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Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P50). In contrast to findings from in-vitro studies, we found a pH-related reduction in P50 in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude.

Fio2 values of a new oxygen mask that exploits efficiencies afforded by sequential gas delivery (SGD) were compared to those of a nonrebreathing mask (NRM) and a Venturi oxygen mask.Prospective, single-blinded, randomized study.Laboratory study.Eight healthy male volunteers.Volunteers breathed through each of the masks at various minute ventilations (VE). Oxygen flows were 2, 4, and 8 L/min to the SGD mask but only 8 L/min to the other masks.Net FIO2 was calculated from end-tidal fractional concentrations of oxygen and CO2 with the alveolar gas equation. Only the SGD mask at an oxygen flow of 8 L/min consistently provided both FIO20.95 (at resting VE) and higher FIO2 than the other masks at all VE. The SGD mask delivered FIO2 comparable to other masks at only a fraction of the oxygen flow and was characterized by a consistent relation between FIO2 and oxygen flow for a given VE.We conclude that SGD can be exploited to provide FIO20.95 with oxygen flows as low as 8 L/min, as well as accurate and efficient dosing of oxygen even in the presence of hyperpnea.

As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of approximately 1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide.

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2directly affects RSA in conscious humans even when changes in tidal volume (VT) and breathing frequency ( F B), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal Pco 2 (Pet CO2 ) to 30, 40, or 50 mmHg in random order at constant VT and F B. The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with Pet CO2 ( P < 0.001). Mean R-R interval did not differ at Pet CO2 of 40 and 50 mmHg but was less at 30 mmHg ( P < 0.05). Because VT and F B were constant, these results support our hypothesis that increased CO2directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.

Object. The ability to map cerebrovascular reactivity (CVR) at the tissue level in patients with moyamoya disease could have considerable impact on patient management, especially in guiding surgical intervention and assessing the effectiveness of surgical revascularization. This paper introduces a new noninvasive magnetic resonance (MR) imaging—based method to map CVR. Preoperative and postoperative results are reported in three cases to demonstrate the efficacy of this technique in assessing vascular reserve at the microvascular level. Methods. Three patients with angiographically confirmed moyamoya disease were evaluated before and after surgical revascularization. Measurements of CVR were obtained by rapidly manipulating end-tidal PCO2 between hypercapnic and hypocapnic states during MR imaging. The CVR maps were then calculated by comparing the percentage of changes in MR signal with changes in end-tidal PCO2. Presurgical CVR maps showed distinct regions of positive and negative reactivity that correlated precisely with the vascular territories supplied by severely narrowed vessels. Postsurgical reactivity maps demonstrated improvement in the two patients with positive clinical outcome and no change in the patient in whom a failed superficial temporal artery—middle cerebral artery bypass was performed. Conclusions. Magnetic imaging—based CVR mapping during rapid manipulation of end-tidal PCO2 is an exciting new method for determining the location and extent of abnormal vascular reactivity secondary to proximal large-vessel stenoses in moyamoya disease. Although the study group is small, there seems to be considerable potential for guiding preoperative decisions and monitoring efficacy of surgical revascularization.

These experiments examined changes in the chemoreflex control of breathing and acid–base balance after 5 days at altitude (3480 m) in six healthy males. The partial pressures of carbon dioxide ( P C O 2 ) at which ventilation increased during isoxic hypoxic and hyperoxic modified rebreathing tests at sea level fell significantly at altitude by mean ± S.E.M. of 12.8 ± 2.51 mmHg and 9.5 ± 1.77 mmHg, respectively, but response slopes above threshold were unchanged. Altitude exposure produced a respiratory alkalosis evidenced by a decrease in mean resting end-tidal P C O 2 from 41 ± 0.84 mmHg at sea level to 32 ± 2.04 mmHg at altitude, but pH did not increase significantly from its sea level value. Blood samples were analyzed to discover acid–base changes, using a modification of the equations for acid–base balance proposed by [Stewart, P.A., 1983. Modern quantitative acid–base chemistry. Can. J. Physiol. Pharmacol. 61, 1444–1461]. While strong ion difference at altitude was not significantly different from its sea level value, albumin concentration was increased significantly from 38.6 ± 0.30 g L−1 to 49.8 ± 0.76 g L−1. We suggest that the respiratory alkalosis was produced by a fall in the chemoreflex threshold and pH was corrected by an elevation in the concentration of weakly dissociated protein anions.

Hyperventilation should speed up elimination of volatile anaesthetic agents from the body, but hyperventilation usually results in hypocapnia. We compared recovery from isoflurane anaesthesia in patients allowed to recover with assisted spontaneous ventilation (control) and those treated with isocapnic hyperpnoea.Fourteen patients were studied after approximately 1 h of anaesthesia with isoflurane. Control patients were allowed to recover in the routine way. Isocapnic hyperpnoea patients received 2-3 times their intraoperative ventilation using a system to maintain end tidal PCO(2) at 45-50 mm Hg. We measured time to removal of the airway and rate of change of bispectral index (BIS) during recovery.With isocapnic hyperpnoea, the time to removal of the airway was markedly less (median and interquartile range values of 3.6 (2.7-3.7) vs 12.1 (6.8-17.2) min, P0.001); mean (SD) BIS slopes during recovery were 11.8 (4.4) vs 4.3 (2.7) min(-1) (P0.01) for isocapnic hyperpnoea and control groups, respectively. Isocapnic hyperpnoea was easily applied in the operating room.Isocapnic hyperpnoea at the end of surgery results in shorter and less variable time to removal of the airway after anaesthesia with isoflurane and nitrous oxide.

We determine whether maintaining normocapnia during hyperoxic treatment of carbon monoxide-exposed research subjects improves cerebral oxygen delivery.This experiment used a randomized, single-blinded, crossover design. We exposed 14 human research subjects to carbon monoxide until their carboxyhemoglobin levels reached 10% to 12%. We then treated each research subject with 60 minutes of hyperoxia with or without normocapnia. Research subjects returned after at least 24 hours, were reexposed to carbon monoxide, and were given the alternate treatment. Relative changes in cerebral oxygen delivery were calculated as the product of blood oxygen content and middle cerebral artery velocity (an index of cerebral blood flow) as measured by transcranial Doppler ultrasonography.Maintaining normocapnia during hyperoxic treatment resulted in significantly higher cerebral oxygen delivery compared with standard oxygen treatment (P.05; 95% confidence interval at 60 minutes 2.8% to 16.7%) as a result of the prevention of hypocapnia-induced cerebral vasoconstriction and more rapid elimination of carbon monoxide due to increased minute ventilation.If severely poisoned patients respond like our research subjects, maintaining normocapnia during initial hyperoxic treatment of carbon monoxide poisoning may lead to increased oxygen delivery to the brain. Determining the effect of such a change in conventional treatment on outcome requires clinical studies.

UNLABELLED Hyperpnea increases anesthetic elimination but is difficult to implement with current anesthetic circuits without decreasing arterial PCO2. To circumvent this, we modified a standard resuscitation bag to maintain isocapnia during hyperpnea without rebreathing by passively matching inspired PCO2 to minute ventilation. We evaluated the feasibility of using this apparatus to accelerate recovery from anesthesia in a pilot study in four isoflurane-anesthetized dogs. The apparatus was easy to use, and all dogs tolerated being ventilated with it. Under our experimental conditions, isocapnic hyperpnea reduced the time to extubation by 62%, from an average of 17.5 to 6.6 min (P = 0.012), but not time from extubation to standing unaided. This apparatus may provide a practical means of applying isocapnic hyperpnea to shorten recovery time from volatile anesthetics. IMPLICATIONS A simple modification to a standard resuscitation bag allows one to increase ventilation without decreasing blood carbon dioxide levels. In dogs, we confirmed that this circuit can be used to accelerate the elimination of and recovery from volatile anesthetics.

Cerebrovascular reactivity can be quantified by correlating blood oxygen level dependent (BOLD) signal intensity with changes in end-tidal partial pressure of carbon dioxide (PCO2). Four 3-min cycles of high and low PCO2 were induced in three subjects, each cycle containing a steady PCO2 level lasting at least 60 sec. The BOLD signal closely followed the end-tidal PCO2. The mean MRI signal intensity difference between high and low PCO2 (i.e., cerebrovascular reactivity) was 4.0 ± 3.4% for gray matter and 0.0 ± 2.0% for white matter. This is the first demonstration of the application of a controlled reproducible physiologic stimulus, i.e., alternating steady state levels of PCO2, to the quantification of cerebrovascular reactivity. Magn Reson Med 45:1011–1013, 2001. © 2001 Wiley-Liss, Inc.

The currently recommended prehospital treatment for carbon monoxide (CO) poisoning is administration of 100% O(2). We have shown in dogs that normocapnic hyperpnea with O(2) further accelerates CO elimination. The purpose of this study was to examine the relation between minute ventilation (V E) and the rate of elimination of CO in humans. Seven healthy male volunteers were exposed to CO (400 to 1,000 ppm) in air until their carboxyhemoglobin (COHb) levels reached 10 to 12%. They then breathed either 100% O(2) at resting V E (4.3 to 9.0 L min) for 60 min or O(2) containing 4.5 to 4.8% CO(2) (to maintain normocapnia) at two to six times resting V E for 90 min. The half-time of the decrease in COHb fell from 78 +/- 24 min (mean +/- SD) during resting V E with 100% O(2) to 31 +/- 6 min (p0. 001) during normocapnic hyperpnea with O(2). The relation between V E and the half-time of COHb reduction approximated a rectangular hyperbola. Because both the method and circuit are simple, this approach may enhance the first-aid treatment of CO poisoning.

We report the development and testing of a simple breathing circuit that maintains isocapnia in human subjects during hypoxic hyperpnea. In addition, the circuit permits rapid switching between two gas mixtures with different partial pressures of oxygen. Eleven volunteers breathed repeated cycles of exposure to air (2 min of 21% O(2), balance N(2)) and hypoxia (2 min of 8.3+/-0.1% O(2), balance N(2)). Hypoxia induced significant increases in minute ventilation, breathing frequency and tidal volume (P0.05) that were consistent over repeated cycles of hypoxia (P0.1, one-way ANOVA). The system successfully maintained isocapnia in all subjects, with an average change in end-tidal CO(2) of only -0.2 mmHg during hyperventilation in hypoxia (range 0.4 to -0.8 mmHg). This system may be suitable for repeated tests of the hypoxic ventilatory response (HVR) and may prove useful for exploring intra- and inter-individual variability of HVR in humans.