Delta VO2 Research Articles

8127 HOMA-IR Predicts Muscle Wasting During Androgen Deprivation Therapy

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. J.M. Garcia: None. Androgen deprivation therapy (ADT) is the primary treatment for advanced and metastatic prostate cancer. However, it induces adverse effects like reduced muscle mass and function, increased adiposity, and insulin resistance (IR). While muscle wasting is a known complication of ADT-induced hypogonadism, the extent to which other factors determine the variability in muscle loss remains unknown. In other diseases, IR is associated with muscle wasting, but its role in this setting of ADT has yet to be addressed. We hypothesized that patients with greater IR pre-ADT would display larger decreases of muscle mass and function after six months of ADT. Insulin and glucose (to calculate HOMA-IR), body composition, and physical function were assessed in patients with prostate cancer prior to and after three and six months of ADT. Body composition was assessed by dual x-ray absorptiometry and physical function by VO2 peak and 6-minute walk test (6MWT). Fasting blood samples were obtained to measure insulin and glucose in plasma. Pre-ADT, HOMA-IR was directly correlated with body mass index (BMI) (r=0.65, p<0.001, n=49), fat mass (r=0.55, p<0.001, n=49), and appendicular skeletal muscle index (ASMI) (r=0.33, p=0.021, n=49) and was inversely correlated with VO2 peak (r= -0.39, p=0.007, n=46). After three months, fat mass (p=0.015) and IR (p=0.0014) increased and VO2 peak decreased (p=0.0007), which persisted at the six-month visit. Appendicular lean mass and ASMI decreased after six months (p<0.0001). Pre HOMA-IR was negatively associated with delta BMI (r=-0.49, p<0.001, n=46), delta lean mass (r=-0.58, p<0.001, n=46), delta ASMI (r=-0.52, p<0.001, n=46), and delta 6MWT (r=-0.37, p=0.011, n=45) and positively correlated with delta VO2 peak (r=0.44, p=0.007, n=36). No associations were found with Pre-ADT HOMA-IR and changes in fat mass. In conclusion, those with greater Pre-ADT HOMA-IR lost more muscle mass, body weight, and 6MWT while unexpectedly showing less decrease in VO2 peak. This data suggests that HOMA-IR could potentially serve as a predictor of muscle mass loss in patients undergoing ADT. We propose that the significant decrease in muscle mass seen with ADT can be exacerbated by pre-existing IR. Presentation: 6/3/2024

8127 HOMA-IR Predicts Muscle Wasting during Androgen Deprivation Therapy

Abstract Disclosure: L. Caeiro: None. L.J. Anderson: None. H. Liu: None. J.M. Garcia: None. Androgen deprivation therapy (ADT) is the primary treatment for advanced and metastatic prostate cancer. However, it induces adverse effects like reduced muscle mass and function, increased adiposity, and insulin resistance (IR). While muscle wasting is a known complication of ADT-induced hypogonadism, the extent to which other factors determine the variability in muscle loss remains unknown. In other diseases, IR is associated with muscle wasting, but its role in this setting of ADT has yet to be addressed. We hypothesized that patients with greater IR pre-ADT would display larger decreases of muscle mass and function after six months of ADT. Insulin and glucose (to calculate HOMA-IR), body composition, and physical function were assessed in patients with prostate cancer prior to and after three and six months of ADT. Body composition was assessed by dual x-ray absorptiometry and physical function by VO2 peak and 6-minute walk test (6MWT). Fasting blood samples were obtained to measure insulin and glucose in plasma. Pre-ADT, HOMA-IR was directly correlated with body mass index (BMI) (r=0.65, p<0.001, n=49), fat mass (r=0.55, p<0.001, n=49), and appendicular skeletal muscle index (ASMI) (r=0.33, p=0.021, n=49) and was inversely correlated with VO2 peak (r= -0.39, p=0.007, n=46). After three months, fat mass (p=0.015) and IR (p=0.0014) increased and VO2 peak decreased (p=0.0007), which persisted at the six-month visit. Appendicular lean mass and ASMI decreased after six months (p<0.0001). Pre HOMA-IR was negatively associated with delta BMI (r=-0.49, p<0.001, n=46), delta lean mass (r=-0.58, p<0.001, n=46), delta ASMI (r=-0.52, p<0.001, n=46), and delta 6MWT (r=-0.37, p=0.011, n=45) and positively correlated with delta VO2 peak (r=0.44, p=0.007, n=36). No associations were found with Pre-ADT HOMA-IR and changes in fat mass. In conclusion, those with greater Pre-ADT HOMA-IR lost more muscle mass, body weight, and 6MWT while unexpectedly showing less decrease in VO2 peak. This data suggests that HOMA-IR could potentially serve as a predictor of muscle mass loss in patients undergoing ADT. We propose that the significant decrease in muscle mass seen with ADT can be exacerbated by pre-existing IR. Presentation: 6/3/2024

Impact of high intensity interval training on coronary atheromatous plaques evaluated by IVUS – a randomized trial

Abstract Background Coronary atheromatous plaque geometry, expressed as plaque burden (PB) or total atheroma volume (TAV) are both strongly related to the risk of acute and recurrent coronary events and outcomes in coronary artery disease (CAD). Exercise training is a cornerstone in the primary and secondary prevention of atherosclerotic complications, but the knowledge of the effect from exercise on coronary atheromatous plaques is sparse. Purpose We assessed the effect of six months supervised high intensity interval training (HIIT) on coronary plaque geometry using intravascular ultrasound in patients with stable CAD following percutaneous coronary intervention (PCI). Methods Sixty patients were randomized to two sessions weekly of supervised HIIT at 85–95% of peak heart rate (n=30) or to follow contemporary preventive guidelines (control group, n=30). The primary endpoint was change in PB and TAV normalized for segment length (TAVnorm) at six-month follow-up. All included patients were on stable lipid lowering therapy at least six weeks prior to inclusion with no further adjustments throughout the study. Results When comparing matched coronary segments at baseline and follow-up, there was a 1.4 percent points larger reduction in average PB (95% CI: 2.7 to 0.1, p=0.036) in the HIIT group compared to the control group. TAVnorm was reduced by 9 mm3 (95% CI: 14.7 to 3.4, p=0.002) after HIIT, with a between group difference of 12 mm3 (95% CI: 19.9 to 4.2, p=0.003). VO2peak improved more in the HIIT group with a difference in delta VO2 peak between groups of 1.7 mL kg–1 min–1 (95% CI: 0.1 to 3.3, p=0.039). There was also a significant larger reduction in body mass index and waist circumference in the HIIT group compared to the control group (both, p=0.021). In both groups a modest, although significant increase was observed for both HDL-cholesterol and ApoA1, but no significant changes in the LDL, ApoB or HbA1c levels were found. Conclusions In patients with established CAD, a regression of PB and TAV was observed in patients undergoing six months of supervised HIIT compared with patients following contemporary preventive guidelines. Our study indicates that exercise increasing VO2 peak counteracts atherosclerotic coronary disease progression and reduces PB and TAV in coronary atheromatous plaques following PCI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was funded by the Liaison Committee for Central Norway Regional Health Authority, the Norwegian University of Science and Technology (NTNU), and the Research Fund at St. Olavs University Hospital

P408 CERTIFICATION FOR COMPETITIVE SPORTS ACTIVITY IN A TEENAGER WITH WPW BY VIA INTRAHYSSIAN ACCESSORY PATHWAY

Abstract The case of a 12–year–old male, height 160 cm, weight 46 kg, who practices water polo at a competitive level is reported. Negative family history of cardiovascular pathologies, general and cardiovascular physical examination within the limits of normality. On the electrocardiographic trace (ECG) presence of delta wave from ventricular pre–excitation from intrahyssian accessory pathway (Fig. 1). Echocardiography + color Doppler was normal. The subject underwent a cardiopulmonary stress test with an incremental ramp protocol and steps of 20 watts / min. Shutdown at 190 watts for muscle exhaustion with peak oxygen consumption (VO2) = 43.9 mL / Kg / min, Heart rate = 197 beats / minute, BP = 210/70 mmHg, VE / VCO2 slope = 27.6. Normal course of the cronotropic and pressure curve. The ventricular pre–excitation delta wave persisted for the entire duration of the test and in recovery (Fig. 2, Fig. 3). Secondary disturbances of ventricular repolarization characterized by ST segment sub–leveling and negative T wave appeared at high load and persisted in the first minutes of recovery, delta VO2 / delta WR = 12. Given the non–disappearance of the delta wave from ventricular pre–excitation during the maximal stress test, the subject was sent to an electrophysiological study and subsequent ablation of the accessory pathway. The electrophysiological study was negative for inducibility of atrial fibrillation (AF) and ventricular arrhythmias. Safe ablation was impossible given the intrahyssian position of the accessory pathway. Considering the negativity of the electrophysiological study due to non inducibility of supraventricular and ventricular arrhythmias, eligibility for competitive sports was granted.

Mechanisms of Exercise Intolerance in Heart Failure with Reduced Ejection Fraction: Influence of COPD

IntroductionExercise intolerance is a hallmark of heart failure with reduced ejection fraction (HFrEF) resulting from a variety of factors including comprised oxygen delivery. A common comorbidity of HFrEF is chronic obstructive pulmonary disease (COPD), which is independently associated with reduced exercise tolerance and cardiac output (Q) as well as peripheral dysfunction similar to HFrEF. It is currently unknown if HFrEF and coexisting COPD (HFrEF+COPD) exhibit worsened exercise tolerance and whether the mechanisms thereof are similar to HFrEF alone. We hypothesized that patients with HFrEF+COPD demonstrate further reductions in peak VO2 and workload subsequent to a lower peak Q and arterio‐mixed venous O2 content difference (C(a‐v)O2) compared to HFrEF alone.MethodsHFrEF+COPD (n=16) and HFrEF (n=17) (age: 57±7 vs 54±6 yrs; EF%: 20±5 vs 21±5; height: 173±7 vs 174±7 cm; weight: 88±14 vs 86±17 kg; all p>0.18) underwent peak exercise testing during right heart catheterization. At rest and peak exercise, invasive hemodynamic, cardiac pressures, and arterial pressures were performed. Heart rate and oxygen uptake (VO2) were measured at rest and peak exercise via 12‐lead ECG and metabolic measurement system, respectively. Convective oxygen delivery was calculated as Q multiplied by CaO2.ResultsPeak exercise VO2 and workload were lower in HFrEF+COPD compared to HFrEF (7.0±1.9 vs. 9.9±2.7 mL/min/kg; 34±7 vs. 45±12 watts; both p<0.01). At peak exercise, Q and stroke volume were lower in HFrEF+COPD than HFrEF (4.8±1.3 vs. 7.0±3.0 L/min; 52±16 vs. 75±28 mL; both p<0.01). Significant relationships existed between delta VO2 and Q (peak exercise minus resting) in HFrEF+COPD and HFrEF (r=0.84 and r=0.89; both p<0.01); however, HFrEF+COPD had a significantly lower slope (p=0.02). Peak exercise C(a‐v)O2 was not different between HFrEF+COPD and HFrEF (12.9±2.3 vs. 12.8±2.6 mL/dL; p=0.89). No differences were present in heart rate or hemoglobin at peak exercise (p>0.73). Delta VO2 and C(a‐v)O2 was significantly related for HFrEF+COPD (r=0.68; p<0.01), but not HFrEF (r=0.14, p=0.57). At peak exercise, HFrEF+COPD had lower convective oxygen delivery (845±239 vs. 1230±517 mL/min; p<0.01).ConclusionsPatients with HFrEF and concurrent COPD demonstrate worsened exercise tolerance compared to HFrEF resulting from reduced oxygen delivery. These data suggest HFrEF with COPD exhibit more severe central and peripheral abnormalities than HFrEF alone.Support or Funding InformationNHLBI RO1 HL126638This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Right Ventricular Outflow Tract Enlargement Prior to Pulmonary Valve Replacement is Associated with Poorer Structural and Functional Outcomes, in Adults with Repaired Tetralogy of Fallot

Pulmonary valve replacement (PVR) is commonly performed late after Tetralogy of Fallot (TOF) repair. We examined the effects of PVR on cardiac structure, function and exercise capacity in adults with repaired TOF. Eighteen adult patients with repaired TOF and severe pulmonary regurgitation (PR) with right ventricular (RV) dilatation requiring PVR for clinical reasons (age; 25±8 years) were recruited to undergo cardiac MRI (1.5T) and cardiopulmonary exercise testing before and 14±3 months after PVR. Reduced indexed RV end-diastolic volume (RVEDVi; 186±32mL/m(2) pre-op vs 114±20mL/m(2) post-op, p<0.001) was observed after PVR. "Normalisation" of RVEDVi (≤108mL/m(2)) was achieved in only seven of 18 patients. Pre-PVR RVEDVi correlated with post-operative change in RVEDVi (change=-72.1±20.4mL/m(2), r=-0.815, p<0.001). Exercise capacity remained high-normal post-PVR (% predicted maximal workload: 93±16% vs 91±12%, p=0.5). Regional RV volumes were assessed; RV outflow tract (RVOT) volumes were compared to the RV muscular corpus. Large pre-PVR RVOT volumes correlated negatively with post-surgical RV ejection fraction, peak VO2 and delta VO2 at anaerobic threshold (p<0.05 for all). Normalisation of RV volume is unlikely to be achieved above a pre-PVR RVEDVi of 165mL/m(2) or more. In particular, an enlarged RVOT prior to PVR predicts suboptimal structural and functional outcomes.

Percent Body Fat is Negatively Correlated to Walking Efficiency in a Group of Obese and Nonobese Men and Women

The influence of body mass index and percent body fat on walking economy is uncertain, and may depend on the population studied. PURPOSE: We examined the relationship between body mass index (BMI: weight (kg)/height (m2), % body fat (%BF) and exercise VO2 during treadmill walking in subjects varying considerably in BMI (18.0 to 50.3) and %BF (15.5 to 52.0). METHODS: 20 males (age: 25.3 ± 6.4 yr.; ht: 176.0 ± 8.1 cm; wt: 95.8 ± 33.4 kg; BMI: 30.3 ± 8.9; % BF: 31.5 ± 8.2) and 21 females (age: 26.6 ± 6.5 yr.; ht: 167.5 ± 23.7 cm; wt: 79.1 ± 23.7 kg; BMI: 27.9 ± 8.0; % BF: 37.6 ± 10.7) completed exercise sessions consisting of level-grade treadmill walking at 1.1 mph (0.5 m/sec), 1.7 mph (0.75 m/sec), 2.2 mph (1.0 m/sec), 2.8 mph (1.25 m/sec), 3.4 mph (1.5 m/sec), 3.9 mph (1.75 m/sec), and 4.5 mph (2.00 m/sec). Subjects exercised for 5 min at each speed, while pulmonary ventilation and gas exchange were measured continuously. %BF was assessed by dual-energy X-ray absorptiometry. Metabolic cost (J/kg/m) was calculated by dividing metabolic power by walking speed, and preferred walking speed was determined from the time required to walk 70 m along a level sidewalk. The relationship between VO2 and walking speed was examined by way of polynomial random coefficient regression (PRCR) that generated linear and quadratic coefficients.. RESULTS: As expected, the VO2 vs. walking speed relationship was curvilinear. Only the quadratic coefficients of the PRCR analysis were significantly correlated with %BF (r = 0.45; p = 0.004) and BMI (r = 0.32; p = 0.039). These results were consistent with the finding that quadratic regression coefficients were significantly higher (p=0.008) in subjects with %BF above the median. The quadratic coefficients of the PRCR were also significantly inversely correlated with minimum metabolic cost speed (r = -0.85; p < 0.001) and preferred walking speed (r = -0.55; p < 0.0001). CONCLUSION: These results suggest that %BF adversely affects walking energy expenditure, primarily by increasing the rate of VO2 increase ("delta VO2") as walking speed increases. In our subjects this was most noticeable at the faster walking speeds, and may explain in part why subjects with high %BF, i.e., those with the greatest PRCR quadratic coefficients, had the lowest preferred walking speeds and lowest minimum metabolic cost walking speeds.

The effect of inhaled anticholinergic drug on dyspnea and on the physiologic function of respiratory system in patients with chronic obstructive pulmonary disease

The mechanism underlying the relief of the sensation of dyspnea during exercise following the inhalation of anticholinergic drug in patients with chronic obstructive pulmonary disease (COPD) has not been fully elucidated. We examined pulmonary function, static respiratory pressure, and dyspneic sensations during exercise before and after the inhalation of oxitropium bromide (OTB) in 14 male patients with COPD. FEV1 and FVC were increased after the inhalation of OTB, whereas RV and the ratio of RV to TLC were decreased after inhalation. Maximum inspiratory pressure (PImax) was significantly increased after the administration of OTB. Dyspneic sensation during exercise, measured as a Borg scale slope (BSS, delta BS/ delta Vo2) were reduced after the inhalation of OTB. There were significant correlations among BSS, PImax and RV/TLC. These results suggest that a reduction in air trapping after the inhalation of OTB may enhance the ability of the to diaphragm generate pressure at a given neural input, resulting in a reduced sensation of dyspnea during exercise in patients with COPD.

Determinant factors of the decrease in aerobic performance in moderate acute hypoxia in women endurance athletes

The purpose of this study was to evaluate the limiting factors of maximal aerobic performance in endurance trained (TW) and sedentary (UW) women. Subjects performed four incremental tests on a cycle ergometer at sea level and in normobaric hypoxia corresponding to 1000, 2500 and 4500 m. Maximal oxygen uptake decrement (Delta VO2 max) was larger in TW at each altitude. Maximal heart rate and ventilation decreased at 4500 m in TW. Maximal cardiac output remained unchanged. In both groups, arterialized oxygen saturation (Sa'O2 max) decreased at and above 2500 m and maximal O2 transport (QaO2 max) decreased from 1000 m. At 4500 m, there was no more difference in QaO2 max between TW and UW. Mixed venous O2 pressure (PvO2 max) was lower and O2 extraction (O2ERmax) greater in TW at each altitude. The primary determinant factor of VO2 max decrement in moderate acute hypoxia in trained and untrained women is a reduced maximal O2 transport that cannot be compensate by tissue O2 extraction.

Excessive oxygen uptake during exercise and recovery in heavy exercise

The aim of this study was to determine whether excessive oxygen uptake (Vo2) occurs not only during exercise but also during recovery after heavy exercise. After previous exercise at zero watts for 4 min, the main exercise was performed for 10 min. Then recovery exercise at zero watts was performed for 10 min. The main exercises were moderate and heavy exercises at exercise intensities of 40 % and 70 % of peak Vo2, respectively. Vo2 kinetics above zero watts was obtained by subtracting Vo2 at zero watts of previous exercise (DeltaVo2). Delta Vo2 in moderate exercise was multiplied by the ratio of power output performed in moderate and heavy exercises so as to estimate the Delta Vo2 applicable to heavy exercise. The difference between Delta Vo2 in heavy exercise and Delta Vo2 estimated from the value of moderate exercise was obtained. The obtained Vo2 was defined as excessive Vo2. The time constant of excessive Vo2 during exercise (1.88+/-0.70 min) was significantly shorter than that during recovery (9.61+/-6.92 min). Thus, there was excessive Vo2 during recovery from heavy exercise, suggesting that O2/ATP ratio becomes high after a time delay in heavy exercise and the high ratio continues until recovery.

The Relationship Between Running Economy And Maximal Oxygen Uptake In Trained Adolescent Female Distance Runners

The independent characteristics of good running economy (lower submaximal VO2) and a high maximal oxygen uptake (VO2max) have been related to distance running success. However, the interaction between these two measurements is not well-defined in young adolescent runners. PURPOSE To evaluate the relationship between running economy (RE) and VO2max in a group of well-trained adolescent female distance runners. METHODS Nineteen subjects (15.9 ± 1.0 yrs; 168 ± 6.3 cm; 55 ± 6.5 kg) performed two 6-min submaximal treadmill runs at 7.0 and 8.0 mph, respectively. Running economy was defined as the VO2 (ml·kg−1 ·min−1) at each speed and the delta VO2 from 7.0 to 8.0 mph. Subsequent to the final RE speed, VO2max was measured using a graded exercise test to maximal voluntary exhaustion. Oxygen consumption was assessed using standard open circuitry spirometry techniques. RESULTS Running economy at 7.0 and 8.0 mph were 41.3 ± 2.7 ml·kg−1 ·min−1 and 46.8 ± 2.9 ml·kg−1 ·min−1, respectively. The delta VO2 averaged 5.5 ± 1.0 ml·kg−1 ·min−1. VO2max averaged 58.0 ± 5.9 ml·kg−1 ·min−1. Pearson correlation analyses revealed a significant relationship between the delta VO2 and VO2max (r = 0.56, p <0.05). However, there were no significant relationships between RE at each velocity and VO2max (r = 0.20 at 7.0 mph; r = 0.38 at 8.0 mph). CONCLUSION Although RE was not significantly related to VO2max, the delta VO2, another measure of economy, was related in a manner that suggested the runners with the highest VO2max tended to be less economical with respect to the change in VO2 from one speed to the next. Future research in this area should focus on the interaction between VO2max and the biomechanical and metabolic influences of RE as it relates to this population. Funding provided by the Indiana Academy of Science and Ball State University

Sensation of breathlessness and respiratory oxygen cost during cycle exercise with and without conscious entrainment of the breathing rhythm.

The conscious entrainment of respiratory rhythm to exercise rhythm (ENT) has been hypothesized to alleviate breathing discomfort and reduce the oxygen (O2) cost of ventilation with a resulting decrease in total O2 uptake (VO2) during rhythmic exercise. This hypothesis has been tested in the study reported here. Eight female subjects performed cycle exercise at 50 rpm under two work load conditions of 40% and 60% of maximal VO2. During a 30-min exercise period at each work load, each subject was asked to breathe under two conditions for 15 min each: (1) spontaneously (non-ENT run), and (2) deliberately entraining the breathing rhythm to the cycling rhythm at preferred coupling ratios of the two rhythms (ENT run). In the ENT run, most subjects chose a ratio of 1:2. In each run, pulmonary ventilation (VE), total VO2 and the breathlessness sensation (BS) were measured at 4-5 min. BS was assessed according to a Borg category scale. The remaining 10 min of each 15-min run were allotted for measurement of the O2 cost of ventilation (delta VO2/delta VE), assessed by a hypercapnia-induced hyperventilation method in which the VO2 of the respiratory muscles (VO2RM) was calculated by multiplying delta VO2/delta VE by the prevailing VE. On average, there were no significant differences in any of the variables, VO2, delta VO2/delta VE, VO2RM and BS, between the non-ENT and ENT runs performed at any work load. However, there were wide variations among the subjects in the differences (delta) between the two runs, and significant correlations were found between delta VO2 vs delta VE, delta VO2 vs delta VO2RM, and delta BS vs delta VO2RM of individual subjects. These results indicate that reductions of the total VO2 and BS with ENT could occur in subjects in whom the VO2RM decreased during ENT.

Endotoxaemia and postoperative hypermetabolism in coronary artery bypass surgery: the role of ketanserin

In a randomized, double-blind clinical study in 29 patients undergoing elective coronary artery surgery, we assessed the role of ketanserin, an inhibitor of serotonin-induced vasoconstriction and weak alpha 1 sympathetic blocker, in reducing endotoxaemia and postoperative hypermetabolism. Male patients without major organ dysfunction were allocated randomly to receive either ketanserin or placebo. Hypermetabolism was defined as an increase in oxygen consumption in the early postoperative hours (delta Vo2). Circulating endotoxin (P = 0.04) and postoperative delta Vo2 (P = 0.03) were lower in the ketanserin patients. Endotoxaemia was associated also with low vascular filling. From these preliminary results we conclude that treatment with ketanserin during cardiac surgery may reduce but not abolish endotoxaemia and postoperative hypermetabolism.

Differential cardiorespiratory response to combined exercise with different combinations of forearm and calf exercise.

The purpose of this study was to examine whether cardiorespiratory responses to combined rhythmic exercise (60 contractions.min-1) was affected by different combinations of upper and lower limb exercise in seven healthy women. Six different rhythmic exercises were compared: 6-min rhythmic handgrip at 10% of isometric maximal voluntary contraction (MVC) (H10); 6-min rhythmic plantar flexion at 10% MVC (P10); exhausting rhythmic handgrip at 50% MVC (H50); exhausting rhythmic plantar flexion at 50% MVC (P50); H50 was added to P10 (P10H50); and P50 was added to H10 (H10P50). Exercise duration, after handgrip was combined with plantar flexion (P10H50), was shorter than that of H50, although the exercise duration of H10P50 was not significantly different from P50. No significant difference was found between the difference from rest in oxygen uptake (delta VO2) during H10P50 and the sum of delta VO2 during H10 and P50. Also, the differences from rest in forearm blood flow (delta FBF) and calf blood flow (delta CBF) during H10P50 were not significantly different from delta FBF in H10 and from delta CBF in P50. In contrast, delta VO2 in P10H50 was lower than the sum of delta VO2 in P10 and H50 (P < 0.05), and delta FBF in P10H50 was lower than that in H50 (P < 0.05), while delta CBF was not significantly different between P10H50 and P10. The changes in heart rate from rest (delta HR) during the combined exercises were lower than the sums of delta HR in the corresponding single exercises (P < 0.05). These results demonstrated an inhibitory summation of several cardiorespiratory responses to combined exercise resulting in a reduction in exercise performance which would seem to occur easily when upperlimb exercise is added to lower limb exercise.

Myocardial VO2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach

We instituted a new approach of measuring mechanically unloaded myocardial oxygen consumption (VO2) by using rat left ventricular (LV) slices in an air-tight chamber filled with oxygenated Tyrode solution. Myocardial slices (300 microns in thickness) freely shortened without external load by electrical field stimulation (St). VO2 without St (n = 6) was 1.69 +/- 0.41 ml O2.min-1.100 g LV-1. VO2 with St (n = 6) increased to 2.28 +/- 0.36 ml O2.min-1.100 g LV-1. VO2 in Ca(2+)-free Tyrode solution irrespective of St was nearly equal to VO2 without St in normal Tyrode solution, indicating that all these VO2 correspond to basal metabolic VO2. The increment in VO2 by St (delta VO2) increased up to twice normal with the extracellular Ca2+ concentration up to 4 times normal. Inhibition of cross-bridge cycling by 2,3-butanedione monoxime (5 and 10 mM) did not decrease delta VO2. These results suggest that delta VO2 consists of VO2 primarily for excitation-contraction coupling but not for cross-bridge cycling.

O2 Uptake Kinetics in Response to Exercise: A Measure of Tissue Anaerobiosis in Heart Failure

Oxygen uptake (VO2) reflects the rate of aerobic regeneration of high-energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for VO2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between VO2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent delta) between their lactic acidosis threshold (LAT) and peak VO2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of VO2 kinetics was quantified as the rise in VO2 from the third to the sixth minute of exercise (delta VO2 [6-3]). Ten age- and size-matched normal subjects served as control subjects. delta VO2 (6-3) was correlated with the increase in lactate (r = 0.71, p < 0.001), hypoxanthine (r = 0.61, p < 0.001), and norepinephrine (r = 0.41, p < 0.01) but not epinephrine in response to exercise in the heart failure patients. The delta VO2 (6-3) and delta lactate were both greater in the patients than in the control subjects at similar absolute work rates (54 +/- 20 and 60 W, respectively). However, the slope of the relationship between delta La and delta VO2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r = 0.66, p < 0.001), but not norepinephrine or epinephrine. In summary, VO2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism.

Exercise Performance in Patients with Uncomplicated Essential Hypertension: Effects of Nifedipine-induced Acute Blood Pressure Reduction

In untreated patients with uncomplicated essential hypertension, exercise induces an abnormal increase in blood pressure; the influences of this increase on exercise were evaluated by a cardiopulmonary exercise test (CPX) performed in control conditions (step 1) and during acute blood pressure reduction (step 2). Patients were classified as (1) normotensive (resting diastolic blood pressure [BPd] less than 90 mm Hg; n = 14), (2) mildly hypertensive (BPd of 90 to 104 mm Hg; n = 9), and (3) moderately to severely hypertensive (BPd greater than or equal to 105 mm Hg; n = 16). For the three groups, peak mean blood pressure during exercise was 125 +/- 5 mm Hg (mean +/- SEM), 144 +/- 3 mm Hg (p less than 0.01 vs normotensive), and 161 +/- 4 mm Hg (p less than 0.01 vs normotensive and p less than 0.01 vs mild hypertension), respectively. Oxygen consumption (VO2) at peak exercise and at ventilatory anaerobic threshold was 26.1 +/- 1.1 and 17.2 +/- 0.5 ml/min/kg, 25.4 +/- 1.1 and 16.9 +/- 0.8 ml/min/kg, and 26.4 +/- 1.3 and 17.5 +/- 1.2 ml/min/kg in normotensive subjects, those with mild hypertension, and those with moderate to severe hypertension, respectively. Fourteen normotensive subjects, six with mild hypertension, and nine with moderate to severe hypertension participated to step 2 (nifedipine vs placebo, double-blind crossover). Nifedipine reduced blood pressure at rest and at peak exercise in those with hypertension. Peak exercise VO2 was unaffected by nifedipine in both normotensive subjects and those with hypertension. With nifedipine, ventilatory anaerobic threshold occurred earlier and at a lower VO2 in mild and in moderate to severe hypertension (delta VO2 = -1.9 and -2.4 ml/min/kg, respectively). These findings might be due to nifedipine-induced redistribution of blood flow during exercise and might be the reason for the complaint of weakness after blood pressure reduction in hypertensive subjects.

Evidence that circulatory oscillations accompany ventilatory oscillations during exercise in patients with heart failure.

Periodic breathing (PB) during exercise in patients with congestive heart failure (CHF) is associated with prominent oscillations (OSC) of O2 uptake (VO2). We hypothesized that the VO2 OSC represent OSC in true O2 exchange, resulting from concomitant cardiac output fluctuations and are not merely due to OSC of lung O2 stores. We compared the amplitude of the OSC of VO2, ventilation (VE), and end-expiratory lung volume (EELV) in 17 patients with CHF and PB and in seven healthy control subjects who volitionally simulated PB. Subjects underwent an incremental and/or a constant work-rate exercise test. VE and VO2 were measured breath by breath. EELV change was estimated by summing the difference between inspiratory and expiratory tidal volumes for each breath. The amplitude of the OSC, delta, is expressed as the ratio of the difference between the peak and nadir of the oscillating variable divided by its mean [delta = (peak - nadir)/mean]. In CHF, during incremental testing, the amplitude of the VE OSC was smaller than that of the VO2 OSC (delta VE = 49 +/- 15% [SD], delta VO2 = 63 +/- 25%, p less than 0.01). In contrast, during volitional PB in the control subjects, VE OSC were larger than VO2 OSC (delta VE = 48 +/- 12%, delta VO2 = 25 +/- 11%, p less than 0.01). This suggests that changing VE itself cannot account for the marked VO2 OSC seen in CHF. In the patients, EELV showed no systematic OSC, did not correlate with delta VO2, and was not significantly different from zero.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen Delivery and Consumption in Head-Injured and Multiple Trauma Patients

Critically ill patients often demonstrate that whole body oxygen consumption (VO2) is dependent on oxygen delivery (DO2). In this retrospective study, the relationship of VO2 to DO2 in patients with isolated head injury (HI, n = 18) was compared to that in patients with multiple trauma (MT, n = 60) without serious head injury. Mean pulmonary capillary wedge pressure, central venous pressure, arterial PCO2, cardiac index, and oxygen delivery were significantly lower in HI, but oxygen consumption was not different in the groups. In both groups, changes in DO2 (delta DO2) within each patient were significantly correlated with changes in VO2 (delta VO2) in that same patient. This relationship was not different between the HI patients, (delta VO2 = (0.20 +/- 0.02) delta DO2), and the MT patients (delta VO2 = (0.17 +/- 0.01) delta DO2). When these groups were further divided into those with high hematocrit (greater than 32%) and low hematocrit (less than 32%), HI patients with a low hematocrit demonstrated a steeper regression slope, with 26 +/- 3% of the DO2 change being reflected in the VO2 change. This was significantly greater than the slope in HI patients with high hematocrit (13 +/- 3%) and the MT patients at high (19 +/- 2%) or low (16 +/- 2%) hematocrits. These data show a correlation between changes in oxygen delivery and consumption that is similar in both head-injury patients and multiple trauma patients without serious head injury. This relationship was greatest in head-injured patients at low hematocrit. This relationship of VO2 and DO2 in both groups suggests an influence of neurohumoral factors rather than local tissue phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma catecholamines and oxygen consumption during weaning from mechanical ventilation

Previous studies on oxygen consumption (VO2) during weaning from mechanical ventilation assumed that an increase in VO2 (delta VO2) reflected oxygen consumption by respiratory muscles (VO2RESP), and proposed delta VO2 as a weaning predictor. We measured VO2 CO2 production (VCO2) and plasma catecholamines in 20 short-term ventilated patients during weaning by SIMV and CPAP. delta VO2 as a percentage of VO2 during spontaneous ventilation (delta VO2%) ranged from 4.8% to 41.5%. VCO2 also increased and correlated with VO2. Plasma adrenaline and noradrenaline increased significantly to levels known to produce considerable increases in metabolic rate. Mean arterial pressure and heart rate concomitantly increased, but spontaneous minute ventilation decreased. Thus, since the increased plasma catecholamines are calorigenic, the assumption that delta VO2 represents VO2RESP is incorrect. Although mean delta VO2% of successfully weaned patients was significantly less than that of failure-to-wean patients, the wide scatter of individual values in the latter group excludes delta VO2% as an accurate weaning predictor.