Increase In Arterial Oxygen Tension Research Articles

Capnodynamic monitoring of lung volume and blood flow in response to increased positive end-expiratory pressure in moderate to severe COVID-19 pneumonia: an observational study

BackgroundThe optimal level of positive end-expiratory pressure (PEEP) during mechanical ventilation for COVID-19 pneumonia remains debated and should ideally be guided by responses in both lung volume and perfusion. Capnodynamic monitoring allows both end-expiratory lung volume ({text{EELV}}_{{{text{CO}}_{2} }}) and effective pulmonary blood flow (EPBF) to be determined at the bedside with ongoing ventilation.MethodsPatients with COVID-19-related moderate to severe respiratory failure underwent capnodynamic monitoring of {text{EELV}}_{{{text{CO}}_{2} }} and EPBF during a step increase in PEEP by 50% above the baseline (PEEPlow to PEEPhigh). The primary outcome was a > 20 mm Hg increase in arterial oxygen tension to inspired fraction of oxygen (P/F) ratio to define responders versus non-responders. Secondary outcomes included changes in physiological dead space and correlations with independently determined recruited lung volume and the recruitment-to-inflation ratio at an instantaneous, single breath decrease in PEEP. Mixed factor ANOVA for group mean differences and correlations by Pearson’s correlation coefficient are reported including their 95% confidence intervals.ResultsOf 27 patients studied, 15 responders increased the P/F ratio by 55 [24–86] mm Hg compared to 12 non-responders (p < 0.01) as PEEPlow (11 ± 2.7 cm H2O) was increased to PEEPhigh (18 ± 3.0 cm H2O). The {text{EELV}}_{{{text{CO}}_{2} }} was 461 [82–839] ml less in responders at PEEPlow (p = 0.02) but not statistically different between groups at PEEPhigh. Responders increased both {text{EELV}}_{{{text{CO}}_{2} }} and EPBF at PEEPhigh (r = 0.56 [0.18–0.83], p = 0.03). In contrast, non-responders demonstrated a negative correlation (r = − 0.65 [− 0.12 to − 0.89], p = 0.02) with increased lung volume associated with decreased pulmonary perfusion. Decreased (− 0.06 [− 0.02 to − 0.09] %, p < 0.01) dead space was observed in responders. The change in {text{EELV}}_{{{text{CO}}_{2} }} correlated with both the recruited lung volume (r = 0.85 [0.69–0.93], p < 0.01) and the recruitment-to-inflation ratio (r = 0.87 [0.74–0.94], p < 0.01).ConclusionsIn mechanically ventilated patients with moderate to severe COVID-19 respiratory failure, improved oxygenation in response to increased PEEP was associated with increased end-expiratory lung volume and pulmonary perfusion. The change in end-expiratory lung volume was positively correlated with the lung volume recruited and the recruitment-to-inflation ratio. This study demonstrates the feasibility of capnodynamic monitoring to assess physiological responses to PEEP at the bedside to facilitate an individualised setting of PEEP.Trial registration: NCT05082168 (18th October 2021).

A Rare Cause of Severe Biventricular Dyssynchrony During Venoarterial Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Failure

A Rare Cause of Severe Biventricular Dyssynchrony During Venoarterial Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Failure

Преоксигенация: терминология, физиологические основы, техники проведения, методики повышения эффективности, особенности у критических пациентов, возможные риски

Преоксигенация является широко распространенным приемом перед индукцией в анестезию и интубацией трахеи, предназначенным для увеличения запасов кислорода в организме и, таким образом, замедления начала десатурации гемоглобина во время апноэ. Показателями эффективности преоксигенации являются увеличение фракции альвеолярного кислорода, увеличение напряжения кислорода в артериальной крови и снижение фракции альвеолярного азота. Конечная точка максимальной преоксигенации — концентрация кислорода в конце выдоха 90 % или концентрация азота в конце выдоха 5 %. Для проведения преоксигенации используются две техники: по дыхательному объему и путем глубоких вдохов. Существуют различные методики для улучшения эффекта преоксигенации. Они включают поднятие головы, апнойную диффузную оксигенацию, использование постоянного положительного давления/положительного давления конца выдоха, двухуровневое положительное давление в дыхательных путях и трансназальную увлажненную быструю инсуффляцию. Преоксигенация с высоким риском включает таких пациентов, как беременные женщины, пациенты, страдающие ожирением, дети, лица пожилого возраста, пациенты с сопутствующими легочными заболеваниями, пациенты на большой высоте. Потенциальные риски преоксигенации включают отсроченное определение пищеводной интубации, абсорбционный ателектаз, продукцию частиц активного кислорода и нежелательные гемодинамические эффекты. Так как преоксигенация по времени не продолжительна, гемодинамические эффекты и накопление частиц активного кислорода незначительны. Абсорбционный ателектаз является следствием преоксигенации. Для снижения риска возникновения абсорбционного ателектаза во время преоксигенации предложено два подхода: умеренное снижение фракции кислорода до 0,8 и использование рекрутмент-маневров, таких как постоянное положительное давление, положительное давление конца выдоха и/или маневры с жизненной емкостью легких. Хотя незначительное давление фракции кислорода уменьшает риск ателектазирования, это происходит за счет снижения кислородного резерва. Техника преоксигенации должна использоваться правильно, с мониторированием концентрации кислорода в конце выдоха. Анестезиолог должен быть ознакомлен с различными методиками проведения преоксигенации, выбирая наиболее подходящую.

Biomarkers of Oxidative Stress for Neonatal Lung Disease.

The transition from prenatal to postnatal life causes a significant increase in arterial oxygen tension and the activation of metabolic pathways enabling the newborn's adaptation to the extra-uterine environment. The balance between pro-oxidant and anti-oxidant systems is critical to preserve cellular functions. Indeed, oxidative stress (OS) occurs when the production of free radicals is not balanced by the activity of intracellular antioxidant systems, contributing to cellular and tissue damage. Perinatal OS may have serious health consequences during the postnatal period and later in life. Namely, OS has been recognized as the major cause of lung injury in newborns, especially those preterm born, due to their immature lung and antioxidant systems. The development of OS biomarkers has gained increasing research interest since they may provide useful insights about pathophysiological pathways underlying OS-mediated pulmonary diseases in newborns. Moreover, their implementation in clinical settings may help to early identify high risk-newborns and to provide targeted treatment. Ideally, a biomarker should demonstrate ease of use, biological validity and reproducibility, high sensitivity and specificity. However, none of the clinically validated biomarkers so far have been qualified for neonatal lung disease. Additionally, the complex technical procedures and the high cost of such determinations have hampered the use of OS biomarkers in clinical practice. This review aims to evaluate the current evidence on the application of biomarkers of oxidative stress for neonatal lung disease and exploring the most relevant issues affecting their implementation in practice, as well as the associated evidence gaps and research limitations.

Transient Improvement of Cerebellar Oligodendroglial Development in a Neonatal Hyperoxia Model by PDGFA Treatment.

In preterm infants, the changes from fetal life to ex-utero conditions often coincide with reduced growth and white matter damage of the cerebellum. The premature increase in arterial oxygen tension caused by preterm birth may dysregulate cerebellar development. In a hyperoxia rat model of white matter damage to mimic a steep increase in oxygen levels by 24h exposure to 80% O2 from postnatal day 6 (P6) to day 7, we analyzed growth factor (GF) synthesis of cerebellar astrocytes. Determination of GF production was performed in astrocytes after Magnetic-activated cell sorting (MACS) isolation from cerebelli after hyperoxia exposure ex vivo, and also in astroglial cultures. Oligodendrocyte progenitor cell (OPC) function was analyzed in cerebellar OPCs isolated by MACS after hyperoxia. Administration of PDGFA from P6 to P11, during hyperoxia and during 4days recovery, was finally tested for protection of oligodendroglia and myelination. As a result, expression of the GFs Pdgfa, Fgf2, and Bdnf was diminished in cerebellar astrocytes in vitro and in vivo. Gene expression of Olig1, Olig2, Sox9, Sox10, and Cnp was reduced in OPCs in vivo. Nasal PDGFA application improved oligodendroglial proliferation after hyperoxia at P7. However, this treatment effect vanished until P9. Impaired MBP expression after hyperoxia was attenuated by PDGFA treatment until P11, but not beyond when PDGFA supply was stopped. In this study on neonatal cerebellar injury, it is documented for the first time that improvement of oligodendroglial proliferation and of myelination can be achieved by PDGFA treatment. However, the treatment benefit is not maintained long term.

Hyperoxia does not affect oxygen delivery in healthy volunteers while causing a decrease in sublingual perfusion

ObjectiveTo determine the human dose‐response relationship between a stepwise increase in arterial oxygen tension and its associated changes in DO2 and sublingual microcirculatory perfusion.MethodsFifteen healthy volunteers breathed increasing oxygen fractions for 10 minutes to reach arterial oxygen tensions of baseline (breathing air), 20, 40, 60 kPa, and max kPa (breathing oxygen). Systemic hemodynamics were measured continuously by the volume‐clamp method. At the end of each period, the sublingual microcirculation was assessed by SDF.ResultsSystemic DO2 was unchanged throughout the study (P slope = .8). PVD decreased in a sigmoidal fashion (max −15% while breathing oxygen, SD18, P slope = .001). CI decreased linearly (max −10%, SD10, P slope < .001) due to a reduction in HR (max −10%, SD7, P slope = .009). There were no changes in stroke volume or MAP. Most changes became apparent above an arterial oxygen tension of 20 kPa.ConclusionsIn healthy volunteers, supraphysiological arterial oxygen tensions have no effect on systemic DO2. Sublingual microcirculatory PVD decreased in a dose‐dependent fashion. All hemodynamic changes appear negligible up to an arterial oxygen tension of 20 kPa.

Infant position in neonates receiving mechanical ventilation.

In patients of various ages undergoing mechanical ventilation (MV), it has been observed that positions other than the standard supine position, such as the prone position, may improve respiratory parameters. The benefits of these positions have not been clearly defined for critically ill newborns receiving MV.This is an update of a review first published in 2005 and last updated in 2013. Primary objectiveTo assess the effects of different positioning of newborn infants receiving MV (supine vs prone, lateral decubitus or quarter turn from prone) in improving short-term respiratory outcomes. Secondary objectiveTo assess the effects of different positioning of newborn infants receiving MV on mortality and neuromotor and developmental outcomes over the long term, and on other complications of prematurity. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), MEDLINE via PubMed (1966 to 22 August 2016), Embase (1980 to 22 August 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 22 August 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised clinical trials comparing different positions in newborns receiving mechanical ventilation. Three unblinded review authors independently assessed trials for inclusion in the review and extracted study data. We used standard methodological procedures as expected by The Cochrane Collaboration and assessed the quality of the evidence using the GRADE approach. If the meta-analysis was not appropriate owing to substantial clinical heterogeneity between trials, we presented review findings in narrative format. We included in this review 19 trials involving 516 participants. Seven of the included studies (N = 222) had not been evaluated in the previous review. Investigators compared several positions: prone versus supine, prone alternant versus supine, prone versus lateral right, lateral right versus supine, lateral left versus supine, lateral alternant versus supine, lateral right versus lateral left, quarter turn from prone versus supine, quarter turn from prone versus prone and good lung dependent versus good lung uppermost.Apart from two studies that compared lateral alternant versus supine, one comparing lateral right versus supine and two comparing prone or prone alternant versus the supine position, all included studies had a cross-over design. In five studies, infants were ventilated with continuous positive airway pressure (CPAP); in the other studies, infants were treated with conventional ventilation (CV).Risks of bias did not differ substantially for different comparisons and outcomes. This update detects a moderate to high grade of inconsistency, similar to previous versions. However, for the analysed outcomes, the direction of effect was the same in all studies. Therefore, we consider that this inconsistency had little effect on the conclusions of the meta-analysis. When comparing prone versus supine position, we observed an increase in arterial oxygen tension (PO2) in the prone position (mean difference (MD) 5.49 mmHg, 95% confidence interval (CI) 2.92 to 8.05 mmHg; three trials; 116 participants; I2= 0). When percent haemoglobin oxygen saturation was measured with pulse oximetry (SpO2), improvement in the prone position was between 1.13% and 3.24% (typical effect based on nine trials with 154 participants; I2= 89%). The subgroup ventilated with CPAP (three trials; 59 participants) showed a trend towards improving SpO2 in the prone position compared with the supine position, although the mean difference (1.91%) was not significant (95% CI -1.14 to 4.97) and heterogeneity was extreme (I2= 95%).Sensitivity analyses restricted to studies with low risk of selection bias showed homogeneous results and verified a small but significant effect (MD 0.64, 95% CI 0.26 to 1.02; four trials; 92 participants; I2= 0).We also noted a slight improvement in the number of episodes of desaturation; it was not possible to establish whether this effect continued once the intervention was stopped. Investigators studied few adverse effects from the interventions in sufficient detail. Two studies analysed tracheal cultures of neonates after five days on MV, reporting lower bacterial colonisation in the alternating lateral position than in the supine posture. Other effects - positive or negative - cannot be excluded in light of the relatively small numbers of neonates studied. This update of our last review in 2013 supports previous conclusions. Evidence of low to moderate quality favours the prone position for slightly improved oxygenation in neonates undergoing mechanical ventilation. However, we found no evidence to suggest that particular body positions during mechanical ventilation of the neonate are effective in producing sustained and clinically relevant improvement.

High PEEP in acute respiratory distress syndrome: quantitative evaluation between improved arterial oxygenation and decreased oxygen delivery

BackgroundPositive end-expiratory pressure (PEEP) is widely used to improve oxygenation and prevent alveolar collapse in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). Although PEEP improves arterial oxygenation predictably, high-PEEP strategies have demonstrated equivocal improvements in ARDS-related mortality. The effect of PEEP on tissue oxygen delivery is poorly understood and is difficult to quantify or investigate in the clinical environment. MethodsWe investigated the effects of PEEP on tissue oxygen delivery in ARDS using a new, high-fidelity, computational model with highly integrated respiratory and cardiovascular systems. The model was configured to replicate published clinical trial data on the responses of 12 individual ARDS patients to changes in PEEP. These virtual patients were subjected to increasing PEEP levels during a lung-protective ventilation strategy (0–20 cm H2O). Measured variables included arterial oxygenation, cardiac output, peripheral oxygen delivery, and alveolar strain. ResultsAs PEEP increased, tissue oxygen delivery decreased in all subjects (mean reduction of 25% at 20 cm H2O PEEP), despite an increase in arterial oxygen tension (mean increase 6.7 kPa at 20 cm H2O PEEP). Changes in arterial oxygenation and tissue oxygen delivery differed between subjects but showed a consistent pattern. Static and dynamic alveolar strain decreased in all patients as PEEP increased. ConclusionsIncremental PEEP in ARDS appears to protect alveoli and improve arterial oxygenation, but also appears to impair tissue oxygen delivery significantly because of reduced cardiac output. We propose that this trade-off may explain the poor improvements in mortality associated with high-PEEP ventilation strategies.

Age-related changes in arterial blood-gas variables in Holstein calves at moderate altitude

The goal of this study was to determine whether peripheral oxygen delivery and efficacy of alveolar-arterial oxygen (A-a O 2 ) transfer, as estimated from the A-a O 2 pressure gradient, are compromised in Holstein calves at moderate altitude. The primary objective was to evaluate age-related changes in arterial blood-gas variables, L-lactate, and hematocrit in healthy calves. The secondary objective was to determine if coughing and nasal discharge, commonly used indicators of respiratory disease, are associated with A-a O 2 gradient. Arterial blood-gas tensions were evaluated in a cohort of 61 dairy calves on one farm at moderate altitude (1,601 m to 1,696 m). Sampling was performed on four occasions at approximately 10, 38, 150, and 261 days of age. Hyperventilation, as indicated by hypocapnia, was evident in calves of all ages. Increasing age was associated with a nonlinear increase in arterial oxygen tension (P,0.001) and a nonlinear decrease in A-a O 2 gradient (P,0.001). The mean A-a O 2 gradient at 10 and 38 days of age was over 18 mmHg, indicating poor efficacy of oxygen transfer. Cough score (P=0.02) but not nasal score (P=0.32) was associated with an in increase in A-a O 2 pressure gradient. Mean hematocrit remained low (,27%) despite hypoxemia. From 38 days of age, median L-lactate concentration remained over 1.5 mmol/L, indicating substantial anaerobic respiration due to inadequate oxygen delivery. Twenty-five percent of calves were treated for respiratory disease. The maximum age at first treatment was 102 days. In conclusion, there was a nonlinear improvement in A-a O 2 transfer efficacy with increasing age, but peripheral oxygen delivery remained compromised. Hyperventilation and impaired A-a O 2 transfer due to functional immaturity of the pulmonary system may be risk factors for respiratory disease in dairy calves at moderate altitude.

Regulation of vascular tone and remodeling of the ductus arteriosus

The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The DA is a normal and essential fetal structure. However, it becomes abnormal if it remains patent after birth. Closure of the DA occurs in two phases: functional closure of the lumen within the first hours after birth by smooth muscle constriction, and anatomic occlusion of the lumen over the next several days due to extensive neointimal thickening in human DA. There are several events that promote the DA constriction immediately after birth: (a) an increase in arterial oxygen tension, (b) a dramatic decline in circulating prostaglandinE(2) (PGE(2)), (c) a decrease in blood pressure within the DA lumen, and (d) a decrease in the number of PGE(2) receptors in the DA wall. Anatomical closure of the DA is associated with the formation of intimal thickening, which are characterized by (a) an area of subendothelial deposition of extracellular matrix, (b) the disassembly of the internal elastic lamina and loss of elastic fiber in the medial layer, and (c) migration into the subendothelial space of undifferentiated medial smooth muscle cells. In addition to the well-known vasodilatory role of PGE(2), our findings uncovered the role of PGE(2) in anatomical closure of the DA. Chronic PGE(2)-EP4-cyclic AMP (cAMP)-protein kinase A (PKA) signaling during gestation induces vascular remodeling of the DA to promote hyaluronan-mediated intimal thickening and structural closure of the vascular lumen. A novel target of cAMP, Epac, has an acute promoting effect on smooth muscle cell migration without hyaluronan production and thus intimal thickening in the DA. Both EP4-cAMP downstream targets, Epac and PKA, regulate vascular remodeling in the DA.

Platelet larceny: spurious hypoxaemia due to extreme thrombocytosis

Rapid oxygen consumption by markedly increased numbers of hypermetabolic leukocytes in leukaemic patients resulting in the apparent diagnosis of hypoxaemia on arterial blood gas analyses is termed leukocyte larceny. In the present report, a case of polycythaemia vera, extreme thrombocytosis, normal leukocyte counts and arterial hypoxaemia in the absence of clinical, radiological or physiological evidence of lung disease is described. This pseudohypoxaemia case was established by pulse oximetry, as well as by incubation of a blood specimen with potassium cyanide, and became less significant after the use of cytoreductive agents showed a proportionate increase in arterial oxygen tension as platelet counts decreased on serial arterial blood gas analyses. The present case report demonstrates spurious hypoxaemia due to extreme thrombocytosis and shows that, beside significant leukocytosis, even markedly elevated platelet counts can cause larceny of arterial blood oxygen.

Survival time in severe hemorrhagic shock after perioperative hemodilution is longer with PEG-conjugated human serum albumin than with HES 130/0.4: a microvascular perspective

IntroductionPreoperative hemodilution is an established practice that is applied to reduce surgical blood loss. It has been proposed that polyethylene glycol (PEG) surface decorated proteins such as PEG-conjugated human serum albumin may be used as non-oxygen-carrying plasma expanders. The purpose of this study was to determine whether there is any difference in survival time after severe hemorrhagic shock following extreme hemodilution using a conventional hydroxyethyl starch (HES)-based plasma expander or PEG-albumin.MethodsExperiments were performed using the hamster skinfold window preparation. Human serum albumin that was surface decorated with PEG was compared with Voluven 6% (Fresenius Kabi, Austria; a starch solution that is of low molecular weight and has a low degree of substitution; HES). These plasma expanders were used for a 50% (blood volume) exchange transfusion to simulate preoperative hemodilution. Exchange transfusion was followed by a 60% (blood volume) hemorrhage to reproduce a severe surgical bleed over a 1 hour period. Observation of the animal was continued for another hour during the shock phase.ResultsThe PEG-albumin group exhibited significantly greater survival rate than did the HES group, in which none of the animals survived the hemorrhage phase of the experiment. Among the treatment groups there were no changes in mean arterial pressure and heart rate from baseline after hemodilution. Both groups experienced gradual increases in arterial oxygen tension and disturbance in acid-base balance, but this response was more pronounced in the HES group during the shock period. Mean arterial pressure remained elevated after the initial hemorrhage period in the PEG-albumin group but not in the HES group. Maintenance of a greater mean arterial pressure during the initial stages of hemorrhage is proposed to be in part due to the improved volume expansion with PEG-albumin, as indicated by the significant decrease in systemic hematocrit compared with the HES group. PEG-albumin treatment yielded higher functional capillary density during the initial stages of hemorrhage as compared with HES treatment.ConclusionThe ability of PEG-albumin to prolong maintenance of microvascular function better than HES is a finding that would be significant in a clinical setting involving preoperative blood management and extreme blood loss.

Response to Recruitment Maneuver Influences Net Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome

Alveolar fluid clearance is impaired in the majority of patients with acute respiratory distress syndrome (ARDS). Experimental studies have shown that a reduction of tidal volume increases alveolar fluid clearance. This study was aimed at assessing the impact of the response to a recruitment maneuver (RM) on net alveolar fluid clearance. In 15 patients with ARDS, pulmonary edema fluid and plasma protein concentrations were measured before and after an RM, consisting of a positive end-expiratory pressure maintained 10 cm H2O above the lower inflection point of the pressure-volume curve during 15 min. Cardiorespiratory parameters were measured at baseline (before RM) and 1 and 4 h later. RM-induced lung recruitment was measured using the pressure-volume curve method. Net alveolar fluid clearance was measured by measuring changes in bronchoalveolar protein concentrations before and after RM. In responders, defined as patients showing an RM-induced increase in arterial oxygen tension of 20% of baseline value or greater, net alveolar fluid clearance (19 +/- 13%/h) and significant alveolar recruitment (113 +/- 101 ml) were observed. In nonresponders, neither net alveolar fluid clearance (-24 +/- 11%/h) nor alveolar recruitment was measured. Responders and nonresponders differed only in terms of lung morphology: Responders had a diffuse loss of aeration, whereas nonresponders had a focal loss of aeration, predominating in the lower lobes. In the absence of alveolar recruitment and improvement in arterial oxygenation, RM decreases the rate of alveolar fluid clearance, suggesting that lung overinflation may be associated with epithelial dysfunction.

Changes in Arterial Oxygen Tension Correlate with Changes in End-expiratory Carbon Monoxide Level

ObjectiveCarbon monoxide (CO) and oxygen compete for haemoglobin binding sites. While the effects of increased inspiratory oxygen fractions on exhaled carbon monoxide concentrations have been studied previously, the relationships between intravascular oxygen tension, blood carboxyhaemoglobin levels and expiratory CO concentrations remain unclear. We therefore studied the effects of increases in arterial oxygen tension as crucial determinant for the displacement of carbon monoxide from its haemoglobin bond during lung passage.MethodsMeasurements of end-expiratory CO concentrations (eCO), arterial oxygen tensions and carboxyhaemoglobin concentrations were performed in 19 patients while breathing air and oxygen.ResultsWith increasing PaO2 (from 11.5 ± 1.9 to 35.2 ± 10.3 kPa) end-expiratory CO concentrations increased from 8.6 ± 4.9 to 16.7 ± 9.4 ppm, p < 0.001, with a mean increase of 0.36 ppm CO per kPa increase in PaO2 (ΔeCO [ppm] = 0.36 *␣ΔPaO2 [kPa]). Increases of arterial oxygen tension correlated with increases of end-expiratory CO concentration (r2 = 0.33). Arterial carboxyhaemoglobin concentrations decreased from 1.06 ± 0.37 during air breathing to 0.92 ± 0.35 % after 5 minutes of oxygen inhalation (p < 0.001).ConclusionsOxygen-induced increases in exhaled CO correlate with increases in arterial oxygen tensions. Furthermore, oxygen inhalation reduces carboxyhaemoglobin levels, supporting the concept of accelerated CO elimination by oxygen via the lungs.

Hemodynamic Response to Sildenafil, Nitric Oxide, and Iloprost in Primary Pulmonary Hypertension

Different vasodilators and different routes of application are used for the treatment of primary pulmonary hypertension (PPH). Recently, sildenafil, a phosphodiesterase-V inhibitor, has been shown to have beneficial hemodynamic effects in PPH. However, the hemodynamic effects of sildenafil have not been characterized and compared to other vasodilators such as inhaled nitric oxide (iNO) or iloprost in PPH in the same group of patients. We investigated prospectively 10 consecutive patients with PPH using iNO, iloprost aerosol, and oral sildenafil to test acute hemodynamic response during right-heart catheterization. iNO, iloprost aerosol, and sildenafil caused a significant fall of mean pulmonary artery pressure and pulmonary vascular resistance (PVR) [p < 0.05]. Correspondingly, cardiac output and mixed venous saturation increased slightly in all groups. Systemic arterial pressure and vascular resistance were mainly unaltered. Using a PVR reduction of > or =20% to define a significant response, 7 of 10 patients were responders to iloprost aerosol, whereas 4 of 10 patients responded to iNO and oral sildenafil. Improvement of oxygenation as indicated by an increase of arterial oxygen tension was observed with iloprost aerosol (p < 0.01). All of the three substances, iNO, iloprost aerosol, and oral sildenafil, significantly improved pulmonary hemodynamics in patients with PPH. The most prominent hemodynamic effects and improvement of oxygenation were observed with iloprost aerosol.

Endotoxin contamination contributes to the pulmonary inflammatory and functional response to Aspergillus fumigatus extract inhalation in heaves horses.

Mould extract inhalation challenges have been used extensively in the investigation of heaves. Such challenges have induced pulmonary neutrophilic inflammation and dysfunction, consistent with, but less severe than the natural disease. However, the method of mould extract production is likely to result in endotoxin contamination. To investigate whether insufficient dose delivery was responsible for the shortfall in response to inhaled extract compared with natural disease, and whether endotoxin contamination of mould extract contributed to the pulmonary inflammation and dysfunction. We measured the response of six heaves horses following inhalation of saline (placebo) and three doses of Aspergillus fumigatus extract. We then compared the response of six heaves horses to A. fumigatus extract inhalation before and after lipopolysaccharide (LPS) depletion. Inhalation challenge with 0.5, 1.6 and 5 mg of A. fumigatus extract resulted in a significant increase in bronchoalveolar lavage fluid (BALF) neutrophil ratio when compared with saline inhalation. Only 1.6 and 5 mg extract inhalation resulted in significant lung dysfunction compared with saline. There was no significant difference between 1.6 and 5 mg extract inhalation with respect to airway neutrophil numbers or lung function, suggesting a plateau in both measured responses. LPS depletion of 1.6 mg A. fumigatus extract resulted in a significant reduction in airway neutrophil numbers and increase in arterial oxygen tension. There was no significant difference between saline and the LPS-depleted A. fumigatus extract challenges with respect to neutrophil count and lung function. The reduction in airway neutrophil numbers was greater than would be predicted by extrapolation from previously reported soluble LPS dose-response inhalation experiments. This study supports a role for other inhalants, in addition to soluble components of A. fumigatus, in the aetiopathogenesis of heaves. Also the amplification in response to LPS when inhaled with A. fumigatus extract, suggests that the role of inhaled endotoxin in the pulmonary inflammation and dysfunction in naturally occurring heaves may currently be underestimated.

COX and the control of the pulmonary circulation

The lung possesses a low resistance circulation that must, at all times, accommodate the entire cardiac output. Moreover, to ensure proper oxygenation of hemoglobin, blood flow must be directed to well-ventilated lung units, i.e., ventilation and perfusion must be matched.Cyclooxygenase (COX)-mediated arachidonic acid (AA) metabolites can influence both pulmonary vascular resistance and ventilation–perfusion matching. In isolated dog and rabbit lungs, ventilation of the right lung with oxygen (O2) and the left lung with nitrogen (N2) resulted in normal perfusion pressures and blood gas tensions. In both species, administration of COX inhibitors resulted in redistribution of blood flow from hypoxic alveoli (N2-ventilated lung) to the well-oxygenated alveoli (O2-ventilated lung) and an increase in arterial oxygen tension, i.e., a COX-mediated AA metabolite or metabolites opposed hypoxic pulmonary vasoconstriction (HPV), but, by virtue of this activity, prevented optimal matching of ventilation with perfusion. The effects of COX inhibition were reversed by prostacyclin (PGI2).These findings are consistent with the hypothesis that COX-derived products of AA metabolism can influence ventilation–perfusion matching in the lung. Moreover, the results of studies in dogs suggest that one such metabolite of AA is PGI2.

Replacement of physiologically autoinhaled nitric oxide in intubated patients.

Autoinhaled nitric oxide (NO) is produced mainly in the upper airways. Orotracheal intubation disrupts the natural autoinhalation of NO from the naso- and oropharynx. The effect of disrupting and then replacing autoinhaled NO on arterial oxygenation was investigated in intubated patients. Two groups of nine patients without lung disease were examined during anaesthesia using an inspired oxygen fraction of 0.50. In both groups, the individually produced NO of the whole respiratory tract and the upper airways was determined. The amount of NO normally autoinhaled from the upper airways was replaced for 5 min after orotracheal intubation in one group. The amount of NO from the upper respiratory tract was 47+/-19 parts per billion (ppb) in the test group and the replaced NO concentration was 48+/-20 ppb. No significant increase in arterial oxygen tension could be detected during the replacement of the autoinhaled NO. Haemodynamic parameters remained unchanged. In the control group, the NO from the upper airways was 34+/-16 ppb. In contrast to the test group, it was not replaced after intubation. These findings suggest that in healthy subjects the autoinhalation of nitric oxide does not play an important role in arterial oxygenation during anaesthesia.

The effects of depth on the cardiac and behavioural responses of double-crested cormorants (Phalacrocorax auritus) during voluntary diving.

Heart rate and dive behaviour were monitored in double-crested cormorants (Phalacrocorax auritus) during shallow (1 m) and deep diving (12 m), after breathing different gas mixtures, to investigate the role of depth and the accompanying changes in blood gas levels in cardiac and behavioural control during voluntary diving. Pre-dive heart rate in both shallow- and deep-diving birds was approximately three times the resting heart rate (137.9+/-17.5 beats min(-1); mean +/- S.D., N=5), falling abruptly upon submersion to around 200-250 beats min(-1). During shallow diving, the initial reduction in heart rate was followed by a secondary, more gradual decline, to around the resting level. In contrast, during deep diving, heart rate stabilised at 200-250 beats min(-1). In dives of similar duration, mean dive heart rate was significantly lower during shallow diving (163.2+/-14.0 beats min(-1)) than during deep diving (216.4+/-7.7 beats min(-1)), but in both cases was significantly above the resting value. The difference in cardiac response is probably due to an increase in arterial oxygen tension (Pa(O(2))) during the descent phase of deep dives (compression hyperoxia). Exposure to a hyperoxic gas mixture before shallow diving significantly increased mean dive heart rate, while exposure to a hypoxic gas mixture in both the shallow and deep dive tanks significantly reduced mean dive heart rate. In contrast, breathing hypercapnic gas before diving had no significant effect on dive heart rate. We suggest that the cardiac response to voluntary diving in double-crested cormorants is strongly influenced by changes in blood oxygen levels throughout the dive. Dive duration was unaffected by alterations in inspired gas composition, but surface interval duration decreased during hyperoxic gas exposure and increased during hypoxic gas exposure. The most efficient dive pattern (highest dive/pause ratio) was observed after hyperoxic exposure. Our study suggests that blood oxygen level is a powerful stimulus that facilitates the cardiac and behavioural adjustments during foraging that are important components of a strategy allowing double-crested cormorants to maximise the time spent under water and, hence, potential foraging time.

Changes in pulmonary blood flow during gaseous and partial liquid ventilation in experimental acute lung injury.

It has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury. After induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group. During partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon. In the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.