Mixed Venous Blood Research Articles

Repercussions of SARS-CoV-2 infection on intrapulmonary shunt in patients undergoing one-lung ventilation

BackgroundHypoxic pulmonary vasoconstriction is the most important regulatory mechanism by which right-to-left shunts decrease during one-lung ventilation (OLV), but the effects of pulmonary microarterial thrombosis and impaired HPV after SARS-CoV-2 infection on intrapulmonary shunt during OLV remain unknown. The aim of this study was to observe the changes of intrapulmonary shunt in patients undergoing thoracoscopic partial pneumonectomy at different periods after SARS-CoV-2 infection compared with patients without SARS-CoV-2 infection history.MethodsA total of 80 patients who underwent elective thoracoscopic partial lung resection and were classified as American Society of Anaesthesiologists (ASA) grades I-II were selected and divided into 4 groups (n = 20 in each group): patients not infected with SARS-CoV-2 (Group A), patients infected with SARS-CoV-2 for 5–8 weeks (Group B), patients infected with SARS-CoV-2 for 9–12 weeks (Group C), and patients infected with SARS-CoV-2 for 13–16 weeks (Group D). For all patients, the same anaesthesia method was adopted, and anaesthesia was maintained with propofol, remifentanil, and cisatracurium. Radial artery and mixed venous blood gases were measured at 10 min of two-lung ventilation (TLV), 15 min of one-lung ventilation (OLV15), and 30 min of OLV (OLV30) in the lateral recumbent position to calculate the intrapulmonary shunt. Multiple linear regression analysis was employed to investigate the association between intrapulmonary shunt and SARS-CoV-2 infection.ResultsQs/Qt at TLV was significantly higher in Groups B and C than in Group A (P < 0.05), and PaO2 at TLV was significantly lower in Groups B and C than in Group A (P < 0.05). Qs/Qt values at OLV15 and OLV30 were significantly higher in Group B, C or D than in Group A (P < 0.05), and PaO2 values at OLV15 and OLV30 were significantly lower in Groups B, C or D than in Group A (P < 0.05). Multiple linear regression analysis revealed that SARS-CoV-2 infection (95%CI -4.245 to -0.679, P = 0.007) was an independent risk factor for increased intrapulmonary shunt during TLV, while SARS-CoV-2 infection (95%CI 0.124 to 3.661, P = 0.036), exacerbation of COVID-19 clinical classification (95%CI -5.203 to -1.139, P = 0.003), and persistent symptoms (95%CI -12.122 to -5.522, P < 0.001) were independent risk factors for increased intrapulmonary shunt during OLV after SARS-CoV-2 infection.ConclusionSARS-CoV-2 infection increased intrapulmonary shunt and reduced oxygenation. Although oxygenation improved at TLV after 13–16 weeks of infection, intrapulmonary shunt and oxygenation under OLV took longer to recover.Trial registrationChinese Clinical Trial Registry, Retrospectively registered, Full date of first registration: 17/05/2023, Registration number: ChiCTR2300071539.

Multi-compartment V/Q lung modeling: Log normal distributions of inspired or expired alveolar gas?

Using a 50-compartment Python-coded mathematical lung model, we compared mixed venous blood flow (Q) distributions and arterial oxygen tension/inspired oxygen fraction (PaO2/FiO2) relationships in lungs modeled with log normal distributions (LND) of inspired (VI) versus expired (VA) alveolar gas volumes. In lungs with normal V/Q heterogeneity, Q versus VA/Q and Q versus VI/Q distributions were similar with either approach, and PaO2/FiO2 sequences remained indistinguishable. In V/Q heterogeneous lungs at high FiO2, VILND generated low Q versus VA/Q shoulders and some negative VA units, while VALND preserved Q versus VA/Q log normality by blood flow diversion from low VI/Q units. We managed VILND-induced negative VA units either by shunt conversion (VI decreased to 0) or VI redistribution simulating collateral ventilation (VI increased till VA = 0). Comparing oxygen transfer: VALND > VILND (redistribution) > VILND (shunt). In V/Q heterogeneous lungs VALND and VILND (redistribution) regained near optimal oxygen transfer on 100% oxygen, while impairment persisted with VILND (shunt). Unlike VALND, VILND (redistribution) produced Q versus VA/Q distributions in V/Q heterogeneity compatible with multiple inert gas (MIGET) reports. VILND (redistribution) is a physiologically-based MIGET-compatible alternative to West's original VALND lung modeling approach.

#1001 Model-based profiling of bicarbonate supplementation during a hemodialysis cycle

Abstract Background and Aims Bicarbonate is delivered to hemodialysis (HD) patients via diffusion following a concentration gradient across the dialyzer membrane. However, the concentration of bicarbonate in the dialysis fluid ([HCO3]d) is usually not individualized for the specific patient's conditions, as no clear guidelines are provided, which leads to suboptimal pre- and post-dialytic plasma bicarbonate concentrations ([HCO3]p) during each treatment cycle. We used a mathematical model to predict the outcomes of a week-long HD cycle with time-dependent [HCO3]d in 24 patients, tuning the [HCO3]d prescription to keep the simulated pre-dialytic [HCO3]p in the range 22-24 mEq/L throughout the week. The [HCO3]d profiles thus developed were then tested, and [HCO3]p during HD compared with those using a constant [HCO3]d in the same patients. Method The compartmental model (Pietribiasi et al PLOS ONE 2023) describes the transport of total CO2, O2, and total buffer base in arterial and mixed-venous blood (plasma and red blood cells), tissues (interstitial and intracellular fluid), and lung capillaries and alveoli, calculating derivate quantities such as bicarbonate concentration, pH, partial pressure of CO2. The patients underwent one week of standard HD with constant [HCO3}d (Week 1, [HCO3]d = 33.6 ± 1.8 mEq/L) consisting of 3 sessions (HD1, HD2, HD3) to estimate the baseline model parameters and, successively, an intervention week (Week 2), during which the model-derived [HCO3]d profiles were implemented. Each profile consisted of a single step increase after 2 hours of HD, the two values of [HCO3]d chosen for each session and patient according to the model's simulations. Blood samples for the blood gas analyzer were taken before and after each session, and each hour during HD2. Results [HCO3]p profiles in Week 2 showed a more linear increase compared those of Week 1 (Fig. 1). The efficacy of the response to the model-based treatment was different depending on whether the intervention aimed to decrease or increase pre-dialytic [HCO3]p during Week 2 (Fig. 2). In the group of patients attempting to decrease pre-dialytic [HCO3]p (Decrease group, n = 10, average [HCO3]d = 31.3 ± 1.5 mEq/L), a significant fraction of sessions achieved the target (60% across the whole week). In contrast, among the patients attempting to increase pre-dialytic [HCO3]p (Increase group, n = 6, average [HCO3]d = 35.3 ± 2.0 mEq/L), the model-based prescription was effective only in increasing post-dialytic concentration (20% of sessions achieved pre-dialytic targets). By comparison, during Week 1 only 30% and 10% of sessions were in the target range for Decrease and Increase groups, respectively. Patients for which we didn't want to alter pre-dialytic [HCO3]p were termed the Neutral group (n = 8, average [HCO3]d = 33.3 ± 2.1 mEq/L, 40% and 50% of sessions in the target [HCO3]p range in Week 1 and 2, respectively). Conclusion The model-based profiling intervention was only partially successful in achieving the targets for pre-dialytic [HCO3]p in Week 2. The reasons why pre-dialytic [HCO3]p were resistant to the model-based [HCO3]d in the Increase group are not clear, but it could be that the increase in the average [HCO3]d was too small (6-7% higher than Week 1). However, in the Decrease group a similar difference was sufficient to produce a more marked decrease in pre-dialytic [HCO3]p. The profiling of [HCO3]d was shown to be effective in reducing the time the patients spend at higher [HCO3]p. Nevertheless, our study demonstrated that, upon refinement, mathematical modeling can be used to develop individualized treatments to pilot the markers of the acid-base response to HD towards desired values.

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study

BackgroundAcute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model.MethodsThis was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied.ResultsPulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs.ConclusionIn an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

Oxygen delivery and consumption in comatose out-of-hospital cardiac arrest patients are affected by blood pressure targets

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Grosserer L. F. Foghts Fond Background Hemodynamic instability is common after resuscitated out-of-hospital cardiac arrest (OHCA). Preventing inadequate oxygen delivery (DO2) to the cells and thus not meeting oxygen demand is crucial to prevent further organ dysfunction. Additionally, oxygen uptake in the cells may be impaired. Oxygen consumption (VO2; the amount of oxygen consumed by the body per minute) could thus also be affected in OHCA. Purpose This study aimed to describe the effect of different mean arterial blood pressure (MAP) and partial arterial oxygen pressure (PaO2) targets on DO2 and VO2. Methods This post-hoc study is based on the BOX trial, a 2x2 factorial design that randomized OHCA patients to a MAP of either 63 mmHg (MAP63) or 77 mmHg (MAP77) and a partial pressure of arterial oxygen of 9 to 10 kPa or a liberal oxygen target of a PaO2 of 13 to 14 kPa at two cardiac centers in Denmark. Pulmonary artery catheters were placed to evaluate cardiac output and collect mixed venous blood samples at prespecified time points. Oxygen blood contents were calculated for arterial (CaO2) and mixed venous blood (CvO2) as Hgb (mg/dl) x 10 x 1.39 x Saturation O2 (proportion) + 0.0225 x PaO2. DO2 = CO x CaO2, and VO2 = CO x (CaO2-CvO2). Results This study included 715 patients (90% of the total cohort with a pulmonary catheter) for analysis. A restrictive or liberal oxygen supplement did not affect DO2 or VO2 during the initial 48 hours. The MAP77 group exhibited on average 11% higher DO2 (95%CI: 6%-15%) and on average a 6% higher VO2 in the first 48 hours (95%CI: 3%-10%) compared to the MAP63 group (see Figure 1). Conclusion Targeting a PaO2 of either 9 to 10 kPa or 13 to 15 kPa resulted in no significant changes in the provision of oxygen to the cells, nor did it increase the consumption of oxygen. In contrast, targeting a MAP of 77 mmHg resulted in an increase in both the provision of oxygen and consumption of oxygen compared to a MAP target of 63 mmHg.Figure 1

Hyperlactataemia is a marker of reduced exercise capacity in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with an array of central and peripheral haemodynamic and metabolic changes. The exact pathogenesis of exercise limitation in HFpEF remains uncertain. Our aim was to compare lactate accumulation and central haemodynamic responses to exercise in patients with HFpEF, non-cardiac dyspnoea (NCD), and healthy volunteers. Right heart catheterization with mixed venous blood gas and lactate measurements was performed at rest and during symptom-limited supine exercise. Multivariable analyses were conducted to determine the relationship between haemodynamic and biochemical parameters and their association with exercise capacity. Of 362 subjects, 198 (55%) had HFpEF, 103 (28%) had NCD, and 61 (17%) were healthy volunteers. This included 139 (70%) females with HFpEF, 77 (75%) in NCD (P=0.41 HFpEF vs. NCD), and 31 (51%) in healthy volunteers (P<0.001 HFpEF vs. volunteers). The median age was 71 (65, 75) years in HFpEF, 66 (57, 72) years in NCD, and 49 (38, 65) years in healthy volunteers (HFpEF vs. NCD or volunteer, both P<0.001). Peak workload was lower in HFpEF compared with healthy volunteers [52W (interquartile range 31-73), 150W (125-175), P<0.001], but not NCD [53W (33, 75), P=0.85]. Exercise lactate indexed to workload was higher in HFpEF at 0.08mmol/L/W (0.05-0.11), 0.06mmol/L/W (0.05-0.08; P=0.016) in NCD, and 0.04mmol/L/W (0.03-0.05; P<0.001) in volunteers. Exercise cardiac index was 4.5L/min/m2 (3.7-5.5) in HFpEF, 5.2L/min/m2 (4.3-6.2; P<0.001) in NCD, and 9.1L/min/m2 (8.0-9.9; P<0.001) in volunteers. Oxygen delivery in HFpEF was lower at 1553mL/min (1175-1986) vs. 1758mL/min (1361-2282; P=0.024) in NCD and 3117mL/min (2667-3502; P<0.001) in the volunteer group during exercise. Predictors of higher exercise lactate levels in HFpEF following adjustment included female sex and chronic kidney disease (both P<0.001). HFpEF is associated with reduced exercise capacity secondary to both central and peripheral factors that alter oxygen utilization. This results in hyperlactataemia. In HFpEF, plasma lactate responses to exercise may be a marker of haemodynamic and cardiometabolic derangements and represent an important target for future potential therapies.

CO2 gap changes compared with cardiac output changes in response to intravenous volume expansion and/or vasopressor therapy in septic shock.

The difference in partial pressure of carbon dioxide (PCO2) between mixed or central venous blood and arterial blood, known as the ∆PCO2 or CO2 gap, has demonstrated a strong relationship with cardiac index during septic shock resuscitation. Early monitoring of the ∆PCO2 can help assess the cardiac output (CO) adequacy for tissue perfusion. To investigate the value of ∆PCO2 changes in early septic shock management compared with CO. This observational prospective study included 76 patients diagnosed with septic shock admitted to Cairo University Hospital's Critical Care Department between December 2020 and March 2022. Patients were categorised by initial resuscitation response, initial ∆PCO2 and 28-day mortality. The primary outcome was the relationship between the ∆PCO2 and CO changes before and after initial resuscitation, with secondary outcomes including ICU length of stay (LOS) and 28-day mortality. Peri-resuscitation ∆PCO2 changes predicted a ≥15% change in the cardiac index (CI) (area under the curve (AUC) 0.727; 95% CI 0.614 - 0.840) with 66.7% sensitivity and 62.8% specificity. The optimal ∆PCO2 change cut-off value was <-1.85, corresponding to a <-22% threshold for a 15% cardiac index increase. The PCO2 gap ratio (gap/gap ratio of T1- PCO2 gap to T0 -PCO2 gap) also predicted a ≥15% change in cardiac index (AUC 745; 95% CI 0.634 - 0.855) with 63.6% sensitivity and 79.1% specificity. The optimal CO2 gap/gap ratio cut-off value was <0.71. A significant difference in 28-day mortality was noted based on the gap/gap ratio. Peri-resuscitation ∆PCO2 and the gap/gap ratio are useful non-invasive bedside markers for predicting changes in CO and preload responsiveness. The current study provides an insight to the PCO2 gap changes during and after early resuscitation of septic shock patients, which correlate to cardiac output changes and might also serve as a fluid responsiveness indicator.

Pharmacokinetics of desflurane uptake and disposition in piglets.

Many respiratory but few arterial blood pharmacokinetics of desflurane uptake and disposition have been investigated. We explored the pharmacokinetic parameters in piglets by comparing inspiratory, end-tidal, arterial blood, and mixed venous blood concentrations of desflurane. Seven piglets were administered inspiratory 6% desflurane by inhalation over 2h, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were detected using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine desflurane concentrations by gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120min during each uptake and disposition phase. Respiratory and hemodynamic parameters were measured simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between the arterial and pulmonary artery blood concentrations by the cardiac output. The rates of desflurane body uptake increased considerably in the initial 5min (79.8ml.min-1) and then declined slowly until 120min (27.0ml.min-1). Similar characteristics of washout were noted during the subsequent disposition phase. Concentration-time curves of end-tidal, arterial, and pulmonary artery blood concentrations fitted well to zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best fitted using a two-compartment model. After 2h, only 21.9% of the desflurane administered had been eliminated from the body. Under a fixed inspiratory concentration, desflurane body uptake in piglets corresponded to constant zero-order infusion, and the 2-h disposition pattern followed first-order kinetics and best fitted to a two-compartment model.

Effects of tasipimidine premedication with and without methadone and dexmedetomidine on cardiovascular variables during propofol-isoflurane anaesthesia in Beagle dogs

ObjectiveTo evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. Study designProspective, placebo-controlled, blinded, experimental trial. AnimalsA group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. MethodsThe dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 μg kg–1 orally and placebo IV; TMP: tasipimidine 30 μg kg–1 orally and methadone 0.2 mg kg–1 IV; and TMPD: tasipimidine 30 μg kg–1 orally with methadone 0.2 mg kg–1 and dexmedetomidine 1 μg kg–1 IV followed by 1 μg kg–1 hour–1.Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. ResultsTasipimidine induced a significant 20–30% reduction in HR and CO with decreases in MAP (10–15%), tbf (40%) and stO2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. Conclusions and clinical relevanceTasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored.

Relationship Between the Mixed Venous-to-Arterial Carbon Dioxide Gradient and Cardiac Index in Acute Pulmonary Embolism.

Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without clinically apparent shock. The purpose of this study was to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy. This was a single-center retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds (OR = 7.9; 95% CI 3.49-18.1, p < 0.001) for an elevated CO2 gap. There was an inverse relationship between CI and CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (p = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in in-hospital mortality (9% vs. 0%; p = 0.10, HR: 1.24; 95% CI: 0.97-1.60; P = 0.085). Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification.

Overdot and overline annotation must be understood to accurately interpret O2MAX physiology with the Fick formula.

Few formulas have been used in exercise physiology as extensively as the Fick formula, which calculates the rate of oxygen consumption (i.e., V.O2) as the product of cardiac output (Q.) and the difference in oxygen content in arterial and mixed venous blood (ΔaO2). Unfortunately, the physiology of maximum V.O2 (V.O2MAX) is often misinterpreted due to a lack of appreciation for the limitations represented by the oft-ignored superscript annotations in the Fick formula. The purpose of this perspective is to explain the meaning of the superscript annotations and highlight how such annotations influence proper interpretation of V.O2MAX physiology with the Fick formula. First, we explain the significance of the overdots above V.O2 and Q., which indicate a measure per unit of time. As we will show, the presence of an overdot above Q. and lack of one above ΔaO2 denotes they are different types of ratios and should be interpreted in the context of one another-not in contrast to each other as is commonplace. Second, we discuss the significance of the overline above the "" in ΔaO2, which indicates the venous sample is an average of blood that comes from mixed sources. The mixed nature of the venous sample has major implications for interpreting the influence of oxygen diffusion and blood flow heterogeneity on V.O2MAX. Ultimately, we give recommendations and insights for using the Fick formula to calculate V.O2 and interpret V.O2MAX physiology.

The Impact of Diabetes on Haemodynamic and Cardiometabolic Responses in Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection (HFpEF) and diabetes mellitus (DM) commonly co-exist. However, it is unclear if DM modifies the haemodynamic and cardiometabolic phenotype in patients with HFpEF. We aimed to interrogate the haemodynamic and cardiometabolic effects of DM in HFpEF. We compared the haemodynamic and metabolic profiles of non-DM patients and patients with DM-HFpEF at rest and during exercise using right heart catheterisation and mixed venous blood gas analysis. Of 181 patients with HFpEF, 37 (20%) had DM. Patients with DM displayed a more adverse exercise haemodynamic response vs HFpEF alone (mean pulmonary arterial pressure: 47 mmHg [interquartile range {IQR} 42-55] vs 42 [38-47], p<0.001; workload indexed pulmonary capillary wedge pressure indexed: 0.80 mmHg/W [0.44-1.23] vs 0.57 [0.43-1.01], p=0.047). HFpEF-DM patients had a lower mixed venous oxygen saturation at rest (70% [IQR 66-73] vs 72 [69-75], p=0.003) and were unable to enhance O2 extraction to the same extent (Δ-28% [-33 to -15] vs -29 [-36 to -21], p=0.029), this occurred at a 22% lower median workload. Resting mixed venous lactate levels were higher in those with DM (1.5 mmol/L [IQR 1.1-1.9] vs 1 [0.9-1.3], p<0.001), and during exercise indexed to workload (0.09 mmol/L/W [0.06-0.13] vs 0.08 [0.05-0.11], p=0.018). Concurrent diabetes and HFpEF was associated with greater metabolic responses at rest, with enhanced wedge driven pulmonary hypertension and relative lactataemia during exercise without appropriate augmentation of oxygen consumption.

Impact of mechanical power and positive end expiratory pressure on central vs. mixed oxygen and carbon dioxide related variables in a population of female piglets.

The use of the pulmonary artery catheter has decreased overtime; central venous blood gases are generally used in place of mixed venous samples. We want to evaluate the accuracy of oxygen and carbon dioxide related parameters from a central versus a mixed venous sample, and whether this difference is influenced by mechanical ventilation. We analyzed 78 healthy female piglets ventilated with different mechanical power. There was a significant difference in oxygen-derived parameters between samples taken from the central venous and mixed venous blood (S O2 = 74.6%, ScvO2 = 83%, p < 0.0001). Conversely, CO2-related parameters were similar, with strong correlation. Ventilation with higher mechanical power and PEEP increased the difference between oxygen saturations, (Δ[ScvO2-S O2 ] = 7.22% vs. 10.0% respectively in the low and high MP groups, p = 0.020); carbon dioxide-related parameters remained unchanged (p = 0.344). The venous oxygen saturation (central or mixed) may be influenced by the effects of mechanical ventilation. Therefore, central venous data should be interpreted with more caution when using higher mechanical power. On the contrary, carbon dioxide-derived parameters are more stable and similar between the two sampling sites, independently of mechanical power or positive end expiratory pressures.

A Dynamic Sheep Model to Induce Pulmonary Hypertension and Right Ventricular Failure.

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript describes the method to induce an ovine PH-RVF model that utilizes left pulmonary artery (LPA) ligation, progressive main pulmonary artery (MPA) banding, and insertion of an RV pressure line for monitoring. The PA cuff and RV pressure tubing are connected to subcutaneous access ports. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV's phenotypic response. Subjects undergo progressive PA band adjustments twice per week for approximately 9weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO2). Subjects can further be exercised on a livestock treadmill while hemodynamic parameters are captured. At the initiation and endpoint of this model, ventricular function and dimensions are assessed using echocardiography. In this model, RV mean and systolic pressure increased to 28±5 and 57±7mmHg at week 1, and further to 44±7 and 93±18mmHg by week 9, respectively. Echocardiography demonstrates characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The rate of PA banding has a significant impact on SvO2 and thus the model can be titrated to elicit varying RV phenotypes. When the PA cuff is tightened rapidly, it can lead to a precipitous decline in SvO2, leading to RV decompensation, whereas a slower, more paced strategy leads to an adaptive RV stress-load response that maintains physiologic SvO2. A faster rate of PA banding will also lead to more severe liver fibrosis. The addition of controlled exercise provides a useful platform for assessing the effects of physical exertion in a PH-RVF model. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and evaluating mechanical circulatory support systems.

Effects of N2 O elimination on the elimination of second gases in a two-step mathematical model of heterogeneous gas exchange.

We have investigated the elimination of inert gases in the lung during the elimination of nitrous oxide (N2 O) using a two-step mathematical model that allows the contribution from net gas volume expansion, which occurs in Step 2, to be separated from other factors. When a second inert gas is used in addition to N2 O, the effect on that gas appears as an extra volume of the gas eliminated in association with the dilution produced by N2 O washout in Step 2. We first considered the effect of elimination in a single gas-exchanging unit under steady-state conditions and then extended our analysis to a lung having a log-normal distribution of ventilation and perfusion. A further increase in inert gas elimination was demonstrated with gases of low solubility in the presence of the increased ventilation-perfusion mismatch that is known to occur during anesthesia. These effects are transient because N2 O elimination depletes the input of that gas from mixed venous blood to the lung, thereby rapidly reducing the magnitude of the diluting action.

To study indication’s outcomes and complications of non-invasive ventilation in acute respiratory failure

Failure of respiratory system in one or both of its gas-exchanging functions- oxygenation of pulmonary arterial blood and carbon-dioxide elimination from mixed venous blood. Non-Invasive Ventilation is an alternative to invasive ventilation in many conditions it is a valuable component in patient management. Its use in acute respiratory failure is widely accepted and well known. To Study the indications, outcomes, and complications of NIV. This is a prospective observational study conducted on 100 patients admitted with either Type-I or Type -II respiratory failure. Various common indications for use of NIV in acute Respiratory Failure are COPD, ILD, Bronchiectasis, Pneumonia, Pulmonary Thromboembolism, Kyphoscoliosis, and Pulmonary Tuberculosis in that order. The overall success rate of NIV is 84%. NIV helps in improving gas exchange in acute respiratory failure irrespective of its type, reduces intubation and length of hospital stay hence, its use as the first modality of treatment in patients without overt contraindications is recommended. Overall, NIV is safe and effective in patients with acute respiratory failure as there are no major complications associated with its use.

#3827 BICARBONATE PROFILING IN HEMODIALYSIS: MATHEMATICAL MODELING OF DATA FROM A CLINICAL TRIAL

Abstract Background and Aims During hemodialysis (HD), bicarbonate and other bases are added to the dialysis fluid to correct chronic acidosis that may develop in kidney-impaired patients, increasing plasma bicarbonate concentration to physiological levels. Previous studies have shown that both exceedingly high and low post-dialysis bicarbonate concentrations are associated with adverse clinical outcomes; however, no clear guidelines for the prescription of bicarbonate concentration in the dialysis fluid are available. Data from a recent controlled clinical trial, carried out at the Department of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw (Poland), were used to identify transport parameters of a mathematical model of acid-base homeostasis in HD patients, as the first step in the implementation of a tool to optimize bicarbonate profiling during HD. Method The study was carried out in 20 chronic patients, undergoing thrice weekly 4-hr HD. The patients underwent three treatment regimens: A) constant dialysis fluid bicarbonate concentration (HCO3,D) equal to 35 mEq/L; B) HCO3,D decreasing from 35 to 30 mEq/L after 2 hrs; C) HCO3,D increasing from 30 to 35 mEq/L after 2 hrs. The patients were divided in two cohorts: for the first (n = 11) treatment schedule was: treatment A during the first and third week, B during the second week and C during the fourth week. For the second cohort (n = 9) treatment C was carried out during the second week and treatment B during the fourth. Data were collected only during the second and third sessions of the week, and acid-base composition was determined using a blood gas analyzer. The mathematical model describes the transport of bicarbonate and dissolved CO2 from dialysis fluid to the patient and can predict changes in the acid-base equilibrium of arterial and venous plasma and erythrocytes, interstitial fluid, and tissue cells, using mass transport equations. The dialysances for bicarbonate (KHCO3) and dissolved CO2 (KCO2) were estimated via least square minimization. Results No significant difference was found comparing patients in the two cohorts, or comparing sessions of the same week. Pre-dialysis plasma bicarbonate, pH, or CO2 partial pressure (PCO2) were significantly lower for treatment B compared to treatment A. Average plasma bicarbonate concentrations for the different treatments are shown in Figure 1 for data and model simulations. Table 1 reports the average values of the estimated parameters for week. No statistically significant difference was found between sessions, cohorts, or treatments. The model fitted bicarbonate data with an average error of 2.5 ± 1.4%, and PCO2 with an error of 4.5 ± 3.6%. Simulations of mixed-venous blood, interstitial fluid, and tissue cells concentrations showed a similar response to different treatments as in arterial blood. Conclusion The model accurately describes plasma bicarbonate data with high accuracy regardless of the treatment conditions. The parameters estimated showed considerable variability between treatments (less so between the sessions of the same week), but without statistical significance. The model can be used to simulate the effect of dialysate bicarbonate profiling on acid-base equilibrium in HD patients.

Larger splenic emptying correlate with slower EPOC kinetics in healthy men and women during supine cycling.

The present study investigated whether larger splenic emptying augments faster excess post-exercise O2 consumption (EPOC) following aerobic exercise cessation. Fifteen healthy participants (age 24 ± 4, 47% women) completed 3 laboratory visits at least 48-h apart. After obtaining medical clearance and familiarizing themselves with the test, they performed a ramp-incremental test in the supine position until task failure. At their final visit, they completed three step-transition tests from 20 W to a moderate-intensity power output (PO), equivalent to [Formula: see text]O2 at 90% gas exchange threshold, where data on metabolic, cardiovascular, and splenic responses were recorded simultaneously. After step-transition test cessation, EPOCfast was recorded, and the first 10min of the recovery period was used for further analysis. Blood samples were collected before and immediately after the end of exercise. In response to moderate-intensity supine cycling ([Formula: see text]O2 = ~ 2.1 L·min-1), a decrease in spleen volume of ~ 35% (p = 0.001) was observed, resulting in a transient increase in red cell count of ~ 3-4% (p = 0.001) in mixed venous blood. In parallel, mean blood pressure, heart rate, and stroke volume increased by 30-100%, respectively. During recovery, mean τ[Formula: see text]O2 was 45 ± 18s, the amplitude was 2.4 ± 0.5 L·min-1, and EPOCfast was 1.69 L·O2. Significant correlations were observed between the percent change in spleen volume and (i) EPOCfast (r = - 0.657, p = 0.008) and (ii) τ[Formula: see text]O2 (r = - 0.619, p = 0.008), but not between the change in spleen volume and (iii) [Formula: see text]O2 peak (r = 0.435, p = 0.105). Apparently, during supine cycling, individuals with larger spleen emptying tend to have slower [Formula: see text] O2 recovery kinetics and a greater EPOCfast.

Saliva versus plasma cytokines as possible predictors of autism severity

The autism spectrum disorders (ASD) are now widely accepted as a pervasive, complex, heterogeneous neurodevelopmental disorders with multiple etiologies, subtypes, and developmental trajectories. There are no available and effective biomarkers for them. Immune dysfunction is seen as an important risk factor contributing to the neurodevelopmental deficit in ASD, and is signified, among other things, by an imbalance of cytokines in the brain and on the periphery. In recent years, saliva has been proposed as a biological material for diagnosing ASD, due to the accessibility and non-invasiveness of the method for its production. However, the question of whether salivary cytokine levels may be used as effective early biomarkers for autism requires further research, including saliva versus plasma/serum comparisons.Aim: a comparative analysis of the levels of cytokines: IL-6, IFNγ, TNFα, IL-1β, IL-4, IL-10, in saliva and blood plasma to identify possible markers of ASD and their severity in children.The study included 11 children with typical neurodevelopment (TDC) and 55 children with ASD, among whom 37 children had mild or moderate autism (according to CARS), and 18 children had severe autism. Samples of unstimulated mixed saliva and venous blood were simultaneously collected from all children. Salivary concentrations of cytokines: IL-6, IFNγ, TNFα, IL-1β, IL-4, IL-10 were determined by multiplex Luminex™ analysis. Plasma levels of cytokines were assessed by ELISA. Differences between groups were tested using the Kruskal-Wallis U-test with post-hoc Conover-Inman comparisons, between samples (saliva/ plasma) are using the Wilcoxon signed-rank test. The correlation between the concentrations of cytokines in plasma and saliva was determined using linear regression by the RMA method.In all examined groups, the levels of IL-6, IFNγ and IL-10 in saliva were significantly lower, and TNFα, IL-1β and IL-4 were higher than the corresponding levels of the same cytokines in plasma. Regardless of health/ disease status, no significant correlations were found between salivary and plasma cytokine levels in children. IL-1β levels were significantly lower and IL-10 levels were higher in the saliva of both groups of children with ASD compared with TDC. No significant differences in salivary cytokine concentrations were found between children with mild and severe ASD.Thus, salivary cytokines can be used as markers of ASD in children, but not the severity of the condition. The absence of correlations in the levels of some pro/anti-inflammatory cytokines between saliva and blood plasma may probably indicate a special immunological status of an ecological niche, the oral cavity.

CARC12: Surgical Correction of De Novo Aortic Valve Insufficiency after Left Ventricular Assist Device Implantation

Background: Development of significant aortic insufficiency (AI) is a common complication associated with prolonged support with continuous-flow left ventricular assist device (CF-LVAD). The aim of this study is to investigate the clinical outcomes after surgical correction of de novo AI after LVAD implantation. Methods: Between January 2013 and June 2022, 190 patients underwent CF-LVAD implantation. Of them, 24 had trivial or less AI before LVAD implantation and developed moderate or greater de novo AI after LVAD implantation. Those who had undergone aortic valve surgery before or concomitant with LVAD surgery were excluded. Among the 24 patients, surgeries were indicated for medically refractory de novo AI in 11 patients, who were included in the current study. Primary endpoint was post-operative improvement in hemodynamics as assessed with right heart catheter examination, and the secondary endpoint was 3-year survival and freedom from death and/or heart failure readmission rate. Results: Correction of de novo AI were accomplished with aortic valve closure with bovine pericardial patch in 10 patients and prosthetic valve replacement in one patient. After surgery, pulmonary artery wedge pressure (PAWP), and cardiac index (CI), mixed venous blood oxygen saturation (SvO2) significantly improved compared with preoperative baseline (Figure). The mean follow-up after LVAD implantation was 1413days, and the 3-year survival rate was 90.9%. The freedom from postoperative moderate or greater AI rate, and the freedom from heart failure readmission rate were both 90.9% at 3 years. Conclusion: In patients who were indicated for surgical correction of de novo AI after LVAD implantation, postoperative hemodynamic improvement and survival were considered favorable.Figure 1. Hemodynamic change in three states