Changes In Pulmonary Blood Flow Research Articles

Severe Lung Dysfunction and Pulmonary Blood Flow during Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is indicated for patients with severe respiratory and/or circulatory failure. The standard technique to visualize the extent of pulmonary damage during ECMO is computed tomography (CT). This single-center, retrospective study investigated whether pulmonary blood flow (PBF) measured with echocardiography can assist in assessing the extent of pulmonary damage and whether echocardiography and CT findings are associated with patient outcomes. All patients (>15 years) commenced on ECMO between 2011 and 2017 with septic shock of pulmonary origin and a treatment time >28 days were screened. Of 277 eligible patients, 9 were identified where both CT and echocardiography had been consecutively performed. CT failed to indicate any differences in viable lung parenchyma within or between survivors and non-survivors at any time during ECMO treatment. Upon initiation of ECMO, the survivors (n = 5) and non-survivors (n = 4) had similar PBF. During a full course of ECMO support, survivors showed no change in PBF (3.8 ± 2.1 at ECMO start vs. 7.9 ± 4.3 L/min, p = 0.12), whereas non-survivors significantly deteriorated in PBF from 3.5 ± 1.0 to 1.0 ± 1.1 L/min (p = 0.029). Tidal volumes were significantly lower over time among the non-survivors, p = 0.047. In prolonged ECMO for pulmonary septic shock, CT was not found to be effective for the evaluation of pulmonary viability or recovery. This hypothesis-generating investigation supports echocardiography as a tool to predict pulmonary recovery via the assessment of PBF at the early to later stages of ECMO support.

Modulation of pulmonary blood flow in patients with acute respiratory failure

BackgroundImpairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention. MethodsSingle-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings. ResultsTen 65 [56–75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO2/FiO2 from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 vs. 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO2/FiO2 increase (R2 = 0.50, p = 0.049). ConclusionsThe assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized in vivo. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.

Retracted: Chest digital dynamic radiography to detect changes in human pulmonary perfusion in response to alveolar hypoxia.

Hypoxic pulmonary vasoconstriction optimises oxygenation in the lung by matching the local-blood perfusion to local-ventilation ratio upon exposure to alveolar hypoxia. It plays an important role in various pulmonary diseases, but few imaging evaluations of this phenomenon in humans. This study aimed to determine whether chest digital dynamic radiography could detect hypoxic pulmonary vasoconstriction as changes in pulmonary blood flow in healthy individuals. Five Asian men underwent chest digital dynamic radiography before and after 60 sec breath-holding at the maximal inspiratory level in upright and supine positions. Alveolar partial pressure of oxygen and atmospheric pressure were calculated using the blood gas test and digital dynamic radiography imaging, respectively. To evaluate the blood flow, the correlation rate of temporal change in each pixel value between the lung fields and left cardiac ventricles was analysed. Sixty seconds of breath-holding caused a mean reduction of 26.7 ± 6.4 mmHg in alveolar partial pressure of oxygen. The mean correlation rate of blood flow in the whole lung was significantly lower after than before breath-holding (before, upright 51.5%, supine 52.2%; after, upright 45.5%, supine 46.1%; both P < 0.05). The correlation rate significantly differed before and after breath-holding in the lower lung fields (upright, 11.8% difference; supine, 10.7% difference; both P < 0.05). The mean radiation exposure of each scan was 0.98 ± 0.09 mGy. No complications occurred. Chest digital dynamic radiography could detect the rapid decrease in pulmonary perfusion in response to alveolar hypoxia. It may suggest hypoxic pulmonary vasoconstriction in healthy individuals.

Detection of Pulmonary Embolism Using a Novel Dynamic Flat-Panel Detector System in Monkeys.

Recently, dynamic chest radiography (DCR) was developed to evaluate pulmonary function using a flat-panel detector (FPD), which can evaluate blood flow in the pulmonary artery without injection of contrast agents. This study investigated the ability of a FPD to measure physiological changes in blood flow and to detect pulmonary embolism (PE) in monkeys.Methods and Results:DCR was performed in 5 monkeys using a FPD. Regions of interest (ROI) were placed in both lung fields of the image, and maximum changes in pixel value (∆pixel value) in the ROI were measured during 1 electrocardiogram cardiac cycle. Next, a PE model was induced using a Swan-Ganz catheter and additional images were taken. The ∆pixel value of the lungs in normal and PE models were compared in both supine and standing positions. The lung ∆pixel value followed the same cycle as the monkey electrocardiogram. ∆pixel values in the upper lung field decreased in the standing as compared to the supine position. In the PE model, the ∆pixel value decreased in the area of pulmonary blood flow occlusion and increased in the contralateral lung as compared to the normal model (normal model 1.287±0.385, PE model occluded side 0.428±0.128, PE model non-occluded side 1.900±0.431). A FPD could detect postural changes in pulmonary blood flow and its reduction caused by pulmonary artery occlusion in a monkey model.

Perioperative CTEPH patient monitoring with 2D phase-contrast MRI reflects clinical, cardiac and pulmonary perfusion changes after pulmonary endarterectomy.

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA.

Augmentation of pulmonary blood flow and cardiac output by non-invasive external ventilation late after Fontan palliation

ObjectivesAlthough a life-preserving surgery for children with single ventricle physiology, the Fontan palliation is associated with striking morbidity and mortality with advancing age. Our primary objective was to evaluate the...

Gas exchange calculation may estimate changes in pulmonary blood flow during veno-arterial extracorporeal membrane oxygenation in a porcine model.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used as rescue therapy for severe cardiopulmonary failure. We tested whether the ratio of CO2 elimination at the lung and the V-A ECMO (V̇co2ECMO/V̇co2Lung) would reflect the ratio of respective blood flows and could be used to estimate changes in pulmonary blood flow (Q̇Lung), i.e., native cardiac output. Four healthy pigs were centrally cannulated for V-A ECMO. We measured blood flows with an ultrasonic flow probe. V̇co2ECMO and V̇co2Lung were calculated from sidestream capnographs under constant pulmonary ventilation during V-A ECMO weaning with changing sweep gas and/or V-A ECMO blood flow. If ventilation-to-perfusion ratio (V̇/Q̇) of V-A ECMO was not 1, the V̇co2ECMO was normalized to V̇/Q̇ = 1 (V̇co2ECMONorm). Changes in pulmonary blood flow were calculated using the relationship between changes in CO2 elimination and V-A ECMO blood flow (Q̇ECMO). Q̇ECMO correlated strongly with V̇co2ECMONorm (r2 0.95–0.99). Q̇Lung correlated well with V̇co2Lung (r2 0.65–0.89, P < = 0.002). Absolute Q̇Lung could not be calculated in a nonsteady state. Calculated pulmonary blood flow changes had a bias of 76 (−266 to 418) mL/min and correlated with measured Q̇Lung (r2 0.974–1.000, P = 0.1 to 0.006) for cumulative ECMO flow reductions. In conclusion, V̇co2 of the lung correlated strongly with pulmonary blood flow. Our model could predict pulmonary blood flow changes within clinically acceptable margins of error. The prediction is made possible with normalization to a V̇/Q̇ of 1 for ECMO. This approach depends on measurements readily available and may allow immediate assessment of the cardiac output response.

Evaluation of a newly developed 2D parametric parenchymal blood flow technique with an automated vessel suppression algorithm in patients with chronic thromboembolic pulmonary hypertension undergoing balloon pulmonary angioplasty

To evaluate the feasibility of two-dimensional parametric parenchymal blood flow (2D-PPBF) to quantify perfusion changes in the lung parenchyma following balloon pulmonary angioplasty (BPA) for treatment of chronic thromboembolic pulmonary hypertension. Overall, 35 consecutive interventions in 18 patients with 98 treated pulmonary arteries were included. To quantify changes in pulmonary blood flow using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed using dedicated software. A reference region of interest (ROI; arterial inflow) in the treated pulmonary artery and a distal target ROI, including the whole lung parenchyma distal to the targeted stenosis, were placed in corresponding areas on DSA pre- and post-BPA. Half-peak density (HPD), wash-in rate (WIR), arrival to peak (AP), area under the curve (AUC), and mean transit time (MTT) were assessed. The ratios of the reference ROI to the target ROI (HPDparenchyma/HPDinflow, WIRparenchyma/WIRinflow; APparenchyma/APinflow, AUCparenchyma/AUCinflow, MTTparenchyma/MTTinflow) were calculated. The relative differences of the 2D-PPBF parameters were correlated to changes in the pulmonary flow grade score. The pulmonary flow grade score improved significantly after BPA (1 versus 3; p<0.0001). Likewise, the mean HPDparenchyma/HPDinflow (-10.2%; p<0.0001), APparenchyma/APinflow (-24.4%; p=0.0007), and MTTparenchyma/MTTinflow (-3.5%; p=0.0449) decreased significantly, whereas WIRparenchyma/WIRinflow (+82.4%) and AUCparenchyma/AUCinflow (+58.6%) showed a significant increase (p<0.0001). Furthermore, a significant correlation between changes of the pulmonary flow grade score and changes of HPDparenchyma/HPDinflow (ρ=-0.21, p=0.04), WIRparenchyma/WIRinflow (ρ=0.43, p<0.0001), APparenchyma/APinflow (ρ=-0.22, p=0.03), AUCparenchyma/AUCinflow (ρ=0.48, p<0.0001), and MTTparenchyma/MTTinflow (ρ=-0.39, p<0.0001) could be observed. The 2D-PPBF technique is feasible for the quantification of perfusion changes following BPA and has the potential to improve monitoring of BPA.

Thrombolytic and Anticoagulant Therapy for Pulmonary Embolism with High and Intermendiate Risk of Early Death. Part 3. An Effect on Pulmonary Perfusion with High and Intermediate Risk of Early Death

Background The advantage of thrombolytic therapy (TLT) over anticoagulant therapy(ACT) in patients with a high risk of early death (hemodynamic disorders) in acute pulmonary embolism is considered proven. But the advantage of thrombolytic therapy over anticoagulant therapy remains uncertain in patients with an intermediate risk. Perfusion lung scintigraphy helps provide a quantitative comparison of changes in pulmonary blood flow with the use of different treatment methods in subgroups of high and intermediate risk of an adverse outcome.The aim of study is to compare the effectiveness of thrombolytic and anticoagulant therapy in the treatment of acute pulmonary embolism in patients with a high and intermediate risk of early death in terms of the dynamics of pulmonary perfusion disorders.Study design: a prospective non-randomized study. The introduction of a thrombolytic was cosidered as intervention. The comparison group consisted of patients who received an anticoagulant. Thrombolysis in patients with intermediate risk was indicated in the absence of a potential threat of hemorrhagic complications, a deficit of pulmonary perfusion above 40%, a high level of pulmonary hypertension and a high probability of cardiac decompensation. The method of comparison was the quantitative result of pulmonary perfusion deficiency.Description of the method Radionuclide and CT studies were carried out using a hybrid system SPECT/CT Discovery NM/CT 670 (GE, USA): the perfusion was evaluated with 80–120 MBq of 99mTc macrotech radiopharmaceutical (RP) (effective equivalent dose of 0.8–1.3 mSv), CT angiography was performed with 70–100 ml of radiopaque substance Visipaque (effective equivalent dose of irradiation 9.4–10.3 mSv). The accumulation deficit of an area equal to a segment was counted as a perfusion deficiency of 5% (subsegmental 2.5%), inferior lobe — 25%, an area equal to the right lung — 55%, the left lung — 45%.Characteristics of the sample In a sample of 503 patients who received treatment at the Intensive Care Unit for Surgical Patients of the N.V. Sklifosovsky Institute for Emergency Medicine from 2011 to 2016, the overall mortality rate was 14.7% (95% CI 11.7; 18.1) (74/503); anticoagulation therapy — 17.8% (95% CI 13.5; 22.8) (50/281); thrombolytic therapy — 10.8% (95% CI 7.1; 15.6) (24/222); p=0.031, Fisher’s test, P=0.60. At a high risk of death, the mortality rate in the thrombolytic therapy group was 30.2% (19/63) versus 47.1% (32/68) in the anticoagulant therapy group; p=0.051, the Fisher’s test; P=0.51. At an intermediate risk, it was 3.2% (5/158) and 8.4% (8/214); p=0.049, the Fisher’s test, P=0.54. Changes in pulmonary perfusion deficiency as a result of treatment were performed in 169 patients who promptly underwent a primary and repeated dynamic scintigraphic study: 127 patients after thrombolysis (of which 38 patients had a high risk and 88 had an intermediate risk) and 42 patients who were treated with an anticoagulant (5 — high risk, 37 — intermediate risk). The groups did not differ in age and gender composition: the mean age was 59±16; Me 61 (49; 71) and 57±14 years; Me 58 (43; 67), respectively; p=0.50 (Mann–Whitney test); men/women: 50/77 and 12/30; p=0.27, the Fisher’s test. The groups differed in the presence of cancer: in the ACT group, the proportion of patients with cancer was 21.4% (9/42), and in the TLT group it was 4.7% (6/127), p=0.003, the Fisher’s test, P=0.85.Results Patients of high and intermediate risk, who received thrombolysis, were in a significantly more serious condition in terms of baseline characteristics. Both methods of treatment were effective. In high-risk patients, perfusion deficiency regressed: from 57±10% (Me 60 (50; 65)) to 31±15% (Me 30 (20; 40)), p&lt;0.00001 (Wilcoxon test), Es=2.08, P=1.00 after TLT; from 38±9% (Me 40 (35; 40)) to 14±8% (Me 10 (10; 20)), p=0.043 (Wilcoxon test), Es=2.72, P=0.93 after ACT. In patients with intermediate risk, perfusion deficiency regressed: from 48±9% (Me 50 (40, 55)) to 24±13% (Me 20 (15; 30)), p&lt;0.00001 (Wilcoxon test) after TLT; from 38±11% (Me 40 (30; 45)) to 24±15% (Me 15 (15; 30)), p=0.00003 (Wilcoxon test) after ACT. The effect size for TLT was Es=2.16, for ACT Es=1.13. The power of the study was P=1.00 and P=0.99.Conclusion Thrombolytic therapy was more effective in restoring pulmonary perfusion compared to anticoagulants in patients with an intermediate risk of early death: the effect of thrombolysis was greater than that of anticoagulant therapy (Es=2.16 and Es=1.13). The absence of the effect of restoring pulmonary perfusion during thrombolysis was noted less frequently compared to the results of anticoagulant therapy: in 5.5% (95% CI 2.2–11.0) vs. 19.0% (95% CI 8.6–34.1).

Cardio-pulmonary MRI for detection of treatment response after a single BPA treatment session in CTEPH patients

Chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with balloon pulmonary angioplasty (BPA) in inoperable patients. Sensitive non-invasive imaging methods are missing to detect treatment response after a single BPA treatment session. Therefore, the aim of this study was to measure treatment response after a single BPA session using cardio-pulmonary MRI. Overall, 29 patients with CTEPH were examined with cardio-pulmonary MRI before and 62 days after their initial BPA session. Pulmonary blood flow (PBF), first-pass bolus kinetic parameters, and biventricular mass and function were determined. Multiple linear regression analysis was implemented to estimate the relationship of PBF change in the treated lobe with treatment change of full width at half maximum (FWHM), cardiac output (CO), ventricular mass index (VMI), pulmonary transit time (PTT) and PBF change in the non-treated lobes. Paired Wilcoxon rank sum test and Spearman rho correlation were used. After BPA regional PBF increased in the treated lobe (p < 0.0001) as well as in non-treated lobes (p = 0.015). PBF treatment changes in the treated lobe were significantly larger compared with the non-treated lobes (p = 0.0049). Change in NT proBNP, MRI-derived mean pulmonary artery pressure (mPAP), PTT, FWHM, right ventricular (RV) ejection fraction, RV stroke volume, CO, VMI and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05). PBF changes in the treated lobe were independently predicted by PTT as well as PBF change in the non-treated lobes. Cardio-pulmonary MRI detects and quantifies treatment response after a single BPA treatment session. • Two months after BPA regional parenchymal pulmonary perfusion (PBF) increased in the total lung parenchyma (p = 0.005), the treated lobes (p < 0.0001) and non-treated lobes (p = 0.015). • The PBF treatment changes in the treated lobe were significantly larger than in the non-treated lobes (p = 0.0049). • Change in NT proBNP, MRI-derived mean pulmonary artery pressure, pulmonary transit time, full width at half maximum, right ventricular (RV) ejection fraction, RV stroke volume, cardiac output, ventricular mass index and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05).

Haemodynamic effects of prenatal caffeine on the cardiovascular transition in ventilated preterm lambs.

BackgroundCaffeine is routinely given to preterm infants hours after birth to treat apnea of prematurity. In view of it’s success, earlier administration in the delivery room is being considered, but little is known about how caffeine may effect the cardiovascular changes during the fetal to neonatal transition. Our aim was to determine the effect of prenatal caffeine administration on haemodynamic parameters in ventilated preterm lambs immediately after birth.MethodsCatheters (carotid artery and jugular vein) and ultrasonic flow probes (pulmonary artery and carotid artery) were implanted in preterm lambs (~126 ±2 days of gestation; term is 147 days), immediately before delivery by caesarean section. Before the cord was clamped, lambs were intubated and a caffeine (10mg/kg caffeine-base; n = 9) or saline (n = 5) infusion was given intravenously to the ewe and lamb over a 15-minute period. Two minutes after clamping the cord, ventilation commenced with a sustained inflation (35 cm H2O for 30 seconds) followed by ventilation for 30 minutes (target tidal volume of 6-8ml/kg).ResultsBlood gas parameters and rectal body temperature were not different between the two groups. Changes in pulmonary blood flow (PBF) and carotid blood flow (CBF) did not differ significantly between groups. PBF increased significantly after ventilation onset in both groups (caffeine p = 0.022, saline p <0.001) and remained elevated thereafter. CBF did not increase but decreased after SI in the caffeine group. Blood pressure, heart rate, and peripheral oxygen saturation did not differ between groups at any stage of the study.ConclusionPrenatal caffeine infusion had no significant effect on acute haemodynamic parameters in ventilated preterm lambs during the cardiorespiratory transition.

Hemodynamic Evaluation of Children with Persistent or Recurrent Pulmonary Arterial Hypertension Following Complete Repair of Congenital Heart Disease.

Persistent or recurrent pulmonary arterial hypertension (PAH) following complete surgical repair of congenital heart disease (CHD) represents one of the largest group of PAH associated with CHD (PAH-CHD) in recent registry studies and seems to have a particularly poor prognosis. However, little is known about this fourth clinical subclass of PAH-CHD, especially in children. The purpose of this study was to assess specific characteristics of invasive hemodynamics of this disease in children, including acute vasodilator testing (AVT) and pulmonary endothelial function (PEF) and to compare to patients with idiopathic PAH (IPAH), who usually present with a similar fatal clinical course. Thirty-two children with PAH were included in the study, twelve of these patients had PAH-CHD subclass 4 (mean age 8.0±3.4years) and twenty children had IPAH (mean age 8.6±4.4years). Cardiac catheterization was performed in all children, including AVT and PEF. PEF was assessed by changes in pulmonary blood flow in response to acetylcholine (Ach) using Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. At baseline, the ratio of mean PA pressure to mean systemic arterial pressure (mPAP/mSAP) was comparably high in both groups (0.78±0.32 vs. 0.80±0.22), while the indexed pulmonary vascular resistance (PVRI) was significantly lower in the PAH-CHD group (12.6±6.8WUxm2) compared to IPAH patients (19.9±10.6WUxm2) (p=0.04). Cardiac index was significantly higher in the PAH-CHD group (4.19±1.09l/min/m2 vs. 3.23±0.76) (p=0.017). However, AVT revealed a significantly larger maximum response (percentage of fall of PVR/SVR ratio during AVT) in the IPAH group (37±22%) compared to the PAH-CHD group (13±23%) (p=0.017). PEF showed no significant difference between both patient groups (PFR 1.69±0.71 vs. 1.73±0.68) (p=0.76). Our study demonstrates significant pulmonary vascular disease in children with persistent or recurrent PAH following complete surgical repair of CHD similar to IPAH patients. Although baseline measures appeared to be more favorable, pulmonary vasoreactivity was markedly impaired in PAH-CHD subclass 4, which may contribute to its negative impact on the long-term outcome of this patient group.

Chronic thromboembolic pulmonary hypertension: Evaluation of 2D-perfusion angiography in patients who undergo balloon pulmonary angioplasty.

To evaluate the feasibility of 2D-perfusion angiography (2D-PA) in order to quantify perfusion changes of the lung parenchyma pre- and post-balloon pulmonary angioplasty (BPA). Thirty consecutive interventions in 16 patients with 99 treated pulmonary artery segments were included. To quantify changes in pulmonary blood flow using 2D-PA, the acquired digital subtraction angiographies (DSA) pre- and post-BPA were post-processed. A reference ROI in the treated pulmonary artery and a distal target ROI in the lung parenchyma were placed in corresponding areas on DSA pre- and post-BPA. Time to peak (TTP), peak density (PD) and area under the curve (AUC) were assessed. The ratios reference ROI to target ROI (TTPparenchyma/TTPinflow; PDparenchyma/PDinflow; AUCparenchyma/AUCinflow) were calculated. Relative differences of the 2D-PA parameters were correlated to changes in the pulmonary-flow-grade-score. The pulmonary-flow-grade-score improved after BPA (p<0.0001). Likewise, the ratio TTPparenchyma/TTPinflow shortened by 10% (p=0.0002), the PDparenchyma/PDinflow increased by 46% (p<0.0001) and the AUCparenchyma/AUCinflow increased by 36% (p<0.0001). A significant correlation between changes in the pulmonary-flow-grade-score and changes in PDparenchyma/PDinflow (ρ=0.48, p<0.0001) and AUCparenchyma/AUCinflow (ρ=0.31, p=0.0018) was observed. Quantification of pulmonary perfusion pre- and post-BPA using 2D-PA is feasible and has the potential to improve monitoring of BPA. • Quantification of BPA results by use of 2D-PA is feasible. • 2D-PA allows objective assessment of changes in lung parenchymal perfusion. • 2D-PA has the potential to optimize BPA.

Vagal denervation inhibits the increase in pulmonary blood flow during partial lung aeration at birth.

Lung aeration at birth significantly increases pulmonary blood flow, which is unrelated to increased oxygenation or other spatial relationships that match ventilation to perfusion. Using simultaneous X-ray imaging and angiography in near-term rabbits, we investigated the relative contributions of the vagus nerve and oxygenation to the increase in pulmonary blood flow at birth. Vagal denervation inhibited the global increase in pulmonary blood flow induced by partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect. The results of the present study indicate that a vagal reflex may mediate a rapid global increase in pulmonary blood flow in response to partial lung aeration. Air entry into the lungs at birth triggers major cardiovascular changes, including a large increase in pulmonary blood flow (PBF) that is not spatially related to regional lung aeration. To investigate the possible underlying role of a vagally-mediated stimulus, we used simultaneous phase-contrast X-ray imaging and angiography in near-term (30days of gestation) vagotomized (n=15) or sham-operated (n=15) rabbit kittens. Rabbits were imaged before ventilation, when one lung was ventilated (unilateral) with 100% nitrogen (N2 ), air or 100% oxygen (O2 ), and after all kittens were switched to unilateral ventilation in air and then ventilation of both lungs using air. Compared to control kittens, vagotomized kittens had little or no increase in PBF in both lungs following unilateral ventilation when ventilation occurred with 100% N2 or with air. However, relative PBF did increase in vagotomized animals ventilated with 100% O2 , indicating the independent stimulatory effects of local oxygen concentration and autonomic innervation on the changes in PBF at birth. These findings demonstrate that vagal denervation inhibits the previously observed increase in PBF with partial lung aeration, although high inspired oxygen concentrations can partially mitigate this effect.

Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD

ABSTRACTThere is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation (E)/CO2 output (CO2) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake (O2), higher E/CO2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak O2 and worse dyspnea were found in patients with higher E/CO2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-O2 exercise (p < 0.05). Higher E/CO2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = −0.72) and blunted changes in PBF from rest to exercise (r = −0.69) (p < 0.01). Ventilation “wasted” in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (DLCO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

The fetal circulation, pathophysiology of hypoxemic respiratory failure and pulmonary hypertension in neonates, and the role of oxygen therapy.

Neonatal hypoxemic respiratory failure (HRF), a deficiency of oxygenation associated with insufficient ventilation, can occur due to a variety of etiologies. HRF can result when pulmonary vascular resistance (PVR) fails to decrease at birth, leading to persistent pulmonary hypertension of newborn (PPHN), or as a result of various lung disorders including congenital abnormalities such as diaphragmatic hernia, and disorders of transition such as respiratory distress syndrome, transient tachypnea of newborn and perinatal asphyxia. PVR changes throughout fetal life, evident by the dynamic changes in pulmonary blood flow at different gestational ages. Pulmonary vascular transition at birth requires an interplay between multiple vasoactive mediators such as nitric oxide, which can be potentially inactivated by superoxide anions. Superoxide anions have a key role in the pathophysiology of HRF. Oxygen (O2) therapy, used in newborns long before our knowledge of the complex nature of HRF and PPHN, has continued to evolve. Over time has come the discovery that too much O2 can be toxic. Recommendations on the optimal inspired O2 levels to initiate resuscitation in term newborns have ranged from 100% (pre 1998) to the currently recommended use of room air (21%). Questions remain about the most effective levels, particularly in preterm and low birth weight newborns. Attaining the appropriate balance between hypoxemia and hyperoxemia, and targeting treatments to the pathophysiology of HRF in each individual newborn are critical factors in the development of improved therapies to optimize outcomes.

Increase in pulmonary blood flow at birth: role of oxygen and lung aeration.

Lung aeration stimulates the increase in pulmonary blood flow (PBF) at birth, but the spatial relationships between PBF and lung aeration and the role of increased oxygenation remain unclear. Using simultaneous phase-contrast X-ray imaging and angiography, we have investigated the separate roles of lung aeration and increased oxygenation in PBF changes at birth using near-term (30 days of gestation) rabbit kits (n = 18). Rabbits were imaged before ventilation, then the right lung was ventilated with 100% nitrogen (N2), air or 100% O2 (oxygen), before all kits were switched to ventilation in air, followed by ventilation of both lungs using air. Unilateral ventilation of the right lung with 100% N2 significantly increased heart rate (from 69.4 ± 4.9 to 93.0 ± 15.0 bpm), the diameters of both left and right pulmonary axial arteries, number of visible vessels in both left and right lungs, relative PBF index in both pulmonary arteries, and reduced bolus transit time for both left and right axial arteries (from 1.34 ± 0.39 and 1.81 ± 0.43 s to 0.52 ± 0.17 and 0.89 ± 0.21 s in the left and right axial arteries, respectively). Similar changes were observed with 100% oxygen, but increases in visible vessel number and vessel diameter of the axial arteries were greater in the ventilated right lung during unilateral ventilation. These findings confirm that PBF increase at birth is not spatially related to lung aeration and that the increase in PBF to unventilated regions is unrelated to oxygenation, although oxygen can potentiate this increase.

Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection.

In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (-10%; range: -52.2% to 4.0%; P < 0.01), 20 minutes (-17.4%; -27.9% to 0.0%; P < 0.01), and 30 minutes (-8.5%; -34.4% to 2.0%; P < 0.01) after CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold.

Echocardiographic Assessment of the Alterations in Pulmonary Blood Flow Associated with Ketamine and Etomidate Administration in Children with Tetralogy of Fallot.

Despite widespread uses of ketamine, the clinical studies determining its effect on pulmonary blood flow in children with tetralogy of Fallot (TOF) are lacking. Furthermore, the quantification of pulmonary blood flow is not possible in these patients, because pulmonary artery catheter is contraindicated. Therefore, the purpose of this study was to evaluate the changes in pulmonary blood flow by intra-operative transesophageal echocardiography after ketamine or etomidate administration in children with TOF. Eleven children each in the two clinical variants of TOF (group A-moderate to severe cyanosis; group B-mild to minimal cyanosis) undergoing intracardiac repair were prospectively studied after endotracheal intubation. A single bolus dose of ketamine (2mg/kg) and etomidate (0.3mg/kg) was administered in a random order after 15minute interval. Hemodynamic, arterial blood gas, and echocardiographic measurements were obtained at 7 consecutive times (T) points (baseline, 1, 2, 4, 6, 8, and 15minutes after drug administration). Ketamine produced a significant reduction in VTI-T (velocity time integrals total of left upper pulmonary vein), RVOT-PG (right ventricular outflow tract peak gradient), and MG (mean gradient) in group A while those in group B had a significant increase in VTI-T, RVOT-PG, and RVOT-MG at time (T1, T2, T4, and T6; P=0.00). This divergent behavior, however, was not observed with etomidate. Etomidate does not change pulmonary blood flow. However, ketamine produces divergent effects; it increases pulmonary blood flow in children with minimal cyanosis and decreases pulmonary blood flow in children with moderate to severe cyanosis.

In vivo support for the new concept of pulmonary blood flow-mediated CO2 gas excretion in the lungs.

To further examine the validity of the proposed concept of pulmonary blood flow-dependent CO2 gas excretion in the lungs, we investigated the effects of intramediastinal balloon catheterization-, pulmonary artery catheterization-, or isoprenaline (ISP)-induced changes in pulmonary blood flow on the end-expiratory CO2 gas pressure (PeCO2 ), the maximal velocity of the pulmonary artery (Max Vp), systemic arterial pressure, and heart rate of anesthetized rabbits. We also evaluated the changes in the PeCO2 in clinical models of anemia or pulmonary embolism. An almost linear relationship was detected between the PeCO2 and Max Vp. In an experiment in which small pulmonary arteries were subjected to stenosis, the PeCO2 fell rapidly, and the speed of the reduction was dependent on the degree of stenosis. ISP produced significant increases in the PeCO2 of the anesthetized rabbits. Conversely, treatment with piceatannol or acetazolamide induced significant reductions in the PeCO2 . Treatment with a cell surface F1/FO ATP synthase antibody caused significant reductions in the PeCO2 itself and the ISP-induced increase in the PeCO2 . Neither the PeCO2 nor SAP was significantly influenced by marked anemia [%hematocrit (Ht), 70 ∼ 47%]. On the other hand, in the presence of less severe anemia (%Ht: 100 ∼ 70%) both the PeCO2 and SAP fell significantly when the rabbits' blood viscosity was decreased. The rabbits in which pulmonary embolisms were induced demonstrated significantly reduced PeCO2 values, which was compatible with the lowering of their Max Vp. In conclusion, we reaffirm the validity of the proposed concept of CO2 gas exchange in the lungs.