Arterial PO2 Research Articles

Increased Serum Erythropoietin despite Normalized Hb Concentration and Arterial O2 Saturation in Chronic Mountain Sickness after Isovolemic Hemodilution

Excessive erythrocytosis (EE) is a hallmark of Chronic Mountain Sickness (CMS), an incapacitating condition among high‐altitude residents. EE is associated with accentuated hypoxemia and neurological symptoms. Periodic hemodilution is a common treatment used to normalize excessive red blood cell count and relieve symptomatology. However, it is unclear whether relief results from an improvement of arterial O2 saturation (SaO2) and/or whether the normalization of Hb affects the erythropoietic stimulus. Thus, we sought to investigate the effect of isovolemic hemodilution on resting arterial PO2 (PaO2), SaO2, arterial O2 content (CaO2), serum EPO, iron profile, and CMS score in CMS subjects. Six CMS and eight non‐CMS male residents of Cerro de Pasco, Peru (4350m), of similar age participated in the study. The CMS group exhibited significantly higher Hb concentration (22.2 ± 1.2 vs 17.8 ± 1.3 g/dl, p<0.001) and CMS score (10.0 ± 6.6 vs 1.1 ± 1.1, p<0.01) with a lower pulse O2 saturation (SpO2; 84.7 ± 1.0 vs 88.3 ± 1.6%, p<0.05). Radial artery catheters were placed to obtain arterial blood measurements. For isovolemic hemodilution, a venous catheter was placed in the arm of CMS subjects to remove ~2–4 units of blood (1675 ± 442 ml) for a reduction of ~19% pre‐hemodilution Hb value. Isovolemia was maintained with an equivalent volume of plasma substitute (Haemaccel®). Baseline PaO2, SaO2, serum EPO, iron, ferritin, and transferrin saturation were similar in both non‐CMS and CMS groups, while CaO2 was higher in CMS (24.4 ± 1.9 vs 20.7 ± 1.6 mlO2/dl, p<0.001). At 36 hours post‐hemodilution, Hb in the CMS group decreased by 20.1 ± 1.6 % (from 22.2 ± 1.2 to 17.7 ± 0.6 g/dl, p<0.001), matching non‐CMS subject values. PaO2 and SaO2 remained essentially unchanged, whereas CaO2 decreased (from 24.4 ± 1.9 to 20 ± 0.8 mlO2/dl, p<0.001). A substantial drop was observed in serum iron (from 112.3 ± 44 to 60.8 ± 30.3 μg/dl, p<0.002) and transferrin saturation (from 28.0 ± 10.8 to 17.7 ± 8.2%, p<0.013). Serum EPO increased significantly after hemodilution (from 25.6 ± 7.6 to 68.2 ± 25.8 mIU/ml, p<0.006), resulting in higher values compared to pre‐hemodilution and non‐CMS subjects (15.9 ± 8.4 mIU/ml). After Hb normalization, CMS symptomatology improved (from 10.0 ± 6.6 to 1.2 ± 1.1, p<0.01) without a significant increase in SaO2. Despite this, serum EPO increased dramatically reflecting erythropoietic stimulus. It is possible that chronic EE determines a higher set‐point for Hb and CaO2 in CMS subjects, and thus even reduction to non‐CMS values is sensed as relative tissue hypoxia due to reduced O2 delivery. In addition, iron depletion could also contribute to EPO expression through inhibition of prolyl hydroxylase enzymes and HIF stabilization.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hydroxycobalamin Reveals the Involvement of Hydrogen Sulfide in the Hypoxic Responses of Rat Carotid Body Chemoreceptor Cells.

Carotid body (CB) chemoreceptor cells sense arterial blood PO2, generating a neurosecretory response proportional to the intensity of hypoxia. Hydrogen sulfide (H2S) is a physiological gaseous messenger that is proposed to act as an oxygen sensor in CBs, although this concept remains controversial. In the present study we have used the H2S scavenger and vitamin B12 analog hydroxycobalamin (Cbl) as a new tool to investigate the involvement of endogenous H2S in CB oxygen sensing. We observed that the slow-release sulfide donor GYY4137 elicited catecholamine release from isolated whole carotid bodies, and that Cbl prevented this response. Cbl also abolished the rise in [Ca2+]i evoked by 50 µM NaHS in enzymatically dispersed CB glomus cells. Moreover, Cbl markedly inhibited the catecholamine release and [Ca2+]i rise caused by hypoxia in isolated CBs and dispersed glomus cells, respectively, whereas it did not alter these responses when they were evoked by high [K+]e. The L-type Ca2+ channel blocker nifedipine slightly inhibited the rise in CB chemoreceptor cells [Ca2+]i elicited by sulfide, whilst causing a somewhat larger attenuation of the hypoxia-induced Ca2+ signal. We conclude that Cbl is a useful and specific tool for studying the function of H2S in cells. Based on its effects on the CB chemoreceptor cells we propose that endogenous H2S is an amplifier of the hypoxic transduction cascade which acts mainly by stimulating non-L-type Ca2+ channels.

Delayed cord clamping does not affect umbilical cord blood gas analysis.

Although delayed umbilical cord clamping has been shown to have significant benefits for both term and preterm infants, currently, data on its impact on blood gas analysis have been scant and conflicting. In a retrospective review, we compared the demographic characteristics and blood gas parameters of 114 delayed cord clamping (DCC-births between 45 and 90s in length; 109 being for 60s) versus 407 early cord clamping births (ECC-immediately after delivery) collected over a 1-year period. Intrapartum care and timing of cord clamping for individual cases were performed at the discretion of obstetricians. The differences were assessed for statistical and clinical significance. The DCC group was found to have significantly higher mean Apgar scores at both 1 and 5min (p < 0.05), as well as lower percentages of nulliparous births, cesarean-section deliveries, epidural anesthesia usage, and major pregnancy-related complications. No significant differences in maternal age, gestational age, neonate birthweight, sex, or in the presence of meconium at birth were observed. A higher umbilical artery pO2 in the DCC group [21 (9) vs. 19 (10) mmHg, p < 0.05] was the only statistically significant difference found out of all the blood gas parameters analyzed. In this study, infants selected for the DCC procedure were found to be overall lower risk than those delivered as per the standard ECC procedure. No clinically significant difference in any blood gas parameter was observed, and therefore, no adjustment to clinical reference intervals is needed for DCC blood gas samples taken after a 1-min delay period.

Comparison of arterial and venous blood gases in patients with obesity hypoventilation syndrome and neuromuscular disease.

OBJECTIVES:Obesity hypoventilation syndrome (OHS) and some neuromuscular diseases (NMD) present with hypercapnic respiratory failure. Arterial blood gas (ABG) analysis is important in the diagnosis, follow-up, and treatment response of these diseases. However, ABG sampling is difficult in these patients because of excessive subcutaneous fat tissue, muscle atrophy, or contracture. The aim of this study is to investigate the value of venous blood gas (VBG), which is an easier and less complicated method, among stable patients with OHS and NMD.METHODS:The study included stable OHS and NMD patients who had been previously diagnosed and followed up between March 2017 and May 2017 in the outpatient clinic. ABG was taken from all patients in room air, and peripheral VBG was taken within 5 min after ABG sampling.RESULTS:Thirty-six patients with OHS and 46 patients with NMD were included in the study. There was a moderate positive correlation between arterial and venous pH values for all patients (rs = 0.590, P < 0.001). There were a strong and very strong positive correlations between arterial and venous pCO2 and HCO3 values (rs = 0.725 and rs = 0.934, respectively) (P < 0.001). There was no correlation between arterial and venous pO2 and saturation values. There was an agreement in Bland–Altman method for the values of ABG and VBG (pH, pCO2, and HCO3).CONCLUSIONS:There was a correlation between ABG and VBG values (pH, pCO2, and HCO3). VBG parameters (pH, pCO2, and HCO3) can be used safely instead of ABG parameters which have many risks, during treatment and follow-up of patients with OHS and NMD.

A Comparative Study of Arterial and Venous Blood Gas Analysis in Critically Ill Patients

Background: Measurement of blood gases is increasingly becoming an essential part of diagnosis, management and monitoring of critically ill patients. In our study we used PVBG and four variables po2, pc02, hco3 and ph of PVBG was compared with ABG and their agreement and correlation assessed.Objective: To study the relationship between ABG and VBG in critically ill patients and to assess the usefulness of VBG as a surrogate for ABG in the initial management of critically ill patients.Methodology: 100 random patients who were considered critically ill based on SOFA score value >/ = 7 admitted in GRMC, Gwalior were taken. P value <0.05 was taken as significant. IBM SPSS was used for analysis.Results: The pHA and pHV shows good correlation and agreement (mean difference is 0.04 (p<o.000) Correlation coefficient is 0.832.(p<0.000 ) 95% limits of agreement are -0.2 to .16 mm Hg). pCO2 A and pCO2V shows good correlation and agreement (mean difference is about 5.7 mmHg (P<0.000),Pearsons correlation coefficient is 0.916.(p <0.000) , 95% limits of agreement is -16 to 4mm Hg). HCO3A and HCO3V shows good agreement and correlation(mean difference between hco3A and hco3V is 1.22( p<0.001), Pearsons correlation coefficient is 0.960 (p<0.000) ,95% limits of agreement is from 6 to -8 mmHg).pO2A and pO2V shows poor correlation and agreement (mean difference is 55.191 (p <0.000),Pearsons correlation coefficient is 0.166 (p< 0.099 ),95% limit of agreement is 4 to 120 mmHg).Conclusion: In our study we found that there is excellent agreement between pH, pCO2 and HCO3 between ABG and VBG in critically ill patients.. The agreement between arterial and venous pO2 is very poor and venous pO2 cannot be reliably used instead of arterial value.

A clinical study of lung function protection in patients with robot assisted laparoscopic radical prostatectomy

Objective To evaluate the effect of manipulative pulmonary protective strategy on the pulmonary function of the patients undergoing robotic assisted laparoscopic radical prostatectomy under multiple-mode monitoring. Methods One hundred and twenty patients who underwent robot-assisted laparoscopic radical prostatectomy were divided into 4 groups (30 cases in each group) according to ASA Ⅰ-Ⅲ. Multimodal monitoring + manual relaxation group (group Mm), multimodal monitoring group (group M), conventional anesthesia + manual relaxation group (group m) and conventional anesthesia group (group C). In group Mm and group M, propofol was infused to achieve the BIS value of 45-55, then we monitored the muscle relaxation to conduct closed-loop infusion of cisatracurium. We also monitored and managed liquid input by vigileo. Group M and group C maintained peak airway pressure (≤30 cmH2O) (1 cmH2O=0.098 kPa) and PETCO2 35-40 mmHg (1 mmHg=0.133 kPa). Group Mm and group m received manual lung recruitment maneuver one times every 30 min after establishment of pneumoperitoneum until the end of operation. Blood gas analysis was performed before anesthesia induction (T1), 15 min after intubation (T2), 10 min after pneumoperitoneum (T3), 30 min after pneumoperitoneum (T4), 60 min after Trendelenburg (T5), 10 min after pneumoperitoneum cessation (T6), 5 min after extubation (T7). Airway peak pressure (Ppeak) and airway plateau pressure (Pplat) were recorded. The value of dynamic lung compliance (Cdyn), spiro-index (RI), dying cavity rate (VD/VT), oxygenation index (PaO2/FiO2) and alveolar arterial PO2 difference (A-aDO2) were calculated at different time points. Results Ppeak of group Mm and group m were more stable than Ppeak of group M and group C at T3 and T4 (P<0.05). Pplat of group Mm and group m were more stable than Pplat of group M and group C at T3 and T5 (P<0.05). Oxygenation indexes of group Mm and group m were higher than indexes of group M and group C at T5-T7 (P<0.05). A-aDO2 and RI were lower than group M and group C at T4, T5, T7 (P<0.05). At T4-T6, Cdyn was higher than Cdyn in group M and group C (P<0.05). Conclusions Manipulative pulmonary protective ventilation can improve the pulmonary function in patients undergoing robotic assisted laparoscopic radical prostatectomy under multimode monitoring. Key words: Robot; Therapeutic laparoscopy; Protective lung ventilation; Multi-mode monitoring; Prostate cancer

Effect of Inhaled Nitric Oxide on Hemodynamics in Lambs with 1½ Ventricle Circulation.

Inhaled nitric oxide (NO) is widely used to treat postoperative pulmonary hypertension in congenital heart disease. It is believed that NO increases cardiac output (CO) by decreasing pulmonary vascular resistance (PVR), leading to increased left ventricular preload. However, the effect of NO on CO in patients with 1½ ventricle circulation remains unclear. To evaluate this, a superior cavopulmonary (SCP) shunt was constructed in 10 juvenile sheep. A PTFE graft was inserted between the superior vena cava (SVC) and the main pulmonary artery (PA). The SVC was clamped at the right atrial junction to establish a 1½ ventricle circulation. Flows, pressures, and arterial blood gases were recorded before and during inhalation of NO. Mean arterial pressure (46.6 ± 5.4 to 44.6 ± 5.9 mm Hg; p = 0.06) and left atrial pressure (4.0 ± 2.5 to 4.0 ± 2.3 mm Hg; p = 1.0) did not change. Mean PA pressure (13.6 ± 2.4 to 11.7 ± 2.9 mm Hg; p = 0.006) and PVR (5.47 ± 2.99 to 4.54 ± 2.61 Wood Units; p = 0.037) decreased significantly. SVC flow (24.8 ± 11.3 to 22.0 ± 9.7 ml/min/kg; p = 0.09) did not change, and CO decreased (140.2 ± 37.2 to 132.1 ± 39.2 ml/min/kg; p = 0.033). Arterial PO2 improved (103.72 ± 29.30 to 132.43 ± 47.02 mm Hg; p = 0.007). In this 1½ ventricle model, NO surprisingly decreased cardiac output (CO) and did not increase left ventricular preload.

Arterial pH and Blood Gas Values in Rats Under Three Types of General Anesthesia: a Chronobiological Study

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

Systemic Oxygen Transport with Rest, Exercise, and Hypoxia: A Comparison of Humans, Rats, and Mice.

The objective of this article is to compare and contrast the known characteristics of the systemic O2 transport of humans, rats, and mice at rest and during exercise in normoxia and hypoxia. This analysis should help understand when rodent O2 transport findings can-and cannot-be applied to human responses to similar conditions. The O2 -transport system was analyzed as composed of four linked conductances: ventilation, alveolo-capillary diffusion, circulatory convection, and tissue capillary-cell diffusion. While the mechanisms of O2 transport are similar in the three species, the quantitative differences are naturally large. There are abundant data on total O2 consumption and on ventilatory and pulmonary diffusive conductances under resting conditions in the three species; however, there is much less available information on pulmonary gas exchange, circulatory O2 convection, and tissue O2 diffusion in mice. The scarcity of data largely derives from the difficulty of obtaining blood samples in these small animals and highlights the need for additional research in this area. In spite of the large quantitative differences in absolute and mass-specific O2 flux, available evidence indicates that resting alveolar and arterial and venous blood PO2 values under normoxia are similar in the three species. Additionally, at least in rats, alveolar and arterial blood PO2 under hypoxia and exercise remain closer to the resting values than those observed in humans. This is achieved by a greater ventilatory response, coupled with a closer value of arterial to alveolar PO2 , suggesting a greater efficacy of gas exchange in the rats. © 2018 American Physiological Society. Compr Physiol 8:1537-1573, 2018.

Progressive severe dyspnea and hypoxia due to primary thyroid lymphoma: steroid administration may be life-saving

Primary Thyroid lymphoma is an uncommon malignancy, which can rarely cause severe dyspnea. Its commonly difficultly diagnosed and rapid diagnosis and management may be lifesaving. Here we report a case presented with sudden thyroid growth and severe dyspnea, who was diagnosed as primary thyroid lymphoma. A 70-year-old woman applied with fatigue, rapidly enlarged goitre and severe progressive dyspnea. She had severe hypoxemia with an artery oxygen saturation of 59.2% and arterial PO2 of 33.9 mmHg. The ultrasound of the neck showed an enlarged thyroid gland with a mass in the left lobe. After admission to the hospital her dyspnea worsened and oxygen and bronchodilator treatment gave no benefit. IV methylprednisolone was administered, and the patient’s symptoms partially improved. Meanwhile in spite of supportive therapy, the patient underwent urgent surgery for acute airway obstruction and thyroidectomy was performed. After surgery the diagnosis was high grade diffuse large B-cell non-Hodgkin’s lymphoma.

Inadequacy of Pulse Oximetry in the Catheterization Laboratory. An Exploratory Study Monitoring Respiratory Status Using Arterial Blood Gases during Cardiac Catheterization with Conscious Sedation

Benzodiazepines and opioids are commonly used for conscious sedation (CS) in cardiac catheterization laboratory (CCL) patients. Both drugs are known to predispose to hypoxemia, apnea and decreased responsiveness to PCO2, resulting in decreased arterial pH and PO2, as well as increased PCO2. We want to determine the effects of CS on arterial blood gas (ABG) in CCL patient, and identify if pulse oximetry monitoring is adequate. We enrolled 18 subjects undergoing elective catheterization. Measurement of ABGs at one-minute intervals was done from the moment of arterial access until case end. The results of ABGs were not available to the clinician who administered sedation. Relationships of pH, PCO2, PaO2 and SaO2 were studied by plotting time series graphs. Significant changes were defined as pH <7.30, SaO2 < 90, and PCO2 > 50 mmHg. No significant change in pH, PCO2, PaO2 and SaO2 was noted in 4/18 (22%) subjects. A significant drop in SaO2 was noted in 4/18 (22%). A significant change in PCO2 and/or pH was noted in 10/18 (55%) cases. Among the 16 (16/18) subjects receiving supplemental oxygen, 7 (7/18, 39%) had no drop in SaO2, but developed respiratory acidosis. At the end of the case, 5/18 (28%) subjects had respiratory acidosis with normal PaO2. Significant hypercarbia and acidosis occurred frequently in this small study during CS in patients undergoing cardiac catheterization. Relying on pulse oximetry alone especially with patients on supplemental oxygen may lead to failure in detecting respiratory acidosis in a significant number of patients.

The Relationship between Arterial and Central Venous Blood Gases Values in Patients Undergoing Mechanical Ventilation after Cardiac Surgery

Background: The most straightforward method of ascertaining arterial PO2, PCO2, and other components of blood gas is to measure them directly from a blood sample. In situations in which arterial puncture cannot be achieved or may be technically difficult, the venous blood sample can be used. Methods: In a prospective analytical study, 80 patients undergoing mechanical ventilation after open-heart surgery in the intensive care unit were evaluated. Simultaneous, matched arterial and central venous blood gas samples were taken from radial artery line and central vein, respectively, when the ABG (arterial blood gases) assessment was needed. Arterial and central venous blood samples were analyzed and data were expressed as mean and ± SD. Results: The Pearson correlation coefficient for pH, PCO2, HCO3, and SatO2 was 0.898, 0.940, 0.840, and 0.567, respectively. There was a significant correlation between arterial and central venous values of pH, PCO2, and HCO3 (P < 0.0001). The mean difference between arterial and central venous PCO2 was -2.44 ± 2.6 mmHg, and the mean venous pH value was only 0.021 ± 0.037 units lower than the mean arterial value. In addition, the calculated mean bicarbonate concentration in venous blood was only about 0.06 ± 1.5 mEq.L higher than the mean arterial value. Conclusions: The central venous PCO2, pH, and HCO3 measured during mechanical ventilation in the intensive care unit approximate arterial values closely enough to permit the estimation of the adequacy of ventilation and acid-base status. The central venous Sat O2 does not reliably parallel the arterial Sat O2. In conclusion, venous blood sampling can potentially reduce the requirement for ABG sampling in special situations.

The Relationship between Arterial and Central Venous Blood Gases Values in Patients Undergoing Mechanical Ventilation after Cardiac Surgery.

BackgroundThe most straightforward method of ascertaining arterial PO2, PCO2, and other components of blood gas is to measure them directly from a blood sample. In situations in which arterial puncture cannot be achieved or may be technically difficult, the venous blood sample can be used.MethodsIn a prospective analytical study, 80 patients undergoing mechanical ventilation after open-heart surgery in the intensive care unit were evaluated. Simultaneous, matched arterial and central venous blood gas samples were taken from radial artery line and central vein, respectively, when the ABG (arterial blood gases) assessment was needed. Arterial and central venous blood samples were analyzed and data were expressed as mean and ± SD.ResultsThe Pearson correlation coefficient for pH, PCO2, HCO3, and SatO2 was 0.898, 0.940, 0.840, and 0.567, respectively. There was a significant correlation between arterial and central venous values of pH, PCO2, and HCO3 (P < 0.0001). The mean difference between arterial and central venous PCO2 was -2.44 ± 2.6 mmHg, and the mean venous pH value was only 0.021 ± 0.037 units lower than the mean arterial value. In addition, the calculated mean bicarbonate concentration in venous blood was only about 0.06 ± 1.5 mEq.L higher than the mean arterial value.ConclusionsThe central venous PCO2, pH, and HCO3 measured during mechanical ventilation in the intensive care unit approximate arterial values closely enough to permit the estimation of the adequacy of ventilation and acid-base status. The central venous Sat O2 does not reliably parallel the arterial Sat O2. In conclusion, venous blood sampling can potentially reduce the requirement for ABG sampling in special situations.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a syndrome, a combination of clinical and physiological observations that describe a pathological state. The pathogenesis of ARDS is not completely clear and there is no gold standard for diagnosis. ARDS is characterized by non-cardiogenic pulmonary edema, inflammation of the lungs, hypoxemia, and decreased lung compliance. Acute is defined as a symptom that occurs within one week of a known risk factor. Early clinical manifestations are shortness of breath (dyspneu and tachypneu) which then quickly develop into respiratory failure. ARDS was first described in 1967 by Asbaugh, et al., then the AECC made a definition that was finally refined by Berlin's criteria. Berlin's criteria divided the degree of hypoxemia into 3, namely mild, moderate, and severe, based on the arterial PO2 / FiO2 ratio and the need for PEEP (5 cm H2O or more) which can be given via endotracheal tube or non-invasive ventilation. Sepsis, aspiration of fluid or gastric contents, and multipe transfusion (&gt;15 units/24 hours) are associated with a high risk of ARDS. Cases of ARDS related to pulmonary sepsis, such as pneumonia, inhalational trauma, and pulmonary contusions are as much as 46% or non-pulmonary sepsis as much as 33%. ARDS management includes oxygen therapy and supportive therapy, such as hemodynamics, pharmacotherapy, and nutrition. Further studies are still needed to get a good outcome for ARDS patients.

Compromised microvascular oxygen delivery increases brain tissue vulnerability with age

Despite the possible role of impaired cerebral tissue oxygenation in age-related cognition decline, much is still unknown about the changes in brain tissue pO2 with age. Using a detailed investigation of the age-related changes in cerebral tissue oxygenation in the barrel cortex of healthy, awake aged mice, we demonstrate decreased arteriolar and tissue pO2 with age. These changes are exacerbated after middle-age. We further uncovered evidence of the presence of hypoxic micro-pockets in the cortex of awake old mice. Our data suggests that from young to middle-age, a well-regulated capillary oxygen supply maintains the oxygen availability in cerebral tissue, despite decreased tissue pO2 next to arterioles. After middle-age, due to decreased hematocrit, reduced capillary density and higher capillary transit time heterogeneity, the capillary network fails to compensate for larger decreases in arterial pO2. The substantial decrease in brain tissue pO2, and the presence of hypoxic micro-pockets after middle-age are of significant importance, as these factors may be related to cognitive decline in elderly people.

Hypnotic agents for induction of general anesthesia in cesarean section patients: A systematic review and meta-analysis of randomized controlled trials

Study objectiveAn ideal induction drug for cesarean section (CS) must have quick action, with minimum side effects such as awareness, hemodynamic compromise, and neonatal depression. Thiopentone is frequently used; however, no reliable evidence is available to support its use as a dedicated hypnotic agent in this setting. DesignA systematic review and meta-analysis, using PRISMA methodology, of randomized controlled trials (RCTs), comparing women undergoing CS using thiopentone with those undergoing CS with propofol, ketamine, or benzodiazepines as hypnotic agents. Data sourcesComprehensive search without language restrictions of MEDLINE, EMBASE, and the Cochrane Controlled Trials Registers until May 2015, with an update in January 2017. Included trials must have reported at least one of the following variables: neonatal arterial or venous umbilical blood gas, maternal systolic blood pressure pre- and post-intubation, or Apgar score. Main resultsA total of 911 patients from 18 RCTs were eligible for quantitative analysis. The increase in maternal systolic blood pressure was smaller in patients administered propofol, compared with those administered thiopentone (weighted mean difference [WMD]: −11.52 [−17.60, −5.45]; p = 0.0002). Induction with propofol also resulted in a significantly lower umbilical arterial pO2 (WMD: −0.12 [−0.20, −0.04]; p = 0.004) than induction with thiopentone. A comparison between propofol and thiopentone revealed no significant differences in other umbilical blood gas parameters or in Apgar scores. In contrast, when comparing ketamine with thiopentone, the number of neonates with a lower Apgar score (<7) at 1 and 5 min was significantly higher in the ketamine group than in the thiopentone group (p = 0.004). ConclusionThe evidence, based on sparse and relatively old trials, indicates that propofol and thiopentone are equally suited for CS. After 1 and 5 min, ketamine yields lower Apgar scores than thiopentone. Additional well-designed trials are needed to reach firmer conclusions.

Maternal undernutrition in late gestation increases IGF2 signalling molecules and collagen deposition in the right ventricle of the fetal sheep heart.

This study investigates the impact of decreased fetal plasma glucose concentrations on the developing heart in late gestation, by subjecting pregnant ewes to a 50% global nutrient restriction. Late gestation undernutrition (LGUN) decreased fetal plasma glucose concentrations whilst maintaining a normoxemic blood gas status. LGUN increased the mRNA expression of IGF2 and IGF2R. Fetal plasma glucose concentrations, but not fetal blood pressure, were significantly correlated with IGF2 expression and the activation of CAMKII in the fetal right ventricle. LGUN increased interstitial collagen deposition and altered the protein abundance of phospho-PLB and phospho-troponin I, regulators of cardiac contractility and relaxation. This study shows that a decrease in fetal plasma glucose concentrations may play a role in the development of detrimental changes in the right ventricle in early life, highlighting CAMKII as a potential target for the development of intervention strategies. Exposure of the fetus to a range of environmental stressors, including maternal undernutrition, is associated with an increased risk of death from cardiovascular disease in adult life. This study aimed to determine the effect of maternal nutrient restriction in late gestation on the molecular mechanisms that regulate cardiac growth and development of the fetal heart. Maternal undernutrition resulted in a decrease in fetal glucose concentrations across late gestation, whilst fetal arterial PO2 remained unchanged between the control and late gestation undernutrition (LGUN) groups. There was evidence of an up-regulation of IGF2/IGF2R signalling through the CAMKII pathway in the fetal right ventricle in the LGUN group, suggesting an increase in hypertrophic signalling. LGUN also resulted in an increased mRNA expression of COL1A, TIMP1 and TIMP3 in the right ventricle of the fetal heart. In addition, there was an inverse relationship between fetal glucose concentrations and COL1A expression. The presence of interstitial fibrosis in the heart of the LGUN group was confirmed through the quantification of picrosirius red-stained sections of the right ventricle. We have therefore shown that maternal undernutrition in late gestation may drive the onset of myocardial remodelling in the fetal right ventricle and thus has negative implications for right ventricle function and cardiac health in later life.

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia.

The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO2 decrease, and they relax as arterial PO2 is re-established. The hypoxic pulmonary vasoconstriction (HPV) is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand, pulmonary arteries also respond to sustained hypoxia with structural and functional remodeling, involving growth of smooth muscle medial layer and later recruitment of adventitial fibroblasts, secreted mitogens from endothelium and changes in the response to vasoconstrictor and vasodilator stimuli. Hypoxic pulmonary arterial vasoconstriction and remodeling are relevant biological responses both under physiological and pathological conditions, to explain matching between ventilation and perfusion, fetal to neonatal transition of pulmonary circulation and pulmonary artery over-constriction and thickening in pulmonary hypertension. Store operated channels (SOC) and receptor operated channels (ROC) are plasma membrane cationic channels that mediate calcium influx in response to depletion of internal calcium stores or receptor activation, respectively. They are involved in both HPV and pathological remodeling since their pharmacological blockade or genetic suppression of several of the Stim, Orai, TRP, or ASIC proteins in SOC or ROC complexes attenuate the calcium increase, the tension development, the pulmonary artery smooth muscle proliferation, and pulmonary arterial hypertension. In this Mini Review, we discussed the evidence obtained in in vivo animal models, at the level of isolated organ or cells of pulmonary arteries, and we identified and discussed the questions for future research needed to validate these signaling complexes as targets against pulmonary hypertension.

Altered autonomic control of heart rate variability in the chronically hypoxic fetus.

Key points Fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, and a decrease in FHRV is associated with fetal compromise. However, the mechanisms by which FHRV is reduced in the chronically hypoxic fetus have yet to be established.The sympathetic and parasympathetic influences on heart rate mature at different rates throughout fetal life, and can be assessed by time domain and power spectral analysis of FHRV.In this study of chronically instrumented fetal sheep in late gestation, we analysed FHRV daily over a 16 day period towards term, and compared changes between fetuses of control and chronically hypoxic pregnancy.We show that FHRV in sheep is reduced by chronic hypoxia, predominantly due to dysregulation of the sympathetic control of the fetal heart rate. This presents a potential mechanism by which a reduction in indices of FHRV predicts fetuses at increased risk of neonatal morbidity and mortality in humans.Reduction in overall FHRV may therefore provide a biomarker that autonomic dysregulation of fetal heart rate control has taken place in a fetus where uteroplacental dysfunction is suspected. Although fetal heart rate variability (FHRV) has long been recognised as a powerful predictor of fetal wellbeing, the mechanisms by which it is reduced in the chronically hypoxic fetus have yet to be established. In particular, the physiological mechanism underlying the reduction of short term variation (STV) in fetal compromise remains unclear. In this study, we present a longitudinal study of the development of autonomic control of FHRV, assessed by indirect indices, time domain and power spectral analysis, in normoxic and chronically hypoxic, chronically catheterised, singleton fetal sheep over the last third of gestation. We used isobaric chambers able to maintain pregnant sheep for prolonged periods in hypoxic conditions (stable fetal femoral arterial PO2 10–12 mmHg), and a customised wireless data acquisition system to record beat‐to‐beat variation in the fetal heart rate. We determined in vivo longitudinal changes in overall FHRV and the sympathetic and parasympathetic contribution to FHRV in hypoxic (n = 6) and normoxic (n = 6) ovine fetuses with advancing gestational age. Normoxic fetuses show gestational age‐related increases in overall indices of FHRV, and in the sympathetic nervous system contribution to FHRV (P < 0.001). Conversely, gestational age‐related increases in overall FHRV were impaired by exposure to chronic hypoxia, and there was evidence of suppression of the sympathetic nervous system control of FHRV after 72 h of exposure to hypoxia (P < 0.001). This demonstrates that exposure to late gestation isolated chronic fetal hypoxia has the potential to alter the development of the autonomic nervous system control of FHRV in sheep. This presents a potential mechanism by which a reduction in indices of FHRV in human fetuses affected by uteroplacental dysfunction can predict fetuses at increased risk.

A New, Noninvasive Method of Measuring Pulmonary Gas Exchange: Results in Normal Subjects and Patients with Lung Disease

MethodsThe person breathes through a device that continually measures and displays the inspired and expired PO2 and PCO2. An oximeter is worn, and the arterial PO2 is calculated from the SpO2 and the oxygen dissociation curve, using the end–tidal PCO2 to account for the effect of PCO2 on the oxygen affinity of hemoglobin. The PO2 difference between the end‐tidal gas and the calculated arterial value is called the Oxygen Deficit. Since the calculation is only accurate when the arterial oxygen saturations are 94% or less, the normal subjects breathed 12.5% oxygen.ResultsStudies were made on 17 patients with a variety of pulmonary diseases who were attending an outpatient clinic. The mean oxygen deficit was 48.7 mm Hg, SE 3.1. This can be contrasted with a mean oxygen deficit of 4.0 mm Hg, SE 0.91 in a group of 30 normal subjects who were previously studied. The p value for the difference between the two groups was &lt; 0.0001. Within the normal subjects, the mean oxygen deficit for the 19 younger participants (ages 22–31) was 2.02 mm Hg, SE 0.84 while that in the 11 older participants (ages 47–88) was 7.53 mm Hg, SE 1.55. The p value for the difference between the young and old groups was 0.0015. The mean oxygen deficit in younger normal subjects is remarkably small. This implies that there is very little difference between the calculated arterial PO2 and the alveolar PO2, consistent with little impairment of gas exchange. However, the mean oxygen deficit in older normal subjects is significantly higher consistent with the increased Alveolar‐arterial (A‐a) PO2 gradient with age, which has been well documented in the literature. Analysis of the factors determining the magnitude of the oxygen deficit showed that the end–tidal PO2 was the most important factor, followed by the end–tidal PCO2, and the calculated arterial PO2. Interestingly the SpO2 had a minor influence in spite of the fact that the oximeter reading is frequently used to guide therapy. The analysis emphasizes the value of measuring the composition of alveolar gas in determining ventilation‐perfusion ratio inequality. Remarkably, this factor is largely ignored in the classical index of impaired pulmonary gas exchange using the ideal alveolar PO2 to calculate the A‐a O2 gradient. We argue that ignoring the actual alveolar value gives an incomplete picture of gas exchange in the lungs because the traditional index is heavily biased by lung units with low ventilation‐perfusion ratios. Therefore, by using the new index of oxygen deficit, we derive a more comprehensive measurement of gas exchange in the lungs.Support or Funding InformationSupported by MediPines IncThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.