Pulmonary Capillary Blood Flow Research Articles

Blood Flow Heterogeneity and Oxygenation in the Lung: Effect of the Hypoxic Pulmonary Vasoconstriction Response Curve

The ability of the lung to take up oxygen can be characterized by its effective diffusing capacity, which is determined by the transport characteristics of the alveolar‐capillary membrane as well as heterogeneity of pulmonary blood flow. At rest, the healthy lung has a high degree of tolerance for pulmonary flow heterogeneity, but under conditions of physiological stress such as exercise, oxygen uptake may be inadequate to satisfy tissue demand if flow is very heterogeneous. We previously used a mathematical model of pulmonary oxygen uptake to examine the ability of hypoxic pulmonary vasoconstriction (HPV) to mitigate flow heterogeneity. In the model, flow heterogeneity is characterized by the coefficient of variation (CV) of pulmonary capillary blood flow. Assuming an initial lognormal distribution of blood flow with a normal level of heterogeneity (CV = 1.66), we simulate flow regulation over a range of oxygen consumption from rest to maximal exercise by adjusting pulmonary flow resistance in each vessel in accordance with an HPV response curve obtained from previously published experimental data. The effect of HPV on vessel flow resistance is assumed to be characterized by a sigmoidal response dependent on the capillary oxygen tension, which is approximated as the mean of the venous and arterial values in each pulmonary capillary; its maximal sensitivity occurs at a stimulus oxygen tension of approximately 30 torr. The purpose of the present study was to determine whether altering the shape of the HPV response curve would result in an improvement in CV reduction. Altering the HPV by shifting the sigmoidal curve to the right by 10 or 20 torr worsened CV, extraction and total pulmonary vascular resistance (PVR). Similar detrimental results were obtained when the range of oxygen tensions over which HPV varied was expanded by a factor of two, increasing the oxygen tension at which the sensitivity of HPV to oxygen tension was maximal. On the other hand, shrinking the range of variation of the HPV curve by a factor of two neither improved nor significantly worsened the CV or extraction, and resulted in a PVR distribution similar to the case of the normal HPV curve. These results demonstrate that the observed shape of the HPV response tends to minimize heterogeneity of pulmonary flow under conditions of exercise.

Физика и физиология вентиляционно-перфузионного сопряжения: обоснование и начальный опыт выбора конечно-экспираторного давления при механической вентиляции легких

Alveolar gas flow competition with pulmonary capillary blood flow for restricted space within lungs during mechanical ventilation, which is well known in respiratory physiology but neglected in everyday clinical practice, is thoroughly discussed in the paper. Anatomical and physiological conditions of oxygen and carbon dioxide counter-diffusion through alveolar-capillary barrier and the role of ventilation-perfusion relationship are described, and the possibility of blood flow displacement from opened alveoli with high pressure inside to poorly ventilated compartments of low intra-alveolar pressures is demonstrated. Commercially available metabolographic and real-time gas analysis monitors from different manufacturers were used for optimal PEEP adjustment by means of pulmonary VO2 and VCO2 shifts comparison, influence of patient volaemic status on the physiologic possibility of alveolar recruitment is discussed. Limitations of modern approach to the mechanical lung ventilation aimed at maximal lung opening in underlined and refuted with consideration on effective diffusion surface changes. Inefficacy of mechanical ventilation is especially obvious when acute respiratory failure follows ventilation-perfusion mismatch, like it appears in COVID-19. Partially it can explain discouraging mechanical ventilation outcomes during current pandemic.

Physics and Physiology of Ventilation-Perfusion Coupling: Substantiation and Initial Experience of End-Expiratory Pressure Choice During Mechanical Ventilation

Alveolar gas flow competition with pulmonary capillary blood flow for restricted space within lungs during mechanical ventilation, which is well known in respiratory physiology but neglected in everyday clinical practice, is thoroughly discussed in the paper. Anatomical and physiological conditions of oxygen and carbon dioxide counter-diffusion through alveolar-capillary barrier and the role of ventilation-perfusion relationship are described, and the possibility of blood flow displacement from opened alveoli with high pressure inside to poorly ventilated compartments of low intra-alveolar pressures is demonstrated. Commercially available metabolographic and real-time gas analysis monitors from different manufacturers were used for optimal PEEP adjustment by means of pulmonary VO2 and VCO2 shifts comparison, influence of patient volaemic status on the physiologic possibility of alveolar recruitment is discussed. Limitations of modern approach to the mechanical lung ventilation aimed at maximal lung opening in underlined and refuted with consideration on effective diffusion surface changes. Inefficacy of mechanical ventilation is especially obvious when acute respiratory failure follows ventilation-perfusion mismatch, like it appears in COVID-19. Partially it can explain discouraging mechanical ventilation outcomes during current pandemic Keywords: ventilation-perfusion relationship, mechanical ventilation, end-expiratory pressure, indirect calorimetry, metabolograph.

Characterizing the Effect of the Hypoxic Vasoconstriction Response Curve on Blood Flow Distribution and Oxygenation in the Lung

The ability of the lung to take up oxygen can be characterized by its effective diffusing capacity, which is determined by the transport characteristics of the alveolar‐capillary membrane as well as heterogeneity of pulmonary blood flow. At rest, the healthy lung has a high degree of tolerance for pulmonary flow heterogeneity, but under conditions of physiological stress such as exercise, oxygen uptake may be inadequate to satisfy tissue demand if flow is very heterogeneous. We previously used a mathematical model of pulmonary oxygen uptake to examine the ability of hypoxic pulmonary vasoconstriction (HPV) to mitigate flow heterogeneity. In the model, flow heterogeneity is characterized by the coefficient of variation (CV) of pulmonary capillary blood flow. Assuming an initial lognormal distribution of blood flow with a normal level of heterogeneity (CV = 1.66), we simulate flow regulation over a range of oxygen consumption from rest to maximal exercise by adjusting pulmonary flow resistance in each vessel in accordance with an HPV response curve obtained from previously published experimental data. The effect of HPV on vessel flow resistance is assumed to be characterized by a sigmoidal response dependent on the capillary oxygen tension, which is approximated as the mean of the venous and arterial values in each pulmonary capillary; its maximal sensitivity occurs at a stimulus oxygen tension of approximately 30 torr. The purpose of the present study was to determine whether altering the shape of the HPV response curve would result in an improvement in CV reduction. Altering the HPV by shifting the sigmoidal curve to the right by 10 or 20 torr worsened CV, extraction and total pulmonary vascular resistance (PVR). Similar detrimental results were obtained when the range of oxygen tensions over which HPV varied was expanded by a factor of two, increasing the oxygen tension at which the sensitivity of HPV to oxygen tension was maximal. On the other hand, shrinking the range of variation of the HPV curve by a factor of two neither improved nor significantly worsened the CV or extraction, and resulted in a PVR distribution similar to the case of the normal HPV curve. These results demonstrate that the observed shape of the HPV response tends to minimize heterogeneity of pulmonary flow under conditions of exercise.Support or Funding InformationSupported by NIH U01 HL133362.

Hypoxia‐induced depolarization of pulmonary arterial smooth muscle cells relies on simultaneous inhibition of K+‐currents and redox state alterations

Hypoxic pulmonary vasoconstriction (HPV) is a physiological response to localized alveolar hypoxia that is intrinsic to the pulmonary circulation. By hypoxia‐induced contraction of pulmonary arterial smooth muscle cells (PASMCs), pulmonary capillary blood flow is redirected to alveolar areas of high oxygen partial pressure (pO2), thus maintaining the ventilation‐perfusion ratio. Although the principle of HPV was recognized decades ago the underlying pathway still remains elusive.Voltage gated K+‐channels (Kv‐channels) are known to be redox‐sensitive and crucial for mediating membrane potential in PASMCs ‐ thereby controlling Ca2+‐entry and subsequently vascular tone. Here, we investigated whether acute hypoxia alters the redox state of isolated PASMCs from mice and if this impacts Kv‐channel activity, membrane potential and intracellular Ca2+‐ level.Kv‐currents and membrane potential in response to hypoxia or the oxidizing agent H2O2 were investigated by whole cell patch clamp experiments (voltage and current clamp, resp.) on freshly isolated murine PASMCs. Simultaneously, pO2 was recorded using an optical oxygen sensor and intracellular Ca2+ was measured by ratiometric FURA‐2 imaging. The redox state was monitored by Raman spectroscopy using an excitation wavelength that was in resonance with the hemeproteins (532 nm).Raman‐spectra values for reduced myoglobin (1607 cm−1) and cytochrome c (1622 cm−1) both increased upon exposure of PASMCs to hypoxia (4 % O2) and returned to the initial value upon reverting to normoxia (21 % O2), thus indicating a shift in the cells' redox state. In accordance, Kv‐currents were dose‐dependently inhibited by hypoxia and H2O2, resulting in a depolarization from −37,5 ± 2 mV (before) to −28.09 ± 2 mV after exposure to hypoxia (Mean ± SEM; n = 23; p = < 0,001; paired t‐test). The oxidizing agent H2O2 (124 nM) mimicked this effect under normoxic conditions by elevating the membrane potential of the PASMCs from −37.4 ± 3 mV (before) to −25,2 ± 4 mV upon application of 124 nM H2O2 (Mean ± SEM; n = 5, p = 0,005, paired t‐test) ‐ thereby triggering a rise in intracellular Ca2+.In conclusion, hypoxia induced a shift in redox state in PASMCs, thereby mediating the inhibition of KV‐channels. The resulting depolarization and Ca2+‐entry may account for the contraction of PASMCs – thus initiating HPV.Support or Funding InformationThis study was funded by the German Research Foundation (DFG, CRC 1213) and the Swedish Research Council (Grant 2016‐04220).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Modeling the Effect of Pulmonary Vascular Flow Regulation on Oxygen Uptake

Pulmonary oxygen uptake is affected by the transport characteristics of the alveolar‐capillary membrane as well as heterogeneity of pulmonary blood flow, both of which can limit the lung's capacity for oxygen transport as characterized by its effective diffusing capacity. In previous work, we showed that while under resting conditions the healthy lung has a high degree of tolerance for pulmonary flow heterogeneity, under conditions of exercise such flow heterogeneity can preclude the high levels of oxygen uptake necessary to meet tissue demand. The goal of the present study is to test the ability of hypoxic pulmonary vasoconstriction (HPV) to mitigate flow heterogeneity and enable adequate oxygen transport levels in the lung to meet tissue needs under conditions of exercise. A mathematical model of pulmonary oxygen uptake is used, in which flow heterogeneity is characterized by the coefficient of variation (CV) of pulmonary capillary blood flow. Assuming an initial lognormal distribution of blood flow with a high degree of heterogeneity, we simulate flow regulation in the cases of rest and exercise by adjusting pulmonary flow resistance in each vessel in accordance with previously published experimental data. The effect of HPV on vessel flow resistance is assumed to be characterized by a sigmoidal response dependent on the capillary oxygen tension, which is approximated as the mean of the venous and arterial values in each capillary. The results show a reduction in the effective CV from a baseline of 2.73 to 1.83 under resting conditions and to 0.66 in the case of exercise. The stronger reduction in heterogeneity under conditions of exercise corresponds to the need for greater flow regulation to minimize heterogeneity under conditions of physiologic stress. The predicted level of heterogeneity in exercise is in general agreement with our previous prediction of the upper limit of CV consistent with the levels of oxygen uptake in literature data for exercising humans. The results demonstrate the essential role of HPV to regulate flow and minimize heterogeneity under conditions of exercise and highlight the need for a functional pulmonary flow regulation mechanism under stressful or pathophysiological conditions.Support or Funding InformationSupported by NIH U01 HL133362.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A Study of Noninvasive Cardiac Output and Other Cardiorespiratory Parameters in Various Neurosurgical Positions

ABSTRACTBackgroundNeurosurgical patients are operated in supine, prone, lateral, and sitting positions, which cause physiological changes in cardiorespiratory parameters. Noninvasive cardiac output (NICO) monitor developed by Novametrix Medical System Inc is a noninvasive cardiac output monitor, which also measures and displays other parameters like stroke volume, cardiac index, pulmonary capillary blood flow, alveolar and dead space ventilation, peak flow rates, airway pressures, and respiratory volumes. We felt that a study using the NICO monitor in anesthetized patients undergoing neurosurgery in different positions would quantify the cardiopulmonary changes, identify risk factors, and improve intraoperative management.Materials and methodsA total of 40 consecutive patients undergoing neurosurgical procedures—20 in prone, 16 in lateral and 4 in sitting position—were studied. The hemodynamic and cardiorespiratory parameters were noted in supine position about 15 minutes after induction of general anesthesia using standard protocol and 15 minutes after giving surgical position using NICO monitor.ConclusionWe conclude that under anesthesia, the prone and sitting positions negatively affect derived cardiac parameters like cardiac output, cardiac index, and stroke volume, and lateral position tends to improve these parameters while the respiratory parameters are not significantly affected.How to cite this articleKarnik HS, Nerurkar AA, Bawankule N. A Study of Noninvasive Cardiac Output and Other Cardiorespiratory Parameters in Various Neurosurgical Positions. Res Inno Anaesth 2016;1(1):19-24.

Effect of protein arginine methyltransferase-1 inhibition on hypoxia-induced vasoconstriction

Hypoxia is defined as a decrease in the oxygen supply to a level below physiological levels which is insufficient to maintain cellular function, in the presence of unrestricted coronary inflow. It is one of the leading causes of global mortality and morbidity, due to its association with the pathology of cancer, cardiovascular disease and stroke. The common feature in these pathologies is the limitation of oxygen availability that participates in the development of these conditions. The pulmonary response to hypoxia, when hypoxia is localized, is hypoxic pulmonary vasoconstriction (HPV). HPV is a physiological and self-regulatory mechanism by which pulmonary capillary blood flow is automatically adjusted to alveolar ventilation for maintaining the optimal balance of ventilation and perfusion. In pathological conditions, HPV occurs as an acute episode during progressive critical illness or as a sustained response with vascular remodeling and pulmonary hypertension. Inspite of the hypoxia-induced shift in the redox status to a more oxidized state, the endothelium-dependent mediators of HPV that cause vasoconstrictor response to hypoxia include nitric oxide (NO), endothelin-1 and angiotensin-II. Indeed, in chronic hypoxia, due to the enhanced reactive oxygen species (ROS) generation, inhibition of endothelial nitric oxide synthase (eNOS) activity and reduced nitric oxide (NO) production there is an imbalance in the vasoconstriction–vasodilation status toward constriction. It is our hypothesis that, in hypoxic stress, a key player in initiating this imbalance is the enzyme, protein arginine methyltransferase-1 (PRMT1) which indirectly affects eNOS activity by increased production of asymmetric dimethylarginine (ADMA), a NOS-inhibitor. Thus, pharmacological inhibition of PRMT1 should restore the cellular and vascular homeostasis in hypoxic conditions.

Real-time in-vivo imaging of pulmonary capillary perfusion using probe-based confocal laser scanning endomicroscopy in pigs: An interventional laboratory study.

Little is known about real-time in-vivo microscopy of pulmonary capillary perfusion because current microscopy requires direct access to lung tissue with surgical intervention such as the thoracic-window technique and open-lung model. To evaluate if probe-based confocal laser scanning endomicroscopy (pCLE) via the trachea allows for real-time in-vivo visualisation of pulmonary capillary density and red blood cell (RBC) velocity in pigs. An interventional animal study. European University Hospital. Nine female domestic pigs (50 to 60 kg) were used. A pCLE probe was positioned in non-dependent, central and dependent lung zones in nine anaesthetised pigs (Alveoflex, Cellvizio, Maunakea, France). After intravenous administration of fluorescein isothiocyanate dextran as contrast agent repetitive pCLE videos were recorded during pressure-controlled ventilation (PCV) or continuous positive airway pressure for 3 min each. Using fluorescein isothiocyanate-labelled RBC erythrocyte velocities in pulmonary capillaries were quantified. Data are expressed as mean ± SD or median with interquartile range (IQR). Capillary density was greater in dependent and central as compared with non-dependent lung zones [[32 (29 to 34) %] and 32 (30 to 34) % vs. 28 (26 to 28) %, respectively, P < 0.05]. During PCV, RBC velocities were higher in larger lung capillaries [diameter >20 μm, 309 μm s(-1) (209 to 397)] than intermediate [diameter 10.1 to 20 μm, 146 μm s(-1) (118 to 235)] and small [diameter <10 μm, 153 μm s(-1) (117 to 236), P < .05]. During continuous positive airway pressure of 1.5 kPa, RBC velocities in dependent lung areas decreased to 47 μm s(-1) (30 to 82) compared with 198 μm s(-1) (148 to 290) during PCV (P < 0.05). pCLE allows endoscopic real-time in-vivo imaging of pulmonary capillary morphology and perfusion. Alterations in pulmonary capillary blood flow induced by different ventilator regimens can be detected. This minimally invasive approach via the endotracheal route is feasible in an experimental setting and may help to understand changes in regional pulmonary capillary perfusion.

Evaluation of the cardiopulmonary status using a noninvasive respiratory profile monitor in chronic obstructive lung disease patients during low-ventilation strategy

Patients with chronic obstructive pulmonary disease (COPD) patients are susceptible to complications, especially volutrauma, during the period of mechanical ventilation; low ventilation is a safe strategy to avoid these complications. Noninvasive capnography is a suitable technique for monitoring and assessing the cardiac and the pulmonary status of these patients during the period of mechanical ventilation. Assessment of the cardiac and the pulmonary status of two COPD patient groups receiving mechanical ventilation with a low tidal volume strategy using a noninvasive CO2 respiratory profile monitor (volumetric capnography). Forty patients were recruited in the respiratory ICU of Abbassia Chest Hospital; these patients were divided into two groups: 20 COPD patients with the predominant pathology of chronic bronchitis (CB) and 20 patients with the predominant pathology of emphysema disease, who presented with clinical and radiological evidence of chronic obstructive lung disease and were in need of mechanical ventilation. All the patients in the study were followed up three times per day until weaning; data were recorded on admission, after 24 h and before weaning using volumetric capnography. There was significant correlation between EtCO2 and arterial PCO2 during the whole period of mechanical ventilation in CB and emphysematous patients; the mean dead-space fraction was significantly higher in the emphysema group than in the CB group. There was a significant negative correlation between the mean values of Vd/Vt and the pulmonary capillary blood flow on admission and after 24 h in the emphysema group. The mean cardiac output, the mean stroke volume, and the pulmonary capillary blood flow increased significantly before extubation in the CB group, in contrast to the emphysema group in which there was an insignificant difference. Volumetric capnography could be helpful in assessing the severity of functional disturbances, and the use of more refined noninvasive parameters will be of value in managing and monitoring COPD patients during the whole period of mechanical ventilation. Egypt J Broncho 2014 8:44–50

Change in pulmonary blood volume changes pulmonary artery systolic storage

BackgroundA fraction of right ventricular stroke volume (pulmonary artery systolic storage, [PASS]), which is stored in pulmonary arteries during systole and then discharged to the capillaries, determines the diastolic pulmonary capillary blood flow and hence the capillary blood volume participating in gas diffusion. Possibility that increases in pulmonary blood volume (PBV) increase PASS, leading to an improved distribution of ventilation-to-perfusion ratios (V/Q ), was examined. Methods and resultsIncluded were 34 obese patients undergoing bariatric surgery. We used a nitrous oxide-airway-pneumotachographic method to measure PASS. The measurements were repeated before and after increasing PBV. In 20 patients, PBV was increased with infusion of crystalloids, which was guided by pulmonary capillary wedge pressure (PCWP). There was a good correlation between change in PASS and change in PBV (r2 = 0.741, P < 0.0001). However, when the baseline PASS was high, changes in PASS were much less. In patients with a pulmonary artery diastolic-pulmonary capillary wedge pressure gradient ≥6 mmHg, the baseline PASS was correlated with pulmonary venous resistance (r2 = 0.644, P = 0.017). In 14 patients, in whom PBV was increased with both changes in position and infusion of crystalloids, the physiologic dead space-to-tidal volume ratio (VD/VT) was measured as an index of the distribution of V/Q. There was a good negative correlation between PASS and VD/VT (r2 = 0.697, P < 0.0001). However, at a high baseline PASS, increases in PBV decreased PASS (P = 0.0006) and increased VD/VT (P = 0.0018). ConclusionsChanges in PBV change PASS and thereby the distribution of V/Q, depending on pulmonary venous resistance, which determines the baseline PASS.

Ventilation and gas exchange in patients with local forms of pulmonary tuberculosis

Summary. The aim of the study was to evaluate pulmonary function in patients with local forms of pulmonary tuberculosis. Ninety three patients with pulmonary tuberculosis and lesion extension ≥ 3 lung segments according to results of lung computed tomography (CT) were included in the study, of them, 21 patients with pulmonary infiltrates, 44 patients with tuberculoma, and 28 patients with cavitation. Spirometry, body plethysmography, measurement of single-breathe diffusion capacity of the lungs for carbon monoxide were performed in all the patients, additionally, perfusion scintigraphy of the lungs was performed in subgroup of 31 patients. Only 21 patients (23 %) had airflow limitation; 24 patients (26 %) had lung hyperinflation with residual volume 140 to 199 % pred. Most of patients (87 %) had reduced lung diffusion capacity; 6 patients with normal diffusion had decreased transfer-coefficient. Spearman's correlation analysis showed significant relationship between ventilation disorders and morphological features of lung lesions in CT scans. Diffusion capacity was significantly associated with morphological disorders of the lungs and with pulmonary capillary blood flow disorders according to perfusion scintigraphy results.

Pulmonary vascular disorders in chronic obstructive pulmonary disease as a target for therapeutic intervention

Summary. A model of chronic obstructive pulmonary disease (COPD) was reproduced in rats by intermittent inhalation of nitrogen dioxide for 60 days. Pulmonary vascular disorders were assessed by perfusion scintigraphy and measuring pulmonary artery smooth muscle reactivity under exposure of vasodilators. Disorders of pulmonary capillary blood flow occurred at early stages of COPD (15 days) and extended not only to segments but to lobes at 60 day of exposure. Dilatability of pulmonary arteries reduced that led to reduction of the smooth muscle relaxation amplitude in response to vasodilators with different mechanisms of action. Starting from 30th day, rats were given angioprotectors (rosuvastatin and sulodexide) to treat vascular disorders. Rosuvastatin did not improve pulmonary microcirculation and pulmonary artery smooth muscle reactivity. Administration of sulodexide resulted in improvement of pulmonary microcirculation with recruitment of reserve areas. Dilatable component of the pulmonary arteries increased leading to enhanced smooth muscle relaxation in response to isoproterenol and especially to nitrosorbide. So, we could assume sulodexide-dependent recovery of NO-dependent mechanism of pulmonary artery smooth muscle relaxation and partial restoration of β-adrenergic vasodilatation.

Increased pulmonary artery systolic storage associated with improved ventilation-to-perfusion ratios in acute respiratory distress syndrome

PurposeThe possibility that the increased pulmonary artery systolic storage (PASS) correlates with an improved distribution of ventilation/perfusion (VA/Q) and hence benefits gas exchange in acute respiratory distress syndrome (ARDS) was examined. Pulmonary artery systolic storage is the fraction of stroke volume stored in PA during systole and then discharged to the capillaries. The increased PASS can augment the diastolic pulmonary capillary blood flow (PCBF), which can then increase capillary blood volume participating in gas diffusion. We examined this by assessing the correlation between PASS and physiologic dead space to tidal volume (VD/VT) ratio. Materials and MethodsIncluded were 17 patients with ARDS. By using nitrous oxide-airway-pneumotachographic method, we measured the instantaneous PCBF, from which PASS was determined. Because PASS is the same as the flow volume of PCBF during diastole, PASS was determined from the flow volume of PCBF during diastole divided by the flow volume of PCBF during a whole cardiac cycle. The VD/VT ratio, used as an index of VA/Q, was measured by using the Bohr equation. ResultsThere was a good inverse correlation between PASS and VD/VT (r2 = 0.785, P < .0001). ConclusionsOur data indicate that the increased PASS correlates with an improved distribution of VA/Q and hence benefits gas exchange in ARDS.

Does pulmonary air embolism affect the pulsatility of pulmonary capillary blood flow in dogs?

The difference in the uptake rate through the lungs between nitrous oxide and oxygen has been shown to represent the pulmonary capillary blood flow (Qc). The pulsatility of Qc, defined as the ratio of maximum Qc and mean Qc (Qc max/Qc), the ratio of Qc max and stroke volume (Qc max/SV), and the ratio of systolic Qc and SV (Vsyst/SV), has been also shown to indicate the pulmonary vasodilation as well as vasoconstriction. We measured Qc by means of body plethysmography in dogs with pulmonary air embolism, in order to evaluate its effect on the pulmonary vasculature. Ten adult dogs were anesthetized with pentobarbital and pancuronium, and were mechanically ventilated. A volume of air (0.5 ml/kg) was injected into the central vein. Although there was no significant change in systemic blood pressure, cardiac output, heart rate, and airway pressure after the injection of air, pulmonary arterial pressure and pulmonary vascular resistance increased significantly. Qc, Qc max, Qc max/Qc, and Qc max/SV decreased significantly after the air injection. Since these findings suggest that the pulmonary air embolism provoked pulmonary vasoconstriction, and attenuated the pulsatility of Qc, optimal pulmonary vasodilation therapy would be recommended to improve the pulmonary hypertension secondary to pulmonary air embolism.

Étude non invasive du recrutement vasculaire pulmonaire lors de l’exercice musculaire

The in vivo study of the pulmonary microcirculation, and its recruitment, is currently not common, although it may be of interest. The intrabreath analysis (IB) of the carbon monoxide (CO) and acetylene (C(2)H(2)) diffusion is used to study the transfer of CO (TLCO) and the pulmonary capillary blood flow (Qs), particularly during exercise. The evolution of the Qs during different stages of exercise has never been reported in healthy subjects. The authors measured the Qs and TL at rest and then during and after short bouts of exercise in 12 healthy subjects. The Qs increased from 5.6 L/min at rest to 13.8 L/min during exercise while the TLCO increased from 11 to 16.7 mmol/kPa/min. A linear relationship was found between the Qs and the TLCO, with Qs values close to those obtained with other techniques. The Qs returned to rest values more rapidly than the TLCO (probably because of the membrane factor). Pulmonary vascular recruitment can be easily studied in healthy subjects. This parameter may be important in the study in pulmonary vascular diseases.

Pulmonary Capillary Blood Flow and Cardiac Output Measurement by Partial Carbon Dioxide Rebreathing in Patients with Acute Respiratory Distress Syndrome Receiving Lung Protective Ventilation

Pulmonary Capillary Blood Flow and Cardiac Output Measurement by Partial Carbon Dioxide Rebreathing in Patients with Acute Respiratory Distress Syndrome Receiving Lung Protective Ventilation

Measurement of Lung Diffusion and Cardiac Output with a Single Breath Gas Absorption Method During Graded Exercise Testing: Reference Values for Clinical Testing

Measurement of lung diffusion and cardiac output with a single breath gas absorption method during graded exercise testing: reference values for clinical testing. Objective: The evaluation of ventilation and gas exchange has become a standard part of clinical exercise testing. We sought to assess the practicality of integrating measurements of lung diffusion for carbon monoxide (DLCO) and non- invasive cardiac output (using pulmonary capillary blood flow QC) into our clinical graded exercise tests. Our objective was to define the responses in normal subjects so that impairment could be detected in patients suspected of having pulmonary or pulmonary vascular disease despite normal resting DLCO and QC. We conducted incremental exercise tests on 20 normal volunteers at 6 levels of exercise ranging between rest and 75% of their measured maximum. The investigational method is based on absorption of CO (for DLCO) and acetylene (for QC) into the pulmonary circulation during a single slow exhalation. The subjects averaged 35 years of age with a maximum work capacity of 76% of predicted maximum. Results: The values increased linearly with workload (QC in L/min = 3.5 + 6.5*VO2 in L/min, and DLCO in ml/min/mmHg = 18.7 + 10.2*VO2 in L/min). From baseline levels the QC increased more than two-fold and the DLCO increased by 50%. The mean deviation of individual measurements from the patient's regressed response was 9.9% and 6.6% respectively. Conclusions: We found the procedure easy to include in our standard graded exercise protocol and the single breath technique readily performed. Normative values were obtained for measurements expressed as a percentage of individual maximum and as actual VO2. At a moderate level of exercise (VO2 1.0 liter) the DLCO and QC should increase at least 20% and 65% respectively above baseline. Since the response of Qc and DLCO to progressive exercise offers pathophysiological information of clinical interest, its application can now be characterized in patients with different disorders including those with normal resting Qc and DLCO.

Pulmonary Capillary Blood Flow and Cardiac Output Measurement by Partial Carbon Dioxide Rebreathing in Patients with Acute Respiratory Distress Syndrome Receiving Lung Protective Ventilation

Partial carbon dioxide rebreathing noninvasively measures the pulmonary capillary blood flow and estimates the cardiac output with the use of a predicted shunt value. It has been reported that the accuracy of the method is decreased in patients with high pulmonary shunt. The aim of this study was to investigate the agreement between partial rebreathing and thermodilution for the determination of pulmonary capillary blood flow and cardiac output in the setting of acute respiratory distress syndrome. Twenty consecutive patients with the acute respiratory distress syndrome were enrolled. Ventilator settings include low tidal volume (6 ml x kg(-1)) and positive end-expiratory pressure + 2 cm H2O higher than the lower inflection point if present or 10 cm H2O if not. Seven pairs of cardiac output and pulmonary capillary blood flows were recorded every 20 min over a 2-h period. The authors determined bias, SD, limit of agreement (95% confidence interval) and percentage error. Bias and agreement for cardiac output measurement were 0.8 +/- 1.2 l x min(-1) (-2.1 to 3.7 l x min(-1)), and percentage error was 36%. Bias and agreement for pulmonary capillary blood flow measurement were -0.1 +/- 0.8 l x min(-1) (-2.1 to 1.9 l x min(-1)), and percentage error was 35%. Dead space, arteriovenous oxygen content difference, mean pulmonary arterial pressure, and baseline cardiac output were independently associated with differences between methods. In patients with the acute respiratory distress syndrome, partial rebreathing cannot yet replace thermodilution for measuring pulmonary capillary blood flow or cardiac output. However, accuracy of the method is close to the boundary of clinical relevance.

A Mathematical Physiological Model of the Pulmonary Capillary Perfusion

This study presents a stratified model that simulates the pulmonary capillary blood flow under influence of different lung volumes. The model includes capillary geometry, capillary wall elasticity, pressure exerted by the heart, blood viscosity, the effect of the chest wall and hydrostatic effects of the lung tissue and of the blood. The model simulates highly pulsatile blood flow with a heterogenous flow distribution down the lungs, in agreement with previous experimental studies. Moreover the model is in agreement with experimentally measured total capillary flow, total capillary volume, total capillary surface area and transition time of red blood cells passing through the pulmonary capillary network. The presented model is the first to describe the link between lung volume and perfusion.