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  • 1
    Electronic Resource
    Electronic Resource
    FAILURE OF THE KETY-SCHMIDT NITROUS OXIDE METHOD FOR DETERMINATION OF MYOCARDIAL BLOOD FLOW (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 18 (1991), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The reliability of the Kety-Schmidt nitrous oxide (N2O) blood–tissue equilibration method was examined in 50 studies of myocardial blood flow in seven conscious, unrestrained sheep using a newly developed carefully validated gas chromatographic assay for N2O.2. In 10 studies the arterial and coronary sinus N2O blood concentration–time curves converged as expected at the end of the 10 min sampling period. In 14 studies they crossed over, and in 26 studies, the curves failed to converge.3. A survey of the literature revealed that such results have been encountered previously but have not been accorded particular significance. An ultimate matching equilibrium between arterial and venous blood N2O concentration–time curves is, however, fundamental to the validity of the method.4. The results indicate that the use of the Kety-Schmidt method with N2O as the indicator gas is invalid as applied to the measurement of myocardial blood flow in this preparation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1991.tb01428.x
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  • 2
    Electronic Resource
    Electronic Resource
    FAILURE OF THE NITROUS OXIDE TISSUE EQUILIBRATION METHOD FOR THE DETERMINATION OF BRAIN AND MYOCARDIAL BLOOD FLOW UNDER CONTROLLED CONDITIONS (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 19 (1992), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Two adult merino ewes were prepared with intravascular cannule for sampling aortic root blood, sagittal sinus blood and coronary sinus blood.2. One week after preparation the animals were anaesthetized then ventilated with a gas mixture containing 10% nitrous oxide (N2O) for 60 min. Serial measurements of brain and myocardial blood flow were made using the N2O tissue equilibration method of Kety and Schmidt.3. N2O failed to achieve matching arteriovenous blood concentration equality and saturation of the relevant tissues. Valid use of the Kety-Schmidt method, therefore, could not be confirmed.4. Because of the failure of the arteriovenous equilibration, serially determined brain and myocardial blood flows were found to decrease with time.5. The use of this method in circumstances where tissue saturation with the indicator gas cannot be ascertained is arbitrary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1992.tb00443.x
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  • 3
    Electronic Resource
    Electronic Resource
    The uptake and elution of lignocaine and procainamide in the hindquarters of the sheep described using mass balance principles (1988)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 16 (1988), S. 31-40 
    Details
    ISSN: 1573-8744
    Keywords: lignocaine ; procainamide ; pharmacokinetics ; mass balance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Mass balance principles were used to describe the uptake and elution of lignocaine (lidocaine) and procainamide in the hindquarters of the sheep. Each of four sheep received a right atrial infusion of either lignocaine · HCl (2.7 mg/min) or procainamide · HCl (5.5mg/min) for 180 min. Paired arterial and inferior vena cava (draining the hindquarters) blood samples were taken at 20-min intervals during the infusion and for 180 min after the infusion. Lignocaine and procainamide mean total body clearances were 2.9 L/min (SD 1.1) and 1.3 L/min (SD 0.2), respectively. An index of the uptake and elution of these drugs in the hindquarters was estimated from the net drug mass per unit hindquarter blood flow;indirect evidence suggested that hindquarter blood flow was constant. All the net mass/flow of procainamide that was taken into the hindquarters during the infusion also eluted after the infusion, demonstrating reversible distribution into the tissues. However, uptake of procainamide was still occurring when blood concentrations were constant, indicating that the concentrations of procainamide in the hindquarters were not in equilibrium with the inferior vena cava concentrations. Lignocaine did not reach constant blood concentrations during the infusion and showed no tendency to reach arteriovenous equilibration; an arteriovenous difference of 22%(SD5%) across the hindquarters was measured during the last 60 min of the infusion. By 180 min after the lignocaine infusions, 79% (SD 8%) of the lignocaine net mass/flow had not eluted from the hindquarters when arterial and venous lignocaine concentrations were not significantly different. This drug could remain uneluted due to metabolism and/or avid tissue binding, and presents difficulties in the interpretation of pharmacokinetic data whether based on arterial or venous blood sampling.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061861
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  • 4
    Electronic Resource
    Electronic Resource
    Tissue distribution of bupivacaine enantiomers in sheep (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 5 (1993), S. 485-491 
    Details
    ISSN: 0899-0042
    Keywords: anaesthetics ; local:bupivacaine ; enantiomers:stereoselective pharmacokinetics ; enantiomers:stereoselective pharmacodynamics ; enantiomers:tissue distribution ; sheep ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: rac-Bupivacaine HCl was infused intravenously to constant arterial blood drug concentrations in sheep using a regimen of 4 mg/min for 15 min followed by 1 mg/min to 24 h. At 24 h, arterial blood was sampled, the animal was killed with a bolus of KCl solution, then rapidly dissected and samples were obtained from heart, brain, lung, kidney, liver, muscle, fat, gut, and rumen. Tissue:blood distribution coefficients for (+)-(R)-bupivacaine exceeded those of (-)-(S)-bupivacaine (P 〈 0.05) for heart, brain, lung, fat, gut, and rumen by an overall mean of 43%. Blood:plasma distribution coefficients of (-)-(S)-bupivacaine exceeded those of (+)-(R)-bupivacaine by a mean of 29% and this offset the tissue:blood distribution coefficients so that the previously significant enantioselective differences disappeared. It is concluded that although enantioselectivity of bupivacame distribution is shown by the measured tissue:blood distribution coefficients, it is not shown when tissue:plasma water distribution coefficients are calculated, suggesting that there is no intrinsic difference between the bupivacaine enantiomers in tissue affinity. Sheep given fatal intravenous bolus doses of rac-bupivacaine had significantly greater concentrations of (+)-(R)-bupivacaine than (-)-(S)-bupivacaine in brain (P = 0.028) and ventricle (P = 0.036); these could augment the greater myocardial toxicity of this enantiomer found in vitro. © 1993 Wiley-Liss, Inc.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/chir.530050702
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