End-tidal CO2 Partial Pressure Research Articles

Acute Beetroot Juice Ingestion Does Not Alter Renal Hemodynamics during Normoxia and Mild Hypercapnia in Healthy Young Adults

Arterial hypercapnia reduces renal perfusion. Beetroot juice (BRJ) increases nitric oxide bioavailability and may improve renal blood flow. We tested the hypothesis that acute consumption of BRJ attenuates both decreases in blood velocity and increases in vascular resistance in the renal and segmental arteries during acute hypercapnia. In fourteen healthy young adults, blood velocity and vascular resistance were measured with Doppler ultrasound in the renal and segmental arteries during five minutes of breathing a carbon dioxide gas mixture (CO2) before and three hours after consuming 500 mL of BRJ. There was no difference between pre- and post-BRJ consumption in the increase in the partial pressure of end-tidal CO2 during CO2 breathing (pre: +4 ± 1 mmHg; post: +4 ± 2 mmHg, p = 0.4281). Segmental artery blood velocity decreased during CO2 breathing in both pre- (by −1.8 ± 1.9 cm/s, p = 0.0193) and post-BRJ (by −2.1 ± 1.9 cm/s, p = 0.0079), but there were no differences between pre- and post-consumption (p = 0.7633). Segmental artery vascular resistance increased from room air baseline during CO2 at pre-BRJ consumption (by 0.4 ± 0.4 mmHg/cm/s, p = 0.0153) but not post-BRJ (p = 0.1336), with no differences between pre- and post-consumption (p = 0.7407). These findings indicate that BRJ consumption does not attenuate reductions in renal perfusion during acute mild hypercapnia in healthy young adults.

Relationship Between Cerebrovascular Reactivity and Cognition Among People With Risk of Cognitive Decline.

Vascular risk factors (e.g., obesity and hypertension) are associated with cerebral small vessel disease, Alzheimer’s disease (AD) pathology, and dementia. Reduced perfusion may reflect the impaired ability of blood vessels to regulate blood flow in reaction to varying circumstances such as hypercapnia (increased end-tidal partial pressures of CO2). It has been shown that cerebrovascular reactivity (CVR) measured with blood-oxygen-level-dependent (BOLD) MRI is correlated with cognitive performance and alterations of CVR may be an indicator of vascular disfunction leading to cognitive decline. However, the underlying mechanism of CVR alterations in BOLD signal may not be straight-forward because BOLD signal is affected by multiple physiological parameters, such as cerebral blood flow (CBF), cerebral blood volume, and oxygen metabolism. Arterial spin labeling (ASL) MRI quantitatively measures blood flow in the brain providing images of local CBF. Therefore, in this study, we measured CBF and its changes using a dynamic ASL technique during a hypercapnia challenge and tested if CBF or CVR was related to cognitive performance using the Mini-mental state examination (MMSE) score. Seventy-eight participants underwent cognitive testing and MRI including ASL during a hypercapnia challenge with a RespirAct computer-controlled gas blender, targeting 10 mmHg higher end-tidal CO2 level than the baseline while end-tidal O2 level was maintained. Pseudo-continuous ASL (PCASL) was collected during a 2-min baseline and a 2-min hypercapnic period. CVR was obtained by calculating a percent change of CBF per the end-tidal CO2 elevation in mmHg between the baseline and the hypercapnic challenge. Multivariate regression analyses demonstrated that baseline resting CBF has no significant relationship with MMSE, while lower CVR in the whole brain gray matter (β = 0.689, p = 0.005) and white matter (β = 0.578, p = 0.016) are related to lower MMSE score. In addition, region of interest (ROI) based analysis showed positive relationships between MMSE score and CVR in 26 out of 122 gray matter ROIs.

High-but not moderate-intensity exercise acutely attenuates hypercapnia-induced vasodilation of the internal carotid artery in young men.

Exercise-induced increases in shear rate (SR) across different exercise intensities may differentially affect hypercapnia-induced vasodilation of the internal carotid artery (ICA), a potential index of cerebrovascular function. We aimed to elucidate the effects of exercise intensity on ICA SR during exercise and post-exercise hypercapnia-induced vasodilation of the ICA in young men. Twelve healthy men completed 30min of cycling at moderate [MIE; 65 ± 5% of age-predicted maximal heart rate (HRmax)] and high (HIE; 85 ± 5% HRmax) intensities. Hypercapnia-induced vasodilation was induced by 3min of hypercapnia (target end-tidal partial pressure of CO2 + 10mmHg) and was assessed at pre-exercise, 5min and 60min after exercise. Doppler ultrasound was used to measure ICA diameter and blood velocity during exercise and hypercapnia tests. SR was not altered during either exercise (interaction and main effects of time; both P > 0.05). ICA conductance decreased during HIE from resting values (5.1 ± 1.3 to 3.2 ± 1.0mL·min-1·mmHg-1; P < 0.01) but not during MIE (5.0 ± 1.3 to 4.0 ± 0.8mL·min-1·mmHg-1; P = 0.11). Consequently, hypercapnia-induced vasodilation declined immediately after HIE (6.9 ± 1.7% to 4.0 ± 1.4%; P < 0.01), but not after MIE (7.2 ± 2.1% to 7.3 ± 1.8%; P > 0.05). Sixty minutes after exercise, hypercapnia-induced vasodilation returned to baseline values in both trials (MIE 8.0 ± 3.1%; HIE 6.4 ± 2.9%; both P > 0.05). The present study showed blunted hypercapnia-induced vasodilation of the ICA immediately after high-intensity exercise, but not a moderate-intensity exercise in young men. Given that the acute response is partly linked to the adaptive response in the peripheral endothelial function, the effects of aerobic training on cerebrovascular health may vary depending on exercise intensity.

Effects of increased respiratory rate on cortical oxygenated hemoglobin during low-intensity exercise

This study aimed to examine whether the end-tidal partial pressure of CO2 (PEtCO2) affects the concentration of oxygenated hemoglobin (O2Hb) measured by near-infrared spectroscopy (NIRS). Participants were examined under the conditions of normal and increased ventilation. We measured O2Hb, mean blood pressure, skin blood flow, PEtCO2, respiratory rate, and minute volume at 30 % of the maximum oxygen uptake during exercise. ΔO2Hb and PEtCO2 during exercise were lower in the increased ventilation than in the normal ventilation condition. Pearson's product-moment correlation analysis showed a significant positive correlation between ΔO2Hb and ΔMAP, ΔSBF, and PEtCO2. Correlation coefficients were 0.249 (p < 0.001) for ΔMAP, 0.343 (p < 0.001) for ΔSBF, and 0.315 (p < 0.001) for PEtCO2. In conclusion, we identified increased ventilation during bicycle ergometer exercise as a significant factor associated with significantly low PEtCO2 and ΔO2Hb.

Repeatability of End‐Tidal Carbon Dioxide and Internal Carotid Artery Blood Flow Responses During Steady‐State Hypercapnia

Cerebrovascular reactivity to hypercapnia is commonly utilized to assess cerebral vascular function. Systemic hypercapnia can be achieved through various methods, including steady-state (SS) carbon dioxide (CO2) delivery. Additionally, in recent years, investigators have begun to more frequently utilize duplex ultrasonography of extracranial vessels (e.g., internal carotid artery) during cerebrovascular reactivity testing due to its ability to simultaneously measure blood velocity and vessel diameter for the calculation of blood flow and thus provide a more complete picture of cerebral vascular regulation. However, to our knowledge, the repeatability of the partial pressure of end-tidal CO2 (PETCO2) and internal carotid artery (ICA) blood flow response to SS hypercapnia has not been evaluated. Therefore, we tested the between-visit and within-day repeatability of PETCO2 and ICA blood flow responses to a SS hypercapnia stimulus. Methods Six young, healthy males participated in the study (age: 21.3 ± 0.3 years; BMI: 24.1 ± 0.6 kg/m2). Three SS hypercapnia tests were performed over the course of two days (one trial on one day and two trials, separated by ~15 min, on another day). PETCO2 (capnography) and right ICA blood velocity and vessel diameter (duplex ultrasonography) were measured at baseline (3 min) and during the administration of 6% CO2 (3 min). Beat-to-beat blood pressure, respiration, and ECG data were also collected throughout the protocol. Results For the between-visit comparison, baseline PETCO2 was similar for Visit 1 and Visit 2 (47.3 ± 0.6 mmHg vs. 47.0 ± 0.6 mmHg; p = 0.67), and the increase in PETCO2 during the hypercapnic stimulus exhibited excellent repeatability (Visit 1: Δ9.5 ± 0.5 mmHg vs. Visit 2: Δ9.0 ± 0.5 mmHg; ICC: 0.94, p < 0.01). ICA blood flow was similar at baseline for Visit 1 and Visit 2 (502 ± 56 ml/min vs. 426 ± 32 ml/min; p = 0.11) and exhibited excellent between-visit repeatability during hypercapnia (Visit 1: 697 ± 75 ml/min vs. Visit 2: 610 ± 73 ml/min; ICC: 0.91, p < 0.01). For the within-day comparison, baseline PETCO2 was similar for Trial 1 and Trial 2 (47.0 ± 0.6 mmHg vs. 46.3 ± 0.7 mmHg; p = 0.14), and the increase in PETCO2 during the hypercapnic stimulus exhibited moderate repeatability (Trial 1: Δ9.0 ± 0.5 mmHg vs. Trial 2: Δ10.0 ± 0.5 mmHg; ICC: 0.64, p = 0.06). ICA blood flow was similar at baseline for Trial 1 and Trial 2 (426 ± 32 ml/min vs. 475 ± 45 ml/min; p = 0.20) and exhibited good within-day repeatability during hypercapnia (Trial 1: 610 ± 73 ml/min vs. Trial 2: 618 ± 47 ml/min; ICC: 0.74, p = 0.03). Conclusion These preliminary data suggest that 1) systemic hypercapnia elicited by a fixed concentration of inspired CO2 exhibits better between-visit than within-day repeatability and 2) between-visit and within-day repeatability of internal carotid artery blood flow during a SS hypercapnia stimulus of 6% inspired CO2 is good to excellent.

Malignant hyperthermia when dantrolene is not readily available

BackgroundMalignant hyperthermia is a rare but life-threatening pharmacogenetic muscle disorder characterized by abnormal hypermetabolic reactions and commonly triggered in susceptible individuals by volatile anesthetics or succinylcholine, or both. Unfortunately, the specific medicine dantrolene is not readily available in many countries including China. The aim of this study was to find the characteristics of malignant hyperthermia under the situation that dantrolene is not readily available.MethodsThe cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. The inclusion criteria were the MH episodes only related to anesthesia. The exclusion criteria were dubious MH episodes only caused by Ketamine administration or MH episodes irrelevant to anesthesia. Independent samples t-test and Pearson’s chi-squared test were applied to assess the difference between the survived and death cases.ResultsNinety-two cases of malignant hyperthermia reported on the most commonly used databases in China from 1985 to 2020 were analyzed. Median (IQR [range]) age was 18.5 (11.8–37.0 [0–70.0]) years. Compared with the survived cases, the death cases had higher maximum end-tidal partial pressure of CO2 (P = 0.033), the maximum arterial partial pressure of CO2 (P = 0.006), temperature first measured when the patient was first discovered abnormal (P = 0.012), and maximum temperature (P < 0.001). Besides, the death cases had less minimum pH (P < 0.001) and higher potassium (P < 0.001) and were more likely to have coagulation disorders (p = 0.018). Concerning treatment, cases used furosemide (P = 0.024), mannitol (P = 0.029), blood purification treatment (P = 0.017) had the advantage on the outcome. Creatine phosphokinase, myoglobin, and MB isoenzyme of creatine phosphokinase differed greatly among cases during the first week. 43 (46.7%) cases had congenital diseases. 12 (13.0%) cases were reported with abnormal laboratory test results or abnormal signs that are possibly relevant before anesthesia.ConclusionsIn countries that dantrolene is not readily available, early warning, diagnosis, and prompt effective therapies are crucial for MH patients to survive.

Relevance of differential control of sympathorespiratory response magnitudes in clinical assessments.

Relevance of differential control of sympathorespiratory response magnitudes in clinical assessments.

Protective Recommendations for Non-invasive Ventilation During COVID-19 Pandemic: A Bench Evaluation of the Effects of Instrumental Dead Space on Alveolar Ventilation

IntroductionWith the current COVID-19 pandemic, concerns have raised regarding the risk for NIV to promote airborne transmission. In case of hospital admission, continuation of therapy in patients undergoing chronic NIV is necessary and several protective circuit configurations have been recommended to reduce the risk of aerosol dissemination. However, all these configurations increase instrumental dead space. We therefore designed this study to evaluate their effects on the tidal volume (VTE) required to preserve stable end-tidal CO2 partial pressure (PETCO2) with constant respiratory rate. MethodsA bench consisting of a test lung connected to an adult-sized mannequin head was set up. The model was ventilated through usual domiciliary configuration (single limb circuit with facial vented mask) which was used as reference. Then, five different circuit configurations including non-vented facial mask with viral/bacterial filter, modification of leak position, and change from single to double-limb circuit were evaluated. For each configuration, pressure support (PS) was gradually increased to reach reference PETCO2. Resulting VTE was recorded as primary outcome. ResultsReference PETCO2 was 38(0)mmHg, with a PS set at 10cmH2O, resulting in a VTE of 432(2)mL. Compared to reference, all the configurations evaluated required substantial increase in VTE to preserve alveolar ventilation, ranging from +79(2) to +216(1)mL. ConclusionsModifications of NIV configurations in the context of COVID-19 pandemic result in substantial increase of instrumental dead space. Re-evaluation of treatment efficiency and settings is crucial whenever protective measures influencing NIV equipment are considered.

A Promising Subject-Level Classification Model for Acute Concussion Based on Cerebrovascular Reactivity Metrics

Concussion imaging research has primarily focused on neuronal disruption with lesser emphasis directed toward vascular dysfunction. However, blood flow metrics may be more sensitive than measures of neuronal integrity. Vascular dysfunction can be assessed by measuring cerebrovascular reactivity (CVR)-the change in cerebral blood flow per unit change in vasodilatory stimulus. CVR metrics, including speed and magnitude of flow responses to a standardized well-controlled vasoactive stimulus, are potentially useful for assessing individual subjects following concussion given that blood flow dysregulation is known to occur with traumatic brain injury. We assessed changes in CVR metrics to a standardized vasodilatory stimulus during the acute phase of concussion. Using a case control design, 20 concussed participants and 20 healthy controls (HCs) underwent CVR assessment measuring blood oxygen-level dependent (BOLD) magnetic resonance imaging using precise changes in end-tidal partial pressure of CO2 (PETCO2). Metrics were calculated for the whole brain, gray matter (GM), and white matter (WM) using sex-stratification. A leave-one-out receiver operating characteristic (ROC) analysis classified concussed from HCs based on CVR metrics. CVR magnitude was greater and speed of response faster in concussed participants relative to HCs, with WM showing higher classification accuracy compared with GM. ROC analysis for WM-CVR metrics revealed an area under the curve of 0.94 in males and 0.90 in females for speed and magnitude of response respectively. These greater than normal responses to a vasodilatory stimulus warrant further investigation to compare the predictive ability of CVR metrics against structural injury metrics for diagnosis and prognosis in acute concussion.

Elevated exercise ventilation in mild COPD is not linked to enhanced central chemosensitivity

BackgroundThe purpose of this study was to determine if altered central chemoreceptor characteristics contributed to the elevated ventilation relative to carbon dioxide production (V̇E/V̇CO2) response during exercise in mild chronic obstructive pulmonary disease (COPD). MethodsTwenty-nine mild COPD and 19 healthy age-matched control participants undertook lung function testing followed by symptom-limited incremental cardiopulmonary exercise testing . On a separate day, basal (non-chemoreflex) ventilation (V̇EB), the central chemoreflex ventilatory recruitment threshold for CO2 (VRTCO2), and central chemoreflex sensitivity (V̇ES) were assessed using the modified Duffin’s CO2 rebreathing method. Resting arterialized blood gas data were also obtained. ResultsAt standardized exercise intensities, absolute V̇E and V̇E/V̇CO2 were consistently elevated and the end-tidal partial pressure of CO2 was relatively decreased in mild COPD versus controls (all p < 0.05). There were no between-group differences in resting arterialized blood gas parameters, basal V̇E, VRTCO2, or V̇ES (all p > 0.05). ConclusionThese data have established that excessive exercise ventilation in mild COPD is not explained by altered central chemosensitivity.

Prognostic value of the cardiorespiratory optimal point during submaximal exercise testing

Abstract Background Peak oxygen consumption (pVO2) is a key parameter in assessing the prognosis of heart failure with reduced ejection fraction (HFrEF) patients (pts). However, it is a less reliable parameter when the cardiopulmonary exercise test (CPET) is not maximal. It is crucial to identify the submaximal exercise variables with the best prognostic power (PP), in order to improve the management of pts that cannot attain a maximal CPET. Purpose The aim of this study was to evaluate and compare the PP of several exercise parameters in submaximal CPET for risk stratification in pts with HFrEF. Methods Prospective evaluation of adult pts with HFrEF submitted to CPET in a tertiary center. A submaximal CPET was defined by a respiratory exchange ratio (RER) ≤1.10. Pts were followed up for at least 1 year for the primary endpoint of cardiac death and urgent heart transplantation/ ventricular assist device implantation. Several CPET parameters were analyzed as potential predictors of the combined endpoint and their PP (area under the curve - AUC) was compared to that of pVO2, using the Hanley and McNeil test. Results CPET was performed in 487 HF pts, of which 317 (66%) performed a submaximal CPET. Pts averaged 57±12 years of age, 77% were male, 45.7% had ischemic cardiomyopathy, with a mean LVEF of 30.4±7.6%, a mean heart failure survival score of 8.6±1.1. The mean pVO2 was 17.1±5.5 ml/kg/min and the mean RER 1.01±0.08. During a mean follow-up (FU) time of 11±1 months, 18 pts (6%) met the primary endpoint. Cardiorespiratory optimal point (OP - VE/VO2) had the highest AUC value (0.915, p=0.001), followed by the partial pressure of end-tidal CO2 at the anaerobic threshold - PETCO2L (0.814, p&amp;lt;0.001). pVO2 presented an AUC of 0.730 (p=0.001). OP≥31 and PETCO2L ≤37mmHg had a sensitivity of 100 and 76.9% and a specificity of 71.1 and 67%, respectively, for the primary outcome. OP presented a significantly higher PP than pVO2 (p=0.048), whether PETCO2L didn't achieve any statistical significance (p=0.164). Pts with anOP≥31 presented a significantly lower survival free of HT during FU (log rank p=0.002). Conclusion OP had the highest PP for HF events of all parameters analyzed for a submaximal CPET. This parameter can help stratify the HF pts physiologically unable to reach a peak level of exercise. Funding Acknowledgement Type of funding source: None

Acute effects of high-volume compared to low-volume resistance exercise on lung function.

The aim of this study was to examine whether a high-volume compared to low-volume resistance exercise session acutely impairs lung function. Fourteen males (age 23.8±6.5 years) with resistance training experience participated in this study. Participants completed two resistance training protocols (high- and low-volume) and a control session (no exercise) with the sequence randomised. High- and low-volume sessions involved 5 sets (5-SETS) and 2 sets (2-SETS), respectively of 10 repetitions at 65% one-repetition maximum for each exercise (bench press, squat, seated shoulder press, and deadlift) with 90-sec recovery between sets. Lung function was evaulated pre- and postsession and respiratory gases were measured during the recovery between sets of exercises. An increase in the ratio of forced expiratory volume in 1 sec (FEV1) to forced vital capacity was found following the 5-SETS compared to 2-SETS (P=0.033). There was a significant reduction in inspiratory capacity following 5-SETS compared to control session (P=0.049). No other lung function parameter was affected postsession. During training sessions, the squat and deadlift required greater ventilatory demands compared to the bench press and shoulder press (P<0.001). Across most exercises during 5-SETS compared to 2-SETS, there was a lower end-tidal CO2 partial pressure. Across most exercises during 5-SETS compared to 2-SETS there was a lower end-tidal CO2 partial pressure (PETCO2) (P≤0.013), although there were no other differences in physiological responses between the sessions. The findings tend to suggest that the ventilatory and respiratory muscle demands of a strenuous resistance exercise session are not great enough to acutely impair indices of lung function.

Evaluation of chemical restraint, isoflurane anesthesia and methadone or tramadol as preventive analgesia in spotted pacas (Cuniculus paca) subjected to laparoscopy

ObjectiveTo evaluate the efficacy and cardiopulmonary effects of ketamine–midazolam for chemical restraint, isoflurane anesthesia and tramadol or methadone as preventive analgesia in spotted pacas subjected to laparoscopy. Study designProspective placebo-controlled blinded trial. AnimalsA total of eight captive female Cuniculus paca weighing 9.3 ± 0.9 kg. MethodsAnimals were anesthetized on three occasions with 15 day intervals. Manually restrained animals were administered midazolam (0.5 mg kg–1) and ketamine (25 mg kg–1) intramuscularly. Anesthesia was induced and maintained with isoflurane 30 minutes later. Tramadol (5 mg kg–1), methadone (0.5 mg kg–1) or saline (0.05 mL kg–1) were administered intramuscularly 15 minutes prior to laparoscopy. Heart rate (HR), respiratory rate, mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), end-tidal CO2 partial pressure (Pe′CO2), end-tidal concentration of isoflurane (Fe′Iso), pH, PaO2, PaCO2, bicarbonate (HCO3−), anion gap (AG) and base excess (BE) were monitored after chemical restraint, anesthesia induction and at different laparoscopy stages. Postoperative pain was assessed by visual analog scale (VAS) for 24 hours. Variables were compared using anova or Friedman test (p < 0.05). ResultsChemical restraint was effective in 92% of animals. Isoflurane anesthesia was effective; however, HR, MAP, pH and AG decreased, whereas Pe′CO2, PaO2, PaCO2, HCO3− and BE increased. MAP was stable with tramadol and methadone treatments; HR, Fe′Iso and postoperative VAS decreased. VAS was lower for a longer time with methadone treatment; SpO2 and AG decreased, whereas Pe′CO2, PaCO2 and HCO3− increased. Conclusions and clinical relevanceKetamine–midazolam provided satisfactory restraint. Isoflurane anesthesia for laparoscopy was effective but resulted in hypotension and respiratory acidosis. Tramadol and methadone reduced isoflurane requirements, provided postoperative analgesia and caused hypercapnia, with methadone causing severe respiratory depression. Thus, the anesthetic protocol is adequate for laparoscopy in Cuniculus paca; however, methadone should be avoided.

Voluntary hypocapnic hyperventilation lasting 5 min and 20 min similarly reduce aerobic metabolism without affecting power outputs during Wingate anaerobic test

Twenty minutes of voluntary hypocapnic hyperventilation prior to exercise reduces the aerobic metabolic rate with a compensatory increase in the anaerobic metabolic rate without affecting exercise performance during the Wingate anaerobic test (WAnT). Thus, pre-exercise hypocapnic hyperventilation may be a useful means of stressing the anaerobic energy system during training, ultimately improving anaerobic exercise performance. However, it remains unclear whether a shorter (e.g., 5 min) pre-exercise hypocapnic hyperventilation is sufficient to reduce the aerobic metabolic rate during high-intensity exercise. We therefore compared the effects of 5-min and 20-min pre-exercise hypocapnic hyperventilation on aerobic metabolism during the 30-s WAnT. Ten healthy young males and one female performed the WAnT following 20 min of spontaneous breathing (control trial) or 5 or 20 min of voluntary hypocapnic hyperventilation. Both the 5-min and 20-min hyperventilation reduced end-tidal CO2 partial pressure (an index of arterial CO2 partial pressure) to ∼23 mmHg, whereas it remained unchanged during the spontaneous breathing. The peak, mean and minimum power outputs during the WAnT did not differ among the three trials. Oxygen uptake during the WAnT was lower in both the 5-min (1493 ± 257 mL min−1) and 20-min (1397 ± 447 mL min−1) hyperventilation trials than during the control trial (1847 ± 286 mL min−1), and was similar in the two hyperventilation trials. These results suggest that 5 min of pre-exercise hypocapnic hyperventilation reduces aerobic metabolism during the 30-s WAnT to a level similar to that seen with the 20-min hyperventilation. Moreover, exercise performance was unaffected, which implies anaerobic metabolism was enhanced.

Cerebrovascular Reactivity Assays Collateral Function in Carotid Stenosis.

In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50–69% stenosis, 70–90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class – including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.

Robust predictive control for respiratory CO2 gas removal in closed-loop mechanical ventilation: An in-silico study

Abstract In this study a physiological closed-loop system for arterial CO2 partial pressure control was designed and comprehensively tested using a set of models of the respiratory CO2 gas exchange. The underlying preclinical data were collected from 12 pigs in presence of severe changes in hemodynamic and pulmonary condition. A minimally complex nonlinear state space model of CO2 gas exchange was identified post hoc in different lung conditions. The control variable was measured noninvasively using the endtidal CO2 partial pressure. For the simulation study the output signal of the controller was defined as the alveolar minute volume set value of an underlying adaptive lung protective ventilation mode. A linearisation of the two-compartment CO2 gas exchange model was used for the design of a model predictive controller (MPC). It was augmented by a tube based controller suppressing prediction errors due to model uncertainties. The controller was subject to comparative testing in interaction with each of the CO2 gas exchange models previously identified on the preclinical study data. The performance was evaluated for the system response towards the following five tests in comparison to a PID controller: recruitment maneuver, PEEP titration maneuver, stepwise change in the CO2 production, breath-hold maneuver and a step in the reference signal. A root mean square error of 2.69 mmHg between arterial CO2 partial pressure and the reference signal was achieved throughout the trial. The reference-variable response of the model predictive controller was superior regarding overshoot and settling time.

Dynamic characteristics of cerebrovascular reactivity or ventilatory response to change in carbon dioxide.

What is the central question of this study? What are the dynamic characteristics of cerebrovascular carbon dioxide reactivity and the central respiratory chemoreflex? What is the main finding and its importance? The transfer function gain from the end-tidal partial pressure of carbon dioxide to cerebral blood flow or ventilation decreased in the high frequency range at rest and during exercise. These findings indicate that the dynamic characteristics of both systems were not constant in all frequency ranges, and this trend was not modified by exercise. The purpose of this study was to examine the dynamic characteristics of cerebrovascular reactivity and ventilatory response to change in arterial CO2 in all frequency ranges at rest using frequency domain analysis, and also to examine whether this is modified by dynamic exercise as with the traditionally determined cerebrovascular CO2 reactivity. In nine healthy young subjects, at rest and during exercise (cycling exercise at constant predetermined work rate corresponding to a level of 0.90lmin-1 ), the dynamic characteristics of cerebrovascular CO2 reactivity and the central respiratory chemoreflex were assessed by transfer function analysis using a binary white-noise sequence (0-7% inspired CO2 fraction) from the end-tidal partial pressure of CO2 ( ) to the mean middle cerebral artery mean blood velocity (MCA Vm ) or minute ventilation ( ), respectively. In the high frequency range, both transfer function gains decreased but, interestingly, the cut-off frequency in the transfer function gain from to MCA Vm response was higher than that from to response at rest (0.024 vs. 0.015Hz) and during exercise (0.030 vs. 0.011Hz), indicating that cerebrovascular CO2 reactivity or central respiratory chemoreflex was not constant in all frequency ranges, and this trend was not modified by exercise. These findings suggest that dynamic characteristics of the cerebrovascular CO2 reactivity or central chemoreflex need to be assessed to identify the whole system because the traditional method cannot identify the property of time response of these systems.

Effect of insulation with bubble wrap and an absorbent pad on heat loss in anaesthetised cats

ABSTRACT Aims: To evaluate the efficacy of insulating the limbs and thorax of cats with a combination of bubble wrap and an absorbent, plastic-lined pad in reducing heat loss during ovariohysterectomy. Methods: A preliminary study was performed to compare heat loss of 1 L bags of Hartmann’s solution heated to 38°C which were either wrapped in two layers of bubble wrap and an absorbent pad (n = 6) or were unwrapped (n = 6). Bags were allowed to cool in a temperature-controlled room and the temperature of the bags was measured every 10 minutes for 60 minutes. The clinical study, included 16 intact female cats undergoing ovariohysterectomy. The cats were premedicated with I/M morphine and either medetomidine or dexmedetomidine, and anaesthesia was induced with I/V propofol and maintained with isoflurane in 100% oxygen. Cats were randomly assigned to either the treatment group (n = 8) whose limbs and thorax wrapped with two layers of bubble wrap and an absorbent pad immediately after induction, or the control group (n = 8) which were unwrapped. Body temperature (measured with an oesophageal temperature probe), heart rate, respiratory rate, mean arterial pressure and partial pressure of end-tidal CO2 were recorded immediately after induction (T start), before surgery started (T surgery), and at the end of isoflurane administration (T end). The times from T end to extubation, from T end to when the cat could maintain sternal recumbency and from T end to when the cat was able to stand, were also recorded. Results: In the preliminary study of heat loss by fluid bags, the mean temperature at 60 minutes was higher in wrapped bags (35.4 (SD 0.2)°C) compared to unwrapped bags (33.0 (SD 0.3)°C; p < 0.01). For cats undergoing ovariohysterectomy, mean body temperature of wrapped cats was higher than that of unwrapped cats both at T surgery (36.0 (SE 0.3) vs. 34.5 (SE 0.3)°C; p = 0.001) and at T end (37.2 (SE 0.5) vs. 36.0 (SE 0.5)°C; p = 0.01). Wrapped cats regained the ability to stand more rapidly that unwrapped cats (26.4 (SE 5.8) vs. 47.0 (SE 5.8) minutes p = 0.01). Conclusions: Wrapping the limbs and thorax of cats undergoing ovariohysterectomy in a combination of bubble wrap and absorbent pads reduced heat loss, which in turn improved recovery time from general anaesthesia. Clinical relevance: This inexpensive and practical method may reduce perioperative hypothermia, in cats undergoing abdominal surgery.

Interpretive Complications Underlying Cerebrovascular Response To Hypercapnia; Significance Of The Central Respiratory Chemoreflex Transient

Cerebral blood flow (CBF) is sensitive to changes in the arterial partial pressure of carbon dioxide (CO2) with cerebrovascular reactivity an established risk factor for stroke and neurodegenerative disease. However, its interpretation can be complicated given subtle differences in cerebrovascular and central respiratory chemoreflex response transients. PURPOSE: To examine to what extent exposure time to CO2 influences CBF response. METHOD: We measured CBF response to hypercapnia (FICO2 = 5%) in five healthy participants for 10 min in the supine position. End-tidal partial pressures of CO2 (PETCO2), minute ventilation (VE), and middle cerebral artery blood velocity (MCAv) were assessed during both the early (3~4 min) and late phases (9~10 min) of exposure. RESULT: We observed elevated VE larger during the late compared to the early phase of exposure (from 11 ± 2 to 29 ± 8 vs. 23 ± 4 L/min, P = 0.047) despite no differences in PETCO2 (P = 0.304). The corresponding increase in MCAv during the late phase was suppressed compared to the early phase (from 48 ± 11 to 58 ± 14 vs. 63 ± 13 cm/sec, P = 0.029). Thus, the response of CBF to change in PETCO2 at late phase was lower than that of early phase (1.1 ± 1 %/mmHg vs. 1.7 ± 1 %/mmHg, P=0.07). CONCLUSION: These findings highlight the importance of considering the central respiratory chemoreflex transient during the clinical assessment of cerebrovascular reactivity.

Cardiorespiratory hysteresis during incremental high-altitude ascent-descent quantifies the magnitude of ventilatory acclimatization.

What is the central question of this study? We assessed the utility of a new metric for quantifying ventilatory acclimatization to high altitude, derived from differential ascent and descent steady-state cardiorespiratory variables (i.e. hysteresis). Furthermore, we aimed to investigate whether the magnitude of cardiorespiratory hysteresis was associated with the development of acute mountain sickness. What is the main finding and its importance? Hysteresis in steady-state cardiorespiratory variables quantifies ventilatory acclimatization to high altitude. The magnitude of cardiorespiratory hysteresis during ascent to and descent from high altitude was significantly related to the development of symptoms of acute mountain sickness. Hysteresis in steady-state chemoreflex drive can provide a simple, non-invasive method of tracking ventilatory acclimatization to high altitude. Maintenance of arterial blood gases is achieved through sophisticated regulation of ventilation, mediated by central and peripheral chemoreflexes. Respiratory chemoreflexes are important during exposure to high altitude owing to the competing influence of hypoxia and hypoxic hyperventilation-mediated hypocapnia on steady-state ventilatory drive. Inter-individual variability exists in ventilatory acclimatization to high altitude, potentially affecting the development of acute mountain sickness (AMS). We aimed to quantify ventilatory acclimatization to high altitude by comparing differential ascent and descent values (i.e. hysteresis) in steady-state cardiorespiratory variables. We hypothesized that: (i)the hysteresis area formed by cardiorespiratory variables during ascent and descent would quantify the magnitude of ventilatory acclimatization; and (ii)larger hysteresis areas would be associated with lower AMS symptom scores during ascent. In 25 healthy, acetazolamide-free trekkers ascending to and descending from 5160m, cardiorespiratory hysteresis was measured in the partial pressure of end-tidal CO2 , peripheral oxygen saturation, minute ventilation, chemoreceptor stimulus index (end-tidal CO2 /peripheral oxygen saturation) and the calculated steady-state chemoreflex drive (SS-CD; minute ventilation/chemoreceptor stimulus index) using portable devices (capnograph, peripheral pulse oximeter and respirometer, respectively). Symptoms of AMS were assessed daily using the Lake Louise questionnaire. We found that: (i)ascent-descent hysteresis was present in all cardiorespiratory variables; (ii)SS-CD is a valid metric for tracking ventilatory acclimatization to high altitude; and (iii)the highest AMS scores during ascent exhibited a significant, moderate and inverse correlation with the magnitude of SS-CD hysteresis (rs =-0.408, P=0.043). We propose that ascent-descent hysteresis is a new and feasible way to quantify ventilatory acclimatization in trekkers during high-altitude exposure.