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Biomedical subjects

Jose G Venegas

Publications and source records attributed to Jose G Venegas.

15 recordsLinked to original sources

Effect of urethral compliance on the steady state p-Q relationships assessed with a mechanical analog of the male lower urinary tract.

AIMS: Using a lumped parameter theoretical model of bladder outlet function, we previously explored the relationship between the tube law of the urethra and the pressure-flow characteristics during micturition [Mijailovich et al., 2004]. To validate this theoretical model, we constructed a mechanical analog of the male lower urinary tract that incorporated elements simulating all relevant parameters of the theoretical model. In addition, we determined the effect of alterations in compliance of the flow-controlling zone on these relationships. METHODS: In the mechanical analog, the bladder neck and urethra were represented by a thin-walled conduit made of latex rubber and the prostate with a fluid filled cuff of variable compliance encircling the conduit. We measured in the same system steady-state pressure-flow (p-Q) and pressure-area (p-A) relationships of the flow-controlling zone. The effects of bladder outlet obstruction and prostatic compliance on these relationships were simulated by varying cuff pressure and capacitative coupling of the cuff, respectively. RESULTS: We demonstrated two previously described flow regimes-critical for low Q, and subcritical for higher Q. In the critical flow regime, the cross-sectional area of the collapsible conduit downstream of the cuff became narrow up to a site where the area suddenly expanded (elastic jump). Pressure losses across the cuff region decreased with increasing Q as the elastic jump approached the cuff, and the jump vanished when Q became subcritical. By altering prostatic cuff compliance and cuff pressure, we showed that an increase in opening pressures was associated with a steeper p-Q relationship. CONCLUSIONS: Using this mechanical analog, the measurements of p-A and p-Q relationships under various experimental conduit conditions validated our previous theoretical model of the male lower urinary tract. Both the experimental measurements and our previous theoretical model predictions indicate that an increase in opening pressure is associated with an increase in the slope of the p-Q relationship which becomes steeper with decreased cuff compliance. These data are in accordance with urodynamic findings in patients with benign prostatic hypertrophy (BPH) and suggest that a reduction in prostatic compliance exacerbates the severity of obstruction.

Adult↗

Viscoelasticity of the trachea and its effects on flow limitation.

To test the hypothesis that peak expiratory flow is determined by the wave-speed-limiting mechanism, we studied the time dependency of the trachea and its effects on flow limitation. For this purpose, we assessed the relationship between transmural pressure and cross-sectional area [the tube law (TL)] of six excised human tracheae under controlled conditions of static (no flow) and forced expiratory flow. We found that TLs of isolated human tracheae followed quite well the mathematical representation proposed by Shapiro (Shapiro AH. J Biomech Eng 99: 126-147, 1977) for elastic tubes. Furthermore, we found that the TL measured at the onset of forced expiratory flow was significantly stiffer than the static TL. As a result, the stiffer TL measured at the onset of forced expiratory flow predicted theoretical maximal expiratory flows far greater than those predicted by the more compliant static TL, which in all cases studied failed to explain peak expiratory flows measured at the onset of forced expiration. We conclude that the observed viscoelasticity of the tracheal walls can account for the measured differences between maximal and "supramaximal" expiratory flows seen at the onset of forced expiration.

Compliance↗

The distribution of ventilation during bronchoconstriction is patchy and bimodal: a PET imaging study.

Recent PET imaging data from bronchoconstricted sheep (Vidal Melo et al., 2005) showed that V /Q distributions were bimodal and topographically patchy, but including a substantial heterogeneity at scales <2.2 ml. In this paper, we reanalyze the experimental data to establish the contribution of ventilation (V (r)) heterogeneity to the bimodality in V /Q . This analysis demonstrates that the distribution of V (r) during bronchoconstriction was bimodal with large patches of severe hypoventilation occupying an average of 41% of the imaged lung. The degree of hypoventilation to these regions was highly correlated with the degree of oxygenation impairment, but was quite variable amongst animals in spite of consistent degrees of mechanical obstruction. Remarkably, those regions were found to be hyperventilated before methacholine and their degree of hyperventilation was correlated with their degree of hypoventilation during bronchoconstriction. These data suggest that improving the uniformity of ventilation at baseline may be a desirable therapeutic target if the risk of severe hypoxemia during asthma attacks is to be minimized and/or the distribution of inhaled pharmaceuticals is to be optimized.

Animals↗

Identifying airways responsible for heterogeneous ventilation and mechanical dysfunction in asthma: an image functional modeling approach.

We present an image functional modeling approach, which synthesizes imaging and mechanical data with anatomically explicit computational models. This approach is utilized to identify the relative importance of small and large airways in the simultaneous deterioration of mechanical function and ventilation in asthma. Positron emission tomographic (PET) images provide the spatial distribution and relative extent of ventilation defects in asthmatic subjects postbronchoconstriction. We also measured lung resistance and elastance from 0.15 to 8 Hz. The first step in image functional modeling involves mapping ventilation three-dimensional images to the computational model and identifying the largest sized airways of the model that, if selectively constricted, could precisely match the size and anatomic location of ventilation defects imaged by PET. In data from six asthmatic subjects, these airways had diameters <2.39 mm and mostly <0.44 mm. After isolating and effectively closing airways in the model associated with these ventilation defects, we imposed constriction with various means and standard deviations to the remaining airways to match the measured lung resistance and elastance from the same subject. Our results show that matching both the degree of mechanical impairment and the size and location of the PET ventilation defects requires either constriction of airways <2.4 mm alone, or a simultaneous constriction of small and large airways, but not just large airways alone. Also, whereas larger airway constriction may contribute to mechanical dysfunction during asthma, degradation in ventilation function requires heterogeneous distribution of near closures confined to small airways.

Adult↗

Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury.

RATIONALE: The prone position is used to improve gas exchange in patients with acute respiratory distress syndrome. However, the regional mechanism by which the prone position improves gas exchange in acutely injured lungs is still incompletely defined. METHODS: We used positron emission tomography imaging of [(13)N]nitrogen to assess the regional distribution of pulmonary shunt, aeration, perfusion, and ventilation in seven surfactant-depleted sheep in supine and prone positions. RESULTS: In the supine position, the dorsal lung regions had a high shunt fraction, high perfusion, and poor aeration. The prone position was associated with an increase in lung gas content and with a more uniform distribution of aeration, as the increase in aeration in dorsal lung regions was not offset by loss of aeration in ventral regions. Consequently, the shunt fraction decreased in dorsal regions in the prone position without a concomitant impairment of gas exchange in ventral regions, thus leading to a significant increase in the fraction of pulmonary perfusion participating in gas exchange. In addition, the vertical distribution of specific alveolar ventilation became more uniform in the prone position. A biphasic relation between regional shunt fraction and gas fraction showed low shunt for values of gas fraction higher than a threshold, and a steep linear increase in shunt for lower values of gas fraction. CONCLUSION: In a surfactant-deficient model of lung injury, the prone position improved gas exchange by restoring aeration and decreasing shunt while preserving perfusion in dorsal lung regions, and by making the distribution of ventilation more uniform.

Animals↗

Self-organized patchiness in asthma as a prelude to catastrophic shifts.

Asthma is a common disease affecting an increasing number of children throughout the world. In asthma, pulmonary airways narrow in response to contraction of surrounding smooth muscle. The precise nature of functional changes during an acute asthma attack is unclear. The tree structure of the pulmonary airways has been linked to complex behaviour in sudden airway narrowing and avalanche-like reopening. Here we present experimental evidence that bronchoconstriction leads to patchiness in lung ventilation, as well as a computational model that provides interpretation of the experimental data. Using positron emission tomography, we observe that bronchoconstricted asthmatics develop regions of poorly ventilated lung. Using the computational model we show that, even for uniform smooth muscle activation of a symmetric bronchial tree, the presence of minimal heterogeneity breaks the symmetry and leads to large clusters of poorly ventilated lung units. These clusters are generated by interaction of short- and long-range feedback mechanisms, which lead to catastrophic shifts similar to those linked to self-organized patchiness in nature. This work might have implications for the treatment of asthma, and might provide a model for studying diseases of other distributed organs.

Asthma↗

Topographic basis of bimodal ventilation-perfusion distributions during bronchoconstriction in sheep.

The distribution of ventilation-perfusion (VA/Q) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional VA/Q is quantified by three-dimensional positron emission tomography (PET) imaging of methacholine-induced bronchoconstriction in sheep. Regional VA/Q ratios were calculated from the imaged kinetics of intravenously injected 13NN-saline bolus, assembled into global VA/Q distributions, and used to estimate gas exchange. During bronchoconstriction, large regions with impaired tracer washout were observed adjacent to regions of normal ventilation. PET-derived VA/Q distributions during bronchoconstriction were consistently bimodal, with areas of low VA/Q receiving a large fraction of Q. The standard deviation of the VA/Q distribution was 38% lower if small-scale (subresolution) heterogeneity (< 2.2 cm3) was ignored. Arterial blood gases predicted from PET data correlated well with measured values for Pa(O2) (r2= 0.91, p < 0.01) and Pa(CO2) (r2= 0.90, p < 0.01). We conclude that the bimodality of VA/Q distributions in bronchoconstriction reflects the involvement of large contiguous regions of hypoventilation with substantial subresolution intraregional VA/Q heterogeneity. Assessment of the subresolution VA/Q heterogeneity is therefore essential to accurately quantify global gas exchange impairment during bronchoconstriction.

Animals↗

Enhanced parameter estimation from noisy PET data: Part II--evaluation.

RATIONALE AND OBJECTIVES: Positron emission tomography (PET) is a minimally invasive imaging modality that provides three-dimensional distribution data for a radioactive tracer concentration within the body. Local functional parameters are estimated from these images by fitting tracer kinetic data with mathematical models. However, in some applications, the reliability of parameter estimates may be hindered by the presence of noise. In the accompanying report in this issue of Academic Radiology, a novel method using principal component analysis (PCA) was presented and used for deriving parametric images of lung function from imaged tracer kinetics of intravenously injected nitrogen 13 (13NN) in saline solution. The PCA method averages 13NN concentrations from groups of voxels (volume elements) selected for their similarity in kinetics, rather than their spatial proximity. The goal of this study is to conduct a Monte Carlo simulation to evaluate the robustness to noise of parameters derived by means of the PCA method. MATERIALS AND METHODS: This evaluation involved: (1) generating "noise-free" synthetic PET images from experimental PET data, (2) adding noise to these images, (3) applying the PCA method to yield parametric images, and (4) comparing these parametric images with original noise-free images. RESULTS: Local parameters recovered by using the PCA method deviated from noise-free parameters on average by less than 1% for up to 32-fold of expected noise levels. These deviations were much less than those (>10%) recovered by using a direct curve-fitting method. CONCLUSION: The novel PCA approach provides robust parametric lung functional images while preserving the spatial resolution of the original images.

Humans↗

Positron emission tomography imaging of regional pulmonary perfusion and ventilation.

Positron emission tomography (PET) imaging is a noninvasive, quantitative method to assess pulmonary perfusion and ventilation in vivo. The core of this article focuses on the use of [13N]nitrogen (13N2) and PET to assess regional gas exchange. Regional perfusion and shunt can be measured with the 13N2-saline bolus infusion technique. A bolus of 13N2, dissolved in saline solution, is injected intravenously at the start of a brief apnea, while the tracer kinetics in the lung is measured by a sequence of PET frames. Because of its low solubility in blood, virtually all 13N2 delivered to aerated lung regions diffuses into the alveolar airspace, where it accumulates in proportion to regional perfusion during the apnea. In contrast, lung regions that are perfused but are not aerated and do not exchange gas (i.e., "shunting" units) do not retain 13N2 during apnea and the tracer concentration drops after the initial peak. Accurate estimates of regional perfusion and regional shunt can be derived by applying a mathematical model to the pulmonary kinetics of a 13N2-saline bolus. When breathing is resumed, specific alveolar ventilation can be calculated from the tracer washout rate, because 13N2 is eliminated almost exclusively by ventilation. Because of the rapid elimination of the tracer, 13N2 infusion scans can be followed by 13N2 inhalation scans that allow determination of regional gas fraction. This article describes insights into the pathophysiology of acute lung injury, pulmonary embolism, and asthma that have been gained by PET imaging of regional gas exchange.

Animals↗

Theoretical analysis of the effects of viscous losses and abdominal straining on urinary outlet function.

AIMS: The aim of this study was to theoretically explore the relationship between the tube law (TL) of the urethra and the pressure-flow (p-Q) relationship during micturition. The understanding of this relation is important for the evaluation of outlet obstruction by urodynamic interpretation of p-Q plots. METHODS: We simulated the outlet function by a lumped theoretical model, and suggested how the TL can be used to quantitatively predict the p-Q relationship of the system. Our analysis considered the relation between the TL and the steady state p-Q plot for various TLs including the hysteresis of the pressure-area relationship. RESULTS AND CONCLUSIONS: The inclusion of pressure losses distal to the flow controlling zone and experimentally measured p-A relations of the urethra in the model lead to the predictions that flow in the flow controlling zone is not always critical but is often in the sub-critical range, that an increase in abdominal pressure can increase the flow under certain conditions, and that hysteresis in the pressure-area relation is correlated to the hysteresis in the p-Q plot.

Abdomen↗

Mechanism by which a sustained inflation can worsen oxygenation in acute lung injury.

BACKGROUND: Sustained lung inflations (recruitment maneuvers [RMs]) are occasionally used during mechanical ventilation of patients with acute lung injury to restore aeration to atelectatic alveoli. However, RMs do not improve, and may even worsen, gas exchange in a fraction of these patients. In this study, the authors sought to determine the mechanism by which an RM can impair gas exchange in acute lung injury. METHODS: The authors selected a model of acute lung injury that was unlikely to exhibit sustained recruitment in response to a lung inflation. In five sheep, lung injury was induced by lavage with 0.2% polysorbate 80 in saline. Positron emission tomography and [13N]nitrogen were used to assess regional lung function in dependent, middle, and nondependent lung regions. Physiologic data and positron emission scans were collected before and 5 min after a sustained inflation (continuous positive airway pressure of 50 cm H2O for 30 s). RESULTS: All animals showed greater loss of aeration and higher perfusion and shunting blood flow in the dependent region. After the RM, Pao2 decreased in all animals by 35 +/- 22 mmHg (P < 0.05). This decrease in Pao2 was associated with redistribution of pulmonary blood flow from the middle, more aerated region to the dependent, less aerated region (P < 0.05) and with an increase in the fraction of pulmonary blood flow that was shunted in the dependent region (P < 0.05). Neither respiratory compliance nor aeration of the dependent region improved after the RM. CONCLUSIONS: When a sustained inflation does not restore aeration to atelectatic regions, it can worsen oxygenation by increasing the fraction of pulmonary blood flow that is shunted in nonaerated regions.

Animals↗

Quantification of regional ventilation-perfusion ratios with PET.

UNLABELLED: The topographic matching of alveolar ventilation (V(A)) and perfusion (Q) is the main determinant of gas exchange efficiency of the lung. However, no pulmonary functional imaging technique has been shown to predict whole-lung gas exchange in health and disease. This study aims to present a PET-based method to estimate regional alveolar ventilation-to-perfusion ratios (V(A)/Q) predictive of arterial blood gases. METHODS: The method is based on the regional tracer kinetics of (13)N-nitrogen ((13)NN) after an intravenous bolus injection during a breath-hold period and subsequent washout from the lungs with resumption of breathing. The method takes into account the presence of inter- and intraregional nonuniformities at length scales smaller than the imaging spatial resolution. An algorithm used regional tracer washout to classify regional V(A)Q/ uniformity. Intraregional V(A)/Q mismatch in nonuniform regions was described with a 2-compartment model. Regional V(A)/Q estimates were combined into a whole-lung distribution of V(A)/Q ratios and were used to compute global arterial blood gases. The method was applied to 3-dimensional PET data from anesthetized and mechanically ventilated sheep before and after methacholine bronchoconstriction (n = 3) and pulmonary embolism (n = 3) and after saline lung lavage (n = 3). RESULTS: PET images revealed regional changes in ventilation and perfusion consistent with the different disease models. Quantification of the images using PET-derived V(A)Q/ distributions showed unimodal and narrow distributions in control conditions that became wider and unimodal after pulmonary embolism and saline lung lavage and bimodal after bronchoconstriction. Images of regional gas exchange allowed for visualization of regional gas exchange. Arterial blood gases estimated from the PET-based V(A)/Q distributions closely agreed with measured values (partial pressure of oxygen, arterial [PaO(2)]: r(2) = 0.97, P < 0.001; partial pressure of carbon dioxide, arterial [PaCO(2)]: r(2) = 0.96, P < 0.001). CONCLUSION: Tracer kinetics analysis of PET images after an intravenous injection of (13)NN provides a quantitative assessment of regional V(A)/Q heterogeneity including that corresponding to length scales smaller than the spatial resolution of the imaging method. Quantification of V(A)/Q mismatch obtained with the presented technique is directly related to severity of gas exchange impairment as determined by arterial blood gases.

Algorithms↗

Changes in regional ventilation after autologous blood clot pulmonary embolism.

BACKGROUND: Previous studies have suggested that pulmonary embolism (PE) and pulmonary artery occlusion result in a shift in alveolar ventilation away from unperfused regions. This study aimed to directly assess changes in regional specific ventilation (sV(A)) due to autologous blood clot PE using positron emission tomography. METHODS: Pulmonary embolism was created in six anesthetized, paralyzed, and mechanically ventilated sheep by injecting cylindrical clots of autologous blood (7 mm in diameter and height). Clots were progressively infused into a central vein until a stable mean pulmonary artery pressure between 30 and 40 mmHg was achieved. A multislice positron emission tomography camera was used to image 15 contiguous, 6.5-mm-thick transverse cross-sections of the chest beginning just above the diaphragm. sV(A) from perfused regions (sV(A),(p)) was assessed as the ventilatory turnover rate of the tracer NN after central venous injection of NN-labeled saline. RESULTS: Pulmonary embolism obstructed flow to 64% of imaged areas. Before PE, (sV(A),(p))was equivalent in areas that would remain perfused and those that would become embolized after PE (0.021 +/- 0.007 0.021 +/- 0.006 s(-1); P = nonsignificant). After PE, sV(A),(p) of areas remaining perfused increased to 0.033 +/- 0.011 s (-1) (P < 0.005). This effect on regional sV(A),(p) could have been caused by active redistribution of sV(A),(p) or by a reduction in tracer concentration of perfused areas due to the dead space common to perfused and embolized regions. Model simulations indicated that the common dead-space effect could only explain a small part of the sV(A),(p) increase. CONCLUSIONS: An increase in sV(A),(p) of perfused regions occurs following PE with 7-mm autologous blood clots. This increase is most likely caused by a shift in ventilation away from embolized areas mediated by hypocapnic pneumoconstriction.

Algorithms↗

Topographical distribution of pulmonary perfusion and ventilation, assessed by PET in supine and prone humans.

Using positron emission tomography (PET) and intravenously injected (13)N(2), we assessed the topographical distribution of pulmonary perfusion (Q) and ventilation (V) in six healthy, spontaneously breathing subjects in the supine and prone position. In this technique, the intrapulmonary distribution of (13)N(2), measured during a short apnea, is proportional to regional Q. After resumption of breathing, regional specific alveolar V (sVA, ventilation per unit of alveolar gas volume) can be calculated from the tracer washout rate. The PET scanner imaged 15 contiguous, 6-mm-thick, slices of lung. Vertical gradients of Q and sVA were computed by linear regression, and spatial heterogeneity was assessed from the squared coefficient of variation (CV(2)). Both CV and CV were corrected for the estimated contribution of random imaging noise. We found that 1) both Q and V had vertical gradients favoring dependent lung regions, 2) vertical gradients were similar in the supine and prone position and explained, on average, 24% of Q heterogeneity and 8% of V heterogeneity, 3) CV was similar in the supine and prone position, and 4) CV was lower in the prone position. We conclude that, in recumbent, spontaneously breathing humans, 1) vertical gradients favoring dependent lung regions explain a significant fraction of heterogeneity, especially of Q, and 2) although Q does not seem to be systematically more homogeneous in the prone position, differences in individual behaviors may make the prone position advantageous, in terms of V-to-Q matching, in selected subjects.

Adult↗

Alterations in regional ventilation, perfusion, and shunt after smoke inhalation measured by PET.

Regional changes in ventilation and perfusion occurring in the early hours after smoke inhalation injury were evaluated through the use of positron emission tomography. Five lambs were imaged before and 1, 2, and 4 h after receiving 100 breaths of cotton smoke. Utilizing a recently developed model of (13)N tracer kinetics (3), we evaluated changes in ventilation, perfusion, shunt, and regional gas content in nondependent, middle, and dependent lung zones. The data demonstrated a progressive development of regional shunt in dependent (dorsal) regions in which perfusion remained the highest throughout the study. These findings, together with decreasing regional ventilation and fractional gas content in the dependent regions, correlated with decreasing arterial Pa(O(2)) values over the course of the study. A negative correlation between regional shunt fraction and regional gas content in dependent and middle regions suggests that shunt was caused by progressive alveolar derecruitment or flooding.

Animals↗