L-Glutamine Therapy Improves Minute Ventilation of Sickle Cell Anemia Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3783-3783
Author(s):  
Henry R. Macan ◽  
Janos Porszasz ◽  
Hideki Tsurugaya ◽  
Rafael L. Razon ◽  
Han Koh ◽  
...  

Abstract We have demonstrated previously that oral L-glutamine administration can improve NAD redox potential in sickle red blood cells (RBC) and decrease the endothelial adhesion rate of sickle RBC. Additionally, preliminary results showed that L-glutamine therapy improved the exercise endurance of sickle cell anemia patients. Following up on this study, minute ventilation and work rate were evaluated. After proper consent, 6 homozygous sickle cell anemia volunteers participated in this two-part study. The first part was incremental work rate testing where the work rate was increased incrementally. The second part was the constant work rate test, in which 80% of the maximum work rate of the incremental test was utilized. Patients were observed for changes in ventilation. These tests were conducted at baseline and after 8 to 12 weeks of therapy with oral L-glutamine at 30 grams a day. There were 6 patients who completed the incremental work rate test and 4 patients who completed the constant work rate test, respectively, at baseline and after treatment. Two of the patients withdrew prior to the completion of the follow-up testing. The results were as follows: On the incremental test, there was an upward trend in peak work rate with an average of 3.5 ± 8.7 watts/min (88.7 ± 25.6 vs. 91.5 ± 21.7; ρ> 0.05). Minute ventilation (VE) showed an average improvement of −4.8 ± 3.9 liters/min (61.2 ± 9.8 vs. 56.4 ± 9.9; ρ value of 0.05). The improved ventilation may be secondary to increased pulmonary blood flow inferring an increased cardiovascular oxygen delivery. On the constant work rate test, there was significant increase in exercise duration with an average of 1.4 ± 0.8 minutes (5.9 ± 1.6 vs. 7.3 ± 1.1; ρ< 0.05). The minute ventilation (VE) showed an average decrease of −11.0 ± 11.6 liters/min (66.5 ± 24.9 vs. 55.5 ± 14.5; ρ> 0.05). This could be indicative of improved oxygen delivery to the exercising musculature despite the absence of a preparatory exercise training program. The data confirm our preliminary report suggesting that L-glutamine therapy improves the exercise endurance of sickle cell anemia patients. Test Mean + SD ρ value Pre Post Paired Δ (two-tailed t-test) Incremental Work Rate Peak Work Rate (watts/min) 88.7 ± 25.6 91.5 ± 21.7 3.5 ± 8.7 0.37 VE (liters/minute) 61.2 ± 9.8 56.4 ± 9.9 −c4.8 ± 3.9 0.05 Constant Work Rate −Duration (minutes) 5.9 ± 1.6 7.3 ± 1.1 1.4 ± 0.8 0.04 −VE (liters/minute) 66.5 ± 24.9 55.5 ± 14.5 −11.0 ± 11.6 0.15

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3729-3729
Author(s):  
Henry R. Macan ◽  
Richard Casaburi ◽  
Hideki Tsurugaya ◽  
Janos Porszasz ◽  
Han Koh ◽  
...  

Abstract We have demonstrated previously that oral L-glutamine administration can improve NAD redox potential in sickle red blood cells (RBC) and decrease the endothelial adhesion rate of sickle RBC. Clinically, there was subjective reporting of increased energy level. To confirm the reporting of increased energy level objectively, a study incorporating exercise tolerance testing was designed. After proper consent, 7 homozygous sickle cell anemia volunteers participated in the study, which was composed of two parts. The first is incremental work rate test where the work rate increased incrementally. The second part is the constant work rate test. In this test the 80% maximum work rate for the incremental test is utilized and the patients are tested for duration of exercise. These tests were conducted at baseline and after 8 to 12 weeks of therapy with oral L-glutamine at 30 grams a day. Two of the patients withdrew prior to completion of the follow up testing. There were 6 patients who completed the incremental work rate test and 4 patients who completed constant work rate test, respectively, at baseline and after treatment. Two of the 6 patients who completed the incremental work rate test at baseline declined to have the constant work rate test, resulting in 4 patients completing the constant work rate test. The results were as following: The work rates were 88 watts at baseline and 91.5 watts after treatment, with p = 0.18, for the incremental work protocol and 5.87 minutes at baseline and 7.27 minutes after treatment, with p = 0.02, for constant work protocol. For the incremental work rate, the data show a trend for increase with L-glutamine treatment. For the constant work protocol, there was a significant improvement in the work rate after treatment with L-glutamine. The data are consistent with the subjective reporting from a previous study suggesting that L-glutamine therapy improved the exercise endurance of sickle cell anemia patients Test Incremental Constant Mean value Peak work rate SD± Duration SD± Pre- 88 watts 25.58± 5.87 minutes 1.65± Post- 91.5 watts 21.69± 7.27 minutes 1.14± Significance P value One-tail test 0.18 0.02


2017 ◽  
Vol 57 (1) ◽  
pp. 117-128
Author(s):  
Dalton M. Pessôa Filho ◽  
Leandro O.C. Siqueira ◽  
Astor R. Simionato ◽  
Mário A.C. Espada ◽  
Daniel S. Pestana ◽  
...  

AbstractThe purpose of this study was to investigate whether a tethered-swimming incremental test comprising small increases in resistive force applied every 60 seconds could delineate the isocapnic region during rapidly-incremented exercise. Sixteen competitive swimmers (male, n = 11; female, n = 5) performed: (a) a test to determine highest force during 30 seconds of all-out tethered swimming (Favg) and the ΔF, which represented the difference between Favg and the force required to maintain body alignment (Fbase), and (b) an incremental test beginning with 60 seconds of tethered swimming against a load that exceeded Fbase by 30% of ΔF followed by increments of 5% of ΔF every 60 seconds. This incremental test was continued until the limit of tolerance with pulmonary gas exchange (rates of oxygen uptake and carbon dioxide production) and ventilatory (rate of minute ventilation) data collected breath by breath. These data were subsequently analyzed to determine whether two breakpoints defining the isocapnic region (i.e., gas exchange threshold and respiratory compensation point) were present. We also determined the peak rate of O2 uptake and exercise economy during the incremental test. The gas exchange threshold and respiratory compensation point were observed for each test such that the associated metabolic rates, which bound the heavy-intensity domain during constant-work-rate exercise, could be determined. Significant correlations (Spearman’s) were observed for exercise economy along with (a) peak rate of oxygen uptake (ρ = .562; p < 0.025), and (b) metabolic rate at gas exchange threshold (ρ = −.759; p < 0.005). A rapidly-incremented tethered-swimming test allows for determination of the metabolic rates that define zones for domain-specific constant-work-rate training.


1985 ◽  
Vol 58 (6) ◽  
pp. 2020-2026 ◽  
Author(s):  
S. N. Hussain ◽  
B. Rabinovitch ◽  
P. T. Macklem ◽  
R. L. Pardy

We assessed the effects of selective restriction of movements of the rib cage (Res,rc) and abdomen (Res,ab) on ventilatory pattern, transdiaphragmatic pressure (Pdi), and electrical activity of the diaphragm (Edi) in five normal subjects exercising at a constant work rate (80% of maximum power output) on a cycle ergometer till exhaustion. Restriction of movements was achieved by an inelastic corset applied tightly around the rib cage or abdomen. Edi was recorded by an esophageal electrode, rectified, and then integrated, and peak values during inspiration were measured. Each subject exercised at the same work rate on 3 days: with Res,rc, with Res,ab, and without restriction (control). Res,rc but not Res,ab reduced exercise time (tlim). Up to tlim, minute ventilation (VE) was similar in all three conditions. At any level of VE, however, Res,rc decreased tidal volume and inspiratory and expiratory time, whereas Res,ab had no effect on the pattern of breathing. Res,ab was associated with higher inspiratory Pdi swings at any level of VE, whereas peak Edi was similar to control. Inspiratory Pdi swings were the same with Res,rc as control, but the peak Edi for a given Pdi was greater with Res,rc (P less than 0.05). During Res,rc the abdominal pressure swings in expiration were greater than with Res,ab and control. We conclude that Res,rc altered the pattern of breathing in normal subjects in high-intensity exercise, decreased diaphragmatic contractility, increased abdominal muscle recruitment in expiration, and reduced tlim. On the other hand, Res,ab had no effect on breathing pattern or tlim but was associated with increased diaphragmatic contractility.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2210-2210
Author(s):  
Adam M Bush ◽  
Matthew Borzage ◽  
Thomas Coates ◽  
John C. Wood

Abstract Neurovascular sequalae are a common occurrence in Sickle Cell Anemia (SCA), with 11% of patients suffering cerebral vascular accident (CVA), or overt stroke by their twentieth birthday and 40% of patients developing silent cerebral infarcts (SCI) by age 14. Elevated transcranial Doppler (TCD) velocity of the middle cerebral artery identifies patients at risk for stroke, and this risk can be reduced by chronic transfusion therapy. However, the specificity of TCD is low causing many patients to be transfused unnecessarily. To further refine cerebrovascular risk stratification, we are studying factors responsible for normal and pathophysiologic cerebral blood flow (CBF) in SCD patients. Cerebral blood flow is increased in SCA patients compared to controls, but is believed to be a compensatory mechanism for chronic anemia and systemic desaturation. In order to test this hypothesis, we studied whole CBF and oxygen delivery (DO2) at rest and in response to hyperoxia in subjects with SCA and sickle cell trait (SCT). All patients were recruited at Children's Hospital Los Angeles through an IRB approved protocol. Informed consent was obtained for all patients. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. EKG, peripheral arterial oxygen saturation (SaO2), and fractional inspired oxygen (fiO2) were measured continuously throughout the study. Imaging consisted of a survey, reference scan, angiography localization, and nine axial phase contrast (PC) images. PC slices were placed inferior to the Circle of Willis, perpendicular to the carotids and basilar arteries. Participants received room air and 100% O2 through a non rebreathing respiratory circuit at 10 L/m. Room air exposure 20 minutes with six PC images collected throughout. Oxygen was delivered for 5 minutes followed by three more PC images. Blood for hemoglobin (HGB) and hematocrit (HCT) were drawn prior to MRI testing. No adverse events were reported upon follow up. Nine patients with SCA (5 male, 22.5 ± 6.7 yo p<0.05) and 3 with sickle cell trait (2 male, 36.7 ± 8.7 yo p<0.05) were studied. Baseline HGB was 25% lower (9.7 ± 1.3 versus 12.9 ± 0.1) and baseline HCT was 41% lower (28.0 ± 3.6 versus 47.3 ± 0.14 SCT) in SCA patients (p<0.05). Baseline whole brain CBF was elevated in SCA (1398 ± 400 ml/min versus 700 ± 172 ml/min). After correcting for HGB and SaO2, DO2 remained higher in SCA (192 ± 75 ml/min versus 105 ± 1.4 ml/min, p<0.05). During hyperoxia, whole brain CBF decreased by 10-15%, but the change was proportional to increased oxygen carrying capacity such that there was no change in DO2 in either populations. The increase in CBF we observed in SCA patients has been described using other modalities. However, we are the first to demonstrate that the increased flow observed is almost double what can be explained by their anemia and arterial desaturation alone. There are several possibilities for this observation. 1) SCA patients could have increased cerebral metabolic rate. If so, their mixed cerebral venous saturation will be normal and the flow is appropriate; 2) SCA patients have a mismatch between cerebral perfusion and metabolic demand, whether much of the increased flow does not effectively unload oxygen. If so, cerebral venous saturation would be high. We are currently optimizing MRI and NIR's technologies to estimate cerebrovascular metabolic rate, mixed cerebral venous saturation, and local supply-demand balance. Figure 1 Baseline CBF and O2 delivery in SCA and control group. ** statically significant population difference Figure 1. Baseline CBF and O2 delivery in SCA and control group. ** statically significant population difference Figure 2 Responce to 100% oxygen exposure. *statistically significant change from baseline Figure 2. Responce to 100% oxygen exposure. *statistically significant change from baseline Disclosures: Coates: Novartis Inc.: Honoraria, Speakers Bureau; Apopharma: Honoraria, Speakers Bureau; Shire: Speakers Bureau. Wood:Shire: Consultancy, Research Funding; Apopharma: Honoraria, Patents & Royalties; Novartis: Honoraria.


1997 ◽  
Vol 83 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Bharath S. Krishnan ◽  
Ron E. Clemens ◽  
Trevor A. Zintel ◽  
Martin J. Stockwell ◽  
Charles G. Gallagher

Krishnan, Bharath S., Ron E. Clemens, Trevor A. Zintel, Martin J. Stockwell, and Charles G. Gallagher. Ventilatory response to helium-oxygen breathing during exercise: effect of airway anesthesia. J. Appl. Physiol. 83(1): 82–88, 1997.—The substitution of a normoxic helium mixture (HeO2) for room air (Air) during exercise results in a sustained hyperventilation, which is present even in the first breath. We hypothesized that this response is dependent on intact airway afferents; if so, airway anesthesia (Anesthesia) should affect this response. Anesthesia was administered to the upper airways by topical application and to lower central airways by aerosol inhalation and was confirmed to be effective for over 15 min. Subjects performed constant work-rate exercise (CWE) at 69 ± 2 (SE) % maximal work rate on a cycle ergometer on three separate days: twice after saline inhalation ( days 1 and 3) and once after Anesthesia ( day 2). CWE commenced after a brief warm-up, with subjects breathing Air for the first 5 min (Air-1), HeO2 for the next 3 min, and Air again until the end of CWE (Air-2). The resistance of the breathing circuit was matched for Air and HeO2. Breathing HeO2 resulted in a small but significant increase in minute ventilation (V˙i) and decrease in alveolar [Formula: see text] in both the Saline (average of 2 saline tests; not significant) and Anesthesia tests. Although Anesthesia had no effect on the sustained hyperventilatory response to HeO2breathing, theV˙i transients within the first six breaths of HeO2 were significantly attenuated with Anesthesia. We conclude that theV˙i response to HeO2 is not simply due to a reduction in external tubing resistance and that, in humans, airway afferents mediate the transient but not the sustained hyperventilatory response to HeO2 breathing during exercise.


2017 ◽  
Vol 122 (4) ◽  
pp. 997-1002 ◽  
Author(s):  
David C. Poole ◽  
Andrew M. Jones

The maximum rate of O2 uptake (i.e., V̇o2max), as measured during large muscle mass exercise such as cycling or running, is widely considered to be the gold standard measurement of integrated cardiopulmonary-muscle oxidative function. The development of rapid-response gas analyzers, enabling measurement of breath-by-breath pulmonary gas exchange, has facilitated replacement of the discontinuous progressive maximal exercise test (that produced an unambiguous V̇o2-work rate plateau definitive for V̇o2max) with the rapidly incremented or ramp testing protocol. Although this is more suitable for clinical and experimental investigations and enables measurement of the gas exchange threshold, exercise efficiency, and V̇o2 kinetics, a V̇o2-work rate plateau is not an obligatory outcome. This shortcoming has led to investigators resorting to so-called secondary criteria such as respiratory exchange ratio, maximal heart rate, and/or maximal blood lactate concentration, the acceptable values of which may be selected arbitrarily and result in grossly inaccurate V̇o2max estimation. Whereas this may not be an overriding concern in young, healthy subjects with experience of performing exercise to volitional exhaustion, exercise test naïve subjects, patient populations, and less motivated subjects may stop exercising before their V̇o2max is reached. When V̇o2max is a or the criterion outcome of the investigation, this represents a major experimental design issue. This CORP presents the rationale for incorporation of a second, constant work rate test performed at ~110% of the work rate achieved on the initial ramp test to resolve the classic V̇o2-work rate plateau that is the unambiguous validation of V̇o2max. The broad utility of this procedure has been established for children, adults of varying fitness, obese individuals, and patient populations.


Author(s):  
Markus Hein ◽  
Kristine Chobanyan-Jürgens ◽  
Uwe Tegtbur ◽  
Stefan Engeli ◽  
Jens Jordan ◽  
...  

Abstract Purpose To test the hypothesis that the combination of endurance training and hypoxia leads to greater improvements in resting and exercise blood pressure in old sedentary individuals compared to endurance training only. Methods We randomly assigned 29 old overweight participants (age: 62 ± 6 years, body mass index (BMI): 28.5 ± 0.5 kg/m2, 52% men) to single blind 8-week bicycle exercise in hypoxia (fraction of inspired oxygen (FIO2) = 0.15) or normoxia (FIO2 = 0.21). Brachial blood pressure was measured at rest, during maximal incremental exercise testing, and during a 30 min constant work rate test, at baseline and after the training period. Results Work rate, heart rate and perceived exertion during training were similar in both groups, with lower oxygen saturation for participants exercising under hypoxia (88.7 ± 1.5 vs. 96.2 ± 1.2%, t(27) = − 13.04, p < 0.001, |g|= 4.85). Office blood pressure and blood pressure during incremental exercise tests did not change significantly in either group after the training program. Systolic blood pressure during the constant work rate test was reduced after training in hypoxia (160 ± 18 vs. 151 ± 14 mmHg, t(13) = 2.44 p < 0.05, |d|= 0.55) but not normoxia (154 ± 22 vs. 150 ± 16 mmHg, t(14) = 0.75, p = 0.46, |d|= 0.18) with no difference between groups over time (F = 0.08, p = 0.77, η2 = 0.01). Conclusion In old individuals hypoxia in addition to exercise does not have superior effects on office or exercise blood pressure compared to training in normoxia. Trial registration number ClinicalTrials.gov No. NCT02196623 (registered 22 July 2014).


1988 ◽  
Vol 64 (1) ◽  
pp. 234-242 ◽  
Author(s):  
K. E. Sietsema ◽  
D. M. Cooper ◽  
J. K. Perloff ◽  
J. S. Child ◽  
M. H. Rosove ◽  
...  

The diversion of systemic venous blood into the arterial circulation in patients with intracardiac right-to-left shunts represents a pathophysiological condition in which there are alterations in some of the potential stimuli for the exercise hyperpnea. We therefore studied 18 adult patients with congenital (16) or noncongenital (2) right-to-left shunts and a group of normal control subjects during constant work rate and progressive work rate exercise to assess the effects of these alterations on the dynamics of exercise ventilation and gas exchange. Minute ventilation (VE) was significantly higher in the patients than in the controls, both at rest (10.7 +/- 2.4 vs. 7.5 +/- 1.2 l/min, respectively) and during constant-load exercise (24.9 +/- 4.8 vs. 12.7 +/- 2.61 l/min, respectively). When beginning constant work rate exercise from rest, the ventilatory response of the patients followed a pattern that was distinct from that of the normal subjects. At the onset of exercise, the patients' end-tidal PCO2 decreased, end-tidal PO2 increased, and gas exchange ratio increased, indicating that pulmonary blood was hyperventilated relative to the resting state. However, arterial blood gases, in six patients in which they were measured, revealed that despite the large VE response to exercise, arterial pH and PCO2 were not significantly different from resting values when sampled during the first 2 min of moderate-intensity exercise. Arterial PCO2 changed by an average of only 1.4 Torr after 4.5-6 min of exercise. Thus the exercise-induced alveolar and pulmonary capillary hypocapnia was of an appropriate degree to compensate for the shunting of CO2-rich venous blood into the systemic arterial circulation.(ABSTRACT TRUNCATED AT 250 WORDS)


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