Changes in respiratory control during and after 48 h of isocapnic and poikilocapnic hypoxia in humans

Ventilatory acclimatization to hypoxia is associated with an increase in ventilation under conditions of acute hyperoxia (VEhyperoxia) and an increase in acute hypoxic ventilatory response (AHVR). This study compares 48-h exposures to isocapnic hypoxia (protocol I) with 48-h exposures to poikilocapnic hypoxia (protocol P) in 10 subjects to assess the importance of hypocapnic alkalosis in generating the changes observed in ventilatory acclimatization to hypoxia. During both hypoxic exposures, end-tidal PO2 was maintained at 60 Torr, with end-tidal PCO2 held at the subject's prehypoxic level (protocol I) or uncontrolled (protocol P). VEhyperoxia and AHVR were assessed regularly throughout the exposures. VEhyperoxia (P < 0.001, ANOVA) and AHVR (P < 0.001) increased during the hypoxic exposures, with no significant differences between protocols I and P. The increase in VEhyperoxia was associated with an increase in slope of the ventilation-end-tidal PCO2 response (P < 0.001) with no significant change in intercept. These results suggest that changes in respiratory control early in ventilatory acclimatization to hypoxia result from the effects of hypoxia per se and not the alkalosis normally accompanying hypoxia.     

Effect of different levels of hyperoxia on breathing in healthy subjects

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.     

Fast and slow components of cerebral blood flow response to step decreases in end-tidal PCO2 in humans

This study examined the dynamics of the middle cerebral artery (MCA) blood flow response to hypocapnia in humans (n = 6) by using transcranial Doppler ultrasound. In a control protocol, end-tidal PCO2 (PETCO2) was held near eucapnia (1.5 Torr above resting) for 40 min. In a hypocapnic protocol, PETCO2 was held near eucapnia for 10 min, then at 15 Torr below eucapnia for 20 min, and then near eucapnia for 10 min. During both protocols, subjects hyperventilated throughout and PETCO2 and end-tidal PO2 were controlled by using the dynamic end-tidal forcing technique. Beat-by-beat values were calculated for the intensity-weighted mean velocity (VIWM), signal power (P), and their instantaneous product (P.VIWM). A simple model consisting of a delay, gain terms, time constants (tauf,on, tauf, off) and baseline levels of flow for the on- and off-transients, and a gain term (gs) and time constant (taus) for a second slower component was fitted to the hypocapnic protocol. The cerebral blood flow response to hypocapnia was characterized by a significant (P < 0.001) slow progressive adaptation in P.VIWM, with gs = 1.26 %/Torr and taus = 427 s, that persisted throughout the hypocapnic period. Finally, the responses at the onset and relief of hypocapnia were asymmetric (P < 0.001), with tauf,on (6.8 s) faster than tauf,off (14.3 s).     

Differences between estimates and measured PaCO2 during rest and exercise in older subjects

Arterial PCO2 (PaCO2) has been estimated during exercise with good accuracy in younger individuals by using the Jones equation (PJCO2) (J. Appl. Physiol. 47: 954-960, 1979). The purpose of this project was to determine the utility of estimating PaCO2 from end-tidal PCO2 (PETCO2) or PJCO2 at rest, ventilatory threshold (VTh), and maximal exercise (Max) in older subjects. PETCO2 was determined from respired gases simultaneously (MGA 1100) with arterial blood gases (radial arterial catheter) in 12 older and 11 younger subjects at rest and during exercise. Mean differences were analyzed with paired t-tests, and relationships between the estimated PaCO2 values and the actual values of PaCO2 were determined with correlation coefficients. In the older subjects, PETCO2 was not significantly different from PaCO2 at rest (-1.2 +/- 4.3 Torr), VTh (0.4 +/- 2.5), or Max (-0.8 +/- 2.7), and the two were significantly (P < 0.05) correlated at Vth (r = 0.84) and Max (r = 0.87) but not at rest (r = 0.47). PJCO2 was similar to PaCO2 at rest (-1.0 +/- 3.9) and Vth (-1. 3 +/- 2.3) but significantly lower at Max (-3.0 +/- 2.6), and the two were significantly correlated at Vth (r = 0.86) and Max (r = 0. 80) but not at rest (r = 0.54). PETCO2 was significantly higher than PaCO2 during exercise in the younger subjects but similar to PaCO2 at rest. PJCO2 was similar to PaCO2 at rest and Vth but significantly lower at Max in younger subjects. In conclusion, our data demonstrate that PaCO2 during exercise is better estimated by PETCO2 than by PJCO2 in older subjects, contrary to what is observed in younger subjects. This appears to be related to the finding that PETCO2 does not exceed PaCO2 during exercise in older subjects, as occurs in the younger subjects. However, PaCO2 at rest is best estimated by PJCO2 in both younger and older subjects.     

Capnography and ventilatory assessment during ambulatory dentoalveolar surgery

PURPOSE: The purpose of this study was to determine whether capnography is a more sensitive monitor than auscultation of breath sounds in detecting ventilatory changes consistent with hypoventilation, obstruction, or apnea and in detecting ventilatory changes that can be associated with oxygen desaturation. PATIENTS AND METHODS: Fifty-five patients received intravenous agents and supplemental oxygen to achieve a state of deep sedation or general anesthesia for removal of impacted third molars. The surgeon/anesthetist monitored respiratory status using a pretracheal stethoscope and direct observation. A blinded observer with no access to the patient or anesthetist monitored respiratory status using capnography. A second observer monitored all respiratory parameters to allow for correlation between clinical and electronic monitors. RESULTS: Ventilatory status was continuously represented by capnogaphy. The Pearson correlation coefficient showed a positive correlation between increased end-tidal CO2 (PETCO2) and decreased oxygen saturation that became stronger with greater positive changes in PETCO2. An additive relationship was found between PETCO2 and respiratory rate (RR), with increased PETCO2 and decreased RR contributing to decreased oxygen saturation. CONCLUSION: Patients with nasal ventilatory exchange maintain this exchange throughout the anesthesia so that sampling of nasal PETCO2 is an effective way to monitor ventilatory status. Respiratory depression or obstructive ventilatory changes detected by capnography showed a high sensitivity and low positive predictive value in detecting oxygen desaturation. The current technology does not show a clinically satisfactory correlation between PETCO2 and oxygen saturation. However, a combined increase in PETCO2 and decrease in RR suggested a trend of decreasing oxygen saturation.     

Indicator cell lines for detection of primary strains of human and simian immunodeficiency viruses

The pulmonary artery pressure (Ppa) responses to short runs of acute hypoxia at two different levels of end-tidal CO2 were measured in nine normal subjects and in 20 patients with moderate to severe obstructive sleep apnea (OSA). In normal subjects the mean increase in Ppa in response to eucapnic hypoxia was 8 +/- 2 mm Hg (SEM) and was not different from the response to hypercapnic hypoxia (9 +/- 2 mm Hg, p > 0.2). In patients with OSA, the mean increase of Ppa was 8 +/- 1 mm Hg to eucapnic hypoxia, and the response to hypercapnic hypoxia was higher at 10 +/- 1 mm Hg (p = 0.01). Pulmonary pressor response to hypoxia was augmented (> 10 mm Hg) by hypercapnia in four of 20 patients with OSA but in none of the normal subjects. Normoxic hypercapnia alone was a weak stimulus, increasing Ppa by > 5 mm Hg in only two of nine patients with OSA studied. In conclusion, Ppa increases in both normal subjects and patients with OSA exposed to a ramp of acute isocapnic hypoxia. There were clear interindividual differences in pulmonary artery response. Hypercapnia did not produce clinical significant changes in Ppa in either group.     

Evaluation of two commercially available carbon dioxide sampling nasal cannulae

Our study compared two commercially available carbon dioxide sampling nasal cannulae for efficacy of oxygenation and relationship of end-tidal carbon dioxide (PETCO2) to arterial carbon dioxide (PaCO2). The two-prong nasal cannula (2PNC) has one prong dedicated to delivering O2 via one naris and the second prong dedicated to sampling exhaled gases via the other naris. The four-prong nasal cannula (4PNC) delivers O2 via a prong in each naris, and samples exhaled gases via another set of prongs in each naris. Forty six patients were divided into three groups, which received either 2 (n = 15), 3 (n = 16), or 4 (n = 15) L/min O2, respectively, and were studied sequentially with standard nasal cannula (SNC), the 2PNC, and then the 4PNC. At each O2 flow rate, PaO2 was equivalent regardless of whether the SNC, 2PNC, or 4PNC was used. Seventy-four percent (34/46) of the 2PNC and 0% (0/46) of the 4PNC PETCO2 values were within +/- 4 torr of the PaCO2 value. The authors conclude that the 2PNC and 4PNC are equally effective compared with an SNC in oxygenating patients, but the PETCO2 measured by the 2PNC provides a superior quantitative estimate of the PaCO2 than that obtained by the 4PNC.     

Effect of a subanesthetic minimum alveolar concentration of isoflurane on two tests of the hypoxic ventilatory response

BACKGROUND: These experiments were designed to study the effect of 0.1 minimum alveolar concentration isoflurane on the hypoxic ventilatory response as measured by two common methods of hypoxic testing: when normocapnic hypoxia was induced abruptly and when it was induced gradually. We hypothesized that any disparity in results would be due to an isoflurane effect that was manifested differently in the two tests. METHODS: After 20 min for uptake and equilibration of 0.1 minimum alveolar concentration end-tidal isoflurane or carrier gas in hyperoxia, isocapnic hypoxia was induced either abruptly over 60-80 s ("step" test) or gradually over 10 min ("ramp" test), followed by 20 min of isocapnic hypoxia at 45 mmHg end-tidal oxygen. Control of the hypoxic and isocapnic stimuli was accomplished accurately by a computer-controlled dynamic end-tidal forcing system. Eight subjects performed each test in the presence and absence of isoflurane. RESULTS: For both step tests and ramp tests, 0.1 minimum alveolar concentration isoflurane had no effect on minute ventilation during the defined periods of hypoxia. With isoflurane, delta VE45, the acute change in ventilation from hyperoxia to hypoxia, was 97 +/- 20% (mean +/- SEM) of the control response for step tests and 100 +/- 25% of the control response for ramp tests. The step tests produced significantly larger acute hypoxic responses than did the ramp tests, but by the end of 20 min of hypoxia, ventilation was similar for both tests. CONCLUSIONS: Neither method of hypoxic testing demonstrated the level of isoflurane effect reported by others. A comparison of the two methods of hypoxic testing suggests that ramp tests, as commonly performed, do not allow adequate time for full expression of the acute hypoxic ventilatory response. Step tests also better separated the opposing hypoxic effects of carotid body stimulation and central ventilatory depression.     

Expired gas monitoring by mass spectrometry in a respiratory intensive care unit

The application of a medical mass spectrometer for the monitoring of respired gases in the respiratory intensive care unit of a community hospital is reviewed. This monitoring system is routinely used with intubated patients for periodic monitoring of end-tidal CO2 tensions (PETCO2), FIO2, and PETO2 dead space to tidal volume ratios, and the determination of AaDO2; the value of these measurements is discussed. It is especially useful for continuous monitoring at critical points in the patient's course such as weaning from the ventilator, determining optimal ventilator settings, monitoring, unstable nonintubated patients, and in better defining the pathophysiological disturbances impeding patient progress, examples of which are presented. Preliminary observations suggest it may also provide a simple technique for determining optimal expiratory retard settings. The initial cost of such a system is justified by the benefit to the patient, i.e., reduction in the frequency of nonessential arterial blood gas determinations, shortened weaning period, and early detection of potentially dangerous trends. Technical problems encountered with this system and potential future uses are also discussed.     

IL-10-mediated suppression of TNF-alpha production is independent of its ability to inhibit NF kappa B activity

It is hypothesized that carotid body chemosensory activity is coupled to neurosecretion. The purpose of this study was to examine whether there was a correspondence between carotid body tissue dopamine (DA) levels and neuronal discharge (ND) measured from the carotid sinus nerve of perfused cat carotid bodies and to characterize interaction between CO2 and O2 in these responses. ND and tissue DA were measured after changing from normoxic, normocapnic control bicarbonate buffer (PO2 >120 Torr, PCO2 25-30 Torr, pH approximately 7.4) to normoxic hypercapnia (PCO2 55-57 Torr, pH 7.1-7.2) or to hypoxic solutions (PO2 30-35 Torr) with normocapnia (PCO2 25-30 Torr, pH approximately 7.4) or hypocapnia (PCO2 10-15 Torr, pH 7.6-7.8). Similar temporal changes for ND and tissue DA were found for all of the stimuli, although there was a much different proportional relationship for normoxic hypercapnia. Both ND and DA increased above baseline values during flow interruption and normocapnic hypoxia, and both decreased below baseline values during hypoxic hypocapnia. In contrast, normoxic hypercapnia caused an initial increase in ND, from a baseline of 175 +/- 12 (SE) to a peak of 593 +/- 20 impulses/s within 4.6 +/- 0.9 s, followed by adaptation, whereas ND declined to 423 +/- 20 impulses/s after 1 min. Tissue DA initially increased from a baseline of 17.9 +/- 1.2 microM to a peak of 23.2 +/- 1.2 microM within 3.0 +/- 0.7 s, then declined to 2.6 +/- 1.0 microM. The substantial decrease in tissue DA during normoxic hypercapnia was not consistent with the parallel changes in DA with ND that were observed for hypoxic stimuli.     

Blood lactate and acid-base balance in graded neonatal hypoxia: evidence for oxygen-restricted metabolism

This study examines the neonatal response to graded hypoxia and determines the arterial PO2 (PaO2) threshold for oxygen-restricted metabolism as confirmed by the development of lactic acidosis and altered oxygen handling. Anesthetized, intubated, and ventilated 3-day-old pigs (n = 56) were randomly assigned to one of five predetermined acute (120 min) graded hypoxia groups: normoxia (PaO2 = 80 Torr) or mild (60 Torr), moderate (40 Torr), moderately severe (30 Torr), or severe (20 Torr) hypoxia. In moderate hypoxia, lactate and acid-base homeostasis were unaltered due to a significant increase in oxygen extraction (P < 0.05) that was sufficient to maintain the arteriovenous oxygen content difference (oxygen uptake). In moderately severe hypoxia, increased arterial lactate and decreased HCO3- and base excess were evidence of anaerobic metabolism, yet pH was unaltered, indicating adequate buffering. In this group, despite the increase in oxygen extraction, oxygen uptake was reduced, indicating the onset of oxygen-restricted metabolism. The severe hypoxia group had significantly increased lactate (21.7 +/- 3.9 mmol/l), decreased pH (7.01 +/- 0.07) and base excess (-21.5 +/- 3.0 mmol/l), and depletion of HCO3- (9.7 +/- 1.6 mmol/l) (P < 0.0001). Here, increases in oxygen extraction were severely limited by availability, resulting in significantly reduced oxygen uptake, anaerobic metabolism, and profound lactic acidosis.     

The pleckstrin homology domain is the principal link between the insulin receptor and IRS-1

Interaction domains located in the NH2 terminus of IRS-1 mediate its recognition by the insulin receptor. Alignment of IRS-1 and IRS-2 reveals two homology regions: the IH1(PH) contains a pleckstrin homology (PH) domain, and the IH2(PTB) contains a phosphotyrosine binding (PTB) domain. A third region in IRS-1 called SAIN was proposed to contain another functional PTB domain. Peptide competition experiments demonstrated that the IH2(PTB) in IRS-2, like the corresponding domain in IRS-1, binds directly to peptides containing NPXY motifs. In contrast, these peptides do not bind to IH1(PH) or the SAIN regions. In 32D cells the IH1(PH) was essential for insulin-stimulated tyrosine phosphorylation of IRS-1 and insulin-stimulated phosphatidylinositol 3-kinase activity and p70(s6k) phosphorylation. In contrast, the IH2(PTB) and the SAIN regions were not required for these insulin actions; however, the IH2(PTB) improved the coupling between IRS-1 and the insulin receptor. Overexpression of the insulin receptor in 32DIR cells increased IRS-1 tyrosine phosphorylation and mediated insulin-stimulated DNA synthesis. The sensitivity of these responses was partially reduced by deletion of either the IH1(PH) or the IH2(PTB) and significantly reduced when both regions were deleted together. Thus, the PH and PTB domains equally couple IRS-1 to high levels of insulin receptor normally expressed in most cells, whereas at low levels of insulin receptors the PTB domain is inefficient and the PH domain is essential for a productive interaction.     

Dynamics of carotid body responses in vitro in the presence of CO2-HCO3-: role of carbonic anhydrase

The role of carbonic anhydrase (CNA) in the dynamics of carotid body (CB) function was tested by studying the effects of the membrane-permeable CNA inhibitor methazolamide on the chemosensory responses of the cat CB, perfused and superfused in vitro with cell-free and modified Tyrode solution at 36.5 +/- 0.5 degrees C in the presence of CO2-HCO3- (PO2 = 120 Torr, PCO2 = 32 Torr, pH = 7.40). The bulk of CO2 flow to the CB from the external milieu was overwhelmingly large relative to the metabolic production of CO2 in the CB. Accordingly, the relative contribution of the endogenous CO2 to the CB responses was small. The chemosensory nerve discharges were recorded from the whole desheathed carotid sinus nerve. The responses to acidic hypercapnia (PCO2 = 50-60 Torr, pH = 7.20-7.10), hypoxia (PO2 = 25 and 50 Torr), perfusate flow interruption, and bolus injections of sodium cyanide (20-40 nmol) were tested. To contrast, we also measured the effects of nicotine (2-4 nmol), which may act at sites other than those for O2 and CO2. Methazolamide (30 mg/l) in the perfusate at constant PCO2 and pH reduced the baseline activity and delayed the responses to step changes in PCO2 (and concomitantly pH) and PO2 and to cyanide but not to nicotine. The steady-state responses to these stimuli, measured as differences from control, were reduced, but not significantly. The initial overshoots seen with step changes in both high PCO2 and low PO2 were eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fever in goldfish is induced by pyrogens but not by handling

OBJECTIVE: To determine whether end-tidal partial pressure of carbon dioxide (PETCO2) was a reliable estimate of PaCO2 in dogs undergoing thoracotomy. DESIGN: Case series. ANIMALS: 18 dogs that underwent thoracotomy. PROCEDURE: PaCO2 and PETCO2 were measured shortly after induction of anesthesia, while dogs were breathing spontaneously; 5 minutes prior to initial skin incision, while dogs were receiving intermittent positive-pressure ventilation (IPPV); 5, 30, and 60 minutes after the thoracic cavity was opened, while dogs were receiving IPPV; and after the thoracic cavity was closed and evacuated, when dogs were again breathing spontaneously. For each period, arterial-end-tidal difference in partial pressure of carbon dioxide (PaCO2-PETCO2) was compared with PaCO2-PETCO2 for the preceding period. RESULTS: Significant changes in PaCO2-PETCO2 from one period to the next were not detected except when values obtained 5 minutes after the thoracic cavity was opened were compared with values obtained 5 minutes before incision. The PaCO2-PETCO2 was not constant for individual dogs. CLINICAL IMPLICATIONS: PETCO2 was not a reliable indicator of adequacy of ventilation during thoracotomy in these dogs, because it differed greatly from PaCO2, and PaCO2-PETCO2 was not consistent.     

Influences of morphine on the ventilatory response to isocapnic hypoxia

BACKGROUND: The ventilatory response to hypoxia is composed of the stimulatory activity from peripheral chemoreceptors and a depressant effect from within the central nervous system. Morphine induces respiratory depression by affecting the peripheral and central carbon dioxide chemoreflex loops. There are only few reports on its effect on the hypoxic response. Thus the authors assessed the effect of morphine on the isocapnic ventilatory response to hypoxia in eight cats anesthetized with alpha-chloralose-urethan and on the ventilatory carbon dioxide sensitivities of the central and peripheral chemoreflex loops. METHODS: The steady-state ventilatory responses to six levels of end-tidal oxygen tension (PO2) ranging from 375 to 45 mmHg were measured at constant end-tidal carbon dioxide tension (P[ET]CO2, 41 mmHg) before and after intravenous administration of morphine hydrochloride (0.15 mg/kg). Each oxygen response was fitted to an exponential function characterized by the hypoxic sensitivity and a shape parameter. The hypercapnic ventilatory responses, determined before and after administration of morphine hydrochloride, were separated into a slow central and a fast peripheral component characterized by a carbon dioxide sensitivity and a single offset B (apneic threshold). RESULTS: At constant P(ET)CO2, morphine decreased ventilation during hyperoxia from 1,260 +/- 140 ml/min to 530 +/- 110 ml/ min (P < 0.01). The hypoxic sensitivity and shape parameter did not differ from control. The ventilatory response to carbon dioxide was displaced to higher P(ET)CO2 levels, and the apneic threshold increased by 6 mmHg (P < 0.01). The central and peripheral carbon dioxide sensitivities decreased by about 30% (P < 0.01). Their ratio (peripheral carbon dioxide sensitivity:central carbon dioxide sensitivity) did not differ for the treatments (control = 0.165 +/- 0.105; morphine = 0.161 +/- 0.084). CONCLUSIONS: Morphine depresses ventilation at hyperoxia but does not depress the steady-state increase in ventilation due to hypoxia. The authors speculate that morphine reduces the central depressant effect of hypoxia and the peripheral carbon dioxide sensitivity at hyperoxia.     

Effects of body temperature on ventilatory response to hypoxia and breathing pattern in man

The ventilatory response to hypoxia (PAO2 55 and 45 Torr) at each of four levels of PACO2 was studied in five healthy subjects before and after a rise in rectal temperature of 1.4 degrees C had been induced by means of a heated flying suit. At a given level of chemical drive both ventilation and mean inspiratory flow increased after heating, frequency relatively more than tidal volume. In isoventilation comparisons mean inspiratory flow was identical in normo- and hyperthermia, whereas the durations of inspiration (TI) and expiration (TE) were proportionately shortened. It is suggested that a rise in temperature shortens TI by affecting a central "clock" and that TE changes are secondary to changes in end-inspiratory volume. The euoxic CO2 response in hyperthermia was suggestive of multiplication between CO2 and temperature. Hypoxic sensitivity was significantly increased, indicating a temperature effect on the arterial chemoreceptors. The breathing pattern was in either temperature condition identical in euoxia and in hypoxia.     

Partial inhibition of AT-EAE by an antibody to ICAM-1: clinico-histological and MRI studies

The aim of this study was to characterise the response to acute hypoxia in pulmonary artery rings isolated from rats exposed to chronic hypoxia for 2 weeks (CH) and following recovery in room air for 24 h (post hypoxic, PH). Large intrapulmonary artery (IPA) rings (internal diameter = 1.5 +/- 0.11 mm; n = 13) from CH and PH rats and age-matched controls were studied. These were precontracted with phenylephrine using standard organ bath procedures at an oxygen tension of 152 mmHg and subjected to an acute hypoxia stimulus (bubbling with 0% O2 giving Po2 = 7 mmHg or 2% O2 giving PO2 = 20 mmHg). Acute hypoxia-induced pulmonary vasoconstriction (HPV) consisted of a transient contraction, a relaxation and a sustained contraction over 30 min. Pulmonary vasoconstriction induced by 0% O2 was significantly reduced in IPA rings from the CH but not PH group compared with the response obtained from the control group. HPV induced by 2% O2 in IPA rings from CH and PH rats was not significantly different from that in control rats not subjected to chronic hypoxia. Mechanical removal of the endothelium or inhibition of nitric oxide (NO) synthase by L-NOARG (300 microM) reduced the contractile phases of HPV in IPA rings from control and CH rats. Carbachol-induced endothelium-dependent relaxation in phenylephrine precontracted IPA rings was significantly attenuated in the CH but not PH group. In conclusion, the present study demonstrates that HPV induced by 0% O2 in rat IPA rings was blunted in CH rats and restored following 24 h in room air, in parallel with changes in endothelium function.     

Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep

Rapid eye movements during rapid-eye-movement (REM) sleep are associated with rapid, shallow breathing. We wanted to know whether this effect persisted during increased respiratory drive by CO2. In eight healthy subjects, we recorded electroencephalographic, electrooculographic, and electromyographic signals, ventilation, and end-tidal PCO2 during the night. Inspiratory PCO2 was changed to increase end-tidal PCO2 by 3 and 6 Torr. During normocapnia, rapid eye movements were associated with a decrease in total breath time by -0.71 +/- 0.19 (SE) s (P < 0.05) because of shortened expiratory time (-0.52 +/- 0.08 s, P < 0.001) and with a reduced tidal volume (-89 +/- 27 ml, P < 0.05) because of decreased rib cage contribution (-75 +/- 18 ml, P < 0.05). Abdominal (-11 +/- 16 ml, P = 0.52) and minute ventilation (-0.09 +/- 0.21 ml/min, P = 0.66) did not change. In hypercapnia, however, rapid eye movements were associated with a further shortening of total breath time. Abdominal breathing was also inhibited (-79 +/- 23 ml, P < 0.05), leading to a stronger inhibition of tidal volume and minute ventilation (-1.84 +/- 0.54 l/min, P < 0.05). We conclude that REM-associated respiratory changes are even more pronounced during hypercapnia because of additional inhibition of abdominal breathing. This may contribute to the reduction of the hypercapnic ventilatory response during REM sleep.     

Estimation of arterial PCO2 in the elderly

Arterial PCO2 (PaCO2), determined directly in the radial artery, was compared with indirect estimates of PCO2 in six elderly men (mean age 73.8 yr). Estimates of PaCO2 included arterialized venous PCO2 (PavCO2); end-tidal PCO2; mean alveolar PCO2, calculated by using a reconstruction of the alveolar oscillation in PCO2 and accounting for the presence of dead space (time-weighted mean for PCO2 throughout the respiratory cycle); and values calculated by using the empirical formula developed by Jones et al. (N. L. Jones, D. G. Robertson, and J. W. Kane. J. Appl. Physiol. 47: 954-960, 1979), which incorporates end-tidal PCO2 and tidal volume (PaCO2 derived from end-tidal PCO2 and VT). Measurements were made at rest and during cycle ergometry at 25 and 50 W while the subjects breathed various gas mixtures (euoxic-eucapnic, hypoxic-eucapnic, hyperoxic-eucapnic, and hyperoxic-hypercapnic). The mean differences between the estimates and the actual PaCO2 at rest and in 25- and 50-W exercise were as follows: PavCO2, 0.3 +/- 0.7 (SD), -0.1 +/- 0.7, and 1.8 +/- 1.2 Torr; end-tidal PCO2, 2.9 +/- 1.7, 4.0 +/- 3.1, and 3.7 +/- 3.2 Torr; time-weighted mean of alveolar PCO2, 2.6 +/- 1.9, 3.3 +/- 3.1, and 3.6 +/- 3.8 Torr; and PaCO2 derived from end-tidal PCO2 and VT, 2.4 +/- 1.3, 1.3 +/- 3.0, and 0.6 +/- 2.9 Torr. It is concluded that mean PavCO2 agreed most closely with mean PaCO2 both at rest and in exercise. All methods of deriving PaCO2 using measurements from the respired gases overestimated arterial values at rest. Of the noninvasive techniques, mean estimates calculated using the regression equation developed by Jones et al. corresponded most closely with PaCO2 in exercise.     

A transcranial doppler ultrasonography study of cerebrovascular CO2 reactivity in mitochondrial encephalomyopathy

BACKGROUND AND PURPOSE: To elucidate the pathogenic role of vascular involvement such as mitochondrial angiopathy in patients with mitochondrial encephalomyopathy (MEM). we used the transcranial Doppler sonography (TCD) method to detect impairment of cerebrovascular CO2 reactivity. METHODS: The cerebral perfusion reserve in 13 MEM patients, including 6 with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) was studied by TCD for different CO2 partial pressures. For the parameter of mean flow velocity, the mean spatial Doppler frequency (fm) was obtained from the right and left middle cerebral arteries and basilar artery under conditions of normocapnia, hypercapnia, and hypocapnia in cases in which hyperventilation was possible. By fitting the obtained fm and the end-tidal CO2 partial pressure (PETCO2) to the exponential formula fm = a x e(K < PETCO2), where a is the theoretical fm at a PETCO2 of 0 mm Hg, the parameter K, an index of CO2 reactivity, was calculated. RESULTS: The K value was lower than control values at at least one site of the middle cerebral arteries and basilar artery of all patients with MELAS as well as the other MEM patients except for one patient with myoclonic epilepsy with ragged-red fiber and one with Kearns-Sayer syndrome. CONCLUSIONS: Our results suggest that there is a high incidence of impairment of cerebrovascular CO2 reactivity in MEM patients. Moreover, the noninvasive TCD method was found useful for evaluation of cerebral hemodynamics in MEM patients.