Inspired O2 Concentration Research Articles

Evaluation of the capnographic monitoring and oxygen delivery functions of three variable oxygen delivery masks

A number of commercial devices that couple oxygen delivery and capnographic monitoring have become available. Many of these devices have been released for clinical use without prior clinical evaluation. We decided to evaluate the oxygen delivery and capnographic monitoring function of two commercially available masks (Capnomask; Mediplus, High Wycombe, Bucks, UK and Oxymask; P3 Medical Ltd, Bristol, UK) as well as the Lifecare variable O2 delivery face mask (Lifecare Hospital Supplies Ltd, Harlow, Essex, UK) designed primarily for O2 delivery but with a CO2 sampling port attached to the side of the mask for the purpose of the study [1]. We conducted a manikin study to evaluate the oxygen delivery and capnographic functions of the three face masks. We constructed a model using a manikin head and a ventilator to simulate ventilation. The manikin ‘breathed’ with two tidal volumes (300 ml and 500 ml) and two expired CO2 concentrations (3.5% and 5%). The experiment was carried out at four respiratory rate frequencies (9, 16, 24, 30 breaths.min−1) and four oxygen flow rates (0, 4, 6 and 10 l.min−1). End-tidal CO2 and oxygen concentration were recorded using a Datex AS/3 monitoring system. The measured CO2 concentrations at an oxygen flow rate of 6 l.min−1 are shown in Fig. 1. Mean (SD) O2 concentrations (6 l.min−1 O2 flow) were a 43% (6%), 43% (5%) and 32% (1.4%) for Capnomask, Oxymask and Lifecare mask respectively over the full range of respiratory rates. ‘Expired’ CO2 recordings for the three dual function masks over the range of respiratory rates. Our findings suggest that the Capnomask recorded higher expired CO2 levels than the Oxymask and Lifecare variable oxygen delivery mask with the side CO2 sampling port. Oxygen delivery over the full range of respiratory rates was very similar for the Capnomask and Oxymask. The Lifecare mask delivered consistently lower inspired O2 concentration than the Capnomask and Oxymask for all of the selected respiratory rates. This may be due to the position of the CO2 sampling tube, which may have interfered with the flow of O2 within the mask. The oxygen delivery function of a mask may be adversely affected by the attachment of the CO2 sampling tube and this is best avoided. We conclude that commercially available face masks with the dual function should be evaluated in the laboratory and if satisfactory function is demonstrated then evaluation in the clinical environment should follow.

Chronic intermittent hypoxia enhances habituation of the arousal response to acute hypoxia in developing rodents

Arousal from sleep is a critical apnea recovery mechanism. Rat pups progressively increase their time to arousal (latency) during repeated exposures to hypoxia (short term habituation‐STH). We hypothesized that postnatal exposure to chronic intermittent hypoxia (CIH) would increase the mean time (over several acute hypoxia exposures) to arousal (long term habituation‐LTH) and would accentuate STH, especially at P15, an age equivalent to the time of the highest incidence of Sudden Infant Death Syndrome (SIDS). Pups and dam were exposed to CIH for a total of 25 days. Each pup was removed at P5, P15, and P25, and exposed to four 3‐min trials of 5% oxygen alternating with 6‐min periods of normoxia. During the hypoxia trials, arousal latency progressively increased in both the Control and CIH groups (STH‐P=0.024). There was a mean increase in latency only in the CIH group (LTH) (P=0.027), most prominent at P15 (<0.001) and P25 (P=0.007). At P15, but not at P5 or P25, the STH was also accentuated in the CIH group (P=0.039). There were corresponding effects on arousal thresholds (inspired O2 concentration and oxyhemoglobin saturation at the time of arousal) and complex effects on heart rate. These results support the hypothesis that exposure to chronic intermittent hypoxia accentuates habituation of the arousal response in developing rat pups, especially in early infancy, and is an important mechanism in SIDS. P01 HD36379.

The multiple inert gas elimination technique (MIGET)

This brief review centers on the multiple inert gas elimination technique (MIGET). This technique, developed in the 1970s, measures the pulmonary exchange of a set of six different inert gases dissolved together in saline (or dextrose) and infused intravenously. It then uses those measurements to compute the distribution of ventilation/perfusion ratios that best explains the exchange of the six gases simultaneously. MIGET is based on the very same mass-conservation principles underlying the classic work of Rahn and Fenn and of Riley and coworkers in the 1950s, which defines the relationship between the ventilation/perfusion ratio and the alveolar and capillary partial pressures of any gas. After a brief history of MIGET, its principles are laid out, its information content is explained, and its limitations are described. It is noted that in addition to quantifying ventilation/perfusion inequality and pulmonary shunting, MIGET can identify and quantify diffusion limitation of O(2) exchange, when present, as well as explain the contributions of extrapulmonary influences such as inspired O(2) concentration, ventilation, cardiac output, Hb concentration/P(50), body temperature and acid/base state on arterial oxygenation. An overview of the technical details of implementing MIGET is given, and the review ends with potential future applications.

Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain

Increasing PaO2 can increase brain tissue PO2 (PbtO2). Nevertheless, the small increase in arterial O2 content induced by hyperoxia does not increase O2 delivery much, especially when cerebral blood flow (CBF) is low, and the effectiveness of hyperoxia as a therapeutic intervention remains controversial. The purpose of this study was to examine the role of regional (r)CBF at the site of the PO2 probe in determining the response of PbtO2 to induced hyperoxia. The authors measured PaO2 and PbtO2 at baseline normoxic conditions and after increasing inspired O2 concentration to 100% on 111 occasions in 83 patients with severe traumatic brain injury in whom a stable xenon-enhanced computed tomography measurement of CBF was available. The O2 reactivity was calculated as the change in PbtO2 x 100/change in PaO2. The O2 reactivity was significantly different (p < 0.001) at the 5 levels of rCBF (<10, 11-15, 16-20, 21-40, and > 40 ml/100 g/min). When rCBF was < 20 ml/100 g/min, the increase in PbtO2 induced by hyperoxia was very small compared with the increase that occurred when rCBF was > 20 ml/100 g/min. Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.

Periodic acceleration (pGz) CPR in a swine model of asphyxia induced cardiac arrest: Short-term hemodynamic comparisons

Asphyxia is one of the most common causes of pediatric cardiac arrest, and becoming a more frequently recognized cause in adults. Periodic acceleration (pGz) is a novel method of cardiopulmonary resuscitation (CPR). pGz is achieved by rapid motion of the supine body headward-footward that generates adequate perfusion and ventilation during cardiac arrest. In a swine ventricular fibrillation cardiac arrest model, pGz produced a higher return of spontaneous circulation (ROSC), superior neurological outcome, less echocardiography evidence of post resuscitation myocardial stunning, and decreased indices of tissue injury. In contrast to standard chest compression CPR, pGz does not produce rib fractures. We investigated the feasibility of pGz in severe asphyxia cardiac arrest and assessed whether beneficial effects seen in the VF model of cardiac arrest could be realized. Sixteen swine weight 4+/-1 kg were anesthetized, tracheally intubated, and instrumented to measure, hemodynamics and echocardiography. Asphyxia was induced by occlusion of the tracheal tube. After loss of aortic pulsations (median time 10 min) animals were observed for three additional minutes following which all were in cardiac arrest. The animals were then randomized to receive 10 min of pGz or standard chest compression ventilation performed with a commercial device (Thumper). A single dose of epinephrine (adrenaline) and sodium bicarbonate were given and defibrillation attempted if appropriate for a maximum of 10 min. Both groups received fractional inspired O2 concentration of 100% during CPR and after resuscitation. Four animals in each group (50%) had an initial ROSC, however only two of the four initial survivors remained alive 3h after ROSC. There were no significant differences in blood pressure, coronary perfusion pressure during CPR and after early ROSC between groups. pGz treated animals had significantly lower pulmonary artery pressure; 20+/-4 mmHg compared to Thumper 46+/-5 mmHg, 30 min after ROSC (p<0.01). Surviving animals in both groups had severe myocardial dysfunction at 30 min after ROSC. At necropsy, 25% of the Thumper treated animals had rib fractures, while none occurred in the pGz group. In a lethal model of asphyxia cardiac arrest, pGz is equivalent to standard CPR, with respect to acute outcomes and resuscitation survival rates but is associated with significantly lower pulmonary artery pressures and does not produce traumatic rib fractures.

Tissue oxygen monitoring in rodent models of shock

Tissue Po(2) (tPo(2)) reflects the balance between local O(2) supply and demand and, thus, could be a useful monitoring modality. However, the consistency and amplitude of the tPo(2) response in different organs during different cardiorespiratory insults is unknown. Therefore, we investigated the effects of endotoxemia, hemorrhage, and hypoxemia on tPo(2) measured in deep and peripheral organ beds. We compared arterial pressure, blood gas and lactate levels, descending aortic and renal blood flow, and tPo(2) in skeletal muscle, bladder epithelium, liver, and renal cortex during 1) LPS infusion (10 mg/kg), 2) sequential removal of 10% of circulating blood volume, and 3) reductions in inspired O(2) concentration in an anesthetized Wistar rat model with values measured in sham-operated animals. Different patterns were seen in each of the shock states, with condition-specific variations in the degree of acidemia, lactatemia, and tissue O(2) responses between organs. Endotoxemia resulted in a rise in bladder tPo(2) and an early fall in liver tPo(2) but no significant change in muscle and renal cortical tPo(2). Progressive hemorrhage, however, produced proportional declines in liver, muscle, and bladder tPo(2), but renal cortical tPo(2) was maintained until profound blood loss had occurred. By contrast, progressive hypoxemia resulted in proportional decreases in tPo(2) in all organ beds. This study highlights the heterogeneity of responses in different organ beds during different shock states that are likely related to local changes in O(2) supply and utilization. Whole body monitoring is not generally reflective of these changes.

Danger of helmet continuous positive airway pressure during failure of fresh gas source supply

To assess the behavior of different helmets after discontinuation of fresh gas flow by disconnection at the helmet inlet, flow generator, or gas source. Randomized physiological study in a university research laboratory. Five healthy volunteers. CPAP (FIO2 50%, PEEP 5 cmH2O) delivered in random sequence with three different helmets: 4Vent (Rüsch), PN500 (Harol), CaStar (StarMed) with antisuffocation valve open or locked. For each helmet all three disconnections were randomly employed up to 4 min. During flow disconnection we measured: respiratory rate and tidal volume by respitrace; inspiratory and expiratory CO2 concentration, and FIO2 from a nostril; SpO2 by pulse oxymetry. Independently of the site of disconnection we observed a fast increase in CO2 rebreathing and minute ventilation, associated with a decrease in inspired O2 concentration. In the absence of an operational safety valve, larger helmet size and lower resistance of the inlet hose resulted in slower increase in CO2 rebreathing. The presence of the safety valve limited the rebreathing of CO2, and the increase in minute ventilation but did not protect from a decrease in FIO2 and loss of PEEP. While the use of a safety valve proved effective in limiting CO2 rebreathing, it did not protect from the risk of hypoxia related to decrease in FIO2 and loss of PEEP. In addition to a safety antisuffocation valve, a dedicated monitoring and alarming systems are needed to employ helmet CPAP safely.

Method for quantifying net anaerobic power in exercising horses

There is no good method for measuring net anaerobic power in exercising horses to allow accurate estimates of total metabolic power. The increase in VO2max when breathing hyperoxic (HO) gas should be accompanied by a stoichiometrically equal (in terms of ATP turnover, i.e. energy equivalents) decrease in plasma lactate accumulation rate (Mlactate). Six 3-year-old Thoroughbreds were trained on an equine treadmill wearing a semi-open flow mask for measurement of VO2. After 4 months the horses ran with reproducible specific VO2max (VO2max/kg bwt). The mask design allowed mixing of O2 or N2 with the inward bias flow of gas so that inspired O2 concentration of the horse could be controlled. While the horse breathed either HO (25.1% O2), normoxic (NO, 21% O2) or hypoxic (LO, 19.5% O2) gas, it ran at a speed sufficient to elicit VO2max in NO while jugular venous blood was drawn at 15 sec intervals over a period of 2 min to determine Mlactate. VO2max/kg bwt was not significantly different between LO and NO conditions, and LO data could not be used in the comparison. The VO2max/kg bwt increased from 2.59 +/- 0.24 (s.d.) to 2.86 +/- 0.24 mlO2 (STPD)/sec/kg in NO and HO, respectively, while Mlactate decreased from 11.5 +/- 4.2 to 9.0 +/- 3.9 mmol/min as VO2 increased. The ratio of delta Mlactate to delta VO2max/kg bwt suggests that Mlactate of approx 11.1 +/- 6.7 mmol/min is associated with net anaerobic power approximately equivalent to 1.0 mlO2 (STPD)/sec/kg of aerobic power (20.1 W/kg(-1)). The high variability in VO2max/kg bwt observed in data from some runs, particularly in LO, suggests that caution must be used when comparing data from the same horse during different runs. This study provides a tool for estimating net anaerobic power and, more accurately, evaluating total metabolic power of horses exercising at or above their aerobic capacities.

Failure of non-invasive ventilation in patients with acute lung injury: observational cohort study

IntroductionThe role of non-invasive positive pressure ventilation (NIPPV) in the treatment of acute lung injury (ALI) is controversial. We sought to assess the outcome of ALI that was initially treated with NIPPV and to identify specific risk factors for NIPPV failure.MethodsIn this observational cohort study at the two intensive care units of a tertiary center, we identified consecutive patients with ALI who were initially treated with NIPPV. Data on demographics, APACHE III scores, degree of hypoxemia, ALI risk factors and NIPPV respiratory parameters were recorded. Univariate and multivariate regression analyses were performed to identify risk factors for NIPPV failure.ResultsOf 79 consecutive patients who met the inclusion criteria, 23 were excluded because of a do not resuscitate order and two did not give research authorization. Of the remaining 54 patients, 38 (70.3%) failed NIPPV, among them all 19 patients with shock. In a stepwise logistic regression restricted to patients without shock, metabolic acidosis (odds ratio 1.27, 95% confidence interval (CI) 1.03 to 0.07 per unit of base deficit) and severe hypoxemia (odds ratio 1.03, 95%CI 1.01 to 1.05 per unit decrease in ratio of arterial partial pressure of O2 and inspired O2 concentration – PaO2/FiO2) predicted NIPPV failure. In patients who failed NIPPV, the observed mortality was higher than APACHE predicted mortality (68% versus 39%, p < 0.01).ConclusionNIPPV should be tried very cautiously or not at all in patients with ALI who have shock, metabolic acidosis or profound hypoxemia.

High inspired oxygen concentrations increase intrapulmonary shunt in anaesthetized horses

ObjectivesTo compare pulmonary function and gas exchange in anaesthetized horses during and after breathing either O2-rich gas mixtures or air. AnimalsSix healthy standard bred trotters (age range 3–12 years; mass range 423–520 kg), four geldings and two mares. Study designRandomized, cross-over experimental study. MethodsHorses were anaesthetized on two occasions with tiletamine-zolazepam after pre-anaesthetic medication with acepromazine, romifidine and butorphanol. After endotracheal intubation and positioning in left lateral recumbency, animals were allowed to breathe spontaneously. One of two, randomly allocated inspired gas treatments was provided: either i) room air (fractional concentration of inspired O2 [FiO2] = 0.21) provided throughout anaesthesia; or ii) an O2-rich gas mixture (FiO2 = >0.95) for 15 minutes, followed by room air. The alternative treatment was delivered at the second anaesthetic. Respiratory and haemodynamic variables and the distribution of ventilation-perfusion (VA/Q) ratios (using the multiple inert gas elimination technique) were determined in the standing conscious horse (baseline) after sedation and during anaesthesia. ResultsBreathing O2-rich gas was associated with a decreased respiratory rate (p = 0.015) increased PaCO2 (p < 0.001) and increased PaO2 (p = 0.004) compared with breathing air. All horses developed intrapulmonary shunt during anaesthesia, but shunt was significantly greater (13 ± 5%) when O2-rich gas was delivered compared with air breathing (5 ± 2%; p = 0.013). Ten minutes after O2-rich gas was replaced by air, shunt remained larger in horses that had initially received oxygen compared with those breathing air (p = 0.042). Mixed venous oxygen tensions were significantly lower during sedation than at baseline (p < 0.001) and during anaesthesia (p < 0.001). ConclusionsDuring dissociative anaesthesia, arterial oxygenation was greater when horses breathed gas containing more than 95% oxygen, compared with when they breathed air. However, breathing O2-rich gas increased intrapulmonary shunt and caused hypoventilation. The intrapulmonary shunt created during anaesthesia by high inspired O2 concentrations remained larger when FiO2 was reduced to 0.21, indicating that absorption atelectasis produced during O2-rich gas breathing persisted throughout anaesthesia. Clinical relevanceIn healthy horses undergoing short-term dissociative anaesthesia, air breathing ensures a level of oxygen delivery that meets tissue demand. There is no benefit to horses in breathing O2-rich gas after the gas supply is discontinued. On the contrary, the degree of shunt induced by breathing O2-rich gas persists. The clinical relevance of this during recovery requires investigation.

Mechanisms of hypoxemia

A fundamental aspect of cardiopulmonary homeostasis is the adequate delivery of oxygen to meet the metabolic demands of the body. Cardiac output, O2-carrying capacity (i.e., hemoglobin concentration and quality), and arterial PO2 (PaO2) determine O2 transport. Relevant to this discussion, arterial hypoxemia commonly occurs in patients with acute respiratory failure (ARF). If arterial hypoxemia is severe enough, it is not compatible with life. The two primary causes of ARF are acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and chronic obstructive lung disease (COPD). Although the treatment for arterial hypoxemia always includes increases in the fractional inspired O2 concentration (FIO2), the degree to which patients’ PaO2 improves and the need for adjuvant therapies differ markedly between these two groups of disease processes. The mechanisms by which arterial hypoxemia occurs in ALI/ARDS and COPD have been characterized using the multiple inert gas elimination technique (MIGET) approach [1]. MIGET provides precise estimates of the distributions of alveolar ventilation and pulmonary perfusion (VA/Q) and their relationships, there is no need to change the FIO2 during measurements, hence avoiding variations in the pulmonary vascular tone, and it facilitates the unraveling of the active interplay between intrapulmonary, namely VA/Q imbalance, intrapulmonary shunt and limitation of alveolar to end-capillary O2 diffusion, and extrapulmonary (i.e., FIO2, total ventilation, cardiac output and oxygen consumption) factors governing hypoxemia [2].

Role of Hypobaria in Fluid Balance Response to Hypoxia

To estimate the separate and combined effects of reduced P(B) and O2 levels on body fluid balance and regulating hormones, measurements were made during reduced PB (altitude, ALT; P(B) = 432 mm Hg, F(I(O2)) = 0.207), reduced inspired O2 concentration (normobaric hypoxia, HYX; P(B) = 614 mm Hg, F(I(O2)) = 0.142), and lowered ambient pressure without hypoxia (normoxic hypobaria HYB; P(B) = 434 mm Hg, F(I(O2)) = 0.296). Nine fit and healthy young men were exposed to these conditions for 10 h in a decompression chamber. Lake Louise AMS scores, urine collections, and blood samples were obtained every 3 h, with recovery measurements 2 h after exposure. AMS was significantly greater during ALT than HYX, as previously reported (J. Appl. Physiol. 81:1908-1910. 1996), because the combination of reduced P(B) and P(O2) over the 10 h favored fluid retention by reducing urine volume, while plasma volume (PV) remained higher than during HYX. At ALT the plasma Na+ fell significantly at 6 h, probably from dilution of extracellular fluid, and antidiuretic hormone (ADH) was highest (p = 0.006 versus HYB). The PV, urine flow, free water clearance, and plasma renin activity (PRA) rose significantly during recovery from ALT as AMS symptoms subsided, suggesting increased intravascular fluid and reduced adrenergic tone. During HYB, the plasma aldosterone (ALDO) and K+ levels were significantly elevated, and PRA was highest and ADH lowest, without fluid retention. During HYX, fluid balance was similar to HYB, but PV and ALDO were significantly lower, and ALDO increased significantly in recovery from HYX. The fluid retention at ALT in AMS-susceptible subjects appears related to a synergistic interaction involving reduced P(B) and ADH and ALDO.

Intraoperative Respiratory Failure in a Patient After Treatment with Bleomycin: Previous and Current Intraoperative Exposure to 50% Oxygen

Patients treated with bleomycin (BLM) are at risk of developing acute respiratory distress syndrome (ARDS) post-operatively, and this has been associated with high intraoperative concentrations of oxygen. We report progressive arterial desaturation noticeable 2 h after the start of a 4-h radical neck dissection for which the anaesthesia included 50% O2 in N2O. The patient had received two courses of bleomycin within the previous 2 months and had undergone an uneventful right hemiglossectomy under shorter but otherwise similar anaesthesia 4 weeks previously. His pulmonary function tests before the second procedure showed a slight depression of diffusing capacity (DLco) to 80% of predicted and minimal airway obstruction consistent with his history of smoking. The pulse oximetric reading during his second procedure reached 75%, but rose to 95% after treatment with methylprednisolone salbutamol and inspired O2 concentrations between 80% and 100%. By the end of the procedure, he satisfied the criteria for ARDS and was transferred to the ICU, where he developed bilateral pneumonia, deteriorated and died of multiple organ failure. This case suggests that the risk of hyperoxic pulmonary damage in patients exposed to bleomycin may increase not only with the degree and duration of hyperoxia in a given exposure, but also with the latent effects of recent previous exposure. Near normality of pulmonary function tests cannot be taken as reassurance, and small changes may have more adverse prognostic significance than in patients who have not been exposed to bleomycin.

EVIDENCE FOR A REDUCED DIAPHRAGMATIC MICROVASCULAR PO2 IN EMPHYSEMA

507 Pulmonary emphysema impairs lung and respiratory muscle function leading to restricted physical capacity and accelerated morbidity and mortality consequent to respiratory muscle failure. In the absence of direct evidence, an O2 supply-demand imbalance within the diaphragm and other respiratory muscles in emphysema has been considered the most likely explanation for this failure. To test this hypothesis, we utilized phosphorescence quenching techniques to measure mean microvascular plasma PO2 (PO2dia, [Poole et al. J. Appl. Physiol. 79: 2050-2057, 1995 ]) within the medial costal diaphragms of control (C, n=5) and emphysematous (E, elastase instilled, n=6) hamsters. PO2dia, mean arterial pressure and blood gases were measured in the spontaneously breathing anesthetized hamster at inspired O2 concentrations of 10 and 21%. Arterial PO2 was decreased in the E hamsters at 21% (C, 90±13; E, 48±7 mmHg, P<0.05) and 10% (C, 55±8; E, 30±3 mmHg, P<0.05) inspired O2. At 21% inspired O2, PO2dia was significantly lower in the emphysema animals (C, 33±2; E, 22±3 mmHg, P<0.05). PO2dia decreased significantly at 10% inspired O2 in both C and E animals but remained lower in E (C, 19±3; E, 11±2 mmHg, P<0.05). We conclude that diaphragmatic microvascular plasma PO2 is decreased in emphysematous hamsters. According to Fick's Law, this will mandate a fall in intramyocyte PO2 thereby providing one possible mechanism for respiratory muscle failure in emphysema. Support: NIH HL-50306 and 17731.

Nitric oxide from neuronal NOS plays critical role in cerebral capillary flow response to hypoxia.

We investigated, using a direct, intravital microscopic technique, whether nitric oxide (NO) from neuronal nitric oxide synthase (nNOS) plays a role in the cerebral capillary flow response to acute hypoxia. Erythrocyte flow in subsurface capillaries of the frontoparietal cortex of adult Sprague-Dawley rats was visualized using epifluorescence videomicroscopy after fluorescent labeling of red blood cells (RBC) in tracer concentrations. The velocity of labeled RBC in individual capillaries was measured off-line using an image analysis system. Hypoxia was produced by lowering the inspired O2 concentration to 15% for 5 min in control animals and in those pretreated with the selective nNOS inhibitor 7-nitroindazole (7-NI; 20 mg/kg ip). In the control group, hypoxia increased RBC velocity by 34 +/- 8%. In the group treated with 7-NI, this response was reversed to a statistically significant 8 +/- 3% decrease. This paradoxical response to hypoxia after 7-NI was observed in nearly all capillaries. 7-NI itself decreased the baseline RBC velocity by 12 +/- 4%. The cerebral hyperemic response to hypoxia was also assessed with the laser Doppler flow (LDF) technique. In control animals, hypoxia produced a 33 +/- 6% increase in LDF, similar to the increase in RBC velocity. After 7-NI treatment, the response to hypoxia was moderately attenuated but still significant at a 19 +/- 2% increase in LDF. These results support the role of NO from nNOS in the cerebral hyperemic response to hypoxia. They imply that 7-NI interfered with a physiological mechanism that was fundamental to cerebral capillary flow regulation and provide direct evidence that cerebral capillary perfusion may be dissociated from a concurrent change in regional tissue perfusion as reflected by LDF. In conclusion, NO from nNOS contributes to the maintenance of RBC flow in cerebral capillaries and plays a critically important role in the selective regulation of cerebral capillary flow during hypoxia.

Hyporeactivity of rat diaphragmatic arterioles after exposure to hypoxia in vivo. Role of the endothelium.

The effect of prior in vivo hypoxia on the in vitro responses to changes in transmural pressure, alpha-adrenoceptor activation, and depolarization with KCl were evaluated in first-order diaphragmatic arterioles. Rats (n = 14 per group) were exposed to normoxia (controls) or to hypoxia (inspired O2 concentration = 10%) for 12 or 48 h. The arteriolar pressure-diameter relationships were recorded over a pressure range from 10 to 200 mm Hg. In separate groups of arterioles (n = 12 per group), the diaphragmatic arteriolar responses to phenylephrine (10(-8) to 10(-5 M) or KCl (10 to 100 mM) were determined after exposure to either room air or hypoxia for 48 h. In half of the arterioles studied, the endothelium was removed. After 12 h of hypoxia, the pressure-diameter relationship was normal in endothelialized arterioles but was shifted upward in de-endothelialized vessels (p < 0.05). After 48 h of hypoxia, the constrictor response to increasing transmural pressure was severely suppressed in all arterioles. The intraluminal diameters during activation with phenylephrine and KCl were larger in arterioles from rats exposed to hypoxia (103 +/- 8 and 81 +/- 7 microns, respectively) than in control arterioles (41 +/- 5 and 54 +/- 6 microns, respectively; p < 0.05 for differences). During maximum phenylephrine- and KCl-induced constriction in de-endothelialized arterioles, diameters averaged 125 +/- 8 and 105 +/- 8 microns, respectively, for arterioles from hypoxic rats and 32 +/- 6 and 40 +/- 5 microns, respectively, for arterioles from control vessels. Exposure to hypoxia results in impairment of diaphragmatic arteriolar smooth muscle reactivity and reversal of the normal inhibitory influence of the endothelium on diaphragmatic arteriolar tone.

Closed-circuit anaesthesia with air

On many occasions, we use O2/air mixtures instead of N2/O/O2/ or O2 alone as a carrier gas to limit the inspired O2 concentration. Most anaesthetic machines currently available are equipped only with a high flow air rotameter. Because nitrogen is inert and less soluble than O2 or N2O we have developed a new simple and safe technique for closed-circuit anaesthesia with air using a conventional anaesthetic machine. With proper recognition of the existence of the FRC and the alveolar membrane, we are able to calculate the required anaesthetic vapour according to the desired inspired concentration and this enables us to practise simple and safe closed-circuit anaesthesia with a conventional anaesthetic machine [1]. Following intubation, the anaesthesia circuit and FRC were primed with the desired O2 and anaesthetic concentrations with high flow anaesthetic/O2/air mixture for several minutes. Thereafter, only the supply of calculated anaesthetic vapour and 200-300 mL min−1 of O2 are required for maintenance of anaesthesia. Air is no longer required after the initial prime of the FRC and the circuit. With IRB approval, 50 patients undergoing various operations requiring general anaesthesia were studied. Inspiratory-expiratory gases were sampled near the ET tube via a gas analyser. Fresh O2 flow rate and change of nitrogen concentration were recorded. Average 235 + 24 mL min−1 of O2 is required during closed-circuit anaesthesia. The average change in nitrogen concentration in the circuit was 2.4 + 0.9% over the 3.2 + 0.9 h duration of closed-circuit anaesthesia. Combined use of O2/air as a carrier gas during anaesthesia provide advantages by avoiding O2 toxicity, and also provides alveolar splinting of the lung and prevents collapse of marginally ventilated alveoli. Because high concentrations and high flow rates of nitrous oxide are not used, environmental pollution is reduced. Following an initial prime of the FRC and the anaesthesia circuit with the desired oxygen-nitrogen mixture, we were able to maintain steady oxygen concentration in the circuit with anaesthetic and a minimal O2 supply. An average 2% drop in O2 concentration over 3 h of surgery indicates minimal outflow of stored body nitrogen along a concentration gradient. This simple closed-circuit anaesthesia technique provides safe anaesthesia with the maintenance of near physiological gas concentrations in the lung.

Ventilation-induced pulmonary vasodilation at birth is modulated by potassium channel activity.

At birth, pulmonary blood flow rapidly increases 8- to 10-fold, and pulmonary arterial pressure falls by 50% within 24 h. The postnatal adaptation of the pulmonary circulation is mediated, in part, by endothelium-derived nitric oxide (EDNO). Recent studies suggest that EDNO may reduce vascular resistance, in part, by activating K+ channels. We hypothesized that K+ channels modulate the changes in pulmonary hemodynamics associated with birth. To test this hypothesis, we studied the effect of K+ channel inhibition on two separate, but interdependent stimuli: 1) mechanical ventilation with low inspired O2 concentrations (designed to maintain normal fetal blood gas tensions) and 2) mechanical ventilation with high inspired O2 concentrations. Tetraethyl-ammonium (TEA, 1 mg/min for 100 min; n = 5), a nonspecific K+ channel blocker, glibenclamide (Gli, 1 mg/min for 30 min; n = 6), an ATP-sensitive K+ channel blocker, or saline (n = 7) was infused into the left pulmonary artery (LPA) of acutely instrumented fetal lambs. The umbilical-placental circulation remained intact, and lambs were ventilated with 0.10 inspired O2 concentration (FIO2) for 60 min, followed by 1.0 FIO2 for 20 min. Neither TEA nor Gli had an effect on basal pulmonary tone. TEA attenuated the increase in LPA flow and decrease in pulmonary vascular resistance in response to mechanical ventilation with 0.10 and 1.0 FIO2; Gli had no effect. These results support the hypothesis that non-ATP-sensitive K+ channels modulate the transition from fetal to neonatal pulmonary circulation.

Effects of hypoxic hypoxia on O2 uptake and heart rate kinetics during heavy exercise.

It is unclear whether hypoxia alters the kinetics of O2 uptake (VO2) during heavy exercise [above the lactic acidosis threshold (LAT)] and how these alterations might be linked to the rise in blood lactate. Eight healthy volunteers performed transitions from unloaded cycling to the same absolute heavy work rate for 8 min while breathing one of three inspired O2 concentrations: 21% (room air), 15% (mild hypoxia), and 12% (moderate hypoxia). Breathing 12% O2 slowed the time constant but did not affect the amplitude of the primary rise in VO2 (period of first 2-3 min of exercise) and had no significant effect on either the time constant or the amplitude of the slow VO2 component (beginning 2-3 min into exercise). Baseline heart rate was elevated in proportion to the severity of the hypoxia, but the amplitude and kinetics of increase during exercise and in recovery were unaffected by level of inspired O2. We conclude that the predominant effect of hypoxia during heavy exercise is on the early energetics as a slowed time constant for VO2 and an additional anaerobic contribution. However, the sum total of the processes representing the slow component of VO2 is unaffected.

COMPARISON OF TWO STRATEGIES TO DELIVER OXYGEN IN PRETERM INFANTS. † 1286

With the advent of new technologies, it has become routine to offer supplemental oxygen to neonates via nasal prongs rather than by increasing the ambient oxygen in the incubator. The rationale for use of nasal prongs is that it provides more constant inspired O2 concentration whereas ambient oxygen is subject to fluctuations due to opening of the incubator doors. Nasal prongs, however, have significant disadvantages including i) nasal trauma, ii) increased restlessness, and iii) increased upper airway resistance with increased work of breathing. It remains subject to inspired O2 fluctuation due to prong dislodgement, which is common. Furthermore, we observed substantial clinical improvement in two preterm infants who had fewer apneas and appeared more comfortable after removing the nasal prongs and increasing the ambient O2 concentration. We hypothesized, therefore, that infants would have less apnea, less desaturation and less bradycardia with increased ambient O2 concentration compared with the nasal canulae. To test this hypothesis we studied 8 preterm infants[birthweight 1160±587g (mean ± SE), study weight 1240±534g, gestational age 28±3wk, postnatal age 28 + 4 d] on 9 occasions. Each study consisted of two consecutive 4 hour epochs where FiO2, hypopharyngeal O2, episodes of desaturation 10 s duration were measured while the infant was given O2 by either nasal prongs or into the isolette to maintain saturations at about 95%. Hypopharyngeal FiO2 was measured using a 10F suction catheter inserted via the nares and through which a 60 cc sample of gas was aspirated and its FiO2 measured with a Miniox O2 analyzer. Although hypopharyngeal O2 concentrations were similar (24 ± 4 vs 23 ± 5%, p = 0.55), we observed significantly greater number of apneas 13.2 ± 3 vs 2.8 ± 7 (p < 0.008) and desaturations 14 ± 3 vs 9 ± 3 (p < 0.008) when using nasal prongs. There was no difference in the number of bradycardias. We conclude that administration of O2 into the isolette is associated with fewer apneas and less desaturations and, for this reason, it may be a superior method of O2 administration in preterm infants. Supported by Children's Hospital Research Foundation & Canadian Lung Association.