Venous O2 Research Articles

New Technology Mimics Physiologic Pulsatile Flow During Cardiopulmonary Bypass.

The VentriFlo True Pulse Pump (Design Mentor, Inc., Pelham, NH, USA) is the first blood pump designed to mimic human arterial waveforms in a standard oxygenation circuit. Our aim was to demonstrate the feasibility and safety of this pump in preparation for future studies to determine possible clinical advantages. We studied four piglets (41.4-46.2 kg): three with an implanted VentriFlo pulsatile pump and one with the nonpulsatile ROTAFLOW pump (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) as a control. Hemodynamics was monitored during 6-h cardiopulmonary bypass (CPB) support and for 2 h after weaning off CPB. The VentriFlo demonstrated physiologic arterial waveforms with arterial pulse pressure of 24.6 ± 5.7 mm Hg. Pump flows (2.0 ± 0.1 L/min in ROTAFLOW; 1.9 ± 0.1 L/min in VentriFlo) and plasma free hemoglobin levels (27.9 ± 12.5 mg/dL in ROTAFLOW; 28.5 ± 14.2 mg/dL in VentriFlo) were also comparable, but systemic O2 extraction (as measured by arterial minus venous O2 saturation) registered slightly higher with the VentriFlo (63.2 ± 6.9%) than the ROTAFLOW (55.4 ± 6.5%). Histological findings showed no evidence of ischemic changes or thromboembolism. This pilot study demonstrated that the VentriFlo system generated pulsatile flow and maintained adequate perfusion of all organs during prolonged CPB.

Low cerebral blood flow after cardiac arrest is not associated with anaerobic cerebral metabolism

Aim of the studyEstimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest. MethodsWe performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery (MFVMCA) by transcranial Doppler. Arterial and jugular blood samples were used for calculation of the jugular venous-to-arterial CO2/arterial to-jugular venous O2 content difference ratio. ResultsAfter cardiac arrest, MFVMCA increased from 26.0[18.6–40.4]cm/sec on admission to 63.9[48.3–73.1]cm/sec after 72h (p<0.0001), with no significant differences between survivors and non-survivors (p=0.4853). The MFVMCA in controls was 59.1[52.8–69.0]cm/sec. The oxygen extraction fraction (O2EF) was 38.9[24.4–47.7]% on admission and decreased significantly to 17.3[12.1–26.2]% at 72h (p<0.0001). The decrease in O2EF was more pronounced in non-survivors (p=0.0173). O2EF in the control group was 35.4[32.4–38.7]%. The jugular bulb-arterial CO2 to arterial-jugular bulb O2 content difference ratio was >1 at all time points after cardiac arrest and did not change during admission, with no differences between survivors and non-survivors. Values in cardiac arrest patients were similar to those in normal subjects. ConclusionsIn this study, low CBF after cardiac arrest is not associated with anaerobic metabolism. Hypoperfusion appears to be the consequence of a decrease of neuronal functioning and metabolic needs. Alternatively, hypoperfusion may decrease cerebral metabolism. Subsequently, metabolism increases in survivors, consistent with resumption of neuronal activity, whereas in non-survivors lasting low metabolism reflects irreversible neuronal damage.

Supplemental Oxygen Study: A Randomized Controlled Study on the Effect of Maternal Oxygen Supplementation during Planned Cesarean Delivery on Umbilical Cord Gases.

The aim was to determine the fetal umbilical blood gas effects of supplemental maternal oxygenation compared with room air (RA) during term planned cesarean delivery. This is a prospective randomized controlled study of singleton planned cesarean deliveries randomized to receive supplemental oxygen (O2) at 10 L per minute (L/min) via facemask or RA. Umbilical cord gases were collected. The primary outcome was umbilical arterial pH level. Secondary outcomes included umbilical cord values and maternal and neonatal outcomes. Data were expressed as median ± interquartile range (IQR). Seventy subjects in total were enrolled, with 65 subjects available for analysis. The median umbilical arterial pO2 was significantly increased in the supplemental O2 group (18 [13.5-20.5] mm Hg) versus RA group (16 [12-18] mm Hg), p = 0.04). The median umbilical venous pO2 was significantly increased in the supplemental O2 group (32 [26.5-36.0] mm Hg) versus RA group (28.5 [22-34.3] mm Hg), p = 0.04). There were no significant differences with other umbilical blood gas values and composite maternal or neonatal complications. Subjects with term singleton gestations receiving O2 at 10 L/min during cesarean delivery compared with RA demonstrated no significant change in umbilical cord pH values. There was a significant increase in umbilical cord arterial and venous O2 levels in those receiving O2.

Decreases in maximal oxygen uptake following long-duration spaceflight: Role of convective and diffusive O2 transport mechanisms.

We have previously predicted that the decrease in maximal oxygen uptake (V̇o2max) that accompanies time in microgravity reflects decrements in both convective and diffusive O2 transport to the mitochondria of the contracting myocytes. The aim of this investigation was therefore to quantify the relative changes in convective O2 transport (Q̇o2) and O2 diffusing capacity (Do2) following long-duration spaceflight. In nine astronauts, resting hemoglobin concentration ([Hb]), V̇o2max, maximal cardiac output (Q̇Tmax), and differences in arterial and venous O2 contents ([Formula: see text]-[Formula: see text]) were obtained retrospectively for International Space Station Increments 19-33 (April 2009-November 2012). Q̇o2 and Do2 were calculated from these variables via integration of Fick's Principle of Mass Conservation and Fick's Law of Diffusion. V̇o2max significantly decreased from pre- to postflight (-53.9 ± 45.5%, P = 0.008). The significant decrease in Q̇Tmax (-7.8 ± 9.1%, P = 0.05), despite an unchanged [Hb], resulted in a significantly decreased Q̇o2 (-11.4 ± 10.5%, P = 0.02). Do2 significantly decreased from pre- to postflight by -27.5 ± 24.5% (P = 0.04), as did the peak [Formula: see text]-[Formula: see text] (-9.2 ± 7.5%, P = 0.007). With the use of linear regression analysis, changes in V̇o2max were significantly correlated with changes in Do2 (R2 = 0.47; P = 0.04). These data suggest that spaceflight decreases both convective and diffusive O2 transport. These results have practical implications for future long-duration space missions and highlight the need to resolve the specific mechanisms underlying these spaceflight-induced changes along the O2 transport pathway.NEW & NOTEWORTHY Long-duration spaceflight elicited a significant decrease in maximal oxygen uptake. Given the adverse physiological adaptations to microgravity along the O2 transport pathway that have been reported, an integrative approach to the determinants of postflight maximal oxygen uptake is needed. We demonstrate that both convective and diffusive oxygen transport are decreased following ~6 mo International Space Station missions.

Plasma amino acids of the transsulfuration pathway and plasma lactate in septic patients.

In sepsis increasing plasma lactate, even if unrelated to hypoperfusion and hypoxia, is a cause of concern. Among the patterns associated with increasing lactate, several plasma amino acid (AA) abnormalities, more in particular those of sulfur AAs, have remained unexplored, and their assessment has been the purpose of our study. A systematic and detailed analysis of 183 simultaneous determinations of plasma AA-grams and lactate, from 12 trauma surgery patients who had developed sepsis, was performed. Sepsis severity ranged from moderate to extreme illness. Correlations between changes in lactate and in AA levels were assessed by regression analysis. Increasing lactate was related to increasing alanine, proline, asparagine, tyrosine, cystathionine, histidine, glutamine, citrulline, methionine, phenylalanine and hydroxyproline (r from 0.62 to 0.36, p < 0.001 for all) and to decreasing taurine (r = -0.62, p < 0.001). Furthermore, increasing lactate was strongly related to increasing cystathionine/taurine ratio (r = 0.77, p < 0.001). These correlations were independent of the simultaneous relationship found between increasing lactate and decreasing mixed venous O2 tension. The overall findings and the correlation with the cystathionine/taurine ratio support the hypothesis that increasing lactate in sepsis may be paralleled by impaired hepatic AA transsulfuration. Because this may disable antioxidant protection by limiting glutathione and taurine availability, the metabolic perturbations associated with septic hyperlactatemia may include enhanced exposure to oxidative stress.

CMR-based blood oximetry via multi-parametric estimation using multiple T2 measurements

BackgroundMeasurement of blood oxygen saturation (O2 saturation) is of great importance for evaluation of patients with many cardiovascular diseases, but currently there are no established non-invasive methods to measure blood O2 saturation in the heart. While T2-based CMR oximetry methods have been previously described, these approaches rely on technique-specific calibration factors that may not generalize across patient populations and are impractical to obtain in individual patients. We present a solution that utilizes multiple T2 measurements made using different inter-echo pulse spacings. These data are jointly processed to estimate all unknown parameters, including O2 saturation, in the Luz-Meiboom (L-M) model. We evaluated the accuracy of the proposed method against invasive catheterization in a porcine hypoxemia model.MethodsSufficient data diversity to estimate the various unknown parameters of the L-M model, including O2 saturation, was achieved by acquiring four T2 maps, each at a different τ180 (12, 15, 20, and 25 ms). Venous and arterial blood T2 values from these maps, together with hematocrit and arterial O2 saturation, were jointly processed to derive estimates for venous O2 saturation and other nuisance parameters in the L-M model. The technique was validated by a progressive graded hypoxemia experiment in seven pigs. CMR estimates of O2 saturation in the right ventricle were compared against a reference O2 saturation obtained by invasive catheterization from the right atrium in each pig, at each hypoxemia stage. O2 saturation derived from the proposed technique was also compared against the previously described method of applying a global calibration factor (K) to the simplified L-M model.ResultsVenous O2 saturation results obtained using the proposed CMR oximetry method exhibited better agreement (y = 0.84× + 12.29, R2 = 0.89) with invasive blood gas analysis when compared to O2 saturation estimated by a global calibration method (y = 0.69× + 27.52, R2 = 0.73).ConclusionsWe have demonstrated a novel, non-invasive method to estimate O2 saturation using quantitative T2 mapping. This technique may provide a valuable addition to the diagnostic utility of CMR in patients with congenital heart disease, heart failure, and pulmonary hypertension.

Differential Responses of Post-Exercise Recovery of Leg Blood Flow and Oxygen Uptake Kinetics in HFpEF versus HFrEF.

The goals of the current study were to compare leg blood flow, oxygen extraction and oxygen uptake (VO2) after constant load sub-maximal unilateral knee extension (ULKE) exercise in patients with heart failure with reduced ejection fraction (HFrEF) compared to those with preserved ejection fraction (HFpEF). Previously, it has been shown that prolonged whole body VO2 recovery kinetics are directly related to disease severity and all-cause mortality in HFrEF patients. To date, no study has simultaneously measured muscle-specific blood flow and oxygen extraction post exercise recovery kinetics in HFrEF or HFpEF patients; therefore it is unknown if muscle VO2 recovery kinetics, and more specifically, the recovery kinetics of blood flow and oxygen extraction at the level of the muscle, differ between HF phenotypes. Ten older (68±10yrs) HFrEF (n = 5) and HFpEF (n = 5) patients performed sub-maximal (85% of maximal weight lifted during an incremental test) ULKE exercise for 4 minutes. Femoral venous blood flow and venous O2 saturation were measured continuously from the onset of end-exercise, using a novel MRI method, to determine off-kinetics (mean response times, MRT) for leg VO2 and its determinants. HFpEF and HFrEF patients had similar end-exercise leg blood flow (1.1±0.6 vs. 1.2±0.6 L/min, p>0.05), venous saturation (42±12 vs. 41±11%, p>0.05) and VO2 (0.13±0.08 vs. 0.11±0.05 L/min, p>0.05); however HFrEF had significantly delayed recovery MRT for flow (292±135sec. vs 105±63sec., p = 0.004) and VO2 (95±37sec. vs. 47±15sec., p = 0.005) compared to HFpEF. Impaired muscle VO2 recovery kinetics following ULKE exercise differentiated HFrEF from HFpEF patients and suggests distinct underlying pathology and potential therapeutic approaches in these populations.

Muscle Near-Infrared Spectroscopy Signals versus Venous Blood Hemoglobin Oxygen Saturation in Skeletal Muscle.

The study aimed to examine the relationship between near-infrared spectroscopy (NIRS) signals and venous hemoglobin oxygen saturation (O2Hb%) and venous oxygen concentration (CvO2). Gastrocnemius muscles (GS) in six dogs were surgically isolated and pump perfused. NIRS signals were recorded, and venous blood samples were collected at constant flow rates (control flow, high flow, and low flow) at rest as well as during electrically stimulated tetanic muscle contractions at rates of one contraction per 2 s (1/2 s) and two contractions per 3 s (2/3 s). Similar data were also collected at three different inspired O2 percentages (12%, 21%, and 100%) with constant blood flow. Complete data from five animals were analyzed; all data from one animal were deleted because of erratic oxy-NIRS signals. Venous O2Hb% ranged from 7.6% to 97.5% across the various experimental conditions. After the NIRS signals were normalized to the physiological range, a high linear correlation was seen between the deoxygenated heme signal (HHbMb%) and the venous O2Hb% (R = 0.92 ± 0.05), between the oxygenated heme signal (HbMbO2%) and the venous O2Hb% (R = 0.92 ± 0.03), between the HHbMb% and the CvO2 (R = 0.89 ± 0.06), and between the HbMbO2% and the CvO2 (R = 0.90 ± 0.05). The overall relationships between HHbMb%, HbMbO2%, and venous O2Hb% as well as between HHbMb%, HbMbO2%, and CvO2 were also linear and highly correlated with R values ranging from 0.81 to 0.90. In this controlled canine muscle model, NIRS signals are highly correlated with venous O2Hb% and CvO2 across a wide range of physiological conditions. The practical application of our results is that for an individual muscle or perhaps muscle group, normalized NIRS HHbMb and HbMbO2 signals accurately reflect the mean venous O2 saturation of the interrogated muscle tissue.

The Effect of Pulsatile Versus Nonpulsatile Blood Flow on Viscoelasticity and Red Blood Cell Aggregation in Extracorporeal Circulation.

BackgroundExtracorporeal circulation (ECC) can induce alterations in blood viscoelasticity and cause red blood cell (RBC) aggregation. In this study, the authors evaluated the effects of pump flow pulsatility on blood viscoelasticity and RBC aggregation.MethodsMongrel dogs were randomly assigned to two groups: a nonpulsatile pump group (n=6) or a pulsatile pump group (n=6). After ECC was started at a pump flow rate of 80 mL/kg/min, cardiac fibrillation was induced. Blood sampling was performed before and at 1, 2, and 3 hours after ECC commencement. To eliminate bias induced by hematocrit and plasma, all blood samples were adjusted to a hematocrit of 45% using baseline plasma. Blood viscoelasticity, plasma viscosity, hematocrit, arterial blood gas analysis, central venous O2 saturation, and lactate were measured.ResultsThe blood viscosity and aggregation index decreased abruptly 1 hour after ECC and then remained low during ECC in both groups, but blood elasticity did not change during ECC. Blood viscosity, blood elasticity, plasma viscosity, and the aggregation index were not significantly different in the groups at any time. Hematocrit decreased abruptly 1 hour after ECC in both groups due to dilution by the priming solution used.ConclusionAfter ECC, blood viscoelasticity and RBC aggregation were not different in the pulsatile and nonpulsatile groups in the adult dog model. Furthermore, pulsatile flow did not have a more harmful effect on blood viscoelasticity or RBC aggregation than nonpulsatile flow.

Cardiac biomarkers in premature calves with respiratory distress syndrome.

The aim of this study was to determine the clinical relevance of cardiac biomarkers [troponin I and T, creatine kinase-MB fraction (CK-MB) and lactate dehydrogenase (LDH)] in premature calves with respiratory distress syndrome. Seventy premature calves were admitted to the clinic within 24 h after birth. Respiratory distress syndrome was diagnosed in premature calves by clinical examination and venous blood gas analysis. Ten healthy calves, aged 5 days, were used as control. Cardiac troponin I and T were analysed using ELISA and ELFA, respectively. Serum CK-MB and LDH were also analysed in an automatic analyser. The calves had low venous pH, pO2, O2 saturation and high pCO2 values consistent with dyspnoea, hypoxaemia, and inadequate oxygen delivery. Mean serum troponin I, troponin T, CK-MB and LDH levels were increased in the premature calves compared to the control group. In conclusion, the results in this study demonstrated that serum CK-MB, troponin I and troponin T concentrations could be used for evaluating myocardial injury in premature calves with respiratory distress syndrome.

Understanding the venous-arterial CO2 to arterial-venous O2 content difference ratio.

Introduction Early identification of tissue hypoperfusion is a cornerstone of shock management [1]. Normal macrohemodynamic and oxygen-derived parameters do not, however, rule out the presence of tissue hypoxia [2]. In this setting, carbon dioxide (CO2)-derived variables may provide information on macroand microvascular blood flow [3] and also on the presence of anaerobic metabolism [4, 5]. Importantly, variations in CO2 occur more rapidly than changes in lactate kinetics, making the former an attractive biomarker for monitoring, especially during the early stages of resuscitation [6, 7].

Can venous-to-arterial carbon dioxide differences reflect microcirculatory alterations in patients with septic shock?

PurposeSeptic shock has been associated with microvascular alterations and these in turn with the development of organ dysfunction. Despite advances in video microscopic techniques, evaluation of microcirculation at the bedside is still limited. Venous-to-arterial carbon dioxide difference (Pv-aCO2) may be increased even when venous O2 saturation (SvO2) and cardiac output look normal, which could suggests microvascular derangements. We sought to evaluate whether Pv-aCO2 can reflect the adequacy of microvascular perfusion during the early stages of resuscitation of septic shock.MethodsProspective observational study including 75 patients with septic shock in a 60-bed mixed ICU. Arterial and mixed-venous blood gases and hemodynamic variables were obtained at catheter insertion (T0) and 6 h after (T6). Using a sidestream dark-field device, we simultaneously acquired sublingual microcirculatory images for blinded semiquantitative analysis. Pv-aCO2 was defined as the difference between mixed-venous and arterial CO2 partial pressures.ResultsProgressively lower percentages of small perfused vessels (PPV), lower functional capillary density, and higher heterogeneity of microvascular blood flow were observed at higher Pv-aCO2 values at both T0 and T6. Pv-aCO2 was significantly correlated to PPV (T0: coefficient −5.35, 95 % CI −6.41 to −4.29, p < 0.001; T6: coefficient, −3.49, 95 % CI −4.43 to −2.55, p < 0.001) and changes in Pv-aCO2 between T0 and T6 were significantly related to changes in PPV (R2 = 0.42, p < 0.001). Absolute values and changes in Pv-aCO2 were not related to global hemodynamic variables. Good agreement between venous-to-arterial CO2 and PPV was maintained even after corrections for the Haldane effect.ConclusionsDuring early phases of resuscitation of septic shock, Pv-aCO2 could reflect the adequacy of microvascular blood flow.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-4133-2) contains supplementary material, which is available to authorized users.

Abstract 14058: Transvascular Total Left Ventricular Unloading for Acute Myocardial Infarction Strikingly Reduced Myocardial Oxygen Consumption, Limited the Infarct Size and Prevented Heart Failure in the long term

Backgrounds: Despite the latest progresses of early reperfusion, myocardial infarction (MI) remains a leading cause of chronic heart failure (CHF). Left ventricular (LV) assist device (VAD) mechanically unloads LV, thus myocardial oxygen consumption (MVO2). Theoretical analysis indicates that the partial VAD (p-VAD) where LV remains ejecting decreases preload (EDV) while increases afterload (ESV), thereby marginally decreases MVO2. In contrast, total LVAD (t-VAD) where LV no longer ejects, markedly decreases ESV as well as EDV, thus markedly reduces MVO2. We examined whether t-VAD in ischemia reperfusion (IR) could reduce the infarct size and prevent heart failure in the long term. Methods: First, in normal dogs, we examined the impact of p-VAD and t-VAD on MVO2 by Fick principle (coronary flow and arterial venous O2 difference). Second, we occluded the left anterior descending coronary artery for 3 hours and reperfused. We started transvascular LVAD (Impella®) from 1 hour after ischemia to 1 hour after reperfusion. We compared cardiac function, infarct size and hormones 1 month after ischemia among 3 groups, control group (IR, n=8), p-VAD (n=6), and t-VAD (n=6). Results: t-VAD markedly decreased MVO2 (p&lt;0.05, Figure 1). 1 month after ischemia, t-VAD normalized LV end-systolic elastance (IR: 6.5±3.2, p-VAD: 9.7±1.3, t-VAD: 12.8±5.1 mmHg/ml, p&lt;0.05) and reduced LV end-diastolic pressure (16.5±2.7, 6.4±2.9, 4.4±1.5 mmHg, p&lt;0.05), and NT proBNP (3391±1364, 2084±348, 1632±228 pg/ml, p&lt;0.05) indicating the successful prevention of heart failure. t-VAD markedly reduced the infarct size by more than 80% relative to IR (p&lt;0.05, Figure 2) despite the fact that it started 1 hour after the onset of ischemia. Conclusions: Transvascular total left ventricular unloading for acute myocardial infarction strikingly reduces the MI size and prevents heart failure in the chronic phase. It might serve as a new therapeutic strategy in the management of patients with acute MI.

High central venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio is associated with poor lactate clearance in septic patients after resuscitation

ObjectiveRecently, the central venoarterial carbon dioxide difference/arterial-central venous oxygen difference (P(v-a)CO2/C(a-v)O2) ratio has been suggested as an additional indicator of anaerobic metabolism. We investigated the relationship between the P(v-a)CO2/C(a-v)O2 ratio and 8-hour lactate clearance (LC) in septic patients after resuscitation. Methods and ResultsWe prospectively obtained 168 sets of measurements from 84 septic patients. The arterial and central venous blood gases were measured simultaneously at enrollment and 8 hours after resuscitation. The P(v-a)CO2/C(a-v)O2 (r = −0.24, P = .028) at T8 was negatively correlated with 8-hour LC after resuscitation in all patients. The patients with 8-hour LC ≥ 10% exhibited significantly lower P(v-a)CO2/C(a-v)O2 ratios and intensive care unit mortality after resuscitation than the patients with 8-hour LC < 10%. The area under the receiver operating characteristic curve of the P(v-a)CO2/C(a-v)O2 ratio for the detection of LC ≥ 10% was the greatest and was significantly better than that of the central venous oxygen saturation and similar to that of the P(v-a)CO2. Moreover, a P(v-a)CO2/C(a-v)O2 < 1.23 at T8 is related to poor 8-hour LC rate (LC ≥ 10%) in the patients with normalized central venous oxygen saturation values (≥70%) after resuscitation. ConclusionsThe high P(v-a)CO2/C(a-v)O2 ratio is associated with poor LC after resuscitation. The P(v-a)CO2/C(a-v)O2 ratio may provide useful information for assessing the LC potential and optimizing the LC rate.

Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain.

Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O2 metabolism (CMRO2 ) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMRO2 and in turn might improve cerebral tissue oxygenation (PtiO2 ) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMRO2 and cerebral PtiO2 from MRI measurements of cerebral blood flow (CBF) and cerebral venous O2 saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMRO2 , or PtiO2 . During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml·100 ml(-1)·min(-1) (hypoxia), P < 0.05] and CMRO2 [1.54 (0.19) to 1.79 (0.25) μmol·ml(-1)·min(-1), P < 0.05] and a dramatic decline in PtiO2 [25.0 to 11.4 (2.7) mmHg, P < 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml·100 ml(-1)·min(-1) (hypoxia + acetazolamide)] and CMRO2 [1.41 (0.09) μmol·ml(-1)·min(-1) (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O2 delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol/min (hypoxia + acetazolamide), P < 0.05]. The net effect was improved cerebral tissue PtiO2 during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P < 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO2 excretion accounts for the improvements in CMRO2 and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO2 and pH in modulating CMRO2 and PtiO2 during acute hypoxia.

CrossTalk proposal: Diffusion limitation of O2 from microvessels into muscle does contribute to the limitation of V̇O2 max.

At maximal oxygen uptake () we know that (1) muscle O2 extraction is not 100%, yet (2) hyperoxia increases . The reason for (1) is diffusion limitation of O2 from the muscle microvessels to the mitochondria. This does not exclude ‘central’ factors from also affecting , as will be explained.

Effects of early hemodynamic resuscitation on left ventricular performance and microcirculatory function during endotoxic shock.

BackgroundMicrocirculation and macrohemodynamics are severely compromised during septic shock. However, the relationship between these two compartments needs to be further investigated. We hypothesized that early resuscitation restores left ventricular (LV) performance and microcirculatory function but fails to prevent metabolic disorders. We studied the effects of an early resuscitation protocol (ERP) on LV pressure/volume loops-derived parameters, sublingual microcirculation, and metabolic alterations during endotoxic shock.MethodsTwenty-five pigs were randomized into three groups: LPS group: Escherichia coli lipopolysaccharide (LPS); ERP group: LPS + ERP based on volume expansion, dobutamine, and noradrenaline infusion; Sham group. LV pressure/volume-derived parameters, systemic hemodynamics, sublingual microcirculation, and metabolic profile were assessed at baseline and after completing the resuscitation protocol.ResultsLPS significantly decreased LV end-diastolic volume, myocardial contractility, stroke work, and cardiac index (CI). Early resuscitation preserved preload, and myocardial contractility, increased CI and heart rate (p < .05). LPS severely diminished sublingual microvascular flow index (MFI), perfused vascular density (PVD), and the proportion of perfused vessels (PPV), while increased the heterogeneity flow index (HFI) (p < .05). Despite MFI was relatively preserved, MVD, PVD, and HFI were significantly impaired after resuscitation (p < .05). The macro- and microcirculatory changes were associated with increased lactic acidosis and mixed venous O2 saturation when compared to baseline values (p < .05). The scatter plot between mean arterial pressure (MAP) and MFI showed a biphasic relationship, suggesting that the values were within the limits of microvascular autoregulation when MAP was above 71 ± 6 mm Hg (R2 = 0.63).ConclusionsEarly hemodynamic resuscitation was effective to restore macrohemodynamia and myocardial contractility. Despite MAP and MFI were relatively preserved, the persistent microvascular dysfunction could explain metabolic disorders. The relationship between micro- and systemic hemodynamia and their impact on cellular function and metabolism needs to be further studied during endotoxic shock.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-015-0049-y) contains supplementary material, which is available to authorized users.

Accuracy of different oxygenation indices in estimating intrapulmonary shunting at increasing infusion rates of dobutamine in horses under general anaesthesia

The aim of this study was to evaluate the correlation of commonly used oxygenation indices with venous admixture (Qs/Qt) in anaesthetised horses under different infusion rates of dobutamine. Six female horses were anaesthetised with acepromazine, xylazine, diazepam, ketamine, and isoflurane, and then intubated and mechanically ventilated with 100% O2. A Swan–Ganz catheter was introduced into the left jugular vein and its tip advanced into the pulmonary artery. Horses received different standardised rates of dobutamine.For each horse, eight samples of arterial and mixed venous blood were simultaneously obtained at fixed times. Arterial and venous haemoglobin (Hb) concentration and O2 saturation, arterial oxygen partial pressure (PaO2), venous oxygen partial pressure (PvO2), and barometric pressure were measured. Arterial (CaO2), mixed venous (CvO2), and capillary (Cc′O2) oxygen contents were calculated using standard formulae. The correlations between F-shunt, arterial oxygen tension to fraction of inspired oxygen ratio (PaO2/FiO2), arterial to alveolar oxygen tension ratio (PaO2/PAO2), alveolar to arterial oxygen tension difference (P[A − a]O2), and respiratory index (P[A − a]O2/PaO2) were tested with linear regression analysis. The goodness-of-fit for each calculated formula was evaluated by means of the coefficient of determination (r2). The agreement between Qs/Qt and F-shunt was analysed with the Bland–Altman test.All tested oxygen tension-based indices were weakly correlated (r2 < 0.2) with the Qs/Qt, whereas F-shunt showed a stronger correlation (r2 = 0.73). F-shunt also showed substantial agreement with Qs/Qt independent of the dobutamine infusion rate. F-shunt better correlated with Qs/Qt than other oxygen indices in isoflurane-anaesthetised horses under different infusion rates of dobutamine.

Venous–arterial CO2 to arterial–venous O2 difference ratio as a resuscitation target in shock states?

Venous–arterial CO2 to arterial–venous O2 difference ratio as a resuscitation target in shock states?

Effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with pre-existing cerebral ischemia

Cerebral injury caused by hypoperfusion during the perioperative period is one of the main causes of disability and death in patients after major surgery. No effective protective or preventative strategies have been identified. This study was designed to evaluate the effects of Ginkgo biloba extract on cerebral oxygen and glucose metabolism in elderly patients with known, pre-existing cerebral ischemia. Sixty ASA (American Society of Anesthesiologists) II-III patients, diagnosed with vertebral artery ischemia by transcranial Doppler ultrasonography (TCD), and scheduled for elective total hip replacement surgery, were enrolled in the study. They were randomly allocated to receive either 1mg/kg Ginkgo biloba extract (G group n=30) or normal saline (D group n=30) after induction of anesthesia. Blood samples were collected from radial artery and jugular venous bulb catheters for blood gas analysis and determination of glucose and lactate concentrations preoperatively, before surgical incision, at the end of surgery, and on post-op day 1. Arterial O2 content (CaO2), jugular venous O2 content (CjvO2), arteriovenous O2 content difference (Da-jvO2), cerebral oxygen extraction rate (CEO2), and arteriovenous glucose and lactate content differences (Da-jvGlu and Da-jvLac) were calculated. There were no significant differences in CaO2 or Da-jvGlu during surgery between groups (p>0.05). However, the Ginkgo group had higher CjvO2, internal jugular venous oxygen saturation (SjvO2) and lower CEO2, Da-jvO2 and Da-jvLac at the end of surgery (T2) and on post-op day 1 (T3) than those in the control group (p<0.05). Ginkgo biloba extract can improve cerebral oxygen supply, decrease cerebral oxygen extraction rate and consumption, and help maintain the balance between cerebral oxygen supply and consumption. It has no effect, however, on cerebral glucose metabolism in elderly patients with known, pre-existing cerebral ischemia.