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J W Severinghaus

Publications and source records attributed to J W Severinghaus.

At least 19 recordsLinked to original sources
PubMed1998

Hans Loeschcke, Robert Mitchell and the medullary CO2 chemoreceptors: a brief historical review.

In the late 1950s, stimulated by reports from Leusen in Belgium and Winterstein in Germany on ventilatory responses to spinal fluid acid, Hans Loeschcke from Göttingen, and Robert Mitchell of the University of California in San Francisco were independently seeking the site of respiratory chemosensitivity to CO2 which they presumed to be mediated by cerebro-spinal fluid hydrogen ions. In 1960 Loeschcke came to San Francisco to join Mitchell for 3 months of intensive hunting for the site of action. This essay describes the events surrounding the localization of ventral medullary superficial (VMS) chemosensitivity to topical acidification, and some of their subsequent and largely independent work on the location, nature and function of this structure. The discovery led to a vast literature on all aspects of the regulation of respiration.

Carbon Dioxide↗
PubMed1998

Human PaCO2 and standard base excess compensation for acid-base imbalance.

OBJECTIVES: Renal and respiratory acid-base regulation systems interact with each other, one compensating (partially) for a primary defect of the other. Most investigators striving to typify compensations for abnormal acid-base balance have reported their findings in terms of arterial pH, PaCO2, and/or HCO3-. However, pH and HCO3- are both altered by both respiratory and metabolic changes. We sought to simplify these relations by expressing them in terms of standard base excess (SBE in mM), which quantifies the metabolic balance and is independent of PaCO2. DESIGN: Meta-analysis. SETTING: Historical synthesis developed via the Internet. PATIENTS: Arterial pH, PaCO2, and/or HCO3- data sets were obtained from 21 published reports of patients considered to have purely acute or chronic metabolic or respiratory acid-base problems. INTERVENTIONS: We used the same data to compute the typical compensatory responses to imbalances of SBE and PaCO2. Relations were expressed as difference (delta) from normal values for PaCO2 (40 torr [5.3 kPa]) and SBE (0 mM). MEASUREMENTS AND MAIN RESULTS: The data of patient compensatory changes conformed to the following equations, as well as to the traditional PaCO2 vs. HCO3- or H+ vs. PaCO2 equations: Metabolic change responding to change in PaCO2: Acute deltaSBE = 0 x deltaPaCO2, hence: SBE = 0, Chronic deltaSBE = 0.4 x deltaPaCO2. Respiratory change responding to change in SBE: Acidosis deltaPaCO2 = 1.0 x deltaSBE, Alkalosis deltaPaCO2 = 0.6 x deltaSBE. CONCLUSION: Data reported by many investigators over the past 35 yrs on typical, expected, or "normal" human compensation for acid-base imbalance may be expressed in terms of the independent variables: PaCO2 (respiratory) and SBE (metabolic).

Acid-Base Equilibrium↗
PubMed1998

Intrathecally, Caine may dis-Able. Reflections on lidocaine for spinal anesthesia.

This paper was presented in September 1997 during a Round Table Discussion on lidocaine toxicity, held at the Nobel Forum, Karolinska Institute, Stockholm, Sweden. The occasion was in honor of Professor emeritus Torsten Gordh, who in August 1997 celebrated his 90th birthday. Torsten Gordh, also present at the Round Table Discussion, was the first anesthesiologist who used lidocaine clinically. Today, when some clinical problems with the intrathecal use of lidocaine are discussed, we are indeed fortunate to have Torsten Gordh still most vital and active in our midst.

Anesthesia, Spinal↗
PubMed1998

Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude cerebral edema.

The mechanism by which hypoxia causes high-altitude cerebral edema (HACE) is unknown. Tissue hypoxia triggers angiogenesis, initially by expressing vascular endothelial growth factor (VEGF), which has been shown to increase extracerebral capillary permeability. This study investigated brain VEGF expression in 32 rats exposed to progressively severe normobaric hypoxia (9-6% O2) for 0 (control), 3, 6, or 12 h or 1, 2, 3, or 6 days. O2 concentration was adjusted intermittently to the limit of tolerance by activity and intake, but no attempt was made to detect HACE. Northern blot analysis demonstrated that two molecular bands of transcribed VEGF mRNA (approximately 3.9 and 4.7 kb) were upregulated in cortex and cerebellum after as little as 3 h of hypoxia, with a threefold increase peaking at 12-24 h. Western blot revealed that VEGF protein was increased after 12 h of hypoxia, reaching a maximum in approximately 2 days. The expression of flt-1 mRNA was enhanced after 3 days of hypoxia. We conclude that VEGF production in hypoxia is consistent with the hypothesis that angiogenesis may be involved in HACE.

Altitude Sickness↗
PubMed1996

Augmented hypoxic cerebral vasodilation in men during 5 days at 3,810 m altitude.

The fractional increase in cerebral blood flow (CBF) velocity (VCBF) from the control value with 5-min steps of isocapnic hypoxia and hyperoxic hypercapnia was measured by transcranial Doppler in six sea-level native men before and during a 5-day sojourn at 3,810 m altitude to determine whether cerebral vasoreactivity to low arterial O2 saturation (SaO2) gradually increased [as does the hypoxic ventilatory response (HVR)] or diminished (adapted, in concert with known slow fall of CBF) at altitude. A control resting PCO2 value was chosen each day during preliminary hyperoxia to set ventilation at 140 ml.kg-1.min-1 for this and the parallel HVR study, attempting to establish control cerebrospinal fluid (CSF) and brain extracellular fluid pH values unaltered by acclimatization. The relationship of CBF to SaO2 was nonlinear, steepening at a lower SaO2. A hyperbolic equation was used to describe hypoxic cerebrovascular reactivity: fractional VCBF = x[60/ (SaO2-40)-1], where X is the fractional increase of VCBF at 70%.X rose from 0.346 +/- 0.104 (SD) at sea level to 0.463 +/- 0.084 on altitude day 5 (P < 0.05 by paired t-test, justified by the a priori experimental plan). For comparison with CO2 sensitivity, from these X values, we estimate the rise in CBF in response to a 1% fall in SaO2 at 80% to be 1.30% at sea level and 1.74% after 5 days at altitude. CBF sensitivity to increased end-tidal PCO2 rose from 4.01 +/- 0.62%/Torr at sea level to 5.12 +/- 0.79%/Torr on day 5 (P < 0.05), as expected, at the lower PCO2 due to the logarithmic relationship of PCO2 to CSF pH. This change was not significant after correction to log PCO2. We conclude that the cerebral vascular response to acute isocapnic hypoxia may increase during acclimatization at high altitude. The mechanism is unknown but is presumably unrelated to the parallel carotid chemosensitization that, in these subjects, increased the HVR by 60% in the same 5-day period from 0.91 +/- 0.38 to 1.46 +/- 0.59 l.min-1.% fall in SaO2-1).

Adult↗
PubMed1996

Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema.

Individuals with a prior history of (susceptible to high altitude pulmonary edema (HAPE-S) have high resting pulmonary arterial pressures, but little data are available on their vascular response to exercise. We studied the pulmonary vascular response to exercise in seven HAPE-S and nine control subjects at sea level and at 3,810 m altitude. At each location, both normoxic (inspired PO2 = 148 Torr) and hypoxic (inspired PO2 = 91 Torr) studies were conducted. Pulmonary hemodynamic measurements included pulmonary arterial and pulmonary arterial occlusion pressures. A multiple regression analysis demonstrated that the pulmonary arterial pressure reactivity to exercise was significantly greater in the HAPE-S group. This reactivity was not influenced by altitude or oxygenation, implying that the response was intrinsic to the pulmonary circulation. Pulmonary arterial occlusion pressure reactivity to exercise was also greater in the HAPE-S group, increasing with altitude but independent of oxygenation. These findings suggest an augmented flow-dependent pulmonary vasoconstriction and/or a reduced vascular cross-sectional area in HAPE-S subjects.

Adult↗