized, nor has their exercise intensity dependence been elucidated. To address these issues, adult male horses underwent incremental treadmill testing to determine their lactate threshold (Tlac) and peak VO2 (VO2 peak), and kinetic features of their VO2 response to "square-wave" work forcings were resolved using exercise transitions from 3 m/s to a below-Tlac speed of 7 m/s or an above-Tlac speed of 12.3 +/- 0.7 m/s (i.e., between Tlac and VO2 peak) sustained for 6 min. VO2 and CO2 output were measured using an open-flow system: pulmonary artery temperature was monitored, and mixed venous blood was sampled for plasma lactate. VO2 kinetics at work levels below Tlac were well fit by a two-phase exponential model, with a phase 2 time constant (tau1 = 10.0 +/- 0.9 s) that followed a time delay (TD1 = 18.9 +/- 1.9 s). TD1 was similar to that found in humans performing leg cycling exercise, but the time constant was substantially faster. For speeds above Tlac, TD1 was unchanged (20.3 +/- 1.2 s); however, the phase 2 time constant was significantly slower (tau1 = 20.7 +/- 3.4 s, P < 0.05) than for exercise below Tlac. Furthermore, in four of five horses, a secondary, delayed increase in VO2 became evident 135.7 +/- 28.5 s after the exercise transition. This "slow component" accounted for approximately 12% (5.8 +/- 2.7 l/min) of the net increase in exercise VO2. We conclude that, at exercise intensities below and above Tlac, qualitative features of VO2 kinetics in the horse are similar to those in humans. However, at speeds below Tlac the fast component of the response is more rapid than that reported for humans, likely reflecting different energetics of O2 utilization within equine muscle fibers.     

Alveolar oxygen uptake and blood flow dynamics in knee extension ergometry

The relationship was studied between the increase in oxygen uptake (VO2) measured breath-by-breath at the mouth, and the increase in femoral artery blood flow measured continuously with pulsed and echo Doppler methods. Five men exercised at 50 W on a knee extension ergometer in both the supine and the upright posture. The kinetics of the responses were determined by curve fitting to obtain the mean response time (MRT = 63% of the time required to achieve steady state). In the upright position, the increase in blood flow (MRT = 12.4 +/- 9.4 s, mean +/- SD) was faster than the increase in VO2 (29.6 +/- 9.3 s). Likewise in the supine position, blood flow increased more rapidly (25.1 +/- 9.7 s vs. 36.7 +/- 9.6 s). It should be noted that the increase in blood flow appeared to be faster than VO2, yet when blood flow adapted more slowly in the supine posture, it had an impact on the adaptation of VO2. This suggests that blood flow might have important effects on metabolism at the onset of submaximal exercise.     

Augmented upper body contribution to oxygen uptake during upper body exercise with concurrent leg functional electrical stimulation in persons with spinal cord injury

The purpose of this pilot study was to compare the contribution of upper body musculature to VO2 with and without concurrent leg FES (LFES). Eight subjects with spinal cord injury, lesion levels range C6-T12, performed upper body exercise (UBE) during no LFES (NOS), LFES at 40 mA (LOS), and 80 mA (HIS), at rest, 60% and 80% of VO2peak. Resting VO2 values were obtained during NOS, LOS and HIS conditions and were then subtracted from their respective whole body VO2 values to give an estimate of upper body VO2. Small and non significant increases were found in the HIS vs NOS condition at 60% VO2peak. Larger differences of 7.8% were found in the HIS vs NOS condition at 80% VO2peak (11.35+/-3.8 ml kg(-1) min(-1) to 12.24+/-4.0 ml kg(-1) min(-1)), although this too was not significant, perhaps due to the small number of subjects in this study and the consequently low statistical power to detect a significant difference. We discuss the implications for these preliminary results in the context of the existing literature on this topic.