Acute plasma volume expansion: effect on metabolism during submaximal exercise.

To examine the effect of acute plasma volume expansion (PVE) on substrate selection during exercise, seven untrained men cycled for 40 min at 72 +/- 2% peak oxygen uptake (VO(2 peak)) on two occasions. On one occasion, subjects had their plasma volume expanded by 12 +/- 2% via an intravenous infusion of the plasma substitute Haemaccel, whereas on the other occasion no such infusion took place. Muscle samples were obtained before and immediately after exercise. In addition, heart rate and pulmonary gas and venous blood samples were obtained throughout exercise. No differences in oxygen uptake or heart rate during exercise were observed between trials, whereas respiratory exchange ratio, blood glucose, and lactate were unaffected by PVE. Muscle glycogen and lactate concentrations were not different either before or after exercise. In addition, there was no difference in total carbohydrate oxidation between trials (control: 108 +/- 2 g; PVE group: 105 +/- 2 g). Plasma catecholamine levels were not affected by PVE. These data indicate that substrate metabolism during submaximal exercise in untrained men is unaltered by acute hypervolemia.     

Left ventricular hemodynamics during exercise recovery

The directional response of human left ventricular stroke volume during exercise recovery is unclear. Stroke volume has been reported to increase and decrease over exercise values during early recovery. The confounding variable may be posture. With the use of pulsed Doppler ultrasound, we tested the hypothesis that there is a significant difference between seated and supine stroke index (SI) during passive recovery from seated ergometer exercise. Thirteen subjects aged 26 +/- 2 yr performed two seated cycle ergometer exercise tests to 70% of predicted maximum heart rate (HR). Recovery was supine on one test and seated on the other. Cardiac index (CI), HR, and SI were calculated during rest, exercise, and 10 min of recovery. At rest, SI and CI were significantly (P less than 0.01) less and HR significantly (P less than 0.01) greater when the subjects were seated than when they were supine. At the last exercise work load, no significant differences were found in any measured variable between tests. During recovery, supine SI was maximal 180 s postexercise (99 +/- 14 ml/m2) and exceeded (P less than 0.01) resting supine (81 +/- 14 ml/m2) and peak exercise (77 +/- 14 ml/m2) SI by 22 and 29%, respectively. Seated SI was constant at peak exercise levels for 2 min. Seated and supine recovery CI never exceeded exercise values. Systolic and diastolic blood pressure recovery curves were similar in the two postures. We conclude that posture significantly affects SI during recovery from submaximal seated exercise. These results have implications for choice of recovery posture after stress testing in cardiac patients where it is desirable to minimize ventricular loading.     

Acute plasma volume expansion alters cardiovascular but not thermal function during moderate intensity prolonged exercise

To investigate the hypothesis that the increase in plasma volume (PV) that typically occurs with training results in improved cardiovascular and thermal regulation during prolonged exercise, eight untrained males (V(O2)peak = 3.52 +/- 0.12 L x min(-1)) performed 90 min of cycle ergometry at 62% V(O2)peak before and after acute PV expansion. Subjects were infused with a PV-expanding solution (dextran (6%) or Pentaspan (10%)) equivalent to 6.7 mL x kg(-1) body mass (PVX) or acted as their own control (CON) in a randomized order. PVX resulted in a calculated 15.8% increase in resting PV, which relative to CON, was maintained throughout the exercise (P < 0.05). During PVX, heart rate was lower (P < 0.05) and stroke volume and cardiac output were higher (P < 0.05) during the exercise. Mean arterial pressure and total peripheral resistance, although altered by exercise (P < 0.05), were not different between the two conditions. Core temperature, which was progressively increased by the exercise (P < 0.01), was not affected by PVX. A similar decrease in body weight was observed between the conditions as a result of the exercise (P < 0.01). These results indicate that acute PVX alters cardiovascular performance without affecting the thermoregulatory response to prolonged cycle exercise.     

Phase plane analysis of left ventricular hemodynamics.

We sought to extract additional physiological information from the time-dependent left ventricular (LV) pressure contour and thereby gain new insights into ventricular function. We used phase plane analysis to characterize high-fidelity pressure data in selected subjects undergoing elective cardiac catheterization. The standard hemodynamic indexes of LV systolic and diastolic function derived from the time-dependent LV pressure contour could be easily obtained using the phase plane method. Additional novel attributes of the phase plane pressure loop, such as phase plane pressure loop area, graphical representation of the isovolumic relaxation time constant, and quantitative measures of beat-to-beat systolic-diastolic coupling were characterized. The asymmetry between the pressures at which maximum isovolumic pressure rise and pressure fall occur, as well as their load dependence, were also easily quantitated. These results indicate that the phase plane method provides a novel window for physiological discovery and has theoretical and applied advantages in quantitative ventricular function characterization.     

Radionuclide left ventricular angiography during exercise in ischemic heart disease.

Radionuclide angiocardiography during exercise is one of the latest advances in nuclear cardiology and is being introduced into clinical practice. In this article the pathophysiological principles of this technique and the method with which it is used to evaluate patients with ischemic heart diseases are outlined, the various patterns of response in these patients are illustrated, and factors that limit the interpretation of the results, including the level of exercise achieved, are discussed.     

Substrate turnover and oxidation during moderate-intensity exercise following acute plasma volume expansion.

In previous work using prolonged, light cycle exercise, we were unable to demonstrate an effect of acute plasma volume (PV) expansion on glucose kinetics or substrate oxidation, despite a decline in whole-body lipolysis (Phillips et al., 1997). However, PV is known to decrease arterial O2 content. The purpose of this study was to examine whether substrate turnover and oxidation would be altered with heavier exercise where the challenge to O2 delivery is increased. Eight untrained males (VO2max = 3.52 +/- 0.12 l/min) twice performed 90 min of cycle ergometry at 62 % VO2peak, both prior to (CON) and following induced plasma volume expansion (Dextran [6 %] or Pentaspan [10 %]) (6.7 ml/kg) (PVX). Glucose and glycerol kinetics were determined with primed constant infusions of [6.6-(2)H2] glucose and [(2)H5] glycerol, respectively. PVX resulted in a 15.8 +/- 2.2 % increase (p < 0.05) in PV. Glucose and glycerol appearance (Ra) and utilization (Rd), although increasing progressively (p < 0.05) with exercise, were not different between conditions. Similarly, no differences in substrate oxidation, either fat or carbohydrate, were observed between the two conditions. Prolonged exercise resulted in an increase (p < 0.05) in plasma glucagon and a decrease (p < 0.05) in plasma insulin during both conditions. With PVX, the exercise-induced increase in glucagon was diminished (p < 0.05). We conclude that impairment in O2 content mediated by an elevated PV does not alter glucose, and glycerol kinetics or substrate oxidation even at moderate exercise intensity.     

Interrelationships between left ventricular volume and output during exercise in healthy subjects.

To better characterize the relationship between left ventricular volume response and improved ventricular ejection and output during supine exercise in normal subjects, 36 healthy asymptomatic volunteers (age 39 +/- 17 yr) were studied with radionuclide ventriculography during recumbent bicycle ergometry. Relative changes in left ventricular end-diastolic and end-systolic volume were measured at rest and during exercise by a modification of the radionuclide counts-based method that accounted for variability in stress blood pool counts. A biphasic response was noted in left ventricular end-diastolic volume with an initial increase in early exercise (8.5 +/- 11% at 200 kpm/min and 11 +/- 12% at 300 kpm/min) followed by a progressive and significant decline at peak exercise (-3.3 +/- 18% at 547 +/- 140 kpm/min; P < 0.05). There was substantial variation in end-diastolic volume response at peak exercise in the group as a whole, which could be more closely related to changes in end-systolic volume (r = 0.84, P < 0.0001) than in heart rate (r = -0.57, P < 0.01) or age (r = 0.36, P < 0.05) of the study subjects. Despite the decline in ventricular filling, systolic function appeared to improve dramatically at peak exercise (change in left ventricular ejection fraction 15.5 +/- 6.4, P < 0.0001). Although not directly related to increasing systolic ejection, end-diastolic volume was directly related to the percent change in stroke volume at peak exercise among the study subjects (r = 0.88, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of left ventricular hemodynamics in physiological hyperspace.

Our laboratory has previously shown that it is possible to elucidate novel physiological relationships by analyzing the left ventricular pressure (P) contour in the phase [time derivative of P (dP/dt) vs. P] plane (Eucker SA, Lisauskas JB, Singh J, and Kovács SJ, J Appl Physiol 90: 2238-2244, 2001). To further characterize cardiac physiology, we introduce a method that combines P-volume (V) and phase plane-derived information in physiological hyperspace. From four-dimensional (P, V, dP/dt, time derivative of V) hyperspace, we consider three-dimensional embedding diagrams having dP/dt, P, and V as coordinate axes. Our method facilitates analysis of physiological function independent of inotropic state and permits assessment of P-V-based relationships in the phase plane and vice versa. To test feasibility, the method was applied to murine hemodynamic data. As predicted from first principles, the area of the P-V loop (ventricular external work) correlated closely (r = 0.97) with phase plane limit cycle area (external power). The P-V plane-derived linear (r = 0.99) end-systolic P-V relationship (maximum elastance) appeared linear in the phase plane (r = 0.85). We conclude that analysis of data in physiological hyperspace is generalizable: it facilitates quantitative characterization of ventricular systolic and diastolic function and can guide discovery of novel physiological relationships.     

Sex differences in left ventricular function and beta-receptor responsiveness following prolonged strenuous exercise.

Sex differences in neuroendocrine and metabolic responses to prolonged strenuous exercise (PSE) have been well documented. The aim of this investigation was to examine sex differences in left ventricular function and cardiac beta-receptor responsiveness following a single bout of PSE. Nine male and eight female triathletes were examined during three separate sessions: before, immediately after, and 24 h following a half-ironman triathlon using dobutamine stress echocardiography. Steady-state graded infusions of dobutamine were used to assess beta-receptor responsiveness. Slopes calculated from linear regressions between dobutamine doses and changes in heart rate and contractility for each participant were used as an index of beta-receptor responsiveness. Despite no change in preload, fractional area change decreased from baseline after the race in both men and women, with a greater decrease in men [men: 54.1% (SD 2.1) to 50.7% (SD 3.4) vs. women: 55.4% (SD 2.7) to 53.3% (SD 2.5); P < 0.05]. The amount of dobutamine necessary to increase heart rate by 25 beats/min [men: 29.6 microg x kg(-1) x min(-1) (SD 6.6) to 42.7 microg x kg(-1) x min(-1) (SD 12.9) vs. women: 23.5 microg x kg(-1) x min(-1) (SD 4.0) to 30.0 microg x kg(-1) x min(-1) (SD 7.8); P < 0.05] and contractility by 10 mmHg/cm2 [men: 20.9 microg x kg(-1) x min(-1) (SD 5.1) to 37.0 microg x kg(-1) x min(-1) (SD 11.5) vs. women: 22.6 microg x kg(-1) x min(-1) (SD 6.4) to 30.7 microg x kg(-1) x min(-1) (SD 7.2); P < 0.05] was greater in both men and women postrace. However, the amount of dobutamine required to induce these changes was greater in men, reflecting larger beta-receptor alterations in male triathletes following PSE relative to women. These data suggest that following an acute bout of PSE, male triathletes demonstrate an attenuated chronotropic and inotropic response to beta-adrenergic stimulation compared with female triathletes.     

Chronic exercise and left ventricular structure and function in healthy human subjects

Twelve healthy well-trained participants in a supervised exercise program (mean age, 41.3 yr) were compared with 12 sedentary control subjects (mean age, 38.9 yr) with physical characteristics similar to the exercised group (EG) before training. Resting echocardiograms revealed significantly lower heart rates (HR) in the EG compared with control group (CG) but no evidence for cardiac structural differences between groups. Radionuclide angiograms performed at rest and during two levels of supine cycling (HR targets: 120 and 140 beats X min-1) resulted in increases in background-corrected end-diastolic counts [EDC(bc)] and confirmed use of the Frank-Starling mechanism in the majority of subjects. Mean values (+/- SD) for ejection fraction (EF) and normalized peak systolic ejection rate (PSER) (P greater than 0.05 between groups) were the following. (Formula: see text) The results suggested that fitness training does not induce significant cardiac enlargement as apparent from measurements at rest or important changes in contractile state during exercise. Increases in exercise stroke volume with such training may be the result of an increased end-diastolic volume.     

Acute plasma volume expansion in the untrained alters the hormonal response to prolonged moderate-intensity exercise.

To investigate the role of an increase in plasma volume (PV), characteristically observed with short-term endurance training, on the endocrine response to prolonged moderate intensity exercise, eight untrained males (VO2 peak = 3.52 +/- 0.12 l x min(-1)) performed 90 min of cycle ergometry at approximately 60% VO2peak both before (CON) and following (PVX) PV expansion. Acute PV expansion, which was accomplished using a solution of Dextran (6%) or Pentispan (10%) (6.7 ml kg(-1)), resulted in a calculated 15.8+/-2.2% increase (p<0.05) in PV. The prolonged exercise resulted in increases (p<0.05) in plasma vasopressin (AVP), plasma rennin activity (PRA), aldosterone (ALD), atrial naturetic peptide (alpha-ANP), and the catecholamines norepinephrine (NE) and epinephrine (EPI). PVX blunted the increases (p<0.05) in AVP, PRA, ALD, NE and EPI, during the exercise itself. The concentration of alpha-ANP was also lower (p<0.05) during exercise following PVX, an effect that could be attributed to the lower resting levels. No differences in osmolality was observed between conditions. These results demonstrate that PVX alters the fluid regulatory hormonal response in untrained subjects to moderate intensity dynamic exercise in a manner similar to that observed following short-term training induced alterations in PV. The specific mechanisms responsible for these alterations remain unclear, but appear to be related directly to the increase in PV.     

Left ventricular function during arm exercise: influence of leg cycling and lower body positive pressure.

The purpose of this study was to characterize left ventricular (LV) diastolic filling and systolic performance during graded arm exercise and to examine the effects of lower body positive pressure (LBPP) or concomitant leg exercise as means to enhance LV preload in aerobically trained individuals. Subjects were eight men with a mean age (+/-SE) of 26.8 +/- 1.2 yr. Peak exercise testing was first performed for both legs [maximal oxygen uptake (Vo(2)) = 4.21 +/- 0.19 l/min] and arms (2.56 +/- 0.16 l/min). On a separate occasion, LV filling and ejection parameters were acquired using non-imaging scintography using in vivo red blood cell labeling with technetium 99(m) first during leg exercise performed in succession for 2 min at increasing grades to peak effort. Graded arm exercise (at 30, 60, 80, and 100% peak Vo(2)) was performed during three randomly assigned conditions: control (no intervention), with concurrent leg cycling (at a constant 15% leg maximal Vo(2)) or with 60 mmHg of LBPP using an Anti G suit. Peak leg exercise LV ejection fraction was higher than arm exercise (60.9 +/- 1.7% vs. 55.9 +/- 2.7%; P < 0.05) as was peak LV end-diastolic volume was reported as % of resting value (110.3 +/- 4.4% vs. 97 +/- 3.7%; P < 0.05) and peak filling rate (end-diastolic volume/s; 6.4 +/- 0.28% vs. 5.2 +/- 0.25%). Concomitant use of either low-intensity leg exercise or LBPP during arm exercise failed to significantly increase LV filling or ejection parameters. These observations suggest that perturbations in preload fail to overcome the inherent hemodynamic conditions present during arm exercise that attenuate LV performance.     

Impairment of left ventricular function during maximal isometric dead lifting

High-intensity short-duration lifting is frequently performed by athletes and laborers. Little is known about the magnitude and pattern of blood pressure response and resultant effects on left ventricular (LV) function during this form of intense isometric exercise. We monitored brachial intra-arterial pressure and LV ejection fraction (LVEF) during upright isometric dead lifting performed on a force platform. Fourteen healthy male subjects (age 27 yr) maintained maximal sustained isometric dead lift (140 +/- 34 kg) for 32 s. LVEF was measured by 99mTc first-pass radionuclide ventriculography. Mean arterial pressure increased from 107 +/- 15 mmHg at rest to a peak of 174 +/- 28 mmHg and fell precipitously to 88 +/- 13 mmHg within 10 s after release of the dead lift. LVEF decreased from 63 +/- 8 to 51 +/- 14% (P less than 0.02) in seven subjects with technically acceptable ventriculograms. We conclude that maximal upright isometric dead-lift exercise produces a marked increase in arterial pressure and corresponding LV afterload that is associated with a transient reduction in LVEF in normal men.     

Evaluation of left ventricular diastolic function at rest and during exercise by gated radionuclide angiocardiography in coronary artery disease patients

The peak filling rate (PFR) is an index of the diastolic function and has been proposed as an excellent parameter for the evaluation and early detection of left ventricular (LV) dysfunction. This study contributes to the assessment of LV diastolic function at rest and during submaximal exercise in 19 normal subjects and in 42 patients with coronary artery disease (CAD). The PFR was compared to the ejection fraction (EF) and the peak ejection rate (PER)--both indexes of systolic LV function--after acquiring a high-resolution time-activity curve (time/frame between 10 and 30 msec) with gated radionuclide angiocardiography. In 23 patients with normal EF at rest (greater than or equal to 50%), PFR and PER were abnormally low in 87% and 43% of the cases respectively. During submaximal exercise in 13 CAD patients, EF, PFR and PER varied very little from baseline values but were significantly reduced compared to the values of normal subjects. The PFR proved to be a very sensitive indicator of LV dysfunction in coronary patients but was not capable of discriminating between one-, two- or three-vessel disease. Our results tend to show the PFR to be a good indicator of LV dysfunction at rest and during exercise and its usefulness for the assessment of LV function is becoming more and more evident in clinical practice.     

Effect of ultra-endurance exercise on left ventricular performance and plasma cytokines in healthy trained men

The purpose of this study was to investigate the effect of ultra-endurance exercise on left ventricular (LV) performance and plasma concentration of interleukin (IL)-6, IL-10, IL-18 and tumour necrosis factor alpha (TNF-α) as well as to examine the relationships between exercise-induced changes in plasma cytokines and those in echocardiographic indices of LV function in ultra-marathon runners. Nine healthy trained men (mean age 30±1.0 years) participated in a 100-km ultra-marathon. Heart rate, blood pressure, ejection fraction (EF), fractional shortening (FS), ratio of early (E) to late (A) mitral inflow peak velocities (E/A), ratio of early (E’) to late (A’) diastolic mitral annulus peak velocities (E’/A’) and E-wave deceleration time (DT) were obtained by echocardiography before, immediately after and in the 90th minute of the recovery period. Blood samples were taken before each echocardiographic evaluation. The ultra-endurance exercise caused significant increases in plasma IL-6, IL-10, IL-18 and TNF-α. Echocardiography revealed significant decreases in both E and the E/A ratio immediately after exercise, without any significant changes in EF, FS, DT or the E/E’ ratio. At the 90th minute of the recovery period, plasma TNF-α and the E/A ratio did not differ significantly from the pre-exercise values, whereas FS was significantly lower than before and immediately after exercise. The increases in plasma TNF-α correlated with changes in FS (r=0.73) and DT (r=-0.73). It is concluded that ultra-endurance exercise causes alterations in LV diastolic function. The present data suggest that TNF-α might be involved in this effect.