Effects of Dexmedetomidine in Improving Oxygenation and Reducing Pulmonary Shunt in High-Risk Pediatric Patients Undergoing One-Lung Ventilation for Thoracic Surgery: A Double-Blind Randomized Controlled Trial.

Background and objectives Pediatric thoracic surgery has unique considerations due to the immaturity of the respiratory system anatomically and physiologically, which presents technical and pharmacological considerations, including the very common technique of one-lung ventilation (OLV), which causes serious complications in children. Therefore, we investigated the effects of dexmedetomidine on oxygenation and pulmonary shunt fraction (Qs/Qt) in high-risk pediatric patients undergoing OLV for thoracic surgery. This randomized controlled trial aimed to investigate dexmedetomidine's effect on the partial pressure of arterial oxygen (PaO2) and pulmonary shunt fraction (Qs/Qt). Methods A total of 63 children underwent thoracic surgery with OLV and were divided into two groups. The dexmedetomidine group (group Dex, n = 32) received dexmedetomidine (0.4 µg/kg/hour), and the placebo group (group placebo, n = 31) received normal saline. Two arterial and central venous blood samples were taken for arterial and venous blood gas analysis at four time points: T1 (10 minutes after mechanical ventilation of total lung ventilation), T2 (10 minutes after OLV), T3 (60 minutes after OLV), and T4 (20 minutes after the end of OLV). At these intervals, the following parameters were measured: PaO2, Qs/Qt, mean arterial pressure (MAP), heart rate (HR), and peak inspiratory pressure (PIP). Results The two groups had no significant differences in FEV1/FVC and baseline pulmonary shunt fraction (Qs/Qt). Dexmedetomidine significantly improved PaO2 compared with placebo during OLV (T2 and T3). There was a significant decrease in Qs/Qt compared with placebo during OLV (T2, T3, and T4). There was a decrease in PIP compared with placebo during OLV (T2 and T3). No statistically significant differences in MAP or HR were observed between the groups. Conclusion Infusion of dexmedetomidine during OLV in high-risk pediatric thoracic surgery reduces shunt and pulmonary shunt fraction Qs/Qt, improves PaO2 and body oxygenation, reduces PIP and pressure load, and maintains hemodynamic stability (MAP, HR).

Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

[Effects of Rhodiola rosea injection on intrapulmonary shunt and blood IL-6 and TNF-α levels during single lung ventilation in patients undergoing radical resection of esophageal cancer].

OBJECTIVE: To explore the effects of Rhodiola rosea injection on pulmonary shunt and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels during single lung ventilation in patients undergoing radical resection of esophageal cancer. METHODS: Forty-six patients undergoing radical operation for esophageal cancer were randomized equally into control group and Rhodiola rosea injection group. In the Rhodiola group, 10 mL of Rhodiola rosea injection was added into 250 mL of normal saline or 5% glucose solution for slow intravenous infusion, and normal saline of the same volume was used in the control group after the patients entered the operation room. At T0, T1 and T3, PaO2 of the patient was recorded and 2 mL of deep venous blood was collected for determination of serum TNF-α and IL-6 levels. The incidence of postoperative atelectasis of the patients was recorded. RESULTS: Compared with those in the control group, the patients receiving Rhodiola rosea injection had significantly higher PaO2 and Qs/Qt at T1 and T2 (P<0.05) and lower serum IL-6 and TNF-α levels at T3 (P<0.05). No significant difference in the incidence of postoperative atelectasis was observed between the two groups (P>0.05). CONCLUSION: Rhodiola rosea injection before anesthesia induction can reduce intrapulmonary shunt during single lung ventilation, improve oxygenation, reduce serum IL-6 and TNF-α levels, and alleviate intraoperative lung injury in patients undergoing radical resection of esophageal cancer.

Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery.

INTRODUCTION: Hypoxic pulmonary vasoconstriction (HPV) can be a challenging clinical problem. It is not fully elucidated where in the circulation the regulation of resistance takes place. It is often referred to as if it is in the arteries, but we hypothesized that it is in the venous side of the pulmonary circulation. METHODS: In an open thorax model, pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels. At the same time the lungs were ventilated with extreme variations of inspired air from 5% to 100% oxygen, making it possible to make combinations of high and low oxygen content through the pulmonary circulation. A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests. Under different combinations of oxygenation, pulmonary vascular resistance (PVR) was calculated. RESULTS: With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein, PVR was doubled. With more extreme hypoxia PVR suddenly decreased. Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins. DISCUSSION: The impact of hypoxia occurs from the alveolar level and forward with the blood flow. The experiments indicated that the regulation of PVR is mediated from the venous side.

Effect of Dexmedetomidine on Oxygen and Intrapulmonary Shunt (Qs/Qt) During One-Lung Ventilation in Pediatric Surgery: A Randomized Controlled Trial.

Background One-lung ventilation (OLV) is a common ventilation technique used during thoracic surgery. It can cause serious complications in children, and hypoxic pulmonary vasoconstriction (HPV) is a protective mechanism against the resulting hypoxia. Dexmedetomidine does not affect HPV, so we will investigate its impact on the partial pressure of oxygen in arterial blood (PaO2) and pulmonary shunt fraction (Qs/Qt). Methods Children who underwent OLV were divided into two equal groups. The Dex group received 0.4 µg/kg/h of dexmedetomidine intravenously. The placebo group received normal saline. Two blood samples were taken to analyze arterial and central venous blood gasses during four time periods: T1, 10 minutes after anesthesia; T2, 10 minutes after OLV; T3, 60 minutes after OLV; and T4, 20 minutes after the end of OLV. Heart rate, mean arterial pressure (MAP), PaO2, Qs/Qt, and peak inspiratory pressure (PIP) values were recorded at these time points. Results Regarding heart rate, the Dex group remained relatively stable, whereas the placebo group showed a slight increase in T3 and T4. Concerning MAP, the Dex group had a reduction at T1 compared with the placebo group and remained similar for other points. PaO2 decreased with OLV. However, the Dex group consistently maintained higher PaO2 values than the placebo, especially in T3 and T4. Concerning Qs/Qt, the Dex group maintained lower time values than the placebo group at OLV. Regarding PIP, the Dex group had significantly lower T2 and T3 than the placebo group. Conclusion Administration of dexmedetomidine in children with OLV improves PaO2 and reduces pulmonary shunt fraction (Qs/Qt), thereby improving oxygen transport. It reduces the maximum PIP values, thereby reducing pressure-related complications.

Changes in Pulmonary Vascular Resistance and Obstruction Score Following Acute Pulmonary Embolism in Pigs.

OBJECTIVES: To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN: Controlled, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (-284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (-8 ± 27 dynes; p = 0.4827) or day 2 (-18 ± 32 dynes; p = 0.0923). CONCLUSIONS: Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.

Active Anchoring Stimuli-Responsive Nano-Craft to Relieve Pulmonary Vasoconstriction by Targeting Smooth Muscle Cell for Hypoxic Pulmonary Hypertension Treatment.

Recently, nanotechnology-based drug delivery platforms in treating pulmonary arterial hypertension (PAH) have gradually emerged. However, large mechanical stress and shear stress in blood vessels greatly affect the retention of nanopreparative materials at lesion sites, severely limiting nanotechnology-based drug delivery. Herein, a stimuli-responsive nanocraft is rationally designed by actively anchoring E-selectin overexpressed on pulmonary arterial endothelial cells (PAECs), under hypoxic conditions, allowing effective accumulation and retention of the drug at the lesion site. Briefly, a nitrobenzene group is incorporated into the framework of a nanocarrier, and then it is simultaneously linked with chitosan. Additionally, the surface of the nanocarrier with sialic acid (SA) and encapsulated the clinically used drug ambrisentan (Am), which enables the anchoring of E-selectin and subsequent drug delivery is modifed. This system facilitates intercellular transport to pulmonary artery smooth muscle cells (PASMCs) when targeting PAECs and specifically responds to a reductive hypoxic microenvironment with elevated nitroreductase in PASMCs. Moreover, compared with free Am, nanoencapsulation and SA-PEG2000-NH2 prolong the blood circulation time, achieving better therapeutic outcomes in preventing vascular remodeling and reversing systolic dysfunction. The originality and contribution of this work reveal the promising value of this pulmonary arterial anchoring stimuli-responsive nanocraft as a novel therapeutic strategy for satisfactory PAH treatment.

Assessing the pulmonary vascular responsiveness to oxygen with proton MRI.

Ventilation-perfusion matching occurs passively and is also actively regulated through hypoxic pulmonary vasoconstriction (HPV). The extent of HPV activity in humans, particularly normal subjects, is uncertain. Current evaluation of HPV assesses changes in ventilation-perfusion relationships/pulmonary vascular resistance with hypoxia and is invasive, or unsuitable for patients because of safety concerns. We used a noninvasive imaging-based approach to quantify the pulmonary vascular response to oxygen as a metric of HPV by measuring perfusion changes between breathing 21% and 30%O2 using arterial spin labeling (ASL) MRI. We hypothesized that the differences between 21% and 30%O2 images reflecting HPV release would be 1) significantly greater than the differences without [Formula: see text] changes (e.g., 21-21% and 30-30%O2) and 2) negatively associated with ventilation-perfusion mismatch. Perfusion was quantified in the right lung in normoxia (baseline), after 15 min of 30% O2 breathing (hyperoxia) and 15 min normoxic recovery (recovery) in healthy subjects (7 M, 7 F; age = 41.4 ± 19.6 yr). Normalized, smoothed, and registered pairs of perfusion images were subtracted and the mean square difference (MSD) was calculated. Separately, regional alveolar ventilation and perfusion were quantified from specific ventilation, proton density, and ASL imaging; the spatial variance of ventilation-perfusion (σ2V̇a/Q̇) distributions was calculated. The O2-responsive MSD was reproducible (R2 = 0.94, P < 0.0001) and greater (0.16 ± 0.06, P < 0.0001) than that from subtracted images collected under the same [Formula: see text] (baseline = 0.09 ± 0.04, hyperoxia = 0.08 ± 0.04, recovery = 0.08 ± 0.03), which were not different from one another (P = 0.2). The O2-responsive MSD was correlated with σ2V̇a/Q̇ (R2 = 0.47, P = 0.007). These data suggest that active HPV optimizes ventilation-perfusion matching in normal subjects. This noninvasive approach could be applied to patients with different disease phenotypes to assess HPV and ventilation-perfusion mismatch.NEW & NOTEWORTHY We developed a new proton MRI method to noninvasively quantify the pulmonary vascular response to oxygen. Using a hyperoxic stimulus to release HPV, we quantified the resulting redistribution of perfusion. The differences between normoxic and hyperoxic images were greater than those between images without [Formula: see text] changes and negatively correlated with ventilation-perfusion mismatch. This suggests that active HPV optimizes ventilation-perfusion matching in normal subjects. This approach is suitable for assessing patients with different disease phenotypes.

Hypoxic pulmonary vasoconstriction does not limit maximal exercise capacity in healthy volunteers breathing 12% oxygen at sea level.

Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8-h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.

Pulmonary Hypertension in Established Bronchopulmonary Dysplasia: Physiologic Approaches to Clinical Care.

Preterm infants with bronchopulmonary dysplasia (BPD) are prone to develop pulmonary hypertension (PH). Strong laboratory and clinical data suggest that antenatal factors, such as preeclampsia, chorioamnionitis, oligohydramnios, and placental dysfunction leading to fetal growth restriction, increase susceptibility for BPD-PH after premature birth. Echocardiogram metrics and serial assessments of NT-proBNP provide useful tools to diagnose and monitor clinical course during the management of BPD-PH, as well as monitoring for such complicating conditions as left ventricular diastolic dysfunction, shunt lesions, and pulmonary vein stenosis. Therapeutic strategies should include careful assessment and management of underlying airways and lung disease, cardiac performance, and systemic hemodynamics, prior to initiation of PH-targeted drug therapies.