Current methods of forcing end-tidal P CO 2 (P ETCO 2 ) and P O 2 (P ETO 2 ) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control P ETCO 2 and P ETO 2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change P ETCO 2 from control (40 mmHg for P ETCO 2 and 100 mmHg for P ETO 2 ) to two target P ETCO 2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), P ETO 2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and P ETCO 2 with P ETO 2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, P ETCO 2 and P ETO 2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for P ETCO 2 was ± 1 mmHg, and for P ETO 2 was ± 4 mmHg. P ETCO 2 varied by ± 1 mmHg and P ETO 2 by ± 5.6 mmHg (S.D.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min −1 ). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.

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.

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 CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) 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 V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.

Fisher. Retinal arteriolar diameter, blood velocity, and blood flow response to an isocapnic hyperoxic provocation. Am J Physiol Heart Circ Physiol 288: H2912-H2917, 2005. First published February 11, 2005 doi:10.1152/ajpheart.01037.2004.-The aim of this study was to simultaneously quantify the magnitude and response characteristics of retinal arteriolar diameter and blood velocity induced by an isocapnic hyperoxic provocation in a group of clinically normal subjects. The sample comprised 10 subjects (mean age, 25 yr; range, 21-40 yr). Subjects initially breathed air for 5-10 min, then breathed O 2 for 20 min, and then air for a final 10-min period via a sequential rebreathing circuit (Hi-Ox; Viasys) to maintain isocapnia. Retinal arteriolar diameter and blood velocity measurements were simultaneously acquired with a Canon laser blood flowmeter (CLBF-100). The response magnitude, time, and lag of diameter and velocity were calculated. In response to hyperoxic provocation, retinal diameter was reduced from control values of 111.6 (SD 13.1) to 99.8 (SD 10.6; P Ͻ 0.001) m and recovered after withdrawal of hyperoxia. Retinal blood velocity and flow concomitantly declined from control values of 32.2 (SD 6.4) mm/s and 9.4 (SD 2.5) l/min to 20.7 (SD 3.4) mm/s and 5.1 (SD 1.3) l/min, respectively (P Ͻ 0.001 for both velocity and flow), and recovered after withdrawal of hyperoxia. The response times and response lags were not significantly different for each parameter between effect and recovery or between diameter and velocity. We conclude that arteriolar retinal vascular reactivity to hyperoxic provocation is rapid with a maximal vasoconstrictive effect occurring within a maximum of 4 min. Although there was a trend for diameter to respond before velocity to the isocapnic hyperoxic provocation, the response characteristics were not significantly different between diameter and velocity. vascular reactivity; laser Doppler velocimetry; isocapnic hyperoxia THE BLOOD SUPPLY TO THE INNER retina is derived from the central retinal artery, whereas the choriocapillaris supplies the outer retina and photoreceptors. The retinal tissue is one of the most metabolically active in the body and, correspondingly, an uninterrupted nutrient supply is essential (50). The inner retinal blood vessels (i.e., past the lamina cribrosa) are thought to be unique due to the absence of an autonomic nerve supply to regulate vascular tone (53). Blood supply to the inner retina is regulated via local feedback signals that alter retinal perfusion in response to changes in systemic blood pressure or the concentration of certain metabolites (11,18). In particular, retinal blood flow is strongly dependent on the partial pressure of oxygen (PO 2 ; Refs. 14,25,31,42,48).The retinal vasculature can be noninvasively visualized and, consequently, its hemodynamic parameters quantified. Impairment of vascular reactivity has been demonstrated in the pathogenesis of various ocular diseases including diabetic retinopathy (13,20,25,32). Administration of O 2 has p...

Some animals have adapted to hypoxia by increasing their haemoglobin affinity for oxygen, but in vitro studies have not shown any change of haemoglobin affinity for oxygen in human high altitude natives or lowlanders acutely acclimatized to high altitude. We conducted the first in vivo study of the oxyhaemoglobin dissociation curve by progressively reducing arterial PO 2 while maintaining normocapnia in lowlanders at sea level, lowlanders sojourning at 3600m for two weeks and native Andeans at the same altitude. We found that the in vivo PO 2 at which haemoglobin is half-saturated (P 50 ) is higher in lowlanders at sea level (32 mmHg) than that measured in vitro (27 mmHg) and that lowlanders and highlanders do significantly increase the in vivo affinity of their haemoglobin for oxygen with exposure to high altitude. These results indicate the value of an in vivo approach for studying the oxyhaemoglobin dissociation curve.iii

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Anaesthesiologists have traditionally been consulted to help design breathing circuits to attain and maintain target end-tidal carbon dioxide (P ET CO 2). The methodology has recently been simplified by breathing circuits that sequentially deliver fresh gas (not containing carbon dioxide (CO 2)) and reserve gas (containing CO 2). Our aim was to determine the roles of fresh gas flow, reserve gas PCO 2 and minute ventilation in the determination of P ET CO 2. We first used a computer model of a non-rebreathing sequential breathing circuit to determine these relationships. We then tested our model by monitoring P ET CO 2 in human volunteers who increased their minute ventilation from resting to five times resting levels. The optimal settings to maintain P ET CO 2 independently of minute ventilation are 1) fresh gas flow equal to minute ventilation minus anatomical deadspace ventilation, and 2) reserve gas PCO 2 equal to alveolar PCO 2. We provide an equation to assist in identifying gas settings to attain a target PCO 2. The ability to precisely attain and maintain a target PCO 2 (isocapnia) using a sequential gas delivery circuit has multiple therapeutic and scientific applications.

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.