Biomedical subjects
J W Severinghaus
Publications and source records attributed to J W Severinghaus.
Augmented hypoxic ventilatory response in men at altitude.
To test the hypothesis that the hypoxic ventilatory response (HVR) of an individual is a constant unaffected by acclimatization, isocapnic 5-min step HVR, as delta VI/delta SaO2 (l.min-1.%-1, where VI is inspired ventilation and SaO2 is arterial O2 saturation), was tested in six normal males at sea level (SL), after 1-5 days at 3,810-m altitude (AL1-3), and three times over 1 wk after altitude exposure (PAL1-3). Equal medullary central ventilatory drive was sought at both altitudes by testing HVR after greater than 15 min of hyperoxia to eliminate possible ambient hypoxic ventilatory depression (HVD), choosing for isocapnia a P'CO2 (end tidal) elevated sufficiently to drive hyperoxic VI to 140 ml.kg-1.min-1. Mean P'CO2 was 45.4 +/- 1.7 Torr at SL and 33.3 +/- 1.8 Torr on AL3, compared with the respective resting control end-tidal PCO2 of 42.3 +/- 2.0 and 30.8 +/- 2.6 Torr. SL HVR of 0.91 +/- 0.38 was unchanged on AL1 (30 +/- 18 h) at 1.04 +/- 0.37 but rose (P less than 0.05) to 1.27 +/- 0.57 on AL2 (3.2 +/- 0.8 days) and 1.46 +/- 0.59 on AL3 (4.8 +/- 0.4 days) and remained high on PAL1 at 1.44 +/- 0.54 and PAL2 at 1.37 +/- 0.78 but not on PAL3 (days 4-7). HVR was independent of test SaO2 (range 60-90%). Hyperoxic HCVR (CO2 response) was increased on AL3 and PAL1. Arterial pH at congruent to 65% SaO2 was 7.378 +/- 0.019 at SL, 7.44 +/- 0.018 on AL2, and 7.412 +/- 0.023 on AL3.(ABSTRACT TRUNCATED AT 250 WORDS)
Medullary CO2 chemoreceptor neuron identification by c-fos immunocytochemistry.
In a search for CO2 chemoreceptor neurons in the brain stem, we used immunocytochemistry to monitor the expression of neuronal c-fos, a marker of increased activity, after 1 h of exposure to CO2 in five groups of Sprague-Dawley rats (294 +/- 20 g): five air breathing controls, three breathing 10% CO2, three breathing 13% CO2, three breathing 15% CO2, and three breathing 15% CO2 and treated with morphine (10 mg/kg sc). After exposure the rats were anesthetized with pentobarbital sodium and perfused intracardially with 4% paraformaldehyde. The brain stem was removed and cryoprotected, and then 50-microns frozen sections were cut and immunostained for the fos protein. Brain stem fos-immunoreactive neurons were plotted and counted in the superficial 0.5 mm of the ventral medullary surface. Thirteen to 15% CO2 evoked fos-like immunoreactivity (FLI) in 321 +/- 146 neurons/rat. Significant CO2-induced labeling was confined within the superficial 150 microns: 67% of identified cells were less than 50 microns below the surface, greater than 90% between 1.0 and 3.0 mm from the midline, and approximately 60% in the rostral half of the medulla. Thirteen to 15% CO2 also evoked FLI in the area of the nucleus tractus solitarius but not in other medullary regions. Morphine (10 mg/kg sc) did not suppress high CO2-evoked FLI in either the ventral medullary surface or the nucleus tractus solitarius, although it eliminated excitement and hyperventilation. We suggest that respiratory CO2 chemoreceptor neurons can be identified in rats by their expression of c-fos after 1 h of hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
Topography of cat medullary ventral surface hypoxic acidification.
The topographic relationship between previously identified medullary ventral surface respiratory chemosensitive regions and brain surface extracellular fluid (ECF) acid production during acute hypoxia was explored in anesthetized, paralyzed, and artificially ventilated cats. Glass pH electrodes (0.8-mm diam, sheathed in stainless steel tubing) were mounted in mechanical contact with surfaces of medullary surface or adjacent pyramids, pons, spinal cord, or parietal cortex. Isocapnic hypoxia of 5 min [at arterial O2 saturation (SaO2) = 48 +/- 10%] reduced pH over rostral (Mitchell) and caudal (Loeschcke) areas by 0.12 +/- 0.09 and 0.07 +/- 0.04, respectively (n = 10, P < 0.05). Change in pH (delta pH) was proportional to desaturation with slopes 100 delta pH/delta SaO2 of 0.45 (rostral) and 0.20 (caudal) (R = 0.91 and 0.88, respectively). pH drop usually began within 3 min of hypoxia, became stable between 5 and 15 min, began to rise within 2 min of reoxygenation, and returned to control within 10 min. During equally hypoxic tests, intermediate area (Schläfke), pons, and spinal cord surfaces showed no significant acid shift. Parietal cortex ECF pH dropped more slowly but steadily by 0.079 +/- 0.034 during 20 min at SaO2 = 50% after a small but significant initial alkaline shift, and acidification of cortical surface continued for > 5 min after reoxygenation. We conclude that medullary ventral chemosensitive regions produce more lactic acid during hypoxia than neighboring brain surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)
Pathophysiologic aspects of the regulation of respiration.
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Oxygen analyzer dangerous--senses nitrous oxide as battery fails.
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Simple, accurate equations for human blood O2 dissociation computations.
Hill's equation can be slightly modified to fit the standard human blood O2 dissociation curve to within plus or minus 0.0055 fractional saturation (S) from O less than S less than 1. Other modifications of Hill's equation may be used to compute Po2 (Torr) from S (Eq. 2), and the temperature coefficient of Po2 (Eq. 3). Variations of the Bohr coefficient with Po2 are given by Eq. 4. S = (((Po2(3) + 150 Po2)(-1) x 23,400) + 1)(-1) (1) In Po2 = 0.385 In (S-1 - 1)(-1) + 3.32 - (72 S)(-1) - 0.17(S6) (2) DELTA In Po2/delta T = 0.058 ((0.243 X Po2/100)(3.88) + 1)(-1) + 0.013 (3) delta In Po2/delta pH = (Po2/26.6)(0.184) - 2.2 (4) Procedures are described to determine Po2 and S of blood iteratively after extraction or addition of a defined amount of O2 and to compute P50 of blood from a single sample after measuring Po2, pH, and S.
Hypoxic chemosensitivity in asthmatic patients two decades after carotid body resection.
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Decreased exercise hyperpnea in patients with bilateral carotid chemoreceptor resection.
Exercise hyperpnea was compared in 5 asthmatics 25 yr after bilateral carotid body resection (BR), 4 others 19 yr after unilateral resection (UR), and 12 controls (C) matched for age and pulmonary flow limitation. In the BR group, ventilation rose less with exercise, mostly because BR experienced less tachypnea. End-tidal PCO2 rose 5.8 +/- 3.2 (P less than 0.05) to 46 Torr at 50 W. In UR and C the same load did not increase PETCO2 significantly (+2.1 and +1.4 Torr, respectively). Arterial-end-tidal PCO2 differences before and 15--45 s postexercise were insignificant in all three groups. Heart rate and blood pressure rose equally in the three groups, suggesting that the ventilatory effects were not secondary to blood flow differences and disclosing no evidence of baroreceptor denervation during glomectomy.
Current trends in continuous blood gas monitoring.
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Reliability of skin (tc)PO2 electrode heating power as a continuous noninvasive monitor of mean arterial pressure in sick newborns.
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A two temperature, two PO2 method of estimating the determinants of tcPO2.
We have prepared an algorithm describing the relationship of tcPO2 to PaO2 and used this with measured values of both tcPO2 and PaO2 under four conditions (two PO2 levels, two temperatures) to generate four equation sets that yielded unique solutions for the four unknown parameters. In adults under a 44 degree C electrode, capillary temperature averaged about 43 degrees C, O2 consumption about 0.0042 ml/gm/min, blood flow about 0.64 ml/gm/min, and diffusion gradient, D, about 32 mm Hg. We have not attempted to define these values in premature or normal newborn infants, because the method requires about one hour of exposure to 100% O2.
Transcutaneous PCO2 electrode design with internal silver heat path.
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Increase of skin O2 diffusion resistance with birthweight.
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Carotid chemoreceptor role in CSF alkalosis at altitude.
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Estimation of skin metabolism and blood flow with tcPO2 and tcPO2 electrodes by cuff occlusion of the circulation.
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Characteristics of non-aqueous electrolytes for transcutaneous oxygen electrodes.
We investigated the characteristics of non-aqueous solvents for tcPO2 electrolytes, using a tcPO2 electrode with three 15 micrometer platinum cathodes set in a polished glass surface, a 17.8 mm2 silver anode covered with a 25 micrometer Telfon membrane, with and without a 12 micrometer cellophane spacer, and polarized at--0.8v. We examined the effect of ethylene glycol (EG) concentration, in water, on O2 sensitivity, stirring effect, in vitro drift, in vitro response time, behaviour on the skin of newborn infants and in vivo response time. We found the following: (1) O2 sensitivity was reduced by increasing EG concentration. (2) phi, the stirring effect (gas/50% glycerine) was 1.01 at 90% EG with cellophane, but higher without cellophane. (3) In vitro drift at 44 degree C electrode temperature, in 43 degree C water (simulating skin), was reduced with 90% EG, 25 micrometer Telfon and no spacer, but increased with a spacer. (4) In vitro response time was increased with EG. (5) Correlations with arterial PO2 in a group of newborns was as excellent with an electrode made with 90% EG and 25 micrometer Telfon, without spacer, as it was with our previous study using aqueous electrolyte and 12 micrometer Telfon wint 12 micrometer cellophane: (tcPO2 = 1.32 + 0.988 PaO2 r = 0.987). In vivo response time was not prolonged. Using EG, the tc PO2 electrode membrane required changing only after 7--9 days, compared with 1--2 days when using aqueous electrolytes. No advantage of using cellophane spacers was identified in these in vivo studies.
Alkaline chloride-free oxygen electrolytes.
The initial and long-term drift of tcPO2 microcathode electrodes has been shown to be substantially less when chloride is removed from the electrolyte, despite the probability that reference electrode EMF is less well defined. In addition to virtually eliminating drift, these electrolytes eliminate silver deposition on the cathode. The most successful electrolyte tested thus far has been 0.2 M K2B4O7 in 95% ethylene glycol, 5% water, both with and without cellophane spacers. The buffering produced by borate appears to prevent the downward drift in CO2 free air probably caused by Ag2 CO3 formation on the anode, after exposure to skin.