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W J Whalen

Publications and source records attributed to W J Whalen.

At least 19 recordsLinked to original sources
PubMed1989

Two-cytochrome metabolic model for carotid body PtiO2 and chemosensitivity changes after hemorrhage.

O2 microelectrode measurements were made in the cat carotid body (CB) at normal control blood pressures (C) and after hemorrhage (H) to reduce mean arterial blood pressure [C, 98.7 +/- 4.6 (SE) mmHg; H, 58.1 +/- 1.8; P less than 0.001; paired t test; n = 9 cats]. Mean tissue PO2 (PtiO2) was significantly lower (C, 78.4 +/- 3.0 Torr; H, 65.3 +/- 4.8; P less than 0.01). Except for two experiments with good autoregulation, the decrease in PtiO2 correlated with the reduction in blood pressure (r = 0.791, P less than 0.005). Measurements of O2 disappearance curves (DCs) and sinus nerve discharge (ND) were obtained after blood supply was occluded for 30-45 s (56 C DCs, 44 H DCs). Disappearance rates (dPO2/dt) were significantly slower after hemorrhage (C, -7.52 +/- 0.47 Torr/s; H, -6.60 +/- 0.44; P less than 0.01), decreasing by 0.656 Torr/s for each 10 Torr fall in PtiO2 (r = 0.626, P less than 0.05). Resting ND before occlusion increased during hypotension (11.6 +/- 2.9% of control, P less than 0.01) and correlated with the decrease in PtiO2 (r = -0.792, P less than 0.005). A computer simulation was performed for a two-cytochrome metabolic model with a second, low-O2-affinity oxidase in addition to normal oxidative metabolism. The effects of cat oxyhemoglobin and blood pH on the O2 DC measurement were also taken into account. The simulation for the two-cytochrome model was consistent with our experimental data and predicts reductions in blood flow and O2 metabolism with hypotension after hemorrhage that have similarities, as well as aspects that disagree, with previous reports in the literature.

Animals↗
PubMed1989

Evidence for second metabolic pathway for O2 from PtiO2 measurements in denervated cat carotid body.

O2 microelectrode studies were conducted in the cat carotid body (CB) to investigate the hypothesis that there is a second, low affinity metabolic pathway for O2 in addition to classical oxidative metabolism. Tissue PO2 (PtiO2) and O2 disappearance rates (dPO2/dt) after brief blood flow occlusion were measured with recessed cathode microelectrodes (tip diameter less than 5 microns) at 150 sites in 15 normal cats (controls) and at 154 sites in 5 cats in which one CB had been denervated 2 or 3 days before the experiments. Mean PtiO2 was slightly higher in denervated CBs: 79.6 +/- 1.6 (SE) Torr compared with 76.4 +/- 2.0 Torr for controls (P = not significant). Mean dPO2/dt was 8.4% faster: -8.42 +/- 0.28 Torr/s compared with -7.77 +/- 0.43 Torr/s for controls (P less than 0.05). The O2 consumption rate (VO2), calculated from dPO2/dt correcting for cat oxyhemoglobin, was 7.5% higher: 1.62 and 1.51 ml.100 g-1.min-1, respectively, for denervated and control CBs (P less than 0.05). The apparent Michaelis-Menten constant, Kmapp (defined as the PtiO2 where dPO2/dt decreased by 50% from the initial rate during the first 3 s after occlusion) was determined for each O2 disappearance curve. After denervation, Kmapp decreased significantly by -47%: 12.0 +/- 1.3 Torr compared with 22.6 +/- 2.5 Torr for controls (P less than 0.01). The data provide evidence for a second metabolic pathway for O2 in the CB that loses its influence on VO2 after denervation.

Animals↗
PubMed1986

Two cytochrome oxygen consumption model and mechanism for carotid body chemoreception.

We have measured sinus nerve discharge, tissue PO2 and oxygen consumption (VO2) in cat carotid bodies under different experimental conditions using our recessed oxygen microelectrode. Our results indicate that the change in chemoreceptor activity with oxygen disappearance following blood flow occlusion can be related to a two cytochrome model for oxygen consumption as previously proposed by Mills and Jöbsis (1972).

Animals↗
PubMed1986

Cat carotid body oxygen metabolism and chemoreception described by a two-cytochrome model.

We have analyzed O2 disappearance curves (DCs) in cat carotid bodies (CBs) measured with our O2 microelectrode, after stopping flow of either blood (108 DCs in 12 cats) or a hemoglobin-free (Locke) perfusion solution (35 DCs in 6 cats). Prior to occlusion, the mean tissue PO2 levels were 74.5 +/- 2.8 (SE) Torr in blood-perfused CBs and 103.4 +/- 2.6 in Locke-perfused CBs. The O2 consumption rates (VO2) determined from the initial 3 s of the DCs were 1.46 +/- 0.08 and 1.50 +/- 0.10 (SE) ml O2 . 100 g-1 . min-1, respectively, for the blood-perfused and Locke-perfused CBs. The change in total sinus nerve activity from the CB was also measured following stopped flow. The nerve activity began to increase immediately, providing further evidence that classic hypoxia is not the mechanism of chemoreceptor discharge. However, about two-thirds of the increased activity in blood-perfused CBs occurred after tissue PO2 levels fell below 20 Torr. As the CB tissue PO2 decreased, the O2 disappearance rate (-dPO2/dt) also decreased for both experimental conditions, indicating that the CB VO2 varies with O2 concentration. The increase in nerve discharge and O2 disappearance rate can be interpreted by a two-cytochrome model for O2 metabolism, with both high and low affinities.

Animals↗
PubMed1981

Cat carotid body: oxygen consumption and other parameters.

Cats were anesthetized with pentobarbital, pump ventilated with air, and given heparin, and the carotid body (CB) was vascularly isolated except for the supplying artery. The CB could be normally blood perfused, or alternatively, perfused with Locke's solution; flow of either could be stopped suddenly. Sinus nerve discharge was measured. Tissue oxygen tension (TPO2) in the CB was measured with an O2 microelectrode. Oxygen consumption rates (VO2) calculated from the disappearance curve of O2 during stopped flow were PO2 dependent. When TPO2 was high (100-130 Torr), VO2 (ml.100 g-1.min-1) averaged 1.9 +/- 0.18 (SE) during blood perfusion and either 1.9 +/- 0.1 during perfusion with Locke's solution equilibrated with 25% O2-5% CO2-70% N2 or 1.4 +/- 0.08 when the Locke's solution was equilibrated with air. This significant effect of CO2 could have been due to the delayed onset of sinus nerve discharge when CO2 was not added to the perfusion solution. The number of red blood cells in histological sections from CB frozen during stopped flow of blood was significantly below normal. We concluded that the similarity of the disappearance curves during stopped flow of blood and Locke's solutions was primarily due to the extrusion of red blood cells. In five experiments the broken-off tip of the O2 microelectrode was found in the core of the CB.

Animals↗
PubMed1980

A hypodermic needle PO2 electrode.

Several glass-covered gold wires (5-10 micrometer diam) connected to an insulated lead wire are embedded with epoxy inside a stainless steel needle (e.g., 25 gauge). The epoxy, glass, and gold wire are carefully ground off down to the bevel of the needle, and the gold wires recessed electrolytically using NaCN. Oxygen tension (PO2) is measured polarographically, usually using a separate Ag-Agcl reference electrode. However, the stainless steel needle, connected to the shield of the coaxial lead, can also be used as the reference. The PO2 electrode shows little or no stir sensitivity and has a response time (to 100%) of 1-2 s.

Electrodes↗
PubMed1980

Marking the tip location of PO2 microelectrodes or glass micropipettes.

The necessity of localizing the PO2 recording sites in the carotid body of cats has led us to modify our O2 microelectrode to be able to mark the position of the tip. Gold is sputtered on the electrode, and then iron is plated on the gold. The carotid body of cats was exposed, and PO2 was recorded at different depths in the body after which iron was deposited. At the end of the experiment, the excised body was placed in a 1:1 mixture of 4% potassium ferrocyanide and 4% acetic acid for 1 h or more. After that, the body was fixed in a 1:1 mixture of 40% formaldehyde and 95% ethyl alcohol for 1-2 days. Paraffin sections cut at 10 micrometer revealed the recording sites as bright blue spots. Since the cathode size can be made as small as 1 micrometer, discrete spots (a few microns or larger depending on current and time) can be produced at the PO2 recording sites. Several locations can be marked in a few minutes without damage to the tissue or the electrode. In 21 cats all of the 62 marked spots were found. In 16 peripheral (depth 50-150 micrometers) locations the PO2 averaged 101 Torr and in 46 deep locations 73 Torr. This technique is applicable to glass micropipettes and is a unique tool in correlating the structure and function of various tissues.

Animals↗
PubMed1976

PO2 in the carotid body perfused and/or superfused with cell-free media.

We measured with a micro-O2 electrode the tissue PO2 (PtO2) in the cat carotid body (CB) to see whether it was adequately oxygenated when perfused or superfused with artificial, cell-free (c-f) solutions (pH = 7.4; temp = 35-38 degrees C). To obtain a relative measure of O2 consumption (VO2), we also measured the rate of disappearance of O2 following stoppage of the blood flow, and compared these disappearance curves with those during stoppage of the c-f perfusion solutions. In 14 cats normal (blood perfusion) PtO2 values ranged from 10 to 104 mmHG; chi = 72 +/- 4 (SE--as used throughout). During 3 h of c-f perfusion with air-equilibrated Locke's solution, PtO2 ranged from 62 to about 160 mmHg; chi = 133 +/- 4. When perfused with Fay's equilibrated with 98% O2-2% CO2 no PtO2 values in the CB were below 300 mmHg (4 cats). In eight additional cats the CB was cleared of blood then superfused with saline equilibrated with 50% O2 underneath and air-equilibrated saline over. Less than 5% of the PtO2 values found were below 5 mmHg. We conclude that most studies on the artificially perfused or superfused CB cannot be invalidated on the basis that the preparations were hypoxic. O2 disappearance curves taken during blood perfusion were significantly faster than during c-f perfusion indicating a marked reduction in VO2 with c-f perfusion.

Animals↗
PubMed1975

Some factors affecting tissue Po2 in the carotid body.

In the carotid body (CB) of the anesthetized cat tissue Po2 (Pto2) measured with a micro O2 electrode averaged about 65 mmHg at normal arterial pressure (mean = 96 mmHg). Pto2 correlated significantly with the hematocrit of the arterial blood but not with % saturation. When arterial pressure was reduced (mean = 58 mmHg) by bleeding Pto2 fell significantly. Phentolamine injection (1 mg/kg iv) at the reduced pressure caused Pto2 to rise significantly. At normal arterial pressure blowing moistened O2 over the CB did not affect Pto2 if the electrode tip was about 90 mum into the CB. At a reduced pressure (and blood flow) the sensitive depth increased to about 301 mum, and to about 600 mum when flow was stopped. We concluded that a) the increased chemoceptor discharge usually seen with hemorrhage is due to reduced Pto2; b) the reduction in Pto2 is probably due to reduced blood flow which is, in turn, caused partly, at least, by sympathetic nervous system activity; c) O2 content, rather than Po2, may determine chemoreceptor discharge rate; and d) there are no barriers in the CB which are impermeable to O2.

Animals↗