Vascular Transit Time Research Articles

Radiolabelled leucocytes in human pulmonary disease.

Radionuclides for leucocyte kinetic studies have progressed from non-gamma emitting cell-labelling radionuclides through gamma emitting nuclides that allow imaging of leucocyte kinetics, to the next goal of positron emission tomography (PET). Mostly the authors' own studies, following on from studies of the early pioneers. From early imaging studies, it appeared that the majority of the marginated granulocyte pool was located in the lungs. However, later work disputed this by demonstrating the exquisite sensitivity of granulocytes to ex vivo isolation and labelling, and that excessive lung activity is artefactual. Following refinement of labelling techniques, it was shown that the majority of marginated granulocytes are located in the spleen and bone marrow. The majority of leucocytes have a pulmonary vascular transit time only a few seconds longer than erythrocytes. The minority showing slow transit, ~5% in healthy persons, is increased in systemic inflammatory disorders that cause neutrophil priming and loss of deformability. Using a range of imaging techniques, including gamma camera imaging, whole-body counting and single photon-emission computerized tomography, labelled granulocytes were subsequently used to image pulmonary trafficking in lobar pneumonia, bronchiectasis, chronic obstructive pulmonary disease and adult respiratory distress syndrome. More recently, eosinophils have been separated in pure form using magnetic bead technology for the study of eosinophil trafficking in asthma. These include advancement of eosinophil imaging, development of monocyte labelling, development of cell labelling with PET tracers and the tracking of lymphocytes.

Free-Breathing 3D Liver Perfusion Quantification Using a Dual-Input Two-Compartment Model

The purpose of this study is to test the feasibility of applying a dual-input two-compartment liver perfusion model to patients with different pathologies. A total of 7 healthy subjects and 11 patients with focal liver lesions, including 6 patients with metastatic adenocarcinoma and 5 with hepatocellular carcinoma (HCC), were examined. Liver perfusion values were measured from both focal liver lesions and cirrhotic tissues (from the 5 HCC patients). Compared to results from volunteer livers, significantly higher arterial fraction, fractional volume of the interstitial space, and lower permeability-surface area product were observed for metastatic lesions, and significantly higher arterial fraction and lower vascular transit time were observed for HCCs (P < 0.05). Significantly lower arterial fraction and higher vascular transit time, fractional volume of the vascular space, and fractional volume of the interstitial space were observed for metastases in comparison to HCCs (P < 0.05). For cirrhotic livers, a significantly lower total perfusion, lower fractional volume of the vascular space, higher fractional volume of the interstitial space, and lower permeability-surface area product were noted in comparison to volunteer livers (P < 0.05). Our findings support the possibility of using this model with 3D free-breathing acquisitions for lesion and diffuse liver disease characterization.

Understanding Ktrans: a simulation study based on a multiple-pathway model

The transfer constant Ktrans is commonly employed in dynamic contrast-enhanced MRI studies, but the utility and interpretation of Ktrans as a potential biomarker of tumor vasculature remains unclear. In this study, computer simulations based on a comprehensive tracer kinetic model with multiple pathways was used to provide clarification on the interpretation and application of Ktrans. Tissue concentration-time curves pertaining to a wide range of transport conditions were simulated using the multiple-pathway (MP) model and fitted using the generalized kinetic (GK) and extended GK models. Relationships between Ktrans and plasma flow Fp, vessel permeability PS and extraction rate EFp under various transport conditions were assessed by correlation and regression analysis. Results show that the MP model provides an alternative two-tier interpretation of Ktrans based on the vascular transit time. Ktrans is primarily associated with Fp and EFp respectively, in the slow and rapid vascular transit states, independent of the magnitude of PS. The relative magnitudes of PS and Fp only serve as secondary constraints for which Ktrans can be further associated with EFp and PS in the slow and rapid transit states, respectively.

Modeling of Tracer Transport Delays for Improved Quantification of Regional Pulmonary ¹⁸F-FDG Kinetics, Vascular Transit Times, and Perfusion.

¹⁸F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary ¹⁸F-FDG kinetics do not account for delays in ¹⁸F-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of ¹⁸F-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic ¹⁸F-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n = 6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. ¹³NN bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of ¹⁸F-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0 to 13.6 s, averaging 6.4 ± 2.9 s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on ¹³NN-PET (R² = 0.92, p < 0.001). By incorporating local vascular transports delays, this model of pulmonary ¹⁸F-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation.

Correlative assessment of tumor microcirculation using contrast‐enhanced perfusion MRI and intravoxel incoherent motion diffusion‐weighted MRI: is there a link between them?

The purpose of this study was to correlate intravoxel incoherent motion (IVIM) imaging with classical perfusion-weighted MRI metrics in human gliomas. Parametric images for slow diffusion coefficient (D), fast diffusion coefficient (D*), and fractional perfusion-related volume (f) in patients with high-grade gliomas were generated. Maps of Fp (plasma flow), vp (vascular plasma volume), PS (permeability surface-area product), ve (extravascular, extracellular volume), E (extraction ratio), ke (influx ratio into the interstitium), and tc (vascular transit time) from dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast-enhanced (DSC) MRI were also generated. A region-of-interest analysis on the contralateral healthy white matter and on the tumor areas was performed and the extracted parameter values were tested for any significant differences among tumor grades or any correlations. Only f could be significantly correlated to DSC-derived vp and tc in healthy brain tissue. Concerning the tumor regions, Fp was significantly positively correlated with D* and inversely correlated with f in DSC measurements. The D*, f, and f × D* values in the WHO grade III gliomas were non-significantly different from those in the grade IV gliomas. There was a trend to significant negative correlations between f and PS as well as between f × D* and ke in DCE experiments. Presumably due to different theoretical background, tracer properties and modeling of the tumor vasculature in the IVIM theory, there is no clearly evident link between D*, f and DSC- and DCE-derived metrics.

Simulation of contrast agent transport in arteries with multilayer arterial wall: impact of arterial transmural transport on the bolus delay and dispersion.

One assumption of DSC-MRI is that the injected contrast agent is kept totally intravascular and the arterial wall is impermeable to contrast agent. The assumption is unreal for such small contrast agent as Gd-DTPA can leak into the arterial wall. To investigate whether the unreal assumption is valid for the estimation of the delay and dispersion of the contrast agent bolus, we simulated flow and Gd-DTPA transport in a model with multilayer arterial wall and analyzed the bolus delay and dispersion qualified by mean vascular transit time (MVTT) and the variance of the vascular transport function. Factors that may affect Gd-DTPA transport hence the delay and dispersion were further investigated, such as integrity of endothelium and disturbed flow. The results revealed that arterial transmural transport would slightly affect MVTT and moderately increase the variance. In addition, although the integrity of endothelium can significantly affect the accumulation of contrast agent in the arterial wall, it had small effects on the bolus delay and dispersion. However, the disturbed flow would significantly increase both MVTT and the variance. In conclusion, arterial transmural transport may have a small effect on the bolus delay and dispersion when compared to the flow pattern in the artery.

Predicting haemorrhage in pre‐hospital traumatic patients: evaluation of the novel heart‐to‐arm time index

Early recognition of hypovolaemia in trauma patients is very important. However, the most often used clinical signs, such as hypotension and tachycardia, lack specificity and sensitivity. We propose a non-invasive index of hypovolaemia, the heart to arm time (iHAT), based on a modified pulse transit time indexed to heart rate. Pulse transit time is the sum of pre-ejection period and vascular transit time. Following pre-load reductions due to hypovolaemia, ventricular diastolic filling time increases causing an increase in pre-ejection-period, pulse transit time, and hence iHAT. One hundred and four consecutive patients with suspected major trauma were enrolled. The primary aim was to evaluate the use of the iHAT for detecting haemorrhage in major trauma. The secondary end point was to compare the specificity and sensitivity of iHAT compared to commonly used indexes. iHAT was calculated in 84 subjects, 11 of whom were haemorrhagic. iHAT discriminated haemorrhagic from non-haemorrhagic group (46.8% vs. 66.9%, P < 0.0001). The cut-off for iHAT with the best compromise between sensitivity (90.9%) and specificity (100%) was reached at the 58.78% level. Comparing haemorrhagic and non-haemorrhagic patients, the area under the ROC curve was 0.952 for iHAT, 0.835 for heart rate, and 0.911 for systolic blood pressure, showing no significant differences. iHAT is a non-invasive index that can identify haemorrhage in trauma patients with high sensitivity and specificity. These data should be considered as an exploration, but any conclusion should be validated in a new set of consecutive patients.

Robust Quantification of Microvascular Transit Times via Linear Dynamical Systems using Two-Photon Fluorescence Microscopy Data

Vascular transit time is an important indicator of microcirculatory health. We present a second-order-plus-dead-time (SOPDT) model for robust estimation of kinetic parameters characterizing microvascular bolus passage using two-photon fluorescence microscopy (2PFM) in anesthetized rats receiving somatosensory stimulation. This methodology enables quantification of transit time, time-to-peak, overshoot, and rate of bolus passage through the microvascular network. The overall transit time during stimulation, of 2.2 ± 0.1 seconds, was shorter (P ~ 0.0008) than that at rest (2.7 ± 0.2 seconds). When compared with conventional γ-variate modeling, the SOPDT modeling yielded better quality of fit both at rest (P<0.0001) and on activation (P<0.001).

Intraocular Hemorrhage After Intra-Arterial Chemotherapy for Retinoblastoma in Sickle Cell Trait

Massive intraocular hemorrhage developed in a child with advanced unilateral retinoblastoma after intrarterial treatment with Melphalan and Topotecan. The child tested positive for sickle cell trait. Sickle cell trait may predispose such children to slower vascular transit time, hypoxia, sickling and vascular occlusion caused by catheter induced decreased flow. Enucleation confirmed the ultrasound and selective angiogram findings in addition to a completely calcified tumor. Clinicians should be on the lookout for the association of sickle-cell disease/trait and intraocular hemorrhages after intraarterial chemotherapy to fully understand its clinical significance.

Inflow‐based vascular‐space‐occupancy (iVASO) MRI

Vascular-space-occupancy (VASO) MRI, a blood nulling approach for assessing changes in cerebral blood volume (CBV), is hampered by low signal-to-noise ratio (SNR) because only 10-20% of tissue signal is recovered when using nonselective inversion for blood nulling. A new approach, called inflow-VASO (iVASO), is introduced in which only blood flowing into the slice has experienced inversion, thereby keeping tissue and cerebrospinal fluid (CSF) signal in the slice maximal and reducing CSF partial volume effects. SNR increases of 198% ± 12% and 334% ± 9% (mean ± SD, n = 7) with respect to VASO were found at TR values of 5 s and 2 s, respectively. When using inflow approaches, data interpretation is complicated by the fact that signal changes are affected by vascular transit times. An optimal TR-range (1.5-2.5 s) was derived in which the iVASO response during activation predominantly reflects arterial/arteriolar CBV (CBV(a)) changes. In this TR-range, perfusion contributions to the signal change are negligible because arterial label has not yet undergone capillary exchange, and arterial and precapillary blood signals are nulled. For TR = 2 s, the iVASO signal change upon visual stimulation corresponded to a CBV(a) increase of 58% ± 7%, in agreement with arteriolar CBV changes previously reported. The onset of the hemodynamic response for iVASO occurred 1.2 ± 0.5 s (n = 7) faster than for conventional VASO.

The effects of pre-ejection period on post-exercise systolic blood pressure estimation using the pulse arrival time technique

Pulse arrival time (PAT) is comprised of the vascular transit time (TT) through the arterial system and the pre-ejection period (PEP) in the heart. It has been used to predict arterial blood pressure (BP) without using a cuff. The aim of this study was to investigate the effects of including the PEP on the accuracy of cuffless systolic BP (SBP) estimation using the PAT technique in post-exercise recovery. Experiments were conducted on 22 normotensive participants. PAT, TT and PEP were determined from simultaneous measurements of the electrocardiogram, photoplethysmogram and impedance cardiogram. Moderate exercise induced significant (p<0.05) increases in SBP and heart rate and significant (p<0.05) decreases in PEP and PAT. Diastolic blood pressure and TT only varied insignificantly (p>0.05). SBP was moderately correlated with PEP (r=-0.61) and PAT (r=-0.81). PAT and PEP were moderately correlated (r=0.67). When SBP was estimated using least-squares methods, the differences between the measured and predicted SBP using PEP, PAT and TT were 0.0±6.6, 0.0±4.9 and 0.0±9.3mmHg, respectively. The findings suggested that PAT gives the best SBP prediction and PEP has some potential to predict blood pressure. The inclusion of PEP in the PAT measurement is necessary to facilitate accurate cuffless blood pressure prediction after exercise.

Comparison of transcranial Doppler ultrasonography and positron emission tomography using a three-dimensional template of the middle cerebral artery

Objective: Transcranial Doppler (TCD) measures blood flow velocities (BFV) and is an indirect method of assessing cerebral blood flow (CBF). Positron emission tomography (PET) is a direct method to measure CBF. This study evaluates the correlations between TCD and PET findingsMethods: Nine patients with a symptomatic carotid artery stenosis, who underwent CEA, were studied pre- and post-operatively on the ipsi- and contralateral sides. Measurements of the BFV, CO2 reactivity, CBF, cerebral blood volume (CBV) and mean vascular transit time (MVTT) were performed using a three-dimensional volume of interest (VOI) for the middle cerebral artery (MCA).Results: CBF in the MCA region, as measured with PET, shows a good correlation with BFV, as measured with TCD, with similar pattern for total, gray and white matter MCA territory (Pearson's correlation coefficients: 0.751, 0.748 and 0.748, respectively). This correlation was found in the pre-operative as well as the post-operative state. No association could be demonstrated between CO2 reactivity and CBV or (Pearson's correlation coefficients: 0.051 and 0.166, respectively).Conclusion: With PET, it is possible to create three-dimensional VOI of arterial territories. CBF measured in these VOI seems to correlate with BFV before and after CEA on ipsi- and contralateral sides, while CBV shows no association with pre-operative CO2 reactivity.

A novel continuous arterial spin labeling approach for CBF measurement in rats with reduced labeling time and optimized signal-to-noise ratio efficiency

To develop a continuous arterial spin labeling (CASL) perfusion imaging method for cerebral blood flow (CBF) measurement in rats with reduced spin-labeling length and optimized signal-to-noise ratio (SNR(f)) per unit time. In the proposed method, the longitudinal magnetization of brain tissue water in the imaging slice is prepared into a proper state before spin-labeling, and a post-tagging delay is employed after spin-labeling. The method was implemented on a 4.7 T small animal scanner. Numerical simulations and in vivo experiments were used to evaluate the performance of the method proposed. With the proposed method, absolute CBF could be measured accurately from normal rat with a spin-labeling pulse as short as 400 ms, and yet employing the same formula as that used in the conventional CASL perfusion imaging method for calculation. The method also showed improved SNR(f) per unit time over the conventional CASL perfusion imaging method and the pulsed arterial spin labeling perfusion imaging method FAIR. Compared to the conventional CASL perfusion imaging method, the proposed method would be advantageous for CBF measurement in small animals having short vascular transit time in terms of SNR(f) per unit time and other benefits brought by shortened spin-labeling pulse.

Peroperative Neuromonitoring during Carotid Endarterectomy in Relation to Preoperative Positron Emission Tomography Findings

Objectives: To compare stump pressure (SP), transcranial Doppler (TCD), electroencephalography (EEG) and selective shunting during carotid endarterectomy (CEA) with preoperative positron emission tomography (PET) parameters. Materials and methods: Preoperative PET measurements and preoperative neuromonitoring were performed in ten patients undergoing CEA for symptomatic carotid artery disease. PET parameters measured were cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral oxygen metabolism (CMRO2), cerebral blood volume (CBV), mean vascular transit time (MVTT) and cerebral perfusion pressure (CPP). Results of these measurements in ipsilateral medial cerebral artery (MCA), ipsilateral hemisphere and total cerebrum were compared with absolute mean SP, mean SP < 40 mmHg, TCD, EEG changes and selective shunting. Results: None of the PET parameters showed any significant correlations with peroperative neuromonitoring findings. There were only trends for correlations of CBF and MVTT with TCD changes and of CPP and CMRO2 with selective shunting. Conclusions: Preoperative PET examinations are not usefull for predicting the need for shunting during CEA.

Factors that Affect Pulse Wave Time Transmission in the Monitoring of Cardiovascular System

Vascular transit time (VTT) can be defined as the first heart sound of the phonocardiography (PCG) signal to its arrival at the photoplethysmography (PPG). Studies have shown that monitoring VTT can be useful as an early prognosis of cardiac diseases. However, there is limited study conducted to understand the physiologic factors that affect VTT at the upper limb. In this study, the effect associated with difference in subject height, weight, heart rate, mean arterial pressure, systolic and diastolic blood pressure was assessed. A study population of 31 healthy Chinese young adults (21 male; age range 20-33 yr) were recruited. PCG and PPG were recorded non-invasively from the fourth costal cartilage at the midclavicular line and right index finger, respectively. A single sample Kolmogorov-Smirnov (K-S) goodness-of-fit hypothesis test, a univariate linear regression analysis, and a multiple linear regression modelling were performed on the VTT measurements and the associated physiologic parameters. The results from the K-S test showed that the physiologic parameters and VTT measurements had a normal cumulative distribution function. Furthermore, all physiologic parameters were significantly and independently related to VTT (P < 0.05). Based on these physiological parameters, a VTT regression model was also derived (r (2) = 0.79). The findings herein suggest that the observed physiologic parameters have significant contributions to the nominal VTT value of a subject. Unlike pulse transit time, the VTT technique has the added advantage that the left ventricular isometric contraction time is not included in the timing derivation.

Peroperative Neuromonitoring during Carotid Endarterectomy in Relation to Preoperative Positron Emission Tomography Findings

To compare stump pressure (SP), transcranial Doppler (TCD), electroencephalography (EEG) and selective shunting during carotid endarterectomy (CEA) with preoperative positron emission tomography (PET) parameters. Preoperative PET measurements and peroperative neuromonitoring were performed in ten patients undergoing CEA for symptomatic carotid artery disease. PET parameters measured were cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral oxygen metabolism (CMRO(2)), cerebral blood volume (CBV), mean vascular transit time (MVTT) and cerebral perfusion pressure (CPP). Results of these measurements in ipsilateral medial cerebral artery (MCA), ipsilateral hemisphere and total cerebrum were compared with absolute mean SP, mean SP<40mmHg, TCD, EEG changes and selective shunting. None of the PET parameters showed any significant correlations with peroperative neuromonitoring findings. There were only trends for correlations of CBF and MVTT with TCD changes and of CPP and CMRO(2) with selective shunting. Preoperative PET examinations are not useful for predicting the need for shunting during CEA.

Functional Reactivity of Cerebral Capillaries

The spatiotemporal evolution of cerebral microcirculatory adjustments to functional brain stimulation is the fundamental determinant of the functional specificity of hemodynamically weighted neuroimaging signals. Very little data, however, exist on the functional reactivity of capillaries, the vessels most proximal to the activated neuronal population. Here, we used two-photon laser scanning microscopy, in combination with intracranial electrophysiology and intravital video microscopy, to explore the changes in cortical hemodynamics, at the level of individual capillaries, in response to steady-state forepaw stimulation in an anesthetized rodent model. Overall, the microcirculatory response to functional stimulation was characterized by a pronounced decrease in vascular transit times (20%+/-8%), a dilatation of the capillary bed (10.9%+/-1.2%), and significant increases in red blood cell speed (33.0%+/-7.7%) and flux (19.5%+/-6.2%). Capillaries dilated more than the medium-caliber vessels, indicating a decreased heterogeneity in vessel volumes and increased blood flow-carrying capacity during neuronal activation relative to baseline. Capillary dilatation accounted for an estimated approximately 18% of the total change in the focal cerebral blood volume. In support of a capacity for focal redistribution of microvascular flow and volume, significant, though less frequent, local stimulation-induced decreases in capillary volume and erythrocyte speed and flux also occurred. The present findings provide further evidence of a strong functional reactivity of cerebral capillaries and underscore the importance of changes in the capillary geometry in the hemodynamic response to neuronal activation.

Dynamic contrast-enhanced CT of head and neck tumors: perfusion measurements using a distributed-parameter tracer kinetic model. Initial results and comparison with deconvolution-based analysis

The objective of this work was to evaluate the feasibility of a two-compartment distributed-parameter (DP) tracer kinetic model to generate functional images of several physiologic parameters from dynamic contrast-enhanced CT data obtained of patients with extracranial head and neck tumors and to compare the DP functional images to those obtained by deconvolution-based DCE-CT data analysis. We performed post-processing of DCE-CT studies, obtained from 15 patients with benign and malignant head and neck cancer. We introduced a DP model of the impulse residue function for a capillary-tissue exchange unit, which accounts for the processes of convective transport and capillary-tissue exchange. The calculated parametric maps represented blood flow (F), intravascular blood volume (v1), extravascular extracellular blood volume (v2), vascular transit time (t1), permeability–surface area product (PS), transfer ratios k12 and k21, and the fraction of extracted tracer (E). Based on the same regions of interest (ROI) analysis, we calculated the tumor blood flow (BF), blood volume (BV) and mean transit time (MTT) by using a modified deconvolution-based analysis taking into account the extravasation of the contrast agent for PS imaging. We compared the corresponding values by using Bland–Altman plot analysis. We outlined 73 ROIs including tumor sites, lymph nodes and normal tissue. The Bland–Altman plot analysis revealed that the two methods showed an accepted degree of agreement for blood flow, and, thus, can be used interchangeably for measuring this parameter. Slightly worse agreement was observed between v1 in the DP model and BV but even here the two tracer kinetic analyses can be used interchangeably. Under consideration of whether both techniques may be used interchangeably was the case of t1 and MTT, as well as for measurements of the PS values. The application of the proposed DP model is feasible in the clinical routine and it can be used interchangeably for measuring blood flow and vascular volume with the commercially available reference standard of the deconvolution-based approach. The lack of substantial agreement between the measurements of vascular transit time and permeability–surface area product may be attributed to the different tracer kinetic principles employed by both models and the detailed capillary tissue exchange physiological modeling of the DP technique.

A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation.

Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro-metabolic and neuro-vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus-driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato-sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo-Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (+/-15) mL/100 g min and baseline oxygen consumption to be 6.7 (+/-1.3) mL O(2)/100 g min. We calculate parametric, linear increases in arterial dilation (R(2)=0.96) and CMRO(2) (R(2)=0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version.

Physiological mechanisms dissociating pulmonary CO2 and O2 exchange dynamics during exercise in humans

During moderate exercise (below the lactate threshold, (thetaL)), muscle CO(2) production ( Q(CO2)) kinetics are monoexponential, with a time constant (tau) similar to that of O(2) consumption. Following a delay incorporating the muscle-lung vascular transit time, Q(CO2) is expressed at the lungs (V(CO2)) with an appreciably longer tau, reflecting the influence of intervening high-capacitance CO(2) stores. Above (thetaL), kinetics become complex, resulting from the conflation of the differing rates of HCO(3)(-) breakdown and degrees of compensatory hyperventilation with that of the underlying aerobic component. During incremental exercise, the increased rate of relative to pulmonary O(2) uptake (V(CO2)) can be used to quantify (thetaL) validly if aerobic and hyperventilatory sources can be ruled out, i.e. (thetaL) is then attributable to the decrease in muscle and blood [HCO(3)(-)]. In many cases, however, very rapid incrementation of work rate and/or prior depletion of CO(2) stores (by volitional or anticipatory hyperventilation) can yield a 'false positive' non-invasive estimation of (thetaL) ('pseudo-threshold') resulting from a slowing of the rate of wash-in of transient CO(2) stores.