In vivo regulation of plasma [H+] in ponies during acute changes in PCO2

1990 ◽  
Vol 68 (1) ◽  
pp. 316-321 ◽  
Author(s):  
H. V. Forster ◽  
C. L. Murphy ◽  
A. G. Brice ◽  
L. G. Pan ◽  
T. F. Lowry
Keyword(s):  
Venous Blood ◽  
Strong Ion Difference ◽  
Mixed Venous Blood ◽  
Arterial Pco2 ◽  
Acute Changes ◽  
Different Levels ◽  
In Vitro Data ◽  
Mixed Venous

The major objective of this study was to test the hypothesis that in ponies the change in plasma [H+] resulting from a change in PCO2 (delta H+/delta PCO2) is less under acute in vivo conditions than under in vitro conditions. Elevation of inspired CO2 and lowering of inspired O2 (causing hyperventilation) were used to respectively increase and decrease arterial PCO2 (Paco2) by 5-8 Torr from normal. Arterial and mixed venous blood were simultaneously sampled in 12 ponies during eucapnia and 5-60 min after Paco2 had changed. In vitro data were obtained by equilibrating blood in a tonometer at five different levels of PCO2. The in vitro slopes of the H+ vs. PCO2 relationships were 0.73 +/- 0.01 and 0.69 +/- 0.01 neq.1-1.Torr-1 for oxygenated and partially deoxygenated blood, respectively. These slopes were greater (P less than 0.001) than the in vivo H+ vs. PCO2 slopes of 0.61 +/- 0.03 and 0.57 +/- 0.03 for arterial and mixed venous blood, respectively. The delta HCO3-/delta pH (Slykes) was 15.4 +/- 1.1 and 17.0 +/- 1.1 for in vitro oxygenated and partially deoxygenated blood, respectively. These values were lower (P less than 0.001) than the in vivo values of 23.3 +/- 2.7 and 25.2 +/- 4.7 Slykes for arterial and mixed venous blood, respectively. In vitro, plasma strong ion difference (SID) increased 4.5 +/- 0.2 meq/l (P less than 0.001) when Pco2 was increased from 25 to 55 Torr. A 3.5-meq/l decrease in [Cl-] (P less than 0.001) and a 1.3 +/- 0.1 meq/l increase in [Na+] (P less than 0.001) accounted for the SID change.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vivo CO2 Buffer Curves of Arterial and Mixed Venous Blood

1971 ◽  
Vol 137 (1) ◽  
pp. 237-242 ◽  
Author(s):  
A. C. Garcia ◽  
Y. L. Lai ◽  
B. A. Attebery ◽  
E. B. Brown
Keyword(s):  
Venous Blood ◽  
Mixed Venous Blood ◽  
Mixed Venous

The Co2 Titration Curve of Mixed Venous Blood

1972 ◽  
Vol 43 (4) ◽  
pp. 553-559 ◽  
Author(s):  
C. T. Kappagoda ◽  
J. B. Stoker ◽  
H. M. Snow ◽  
R. J. Linden
Keyword(s):  
Titration Curve ◽  
Venous Blood ◽  
Mixed Venous Blood ◽  
Ph Values ◽  
Titration Curves ◽  
Mixed Venous

1. Simultaneous CO2 titration curves of arterial and mixed venous blood were determined in both dog and man in vivo. 2. The slopes of the CO2 titration curves of mixed venous blood were significantly less than those of the corresponding arterial curves. 3. The non-respiratory pH values of the CO2 titration curves of mixed venous blood were significantly greater than those of the corresponding arterial curves. 4. The theoretical explanations of these differences have been discussed.

scholarly journals Arterial and Mixed Venous Blood Gas Status during Apnoea of Intubation — Proof of the Christiansen-Douglas-Haldane Effect in Vivo

1989 ◽  
Vol 17 (3) ◽  
pp. 325-331 ◽  
Author(s):  
F. O. Mertzlufft ◽  
L. Brandt ◽  
M. Stanton-Hicks ◽  
W. Dick
Keyword(s):  
Partial Pressure ◽  
Venous Blood ◽  
Mixed Venous Blood ◽  
Rapid Adjustment ◽  
Venous Blood Gas ◽  
Clinical Conditions ◽  
Lung Capillaries ◽  
Mixed Venous ◽  
Haldane Effect

The Christiansen-Douglas-Haldane effect, in short the Haldane effect, describes the dependence of the CO2 binding of blood on the degree of oxygenation of haemoglobin. Under the physiological conditions of an ‘open’ system between blood and alveoli the partial pressure of arterial C02 (PaCO2), must be less than that of mixed venous blood (P[Formula: see text]CO2). During the unphysiological conditions of a ‘closed’ system, e.g. hyperoxic apnoea, i.e. continuous oxygen uptake without CO2 delivery by the lungs, the Paco2 will not only approximate the P[Formula: see text]CO2 but will even exceed it. Without the Haldane effect, rapid adjustment of Paco2 to P[Formula: see text]CO2 would be expected during apnoea due to the lack of CO2 excretion. If however, as undertaken in this study, ongoing oxygenation (high alveolar Po2 (PACO2) with concomitant lack of C02 delivery (apnoea, i. e. the C02 concentration remains constant) lead to a continuing sufficient oxygenation of blood during its passage through the lung capillaries, then this leads to a rightwards shift of the CO2 binding curve — the Haldane effect. The resulting increase in Pco2 as shown here actually leads to an arterial-mixed venous CO2 partial pressure difference (a[Formula: see text]DPco2) of 2.8±1.8 mmHg. The results described substantiate for the first time the existence of the Haldane effect under clinical conditions.

Blood oxygen transport in the free-swimming hagfish, Eptatretus cirrhatus

1986 ◽  
Vol 123 (1) ◽  
pp. 43-53 ◽  
Author(s):  
R. M. Wells ◽  
M. E. Forster ◽  
W. Davison ◽  
H. H. Taylor ◽  
P. S. Davie ◽  
...  
Keyword(s):  
Venous Blood ◽  
Mixed Venous Blood ◽  
Oxygen Binding ◽  
Blood Oxygen ◽  
Binding Data ◽  
Gas Measurements ◽  
Hyperbolic Equilibrium

Arterial and mixed venous blood were sampled through chronically implanted cannulae from rested and swimming hagfish. PaO2 remained high when hagfish were swum for 15 min at a velocity of 20 cm s-1. PvO2 fell from 17.2 mmHg at rest to 3.5 mmHg after swimming, and the arteriovenous pH difference increased from 0.15 to 0.25 pH units. Whole blood oxygen equilibrium curves were essentially hyperbolic (Hill's n value = 1.38) and gave a half-saturation PO2 (P50) value of 12.3 mmHg at pH 7.8 and 16 degrees C. A CO2-Bohr factor (phi = delta logP50/delta pH) of −0.43 and a limited buffering capacity of the blood, amounting to approx. 4 slykes, were observed. The role of the blood in transporting oxygen and carbon dioxide both at rest and after swimming is established by in vivo blood gas measurements and in vitro oxygen-binding data. The low internal PvO2 at rest is close to the P50 measured under similar conditions and the hyperbolic equilibrium curve permits further oxygen unloading when PvO2 falls during swimming.

Plasma [H+] regulation and whole blood [CO2] in exercising ponies

1990 ◽  
Vol 68 (1) ◽  
pp. 309-315 ◽  
Author(s):  
H. V. Forster ◽  
C. L. Murphy ◽  
A. G. Brice ◽  
L. G. Pan ◽  
T. F. Lowry
Keyword(s):  
Steady State ◽  
Whole Blood ◽  
Submaximal Exercise ◽  
Treadmill Running ◽  
Strong Ion Difference ◽  
Venous Pco2 ◽  
Arterial Plasma ◽  
Mixed Venous

The major objective was to determine in ponies whether factors in addition to changes in blood PCO2 contribute to changes in plasma [H+] during submaximal exercise. Measurements were made to establish in vivo plasma [H+] at rest and during submaximal exercise, and CO2 titration of blood was completed for both in vitro and acute in vivo conditions. In 19 ponies arterial plasma [H+] was decreased from rest 4.5 neq/l (P less than 0.05) during the 7th min of treadmill running at 6 mph, 5% grade (P less than 0.5). A 5.6-Torr exercise hypocapnia accounted for approximately 2.9 neq/l of this reduced [H+]. The non-PCO2 component of this alkalosis was approximately neq/l, and it was due presumably to a 1.7-meq/l increase from rest in the plasma strong ion difference (SID). Despite the arterial hypocapnia, mixed venous PCO2 was 2.7 Torr above rest during steady-state exercise. Nevertheless, mixed venous plasma [H+] was 1.2 neq/l above rest during exercise, which was presumably due to the increase in SID. Also studied was the effect of submaximal exercise on whole blood CO2 content (CCO2). In vitro, at a given PCO2 there was minimal difference in CCO2 between rest and exercise blood, but plasma [HCO3-] was greater for exercise blood than for rest blood. In vivo, during steady-state exercise, arterial plasma blood. In vivo, during steady-state exercise, arterial plasma [HCO3-] was unchanged or slightly elevated from rest, but CaCO2 was 4 vol% below rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of Toxicokinetics in Risk Assessment Based on In Vitro Data

1993 ◽  
Vol 21 (2) ◽  
pp. 173-180
Author(s):  
Gunnar Johanson
Keyword(s):  
Risk Assessment ◽  
Whole Body ◽  
External Exposure ◽  
Target Dose ◽  
Toxic Response ◽  
Route Of Exposure ◽  
Vitro Data ◽  
In Vitro Data

This presentation addresses some aspects of the methodology, advantages and problems associated with toxicokinetic modelling based on in vitro data. By using toxicokinetic models, particularly physiologically-based ones, it is possible, in principle, to describe whole body toxicokinetics, target doses and toxic effects from in vitro data. Modelling can be divided into three major steps: 1) to relate external exposure (applied dose) of xenobiotic to target dose; 2) to establish the relationship between target dose and effect (in vitro data, e.g. metabolism in microsomes, partitioning in tissue homogenates, and toxicity in cell cultures, are useful in both steps); and 3) to relate external exposure to toxic effect by combining the first two steps. Extrapolations from in vitro to in vivo, between animal and man, and between high and low doses, can easily be carried out by toxicokinetic simulations. In addition, several factors that may affect the toxic response by changing the target dose, such as route of exposure and physical activity, can be studied. New insights concerning the processes involved in toxicity often emerge during the design, refinement and validation of the model. The modelling approach is illustrated by two examples: 1) the carcinogenicity of 1,3-butadiene; and 2) the haematotoxicity of 2-butoxyethanol. Toxicokinetic modelling is an important tool in toxicological risk assessment based on in vitro data. Many factors, some of which can, and should be, studied in vitro, are involved in the expression of toxicity. Successful modelling depends on the identification and quantification of these factors.

Effects of cocaine on incremental treadmill exercise in horses

1993 ◽  
Vol 75 (6) ◽  
pp. 2727-2733 ◽  
Author(s):  
K. H. McKeever ◽  
K. W. Hinchcliff ◽  
D. F. Gerken ◽  
R. A. Sams
Keyword(s):  
Right Ventricular ◽  
Blood Lactate ◽  
Venous Blood ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Ventricular Pressure ◽  
Mixed Venous Blood ◽  
Work Intensity ◽  
Venous Blood Lactate ◽  
Mixed Venous

Four mature horses were used to test the effects of two doses (50 and 200 mg) of intravenously administered cocaine on hemodynamics and selected indexes of performance [maximal heart rate (HRmax), treadmill velocity at HRmax, treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l, maximal mixed venous blood lactate concentration, maximal treadmill work intensity, and test duration] measured during an incremental treadmill test. Both doses of cocaine increased HRmax approximately 7% (P < 0.05). Mean arterial pressure was 30 mmHg greater (P < 0.05) during the 4- to 7-m/s steps of the exercise test in the 200-mg trial. Neither dose of cocaine had an effect on the responses to exertion of right atrial pressure, right ventricular pressure, or maximal change in right ventricular pressure over time. Maximal mixed venous blood lactate concentration increased 41% (P < 0.05) with the 50-mg dose and 75% (P < 0.05) with the 200-mg dose during exercise. Administration of cocaine resulted in decreases (P < 0.05) in the treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l from 6.9 +/- 0.5 and 6.8 +/- 0.9 m/s during the control trials to 4.4 +/- 0.1 m/s during the 200-mg cocaine trial. Cocaine did not alter maximal treadmill work intensity (P > 0.05); however, time to exhaustion increased by approximately 92 s (15%; P < 0.05) during the 200-mg trial.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

2021 ◽  
Vol 7 (3) ◽  
pp. 163 ◽  
Author(s):  
Sabelle Jallow ◽  
Nelesh P. Govender
Keyword(s):  
Pathogenic Fungi ◽  
Candida Spp ◽  
Fungal Cell ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Synthase Inhibitor ◽  
Increased Activity ◽  
In Vitro Data

Ibrexafungerp (formerly SCY-078 or MK-3118) is a first-in-class triterpenoid antifungal or “fungerp” that inhibits biosynthesis of β-(1,3)-D-glucan in the fungal cell wall, a mechanism of action similar to that of echinocandins. Distinguishing characteristics of ibrexafungerp include oral bioavailability, a favourable safety profile, few drug–drug interactions, good tissue penetration, increased activity at low pH and activity against multi-drug resistant isolates including C. auris and C. glabrata. In vitro data has demonstrated broad and potent activity against Candida and Aspergillus species. Importantly, ibrexafungerp also has potent activity against azole-resistant isolates, including biofilm-forming Candida spp., and echinocandin-resistant isolates. It also has activity against the asci form of Pneumocystis spp., and other pathogenic fungi including some non-Candida yeasts and non-Aspergillus moulds. In vivo data have shown IBX to be effective for treatment of candidiasis and aspergillosis. Ibrexafungerp is effective for the treatment of acute vulvovaginal candidiasis in completed phase 3 clinical trials.

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