Myocytes Oxygenation and High Energy Phosphate Levels during Hypoxia

Decrease of ambient oxygen level has been used in myocytes culture experiments in examining the responsiveness to stress secondary to hypoxia. However, none of these studies measure the myocytes oxygenation levels resulting in ambiguity as to whether there is insufficient oxygen delivery. This study examined the hypothesis that at a basal myocardial work state, adequate myocyte oxygenation would be maintained until extremely low arterial pO₂ levels were reached. Myocyte pO₂ values in normal dogs were calculated from the myocardial deoxymyoglobin (Mb- δ) levels using ¹H-spectroscopy (MRS) and were normalized to Mb-δ obtained after complete LAD occlusion. During Protocol 1 (n = 6), Mb-δ was measured during sequential reductions of the oxygen fraction of inspired gas (FIO₂) from 40, 21, 15, 10, and 5%, while in protocol 2 (n = 10) Mb-δ was measured at FIO₂ of 3%. Protocol 3 (n = 9) evaluated time course of Mb-δ during prolonged exposure to FIO₂ of 5%. Myocardial blood flow (MBF) was measured with microspheres and high energy phosphate (HEP) levels were determined with ³¹P-MRS. MVO₂ progressively increased in response to the progressive reduction of FIO₂ that is accompanied by increased LV pressure, heart rate, and MBF. Mb-δ was undetectable during FIO₂ values of 21, 15, 10, and 5%. However, FIO₂ of 3% or prolonged exposure to FIO₂ of 5% caused progressive increases of Mb-δ which were associated with decreases of PCr, ATP and the PCr/ATP ratio, as well as increases of inorganic phosphate. The intracellular PO₂ values for 20% reductions of PCr and ATP were approximately 7.4 and 1.9 mmHg, respectively. These data demonstrate that in the in vivo system over a wide range of FIO₂ and arterial pO₂ levels, the myocyte pO₂ values remain well above the K_m value with respect to cytochrome oxidase, and oxygen availability does not limit mitochondrial oxidative phosphorylation at 5% FIO₂.     

Impact of Exercise and Moderate Hypoxia on Glycemic Regulation and Substrate Oxidation Pattern

Objective

We examined metabolic and endocrine responses during rest and exercise in moderate hypoxia over a 7.5 h time courses during daytime.

Methods

Eight sedentary, overweight men (28.6±0.8 kg/m²) completed four experimental trials: a rest trial in normoxia (FiO₂ = 20.9%, NOR-Rest), an exercise trial in normoxia (NOR-Ex), a rest trial in hypoxia (FiO₂ = 15.0%, HYP-Rest), and an exercise trial in hypoxia (HYP-Ex). Experimental trials were performed from 8:00 to 15:30 in an environmental chamber. Blood and respiratory gas samples were collected over 7.5 h. In the exercise trials, subjects performed 30 min of pedaling exercise at 60% of VO₂max at 8:00, 10:30, and 13:00, and rested during the remaining period in each environment. Standard meals were provided at 8:30, 11:00, and 13:30.

Results

The areas under the curves for blood glucose and serum insulin concentrations over 7.5 h did not differ among the four trials. At baseline, %carbohydrate contribution was significantly higher in the hypoxic trials than in the normoxic trials (P<0.05). Although exercise promoted carbohydrate oxidation in the NOR-Ex and HYP-Ex trials, %carbohydrate contribution during each exercise and post-exercise period were significantly higher in the HYP-Ex trial than in the NOR-Ex trial (P<0.05).

Conclusion

Three sessions of 30 min exercise (60% of VO₂max) in moderate hypoxia over 7.5 h did not attenuate postprandial glucose and insulin responses in young, overweight men. However, carbohydrate oxidation was significantly enhanced when the exercise was conducted in moderate hypoxia.     

The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise

Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO₂ to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO₂ and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO₂ and O₂ chemoreception on the regulation ventilation (E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF), E, end-tidal PCO₂, respiratory compensation threshold (RC) and ventilatory response to exercise (E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO₂ = 0.10) with and without augmenting the fraction of inspired CO₂ (FICO₂). During exercise in normoxia, augmenting FICO₂ elevated MCAv throughout exercise and lowered both RC onset andE slope below RC (P<0.05). In hypoxia, MCAv and E slope below RC during exercise were elevated, while the onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO₂ in hypoxia increased E at RC (P<0.05) but no difference was observed in RC onset, MCAv, or E slope below RC (P>0.05). The E slope above RC was unchanged with either hypoxia or augmented FICO₂ (P>0.05). We found augmenting FICO₂ increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the ‘normal’ cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO₂. Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO₂ is blunted.     

Intrapulmonary Vascular Dilatation Evaluated by 99mTc-MAA Scintigraphy and Its Association with Portal Hypertension in Schistosomiasis

Background

Portal hypertension is responsible for various complications in patients with schistosomiasis, among them intrapulmonary vascular dilations (IPVD). In cirrhotic patients the presence of IPVD is a sign of poor prognosis, but in patients with hepatosplenic schistosomiasis (HSS) there are no studies assessing the significance of this change. The aim of this study was to evaluate the occurrence of IPVD through ^99mTc-MAA scintigraphy in patients with HSS and its relationship with clinical, laboratory, endoscopic and ultrasound parameters.

Methods

Cross-sectional study evaluating 51 patients with HSS. Patients were diagnosed with IPVD when the brain uptake of ^99mTc-MAA was higher than 6%. Subsequently, they were divided according to presence (G1) or absence (G2) of IPVD and variables were compared between groups.

Results

Overall, 51 patients with mean age of 56±12 years were assessed. IPVD was observed in 31 patients (60%). There was no statistically significant differences between groups when clinical, laboratory and endoscopic parameters were compared. Regarding ultrasound parameters, the splenic vein diameter was smaller in G1 (0.9±0.3 cm) compared to G2 (1.2±0.4 cm), p = 0.029.

Conclusion

In patients with HSS, the occurrence of IPVD by ^99mTc-MAA scintigraphy was high and was associated with lower splenic vein diameter, which can be a mechanism of vascular protection against portal hypertension. However, more studies are needed to determine the clinical significance of the early diagnosis and natural evolution of IPVD in this population.     

The oxygen delivery response to acute hypoxia during incremental knee extension exercise differs in active and trained males

Background

It is well known that hypoxic exercise in healthy individuals increases limb blood flow, leg oxygen extraction and limb vascular conductance during knee extension exercise. However, the effect of hypoxia on cardiac output, and total vascular conductance is less clear. Furthermore, the oxygen delivery response to hypoxic exercise in well trained individuals is not well known. Therefore our aim was to determine the cardiac output (Doppler echocardiography), vascular conductance, limb blood flow (Doppler echocardiography) and muscle oxygenation response during hypoxic knee extension in normally active and endurance-trained males.

Methods

Ten normally active and nine endurance-trained males (VO_2max = 46.1 and 65.5 mL/kg/min, respectively) performed 2 leg knee extension at 25, 50, 75 and 100% of their maximum intensity in both normoxic and hypoxic conditions (FIO₂ = 15%; randomized order). Results were analyzed with a 2-way mixed model ANOVA (group × intensity).

Results

The main finding was that in normally active individuals hypoxic sub-maximal exercise (25 – 75% of maximum intensity) brought about a 3 fold increase in limb blood flow but decreased stroke volume compared to normoxia. In the trained group there were no significant changes in stroke volume, cardiac output and limb blood flow at sub-maximal intensities (compared to normoxia). During maximal intensity hypoxic exercise limb blood flow increased approximately 300 mL/min compared to maximal intensity normoxic exercise.

Conclusion

Cardiorespiratory fitness likely influences the oxygen delivery response to hypoxic exercise both at a systemic and limb level. The increase in limb blood flow during maximal exercise in hypoxia (both active and trained individuals) suggests a hypoxic stimulus that is not present in normoxic conditions.

     

Synthesis and evaluation of a novel Tc-labeled bioreductive probe for tumor hypoxia imaging

Tumor hypoxia is closely associated with the malignant progression and/or the high metastatic ability of tumors and often induces resistance to chemo- and/or radiotherapy. Thus, the detection and evaluation of hypoxia is important for the optimization of cancer therapy. We designed a novel ^99mTc-labeled probe for tumor hypoxia imaging that utilizes bioreductive reactions in hypoxic cells. This probe, which contains a 4-nitrobenzyl ester group, is reduced in hypoxic cells to produce a corresponding carboxylate anion that cannot penetrate cell membranes because of its hydrophilicity and negative charge; therefore, it is expected to be trapped inside hypoxic cells. Based on this unique strategy, we synthesized the Technetium-99m (^99mTc)-labeled probe ^99mTc-SD32. The uptake of ^99mTc-SD32 in tumor cells was investigated under normoxic and hypoxic conditions. ^99mTc-SD32 showed sufficient accumulation and good retention in hypoxic cells. In addition, we demonstrated that ^99mTc-SD32 was subjected to bioreduction in hypoxic cells and was trapped as the corresponding carboxylate anion. These results indicated that ^99mTc-SD32 would be a promising agent for in vivo hypoxia imaging.     

99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI

Purpose

To compare the potential application of ^99mTc-3P-Arg-Gly-Asp (^99mTc-3P₄-RGD₂) scintimammography (SMM) and ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions.

Method

Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. ^99mTc-3P₄-RGD₂ and ^99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases.

Results

The mean T/NT ratio of ^99mTc-3P₄-RGD₂ in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of ^99mTc-3P₄-RGD₂ SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of ^99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of ^99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for ^99mTc-3P₄-RGD₂ SMM (area = 0.851) was higher than that for ^99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant.

Conclusion

^99mTc-3P₄-RGD₂ SMM does not provide any significant advantage over the established ^99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of ^99mTc-3P₄-RGD₂ SMM was significantly higher than that of ^99mTc-MIBI SMM. Both tracers could offer an alternative method for elucidating non-diagnostic mammograms.     

Maximum Running Speed of Captive Bar-Headed Geese Is Unaffected by Severe Hypoxia

While bar-headed geese are renowned for migration at high altitude over the Himalayas, previous work on captive birds suggested that these geese are unable to maintain rates of oxygen consumption while running in severely hypoxic conditions. To investigate this paradox, we re-examined the running performance and heart rates of bar-headed geese and barnacle geese (a low altitude species) during exercise in hypoxia. Bar-headed geese (n = 7) were able to run at maximum speeds (determined in normoxia) for 15 minutes in severe hypoxia (7% O₂; simulating the hypoxia at 8500 m) with mean heart rates of 466±8 beats min⁻¹. Barnacle geese (n = 10), on the other hand, were unable to complete similar trials in severe hypoxia and their mean heart rate (316 beats.min⁻¹) was significantly lower than bar-headed geese. In bar-headed geese, partial pressures of oxygen and carbon dioxide in both arterial and mixed venous blood were significantly lower during hypoxia than normoxia, both at rest and while running. However, measurements of blood lactate in bar-headed geese suggested that anaerobic metabolism was not a major energy source during running in hypoxia. We combined these data with values taken from the literature to estimate (i) oxygen supply, using the Fick equation and (ii) oxygen demand using aerodynamic theory for bar-headed geese flying aerobically, and under their own power, at altitude. This analysis predicts that the maximum altitude at which geese can transport enough oxygen to fly without environmental assistance ranges from 6,800 m to 8,900 m altitude, depending on the parameters used in the model but that such flights should be rare.     

Effects of Intermittent Training on Anaerobic Performance and MCT Transporters in Athletes

This study examined the effects of intermittent hypoxic training (IHT) on skeletal muscle monocarboxylate lactate transporter (MCT) expression and anaerobic performance in trained athletes. Cyclists were assigned to two interventions, either normoxic (N; n = 8; 150 mmHg P_IO₂) or hypoxic (H; n = 10; ∼3000 m, 100 mmHg P_IO₂) over a three week training (5×1 h-1h30.week⁻¹) period. Prior to and after training, an incremental exercise test to exhaustion (EXT) was performed in normoxia together with a 2 min time trial (TT). Biopsy samples from the vastus lateralis were analyzed for MCT1 and MCT4 using immuno-blotting techniques. The peak power output (PPO) increased (p<0.05) after training (7.2% and 6.6% for N and H, respectively), but VO₂max showed no significant change. The average power output in the TT improved significantly (7.3% and 6.4% for N and H, respectively). No differences were found in MCT1 and MCT4 protein content, before and after the training in either the N or H group. These results indicate there are no additional benefits of IHT when compared to similar normoxic training. Hence, the addition of the hypoxic stimulus on anaerobic performance or MCT expression after a three-week training period is ineffective.     

Effect of acute hypoxia on respiratory muscle fatigue in healthy humans

Background

Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.

Methods

Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO₂ = 80%) and hyperoxic (FiO₂ = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P_di,tw ) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P_ga,tw ) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.

Results

Hypoxia enhanced hyperpnoea-induced P_di,tw and P_ga,tw reductions both immediately after hyperpnoea (P_di,tw : normoxia -22 ± 7% vs hypoxia -34 ± 8% vs hyperoxia -21 ± 8%; P_ga,tw : normoxia -17 ± 7% vs hypoxia -26 ± 10% vs hyperoxia -16 ± 11%; all P < 0.05) and after 30 min of recovery (P_di,tw : normoxia -10 ± 7% vs hypoxia -16 ± 8% vs hyperoxia -8 ± 7%; P_ga,tw : normoxia -13 ± 6% vs hypoxia -21 ± 9% vs hyperoxia -12 ± 12%; all P < 0.05). No significant difference in P_di,tw or P_ga,tw reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.

Conclusions

These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O₂ transport as during exercise in altitude or in hypoxemic patients.     

Maternal Hypoxia Decreases Capillary Supply and Increases Metabolic Inefficiency Leading to Divergence in Myocardial Oxygen Supply and Demand

Maternal hypoxia is associated with a decrease in left ventricular capillary density while cardiac performance is preserved, implying a mismatch between metabolism and diffusive exchange. We hypothesised this requires a switch in substrate metabolism to maximise efficiency of ATP production from limited oxygen availability. Rat pups from pregnant females exposed to hypoxia (FIO₂=0.12) at days 10-20 of pregnancy were grown to adulthood and working hearts perfused ex vivo. ¹⁴C-labelled glucose and ³H-palmitate were provided as substrates and metabolism quantified from recovery of ¹⁴CO₂ and ³H₂O, respectively. Hearts of male offspring subjected to Maternal Hypoxia showed a 20% decrease in cardiac output (P<0.05), despite recording a 2-fold increase in glucose oxidation (P<0.01) and 2.5-fold increase (P<0.01) in palmitate oxidation. Addition of insulin to Maternal Hypoxic hearts, further increased glucose oxidation (P<0.01) and suppressed palmitate oxidation (P<0.05), suggesting preservation in insulin signalling in the heart. In vitro enzyme activity measurements showed that Maternal Hypoxia increased both total and the active component of cardiac pyruvate dehydrogenase (both P<0.01), although pyruvate dehydrogenase sensitivity to insulin was lost (NS), while citrate synthase activity declined by 30% (P<0.001) and acetyl-CoA carboxylase activity was unchanged by Maternal Hypoxia, indicating realignment of the metabolic machinery to optimise oxygen utilisation. Capillary density was quantified and oxygen diffusion characteristics examined, with calculated capillary domain area increased by 30% (P<0.001). Calculated metabolic efficiency decreased 4-fold (P<0.01) for Maternal Hypoxia hearts. Paradoxically, the decline in citrate synthase activity and increased metabolism suggest that the scope of individual mitochondria had declined, rendering the myocardium potentially more sensitive to metabolic stress. However, decreasing citrate synthase may be essential to preserve local PO₂, minimising regions of hypoxia and hence maximising the area of myocardium able to preserve cardiac output following maternal hypoxia.     

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia,Normobaric Hypoxia,Hypobaric Hypoxia and Genuine High Altitude

BackgroundThere has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses.ResultsAll 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO₂ lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S’, lateral S’, tricuspid S’ and A’ velocities and RVSP were higher and SpO₂ lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO₂ was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A’ was higher with GHA compared with NH at 15 minutes post exercise.ConclusionsGHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO₂ levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO_2, RVSP and RV cardiac function.     

Metabolic Adaptations May Counteract Ventilatory Adaptations of Intermittent Hypoxic Exposure during Submaximal Exercise at Altitudes up to 4000 m

Intermittent hypoxic exposure (IHE) has been shown to induce aspects of altitude acclimatization which affect ventilatory, cardiovascular and metabolic responses during exercise in normoxia and hypoxia. However, knowledge on altitude-dependent effects and possible interactions remains scarce. Therefore, we determined the effects of IHE on cardiorespiratory and metabolic responses at different simulated altitudes in the same healthy subjects. Eight healthy male volunteers participated in the study and were tested before and 1 to 2 days after IHE (7×1 hour at 4500 m). The participants cycled at 2 submaximal workloads (corresponding to 40% and 60% of peak oxygen uptake at low altitude) at simulated altitudes of 2000 m, 3000 m, and 4000 m in a randomized order. Gas analysis was performed and arterial oxygen saturation, blood lactate concentrations, and blood gases were determined during exercise. Additionally baroreflex sensitivity, hypoxic and hypercapnic ventilatory response were determined before and after IHE. Hypoxic ventilatory response was increased after IHE (p<0.05). There were no altitude-dependent changes by IHE in any of the determined parameters. However, blood lactate concentrations and carbon dioxide output were reduced; minute ventilation and arterial oxygen saturation were unchanged, and ventilatory equivalent for carbon dioxide was increased after IHE irrespective of altitude. Changes in hypoxic ventilatory response were associated with changes in blood lactate (r = −0.72, p<0.05). Changes in blood lactate correlated with changes in carbon dioxide output (r = 0.61, p<0.01) and minute ventilation (r = 0.54, p<0.01). Based on the present results it seems that the reductions in blood lactate and carbon dioxide output have counteracted the increased hypoxic ventilatory response. As a result minute ventilation and arterial oxygen saturation did not increase during submaximal exercise at simulated altitudes between 2000 m and 4000 m.     

Prognostic Value of Radiological Response to Chemotherapy in Patients with Osteosarcoma

Background

Chemotherapy is essential to improve the prognosis of the patients with osteosarcoma, and the response to chemotherapy is an important prognostic factor. In this study, the impact of various radiological examinations on overall survival (OS) and event-free survival (EFS) was evaluated.

Method

Eighty-two patients with high-grade osteosarcoma were included in this study, and we evaluated the following factors for prognostic significance: age (≥40 years), gender (male), tumor location (truncal site), metastatic disease, histological response to chemotherapy, radiological response to chemotherapy assessed using X-ray, angiography, CT, MRI, ²⁰¹Tl scintigraphy, and ^99mTc-MIBI scintigraphy (^99mTc-MIBI), and combined radiological score (CRS).

Results

Univariate analyses revealed that metastatic disease, histological response, ^99mTc-MIBI, and CRS were significantly correlated with OS. Multivariate analyses showed that metastatic disease (OS: HR 35.9, P<0.001; EFS: HR 17.32, P<0.001) was an independent predictor of OS and EFS. Tumor location (HR 36.1, P = 0.003), histological response (HR 31.1, P = 0.036), and ^99mTc-MIBI (HR 18.4, P = 0.038) were significant prognostic factors for OS. Moreover, CRS was a marginally significant predictor of OS and EFS.

Conclusion

The chemotherapeutic effects evaluated by ^99mTc-MIBI and CRS could be considered as prognostic factors in osteosarcoma.     

Determinants and Improvement of Electrocardiographic Diagnosis of Left Ventricular Hypertrophy in a Black African Population

Background

Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor. The electrocardiogram (ECG) has been shown to be a poor tool in detecting LVH due to cardiac and extracardiac factors. We studied the determinants and possibility of improving the test performance of the ECG in a group of Black Africans.

Methods

We studied echocardiograms and electrocardiograms of 182 Cameroonian patients among whom 113 (62.1%) were having an echocardiographic LVH. Echocardiographic LVH was defined as Left Ventricular Mass Indexed to height ^2.7(LVMI)>48 g/m^2.7 in men, and >44 g/m ^2.7 in women or Body Surface Area ≥116 g/m² in men, and ≥96 g/m² in women. Test performances were calculated for 6 classic ECG criteria Sokolow-Lyon, Cornell, Cornell product, Gubner-Ungerleiger, amplitudes of R in aVL, V₅ and V₆.

Results

The most sensitive criteria were Cornell (37.2%) and Sokolow-Lyon index (26.5%). The most specific criteria were Gubner (98.6%), RaVL (97.1%), RV₅/V₆ (95.7%) and Cornell product (94.2%). The performance of the ECG in diagnosing LVH significantly increased with the severity of LVH for Cornell index (r = 0.420, p<0.0001) and Sokolow index (r = 0.212, p = 0.002). It decreased with body habitus (r = −0.248, p = 0.001) for Sokolow-Lyon index. Cornell index was less affected (age p = 0.766; body habitus: p = 0.209). After sex-specific adjustment for BMI, Cornell BMI sensitivity increased from 37.2% to 69% (r = 0.472, p<0.0001), and Sokolow-Lyon BMI sensitivity increased from 26.5% to 58.4% (r = 0.270, p<0.001).

Conclusion

The test performance of the ECG in diagnosing LVH is low in this Black African population, due to extracardiac factors such as age, sex, body habitus, and cardiac factors such as LVH severity and geometry. However, this performance is improved after adjustment for extracardiac factors.     

A Novel 99mTc-Labeled Molecular Probe for Tumor Angiogenesis Imaging in Hepatoma Xenografts Model: A Pilot Study

Introduction

Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether ^99mTc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis.

Methods

The RRL peptide was designed and radiosynthesized with ^99mTc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. ^99mTc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of ^99mTc-RRL was also explored.

Results

The labeling efficiencies of ^99mTc-RRL reached 76.9%±4.5% (n = 6) within 30–60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that ^99mTc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of ^99mTc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2–6 h after injection of ^99mTc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with ^99mTc-RRL was comparable with that of ¹⁸F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of ^99mTc-RRL with R² = 0.821.

Conclusion

^99mTc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas.     

Effects of Slow Deep Breathing at High Altitude on Oxygen Saturation,Pulmonary and Systemic Hemodynamics

Slow deep breathing improves blood oxygenation (Sp_O2) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2–3 days (Study A; N = 39) or at 5400 m for 12–16 days (Study B; N = 28). Study variables, including Sp_O2 and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp_O2 (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.     

Influence of Hypoxic Interval Training and Hyperoxic Recovery on Muscle Activation and Oxygenation in Connection with Double-Poling Exercise

Here, we evaluated the influence of breathing oxygen at different partial pressures during recovery from exercise on performance at sea-level and a simulated altitude of 1800 m, as reflected in activation of different upper body muscles, and oxygenation of the m. triceps brachii. Ten well-trained, male endurance athletes (25.3±4.1 yrs; 179.2±4.5 cm; 74.2±3.4 kg) performed four test trials, each involving three 3-min sessions on a double-poling ergometer with 3-min intervals of recovery. One trial was conducted entirely under normoxic (No) and another under hypoxic conditions (Ho; F_iO₂ = 0.165). In the third and fourth trials, the exercise was performed in normoxia and hypoxia, respectively, with hyperoxic recovery (HOX; F_iO₂ = 1.00) in both cases. Arterial hemoglobin saturation was higher under the two HOX conditions than without HOX (p<0.05). Integrated muscle electrical activity was not influenced by the oxygen content (best d = 0.51). Furthermore, the only difference in tissue saturation index measured via near-infrared spectroscopy observed was between the recovery periods during the NoNo and HoHOX interventions (P<0.05, d = 0.93). In the case of HoHo the athletes’ P_mean declined from the first to the third interval (P < 0.05), whereas P_mean was unaltered under the HoHOX, NoHOX and NoNo conditions. We conclude that the less pronounced decline in P_mean during 3 x 3-min double-poling sprints in normoxia and hypoxia with hyperoxic recovery is not related to changes in muscle activity or oxygenation. Moreover, we conclude that hyperoxia (F_iO₂ = 1.00) used in conjunction with hypoxic or normoxic work intervals may serve as an effective aid when inhaled during the subsequent recovery intervals.     

The Positive Effects of Priming Exercise on Oxygen Uptake Kinetics and High-Intensity Exercise Performance Are Not Magnified by a Fast-Start Pacing Strategy in Trained Cyclists

The purpose of this study was to determine both the independent and additive effects of prior heavy-intensity exercise and pacing strategies on the VO2 kinetics and performance during high-intensity exercise. Fourteen endurance cyclists (VO₂max  = 62.8±8.5 mL.kg⁻¹.min⁻¹) volunteered to participate in the present study with the following protocols: 1) incremental test to determine lactate threshold and VO₂max; 2) four maximal constant-load tests to estimate critical power; 3) six bouts of exercise, using a fast-start (FS), even-start (ES) or slow-start (SS) pacing strategy, with and without a preceding heavy-intensity exercise session (i.e., 90% critical power). In all conditions, the subjects completed an all-out sprint during the final 60 s of the test as a measure of the performance. For the control condition, the mean response time was significantly shorter (p<0.001) for FS (27±4 s) than for ES (32±5 s) and SS (32±6 s). After the prior exercise, the mean response time was not significantly different among the paced conditions (FS = 24±5 s; ES = 25±5 s; SS = 26±5 s). The end-sprint performance (i.e., mean power output) was only improved (∼3.2%, p<0.01) by prior exercise. Thus, in trained endurance cyclists, an FS pacing strategy does not magnify the positive effects of priming exercise on the overall VO2 kinetics and short-term high-intensity performance.     

Comparison of “Live High-Train Low” in Normobaric versus Hypobaric Hypoxia

We investigated the changes in both performance and selected physiological parameters following a Live High-Train Low (LHTL) altitude camp in either normobaric hypoxia (NH) or hypobaric hypoxia (HH) replicating current “real” practices of endurance athletes. Well-trained triathletes were split into two groups (NH, n = 14 and HH, n = 13) and completed an 18-d LHTL camp during which they trained at 1100–1200 m and resided at an altitude of 2250 m (P_iO₂  = 121.7±1.2 vs. 121.4±0.9 mmHg) under either NH (hypoxic chamber; F_iO₂ 15.8±0.8%) or HH (real altitude; barometric pressure 580±23 mmHg) conditions. Oxygen saturations (S_pO₂) were recorded continuously daily overnight. P_iO₂ and training loads were matched daily. Before (Pre-) and 1 day after (Post-) LHTL, blood samples, VO_2max, and total haemoglobin mass (Hb_mass) were measured. A 3-km running test was performed near sea level twice before, and 1, 7, and 21 days following LHTL. During LHTL, hypoxic exposure was lower for the NH group than for the HH group (220 vs. 300 h; P<0.001). Night S_pO₂ was higher (92.1±0.3 vs. 90.9±0.3%, P<0.001), and breathing frequency was lower in the NH group compared with the HH group (13.9±2.1 vs. 15.5±1.5 breath.min⁻¹, P<0.05). Immediately following LHTL, similar increases in VO_2max (6.1±6.8 vs. 5.2±4.8%) and Hb_mass (2.6±1.9 vs. 3.4±2.1%) were observed in NH and HH groups, respectively, while 3-km performance was not improved. However, 21 days following the LHTL intervention, 3-km run time was significantly faster in the HH (3.3±3.6%; P<0.05) versus the NH (1.2±2.9%; ns) group. In conclusion, the greater degree of race performance enhancement by day 21 after an 18-d LHTL camp in the HH group was likely induced by a larger hypoxic dose. However, one cannot rule out other factors including differences in sleeping desaturations and breathing patterns, thus suggesting higher hypoxic stimuli in the HH group.