Increase of free Mg<Superscript>2+</Superscript>in the skeletal muscle of chronic fatigue syndrome patients

In a previous study we evaluated muscle blood flow and muscle metabolism in patients diagnosed with chronic fatigue syndrome (CFS). To better understand muscle metabolism in CFS, we re-evaluated our data to calculate free Magnesium levels in skeletal muscle. Magnesium is an essential cofactor in a number of cell processes. A total of 20 CFS patients and 11 controls were evaluated. Phosphorus magnetic resonance spectroscopy from the medial gastrocnemius muscle was used to calculate free Mg²⁺ from the concentrations and chemical shifts of Pi, PCr, and beta ATP peaks. CFS patients had higher magnesium levels in their muscles relative to controls (0.47 + 0.07 vs 0.36 + 0.06 mM, P < 0.01), although there was no difference in the rate of phosphocreatine recovery in these subjects, as reported earlier. This finding was not associated with abnormal oxidative metabolism as measured by the rate of recovery of phosphocreatine after exercise. In summary, calculation of free Mg²⁺ levels from previous data showed CFS patients had higher resting free Mg²⁺ levels compared to sedentary controls.     

Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.     

Normal Muscle Oxygen Consumption and Fatigability in Sickle Cell Patients Despite Reduced Microvascular Oxygenation and Hemorheological Abnormalities

Background/Aim

Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue.

Methods

We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients.

Results

Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects.

Conclusions

Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit mitochondrial respiration but increases muscle microvascular blood flow.     

Effects of compression on muscle tissue oxygenation at the onset of exercise

The effects of compression on gastrocnemius medialis muscle oxygenation and hemodynamics during a short-term dynamic exercise was investigated in a sample of 15 male subjects (mean ± SD; age 25.8 ± 4.9 years; mass 70.6 ± 4.3 kg). Elastic compression sleeves were used to apply multiple levels of compression to the calf muscles during exercise, and noncompressive garments were used for the control condition. Tissue hemoglobin oxygen saturation was measured as the relative "tissue oxygen index" (TOI) with a near-infrared spectrometer. The recovery of TOI during exercise was determined from the slope of oxygenation recovery in a nonoccluded situation. The TOI recovery rate during the first 2 minutes of the exercise was 24% higher (p = 0.042) for the compression condition than for the control condition. A significant correlation (r = 0.61, p = 0.012) between the level of compression and the tissue oxygenation recovery during exercise was observed. Muscle energy use was determined from the rate of decline of TOI immediately upon arterial occlusion during early exercise. Muscle energy use measured during the occluded situation was not significantly influenced by compression. Based on these results, it was concluded that compression induced changes in tissue blood flow and perfusion appear to result in improved oxygenation during short-term exercise. Assuming that increased muscle oxygen availability positively influences performance, compression of muscles may enhance performance especially in sports that require repeated short bouts of exercise.     

Autonomic and vascular responses to reduced limb perfusion.

The purpose of this study was to examine hemodynamic responses to graded muscle reflex engagement in human subjects. We studied seven healthy human volunteers [24 +/- 2 (SE) yr old; 4 men, 3 women] performing rhythmic handgrip exercise [40% maximal voluntary contraction (MVC)] during ambient and positive pressure exercise (+10 to +50 mmHg in 10-mmHg increments every minute). Muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and mean blood velocity were recorded. Plasma lactate, hydrogen ion concentration, and oxyhemoglobin saturation were measured from venous blood. Ischemic exercise resulted in a greater rise in both MSNA and MAP vs. nonischemic exercise. These heightened autonomic responses were noted at +40 and +50 mmHg. Each level of positive pressure was associated with an immediate fall in flow velocity and forearm perfusion pressure. However, during each minute, perfusion pressure increased progressively. For positive pressure of +10 to +40 mmHg, this was associated with restoration of flow velocity. However, at +50 mmHg, flow was not restored. This inability to restore flow was seen at a time when the muscle reflex was clearly engaged (increased MSNA). We believe that these findings are consistent with the hypothesis that before the muscle reflex is clearly engaged, flow to muscle is enhanced by a process that raises perfusion pressure. Once the muscle reflex is clearly engaged and MSNA is augmented, flow to muscle is no longer restored by a similar rise in perfusion pressure, suggesting that active vasoconstriction within muscle is occurring at +50 mmHg.     

Post pressure hyperemia in the rat

In prior studies in man, we have demonstrated that pressure-induced hyperemia lasts for prolonged periods as compared to the short-term hyperemia created by proximal arterial occlusion. We have analyzed this phenomenon in our well-studied rat model of skin blood flow. Skin blood flow was measured using laser Doppler techniques in Wistar Kyoto rats at the back, a nutritively perfused site, and at the plantar surface of the paw, where arteriovenous anastomotic perfusion dominates. A customized pressure feedback control device was used to vary applied pressures. At the back, pressures in excess of 80 mmHg resulted in occlusion, whereas at the paw 150 mmHg was required. The peak hyperemic flow after release of pressure was comparable to that elicited by proximal arterial occlusion with a blood pressure cuff. However, the post pressure hyperemia peak descended to a plateau value, which was 50-100% greater than baseline and continued for up to 20 min while the peak following proximal arterial occlusion returned to baseline within 4 min. At the back, post pressure hyperemia reached a maximum after application of 100 mmHg pressure. The application of higher pressures than required for occlusion produced no greater hyperemic response. At the paw, maximum post pressure hyperemia occurred at 100 mmHg, although this pressure level was not totally occlusive. Higher pressures resulted in no greater hyperemia. At the back, 10 min of occlusion produced a maximal peak value whereas 1 min was sufficient at the paw. The application of pressure to a heated probe with subsequent release, produced a hyperemic response. Normalized to baseline blood flow, there was no difference between the hyperemic responses at basal skin temperature and at 44 degrees C. There is a prolonged hyperemic response following local pressure occlusion compared to a much shorter period following proximal ischemic occlusion. One can presume two different mechanisms, one related to ischemia and the other a separate pressure related phenomenon. The thermal vasodilatory response is additive, not synergistic with the post pressure hyperemia we have demonstrated. This finding suggests that different mechanisms are involved in thermal vasodilation and post pressure hyperemia.     

Noninvasive optical characterization of muscle blood flow,oxygenation, and metabolism in women with fibromyalgia

Introduction

Women with fibromyalgia (FM) have symptoms of increased muscular fatigue and reduced exercise tolerance, which may be associated with alterations in muscle microcirculation and oxygen metabolism. This study used near-infrared diffuse optical spectroscopies to noninvasively evaluate muscle blood flow, blood oxygenation and oxygen metabolism during leg fatiguing exercise and during arm arterial cuff occlusion in post-menopausal women with and without FM.

Methods

Fourteen women with FM and twenty-three well-matched healthy controls participated in this study. For the fatiguing exercise protocol, the subject was instructed to perform 6 sets of 12 isometric contractions of knee extensor muscles with intensity steadily increasing from 20 to 70% maximal voluntary isometric contraction (MVIC). For the cuff occlusion protocol, forearm arterial blood flow was occluded via a tourniquet on the upper arm for 3 minutes. Leg or arm muscle hemodynamics, including relative blood flow (rBF), oxy- and deoxy-hemoglobin concentration ([HbO₂] and [Hb]), total hemoglobin concentration (THC) and blood oxygen saturation (StO₂), were continuously monitored throughout protocols using a custom-built hybrid diffuse optical instrument that combined a commercial near-infrared oximeter for tissue oxygenation measurements and a custom-designed diffuse correlation spectroscopy (DCS) flowmeter for tissue blood flow measurements. Relative oxygen extraction fraction (rOEF) and oxygen consumption rate (rVO₂) were calculated from the measured blood flow and oxygenation data. Post-manipulation (fatiguing exercise or cuff occlusion) recovery in muscle hemodynamics was characterized by the recovery half-time, a time interval from the end of manipulation to the time that tissue hemodynamics reached a half-maximal value.

Results

Subjects with FM had similar hemodynamic and metabolic response/recovery patterns as healthy controls during exercise and during arterial occlusion. However, tissue rOEF during exercise in subjects with FM was significantly lower than in healthy controls, and the half-times of oxygenation recovery (Δ[HbO₂] and Δ[Hb]) were significantly longer following fatiguing exercise and cuff occlusion.

Conclusions

Our results suggest an alteration of muscle oxygen utilization in the FM population. This study demonstrates the potential of using combined diffuse optical spectroscopies (i.e., NIRS/DCS) to comprehensively evaluate tissue oxygen and flow kinetics in skeletal muscle.     

Regional Blood Flow in the Upper Extremity during and after Exposure to Acute Normobaric Hypoxia

Cardiovascular indices were analyzed in young healthy males exposed to normobaric hypoxia (breathing a gas mixture containing 10% O₂ for 16 min). There was a marked variation in individual responses. A linear relationship was observed between the individual blood oxygen saturation at the end of exposure and the baseline muscle blood flow (MBF). Moreover, blood oxygen saturation decreased in subjects with an initially high forearm MBF and remained unchanged or even slightly increased in subjects with a low forearm MBF. After hypoxic exposure (10–15 min), the MBF continued to decrease, venous capacity increased, and postocclusion hyperemic response decreased. It is suggested that hypoxic exposure activates the neuroreflex mechanisms regulating the peripheral blood flow and that the peripheral vascular response to acute hypoxia depends largely on the baseline blood flow in skeletal muscles.     

Hyperemic flow heterogeneity within the calf, foot, and forearm measured with continuous arterial spin labeling MRI

Arterial spin labeling (ASL) is a noninvasive magnetic resonance imaging (MRI) technique for microvascular blood flow measurement. We used a continuous ASL scheme (CASL) to investigate the hyperemic flow difference between major muscle groups in human extremities. Twenty-four healthy subjects with no evidence of vascular disease were recruited. MRI was conducted on a 3.0 Tesla Siemens Trio whole body system with a transmit/receive knee coil. A nonmagnetic orthopedic tourniquet system was used to create a 5-min period of ischemia followed by a period of hyperemic flow (occlusion pressure = 250 mmHg). CASL imaging, lasting from 2 min before cuff inflation to 3 min after cuff deflation, was performed on the midcalf, midfoot, and midforearm in separate sessions from which blood flow was quantified with an effective temporal resolution of 16 s. When muscles in the same anatomic location were compared, hyperemic flow was found to be significantly higher in the compartments containing muscles known to have relatively higher slow-twitch type I fiber compositions, such as the soleus muscle in the calf and the extensors in the forearm. In the foot, the plantar flexors exhibited a slightly delayed hyperemic response relative to that of the dorsal compartment, but no between-group flow difference was observed. These results demonstrate that CASL is sensitive to flow heterogeneity between diverse muscle groups and that nonuniform hyperemic flow patterns following an ischemic paradigm correlate with relative fiber-type predominance.     

Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure.

We tested the hypothesis that the oral alpha1-adrenergic agonist, midodrine, would limit the fall in arterial pressure observed during exercise in patients with pure autonomic failure (PAF). Fourteen subjects with PAF underwent a stand test, incremental supine cycling exercise (25, 50, and 75 W), and ischemic calf exercise, before (control) and 1 h after ingesting 10 mg midodrine. Heart rate (ECG), beat-to-beat blood pressure (MAP, arterial catheter), cardiac output (Q, open-circuit acetylene breathing), forearm blood flow (FBF, Doppler ultrasound), and calf blood flow (CBF, venous occlusion plethysmography) were measured. The fall in MAP after standing for 2 min was similar ( approximately 60 mmHg; P = 0.62). Supine MAP immediately before cycling was greater after midodrine (124 +/- 6 vs 117 +/- 6 mmHg; P < 0.03), but cycling caused a workload-dependent hypotension (P < 0.001), whereas increases in Q were modest but similar. Midodrine increased MAP and total peripheral resistance (TPR) during exercise (P < 0.04), but the exercise-induced fall in MAP and TPR were similar during control and midodrine (P = 0.27 and 0.14). FBF during cycling was not significantly reduced by midodrine (P > 0.2). By contrast, recovery of MAP after cycling was faster (P < 0.04) after midodrine ( approximately 25 mmHg higher after 5 min). Ischemic calf exercise evoked similar peak CBF in both trials, but midodrine reduced the hyperemic response over 5 min of recovery (P < 0.02). We conclude midodrine improves blood pressure and TPR during exercise and dramatically improves the recovery of MAP after exercise.     

Local vascular responses affecting blood flow in postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is defined by orthostatic intolerance associated with abnormal upright tachycardia. Some patients have defective peripheral vasoconstriction and increased calf blood flow. Others have increased peripheral arterial resistance and decreased blood flow. In 14 POTS patients (13-19 yr) evenly subdivided among low-flow POTS (LFP) and high-flow POTS (HFP) we tested the hypothesis that myogenic, venoarteriolar, and reactive hyperemic responses are abnormal. We used venous occlusion plethysmography to measure calf venous pressure and blood flow in the supine position and when the calf was lowered by 40 cm to evoke myogenic and venoarteriolar responses and during venous hypertension by 40-mmHg occlusion to evoke the venoarteriolar response. We measured calf reactive hyperemia with plethysmography and cutaneous laser-Doppler flowmetry. Baseline blood flow in LFP was reduced compared with HFP and control subjects (0.8 +/- 0.2 vs. 4.4 +/- 0.5 and 2.7 +/- 0.4 ml.min-1.100 ml-1) but increased during leg lowering (1.2 +/- 0.5 ml.min-1. 100 ml-1) while decreasing in the others. Baseline peripheral arterial resistance was increased in LFP and decreased in HFP compared with control subjects (39 +/- 13 vs. 15 +/- 3 and 22 +/- 5 mmHg.ml-1. 100 ml. min) but decreased to 29 +/- 13 mmHg.ml-1.100 ml. min in LFP during venous hypertension. Resistance increased in the other groups. Maximum calf hyperemic flow and cutaneous flow were similar in all subjects. The duration of hyperemic blood flow was curtailed in LFP compared with either control or HFP subjects (plethysmographic time constant = 20 +/- 2 vs. 29 +/- 4 and 28 +/- 4 s; cutaneous time constant = 60 +/- 25 vs. 149 +/- 53 s in controls). Local blood flow regulation in low-flow POTS is impaired.     

Noninvasively determined muscle oxygen saturation is an early indicator of central hypovolemia in humans.

Ten healthy human volunteers were subjected to progressive lower body negative pressure (LBNP) to the onset of cardiovascular collapse to compare the response of noninvasively determined skin and fat corrected deep muscle oxygen saturation (SmO2) and pH to standard hemodynamic parameters for early detection of imminent hemodynamic instability. Muscle SmO2 and pH were determined with a novel near infrared spectroscopic (NIRS) technique. Heart rate (HR) was measured continuously via ECG, and arterial blood pressure (BP) and stroke volume (SV) were obtained noninvasively via Finometer and impedance cardiography on a beat-to-beat basis. SmO2 and SV were significantly decreased during the first LBNP level (-15 mmHg), whereas HR and BP were late indicators of impending cardiovascular collapse. SmO2 declined in parallel with SV and inversely with total peripheral resistance, suggesting, in this model, that SmO2 is an early indicator of a reduction in oxygen delivery through vasoconstriction. Muscle pH decreased later, suggesting an imbalance between delivery and demand. Spectroscopic determination of SmO2 is noninvasive and continuous, providing an early indication of impending cardiovascular collapse resulting from progressive reduction in central blood volume.     

Regional difference of blood flow in anesthetized rats during reduced gravity induced by parabolic flight.

To examine a hypothesis that change in regional blood flow due to decreased hydrostatic pressure gradient and redistribution of blood during reduced gravity (rG) is different between organs, changes in cerebrocortical blood flow (CBF) and blood flow in the temporal muscle (MBF) with exposure to rG were measured in anesthetized rats in head-up tilt and flat positions during parabolic flight. Carotid arterial pressure (CAP), jugular venous pressure (JVP), and abdominal aortic pressure were also measured simultaneously. In the head-up tilt group, CBF increased by 15 +/- 3% within 3 s of entry into rG and rapidly recovered during rG. MBF also increased, but the change was significantly greater than that of CBF. JVP increased by 1.8 +/- 0.5 mmHg, probably due to loss of hydrostatic pressure gradient, since the measuring point of JVP was 2-3 cm above the hydrostatic indifference point. CAP and abdominal aortic pressure increased by 16.7 +/- 2 and 7.7 +/- 2 mmHg, respectively, compared with the 1-G condition. Muscle vascular resistance [(CAP-JVP)/MBF] decreased on entry into rG, but no significant change was observed in cerebrocortical vascular resistance [(CAP-JVP)/CBF]. In the flat group, no significant change was observed in all the variables. The results indicate that arteriolar vasodilatation occurs in the temporal muscle but not in the cerebral cortex. Thus the blood flow control mechanism at the onset of rG is different between intra- and extracranial organs.     

Failure of oxygen radical scavengers to modify fatigue in electrically stimulated muscle.

We used in situ gastrocnemius muscle of anaesthetized dogs to test the hypothesis that O2 radical production during muscle contraction contributes to fatigue. Muscle tension was measured with a force transducer and blood flow was monitored with an electromagnetic flow probe. Muscle contractions were produced by stimulating the nerve for 15 min at 20 Hz, 12 trains/min, and a duty cycle of 0.25. Three groups of seven animals were given an infusion of 0.2 mL.min-1 of either saline, low-dose oxygen radical scavengers (250 IU.mL-1 superoxide dismutase, 640 IU.mL-1 polyethylene glycol (PEG)-catalase, 0.25 mg.mL-1 deferoxamine, and 0.1 mg.mL-1 oxypurinol), or high-dose oxygen radical scavengers (3300 IU.mL-1 superoxide dismutase, 6600 IU.mL-1 PEG-catalase, 2.5 mg.mL-1 deferoxamine, and 0.1 mg.mL-1 oxypurinol). Blood flow and vascular resistance of the gastrocnemius muscle during stimulation did not differ among groups. After 15 min of stimulation, the developed tension (represented as a percentage of initial tension developed) was 66 +/- 7% in the saline treated group, 70 +/- 6% in the low-dose group, and 70 +/- 4% in the high-dose group. The change in tension during recovery was not significant in the control or low-dose groups. However, there was partial recovery in the high-dose group. In conclusion, in this preparation, oxygen radical scavengers did not delay the development of decreased muscle tension.     

A geometry-based model for non-invasive estimation of pressure gradients over iliac artery stenoses

The aim of this study was to develop and verify a model that provides an accurate estimation of the trans-lesion hyperemic pressure gradient in iliac artery stenoses in seconds by only using patient-specific geometric properties obtained from 3-dimensional rotational angiography (3DRA).Twenty-one patients with symptomatic peripheral arterial disease (PAD), iliac artery stenoses and an ultrasound based peak systolic velocity ratio between 2.5 and 5.0 underwent 3DRA and intra-arterial pressure measurements under hyperemic conditions. For each lesion, geometric properties were extracted from the 3DRA images using quantitative vascular analysis software. Hyperemic blood flow was estimated based on stenosis geometry using an empirical relation. The geometrical properties and hyperemic flow were used to estimate the pressure gradient by means of the geometry-based model. The predicted pressure gradients were compared with in vivo measured intra-arterial pressure measurements performed under hyperemic conditions.The developed geometry-based model showed good agreement with the measured hyperemic pressure gradients resulting in a concordance correlation coefficient of 0.86. The mean bias ± 2SD between the geometry-based model and in vivo measurements was comparable to results found by evaluating the actual computational fluid dynamics model (−1.0 ± 14.7 mmHg vs −0.9 ± 12.7 mmHg).The developed model estimates the trans-lesional pressure gradient in seconds without the need for an additional computational fluid dynamics software package. The results justify further study to assess the potential use of a geometry-based model approach to estimate pressure gradient on non-invasive CTA or MRA, thereby reducing the need for diagnostic angiography in patients suffering from PAD.     

Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease

Homogeneity of microvascular resistance in different perfusion areas of the same heart is generally assumed. We investigated the effect of the severity of an epicardial stenosis on microvascular resistance in 27 patients with coronary artery disease and stable angina. All patients had an angiographically normal coronary artery, an artery with an intermediate lesion, and an artery with a severe lesion; the latter was treated with angioplasty. In each patient, distal blood flow velocity and pressure were measured during baseline and maximal hyperemia (induced by intracoronary adenosine) using a Doppler and pressure guide wire, respectively. The ratio of mean distal pressure to average peak blood flow velocity was used as an index for the microvascular resistance (MRv). Within patients, the hyperemic MRv was higher in arteries with more severe stenosis (P = 0.021). After percutaneous transluminal coronary angioplasty (PTCA), the hyperemic MRv decreased (pre-PTCA, 2.6 vs. post-PTCA, 1.9 mmHg.cm(-1)s(-1), P < 0.01) toward the value of the reference artery (1.7 mmHg.cm(-1)s(-1); P = 0.67). We conclude that there is a positive association between coronary lesion severity and variability of distal microvascular resistance that normalizes after angioplasty. This study challenges the concept of uniform distribution of hyperemic MRv that is relevant for the interpretation of both noninvasive and invasive diagnostic tests.     

Metabolic adaptations to repeated periods of contraction with reduced blood flow in canine skeletal muscle

Background  

Patients suffering from Intermittent Claudication (IC) experience repeated periods of muscle contraction with low blood flow, throughout the day and this may contribute to the hypothesised skeletal muscle abnormalities. However, no study has evaluated the consequences of intermittent contraction with low blood flow on skeletal muscle tissue. Our aim was to generate this basic physiological data, determining the 'normal' response of healthy skeletal muscle tissue. We specifically proposed that the metabolic responses to contraction would be modified under such circumstances, revealing endogenous strategies engaged to protect the muscle adenine nucleotide pool. Utilizing a canine gracilis model (n = 9), the muscle was stimulated to contract (5 Hz) for three 10 min periods (separated by 10 min rest) under low blood flow conditions (80% reduced), followed by 1 hr recovery and then a fourth period of 10 min stimulation. Muscle biopsies were obtained prior to and following the first and fourth contraction periods. Direct arterio-venous sampling allowed for the calculation of muscle metabolite efflux and oxygen consumption.     

Physiological flow analysis in significant human coronary artery stenoses

To evaluate the local hemodynamics in flow limiting coronary lesions, computational hemodynamics was applied to a group of patients previously reported by Wilson et al. (1988) with representative pre-angioplasty stenosis geometry (minimal lesion size d(m)=0.95 mm; 68% mean diameter stenosis) and with measured values of coronary flow reserve (CFR) in the abnormal range (2.3+/-0.1). The computations were at mean flow rates (Q) of 50, 75 and 100 ml/min (the limit of our converged calculations). Computed mean pressure drops Deltap were approximately 9 mmHg for basal flow (50 ml/min), approximately 27 mmHg for elevated flow (100 ml/min) and increased to an extrapolated value of approximately 34 mmHg for hyperemic flow (115 ml/min), which led to a distal mean coronary pressure p(rh) of approximately 55 mmHg, a level known to cause ischemia in the subendocardium (Brown et al., 1984), and consistent with the occurrence of angina in the patients. Relatively high levels of wall shear stress were computed in the narrow throat region and ranged from about 600 to 1500 dyn/cm(2), with periodic (phase shifted) peak systolic values of about 3500 dyn/cm(2). In the distal vessel, the interaction between the separated shear layer wave, convected downstream by the core flow, and the wall shear layer flow, led to the formation of vortical flow cells along the distal vessel wall during the systolic phase where Reynolds numbers Re(e)(t) were higher. During the phasic vortical mode observed at both basal and elevated mean flow rates, wide variations in distal wall shear stress occurred, distal transmural pressures were depressed below throat levels, and pressure recovery was larger farther along the distal vessel. Along the constriction (convergent) and throat segments of the lesion the pulsatile flow field was principally quasi-steady before flow separation occurred. The flow regimes were complex in the narrow mean flow Reynolds number range Re(e)=100-230 and a frequency parameter of alphae=2.25. The shear layer flow disturbances diminished in strength due to viscous damping along the distal vessel at these relatively low values of Re(e), typical of flow through diseased epicardial coronary vessels. The distal hyperemic flow field was likely to be in an early stage of turbulent flow development during the peak systolic phase.     

Hyperbaric hyperoxia reduces exercising forearm blood flow in humans

Hypoxia during exercise augments blood flow in active muscles to maintain the delivery of O(2) at normoxic levels. However, the impact of hyperoxia on skeletal muscle blood flow during exercise is not completely understood. Therefore, we tested the hypothesis that the hyperemic response to forearm exercise during hyperbaric hyperoxia would be blunted compared with exercise during normoxia. Seven subjects (6 men/1 woman; 25 ± 1 yr) performed forearm exercise (20% of maximum) under normoxic and hyperoxic conditions. Forearm blood flow (FBF; in ml/min) was measured using Doppler ultrasound. Forearm vascular conductance (FVC; in ml·min(-1)·100 mmHg(-1)) was calculated from FBF and blood pressure (in mmHg; brachial arterial catheter). Studies were performed in a hyperbaric chamber with the subjects supine at 1 atmospheres absolute (ATA) (sea level) while breathing normoxic gas [21% O(2), 1 ATA; inspired Po(2) (Pi(O(2))) ≈ 150 mmHg] and at 2.82 ATA while breathing hyperbaric normoxic (7.4% O(2), 2.82 ATA, Pi(O(2)) ≈ 150 mmHg) and hyperoxic (100% O(2), 2.82 ATA, Pi(O(2)) ≈ 2,100 mmHg) gas. Resting FBF and FVC were less during hyperbaric hyperoxia compared with hyperbaric normoxia (P < 0.05). The change in FBF and FVC (Δ from rest) during exercise under normoxia (204 ± 29 ml/min and 229 ± 37 ml·min(-1)·100 mmHg(-1), respectively) and hyperbaric normoxia (203 ± 28 ml/min and 217 ± 35 ml·min(-1)·100 mmHg(-1), respectively) did not differ (P = 0.66-0.99). However, the ΔFBF (166 ± 21 ml/min) and ΔFVC (163 ± 23 ml·min(-1)·100 mmHg(-1)) during hyperbaric hyperoxia were substantially attenuated compared with other conditions (P < 0.01). Our data suggest that exercise hyperemia in skeletal muscle is highly dependent on oxygen availability during hyperoxia.     

Critical oxygen tension in rat brain: a combined (31)P-NMR and EPR oximetry study

The relationship between cerebral interstitial oxygen tension (Pt(O(2))) and cellular energetics was investigated in mechanically ventilated, anesthetized rats during progressive acute hypoxia to determine whether there is a "critical" brain Pt(O(2)) for maintaining steady-state aerobic metabolism. Cerebral Pt(O(2)), measured by electron paramagnetic resonance oximetry, decreased proportionately to inspired oxygen fraction. (31)P-nuclear magnetic resonance measurements revealed no changes in P(i), phosphocreatine (PCr)/P(i) ratio, or intracellular pH when arterial blood oxygen tension (Pa(O(2))) was reduced from 145.1 +/- 11.7 to 56.5 +/- 4.4 mmHg (means +/- SE). Intracellular acidosis, a sharp rise in P(i), and a decline in the PCr/P(i) ratio developed when Pa(O(2)) was reduced further to 40.7 +/- 2.3 mmHg. The corresponding Pt(O(2)) values were 15.1 +/- 1.8, 8.8 +/- 0.4, and 6.8 +/- 0.3 mmHg. We conclude that over a range of decreasing oxygen tensions, cerebral oxidative metabolism is not sensitive to oxygen concentration. Oxygen becomes a regulatory substrate, however, when Pt(O(2)) is decreased to a critical level.