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Biomedical subjects

C V Greenway

Publications and source records attributed to C V Greenway.

At least 19 recordsLinked to original sources

Venoconstriction of hepatic capacitance vessels during hemorrhage in cats: afferent mechanisms.

Cats anesthetized with pentobarbital sodium were hemorrhaged (1 ml.min-1.kg body wt-1) until arterial pressure declined to 55 mmHg. Hepatic volume was recorded by plethysmography. Hemorrhage volume was 21.1 +/- 4.7 (SD) ml/kg, and hepatic volume declined by 4.0 +/- 1.7 ml/kg. These responses were markedly reduced by four procedures that prevented decreases in carotid arterial and central venous pressures and eliminated vagal conduction. When any three of these four procedures were carried out, the remaining stimulus caused a significant increase in the size of the hepatic volume decrease. The results suggest that arterial receptors (baro- and/or chemoreceptors) in the carotid arterial bed or brain and venous baroreceptors in the right atrium and superior and inferior venae cavae are involved in hepatic capacitance responses to hemorrhage. The responses were linearly related to the stimuli, and hepatic blood volume changed by 1.7 +/- 1.1 and 0.030 +/- 0.016 ml/kg for each 1-mmHg change in venous and carotid arterial pressures, respectively. The maximal responses to these afferent stimuli applied individually were not significantly different (-4.2 +/- 1.8 ml/kg) and were not additive, suggesting overlapping redundant systems. The possibility of baroreceptors in superior vena cava has not previously been documented.

Afferent Pathways↗

Venoconstriction of hepatic capacitance vessels during hemorrhage in cats: efferent mechanisms.

Cats anesthetized with pentobarbital sodium were hemorrhaged (1 ml.min-1.kg body wt-1) until arterial pressure declined to 55 mmHg. Hepatic volume was recorded by plethysmography. In controls, 20 +/- 5 (SD) ml/kg was removed and hepatic volume decreased 3.6 +/- 0.8 ml/kg. Splanchnic nerve section or administration of hexamethonium-atropine reduced hemorrhage volumes (to 10.3 +/- 2.3 and 4.8 +/- 1.8 ml/kg, respectively) and liver volume changes (to 1.5 +/- 0.5 and 0.7 +/- 0.3 ml/kg, respectively). Section of only the hepatic nerves had no effect on hemorrhage volume or the decrease in hepatic volume. Section of the hepatic nerves after removal of the adrenals and kidneys also had no significant effect on hemorrhage volume or the decrease in liver volume. We conclude that the hepatic capacitance response to hemorrhage does not require direct sympathetic venoconstriction of the hepatic capacitance vessels. Changes in inferior vena caval pressure play a significant but small role. The splanchnic nerves (excluding hepatic nerves) play a major role, possibly by splanchnic arteriolar constriction. Whereas the liver comprises only 2.5% of the body weight, it contributed 18% of the hemorrhage volume.

Adrenalectomy↗

Ultrasonic crystal measurement of blood volume changes in liver and spleen.

Two methods of measurement of splenic and hepatic vascular capacitance responses were compared in cats anesthetized with pentobarbital. For the spleen, measurements using ultrasonic crystals were compared with recordings of splenic weight. The cube of the relative change in thickness at one point on the longitudinal axis of the spleen was closely correlated with the overall change in spleen weight. For the liver, measurements by ultrasonic crystals were compared with plethysmographic recordings of liver volume. Individual measurements of cubed relative thickness did not correlate well with plethysmographic volume, and two sets of crystals on the same liver lobe gave different estimates of relative liver volume. However, averaged measurements for a group of animals showed similar means by the two methods. We conclude that ultrasonic crystals, when appropriately attached, can reliably monitor changes in splenic volume, but that for the liver, the variability in thickness responses at different sites on different livers is high. Unless a large number of observations are made, the results will be unreliable.

Animals↗

Quantitative proton nuclear magnetic resonance of plasma for screening hepatic metabolism during ethanol infusion in cats.

The effects of increasing blood ethanol levels on hepatic metabolism were studied in anesthetized cats whose prior fluid intake contained ethanol for 24 days. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of blood volume. For ethanol, Vmax was 106 +/- 15 mumol.min-1.100 g-1 liver and Km was 164 +/- 31 microM. A previous study showed that there were no changes in O2 uptake by the liver, suggesting other oxidative processes were suppressed during ethanol metabolism. In this study, proton nuclear magnetic resonance spectroscopy was used to simultaneously screen several plasma metabolites to elucidate other metabolic processes that may be perturbed in the liver during ethanol infusion. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose above 0.5 Vmax. Thus, lactate oxidation is one process that can be suppressed to allow ethanol oxidation without additional O2 uptake by the liver. In addition, no release of acetate from the liver occurred during ethanol metabolism in these experiments. This surprising finding suggests ethanol metabolism may, under some conditions or in some species, result in fatty acid synthesis rather than acetate release. Eight other major metabolites remained unchanged during ethanol infusion.

Acetates↗

Blockade of reflex venous capacitance responses in liver and spleen by hexamethonium, atropine, and surgical section.

Since hexamethonium and surgical section have been used to prevent reflex splanchnic capacitance responses, we examined the effectiveness of these procedures in blocking responses to direct stimulation of preganglionic fibres in the splanchnic nerves. Liver blood volume was measured by plethysmography and splenic blood volume by weighing in cats anesthetized by pentobarbital. The cats were adrenalectomized to prevent adrenal catecholamine secretion in response to splanchnic nerve stimulation. Hexamethonium (10 and 20 mg/kg) alone or atropine (1 mg/kg) alone caused only a small variable block of the responses to preganglionic nerve stimulation. A combination of the two drugs essentially produced a complete block of the liver capacitance response, but a significant response still persisted in the spleen. Surgical section of the postganglionic nerve bundles around the hepatic and splenic arteries completely abolished the responses to preganglionic stimulation. It is concluded that a relatively complete block of reflex splanchnic capacitance responses requires either a combination of hexamethonium and atropine or surgical section of the postganglionic nerves.

Adrenal Glands↗

Pre- and post-sinusoidal origin of hepatic exudate in anesthetized cats.

In cats anesthetized with pentobarbital, hepatic venous pressure was increased to cause drops of exudate to appear on the surface of the liver. These drops were collected during steady-state infusions of small doses of ethanol and galactose when there was a large arteriovenous gradient across the liver. Comparison of the concentrations of these substances in arterial, portal, and hepatic venous blood and exudate showed that the exudate concentrations were slightly higher than the hepatic venous concentrations but markedly lower than arterial and portal blood concentrations. We conclude that the exudate cannot be entirely formed in the space of Mall (presinusoidal) but a substantial part is postsinusoidal in origin. If the exudate is a mixture of fluids equilibrated with inflowing and outflowing blood, then 75-80% of the exudate is postsinusoidal and 20-25% is presinusoidal in origin.

Animals↗

Index of contractility: quantitative analysis of hepatic venous distensibility.

The low-pressure resistance vessels of the splanchnic circulation are passively distensible, and changes in regional blood pressures can lead to large changes in vascular resistance. The relationship between distending blood pressure (Pd) and vascular resistance (R) is described as a constant, the index of contractility (IC) where IC = R x Pd3. IC was derived in an isolated blood-perfused liver and was confirmed in vivo for both pre- and postsinusoidal resistance sites. IC does not change passively in response to wide changes in blood flow or hepatic outflow pressure. IC is dramatically altered in response to active vasoconstriction. In vivo, the presinusoidal IC rose from a control level of 12.2 +/- 4.2 to 92.7 +/- 20.6 IC units (mmHg4.ml-1.min.kg body wt) in response to 1.25 micrograms.kg-1.min-1 norepinephrine intraportal; the postsinusoidal IC rose from 20.4 +/- 2.3 to 59.6 +/- 14.2 IC units. IC reflects resistance changes secondary to active contractile responses independent of the passive consequences of the distensible nature of the resistance sites. We suggest that these concepts can be applied to any vascular bed with distensible resistance vessels.

Animals↗

Quantitative integration of the cardiovascular system and synthesis of drug actions: another attempt.

This article describes the latest version of a computer program, first published in 1982, that attempts to integrate quantitatively the physiological and pharmacological knowledge of the cardiovascular system. This new version incorporates pressure-induced autoregulation of arterioles, distensibility of venous and pulmonary resistances, and some aspects of pericardial constraint on cardiac function. The program allows the researcher or student to explore the complex interactions resulting from changes in a wide variety of cardiovascular parameters and to synthesize the cardiovascular actions of drugs in the human, dog, or cat. The program can be run on an IBM-compatible computer with math coprocessor and with DOS as the operating system. The program can be modified by licensed users of QuickBasic. The program is available on diskette from the authors. This model represents our attempt to put together some of the complex interactions within the cardiovascular system. Every relationship, every initialized parameter, and every drug action can be questioned and alternatives can be proposed. However, the model allows these alternatives to be tested and their consequences to be predicted. We believe that the value of the model lies in the thought, discussion, and experiments that can be generated by this process.

Cardiovascular System↗

Acute and chronic ethanol on hepatic oxygen ethanol and lactate metabolism in cats.

The effects of increasing blood ethanol levels on hepatic hemodynamics and O2, ethanol, and lactate metabolism were studied in two groups of anesthetized cats: a control group and a group whose prior fluid intake contained 2, 4, then 8% ethanol for 24 days. Within each group, responses were compared in cats with acutely denervated and innervated livers. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to allow hemodynamic measurements and repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cats' blood volume. Vmax for ethanol was 105 +/- 9 and 91 +/- 6 mumol.min-1 g liver-1 and Km was 136 +/- 18 and 168 +/- 24 microM for control and chronic alcohol groups, respectively. There was no stimulation of ethanol metabolism after chronic administration. O2 uptake by the liver was not altered during acute ethanol administration in any group and base-line O2 uptakes before acute administration of ethanol were not different between normal and chronic ethanol groups. No evidence for a hypermetabolic state induced by chronic ethanol administration was seen in innervated or acutely denervated livers. Oxidation of ethanol required 40-45% of normal O2 uptake; thus other oxidative processes must have been suppressed during ethanol metabolism. Hepatic lactate uptake remained unaltered when ethanol metabolism was less than 0.5 Vmax, but was suppressed on an equimolar basis with ethanol metabolism when ethanol metabolism rose to greater than 0.5 Vmax. Thus lactate metabolism is one process that can be suppressed to allow ethanol metabolism without additional O2 uptake by the liver.

Alcohol Drinking↗

Effects of hepatic blood flow on hepatic ethanol kinetics measured in cats and predicted from the parallel tube model.

In cats anesthetized with pentobarbital, a long-circuit technique was used to measure hepatic blood flow while portal flow was varied from 0 to 300% of normal in random steps. Arterial, portal, and hepatic venous blood samples were analyzed for ethanol concentrations during continuous infusion of ethanol (20 mumol/(min.kg body weight) into the reservoir. Measured values for logarithmic mean sinusoidal ethanol concentration, hepatic venous ethanol concentration, hepatic ethanol uptake, and ethanol extraction were compared with the values predicted by the parallel tube model for hepatic uptake of substrates using Vmax and Km determined in each cat at the start of the experiment. Measured and predicted values were very similar at all blood flows above 65% control, but statistical regression analysis indicated a small but highly significant deviation of the measured values from the predicted values. At low flows, measured values of logarithmic mean sinusoidal and hepatic venous concentrations markedly exceeded the predicted values in most cats. The results indicate that the parallel tube model, which assumes all sinusoids are identical and equally perfused, provides a useful approximation for the effects of hepatic blood flow on hepatic ethanol kinetics except at low flows. However, there appears to be a significant degree of sinusoidal heterogeneity that results in a better fit to the distributed model. Our previously reported data for hepatic galactose uptake followed a similar pattern when reanalyzed in this more rigorous way.

Animals↗

Derecruitment in cat liver: extension of undistributed parallel tube model to effects of low hepatic blood flow on ethanol uptake.

Previous studies showed two deviations from the predictions of the undistributed parallel tube model for hepatic uptake of substrates: a small deviation at high flows and a large deviation at low flows. We have examined whether these deviations could be described by a single correction factor. In cats anesthetized with pentobarbital, a hepatic venous long-circuit technique with an extracorporeal reservoir was used to vary portal flow and hepatic venous pressure, and allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic uptake of ethanol was measured over a wide range of blood flows and when intrahepatic pressure was increased at low flows. This uptake could be described by the parallel tube model with a correction for hepatic blood flow: Uptake = Vmax max.(1 - e-kF).c/(Km + c). In 22 cats, Vmax max = 90 +/- 5 mumols/(min.100 g liver), k = 0.021 +/- 0.0015 when flow (F) was in millilitres per minute per 100 g liver, and Km = 150 +/- 20 microM when c is the log mean sinusoidal concentration. (1 - e-kF) represents the proportion of sinusoids perfused and metabolically active. A dynamic interpretation of this proportion is related to intermittency (derecruitment) of sinusoidal flow. Half the sinusoids were perfused at a flow of 33 mL/(min.100 g liver) and the liver was essentially completely perfused (greater than 95%) at the normal flow of 150 mL/(min.100 g liver). Derecruitment was not changed by raising hepatic venous pressure, and it was not related to hepatic venous resistance.

Anesthesia↗

Changes in hepatic blood volume on galactose and indocyanine green uptake by cat liver.

The liver has important functions as a blood volume reserve and in uptake and metabolism of many substrates. This study examines whether changes in hepatic blood volume modify the uptakes of model substrates galactose and indocyanine green (ICG) in cats anesthetized with pentobarbital sodium. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to control hepatic flow and venous pressure and to allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic blood volume was measured by plethysmography. Galactose and ICG were infused intravenously at constant rates for 200 min in each of three series of experiments. The first series were time controls. In the second series, hepatic blood volume was increased by raising hepatic venous pressure. In the third series hepatic blood volume was decreased by hepatic nerve stimulation and infusions of norepinephrine and angiotensin. Hepatic congestion resulted in small increases in blood galactose levels, suggesting mild impairment of hepatic galactose metabolism. Decreases in liver blood volume did not modify hepatic galactose metabolism. Increases in hepatic blood volume facilitated while decreases inhibited ICG uptake, but the effects were small. Sinusoidal velocity and transit time have minor effects on uptake even for protein-bound substrates. In summary, large changes in hepatic blood volume had minor effects on galactose and ICG blood concentrations, suggesting that the metabolic functions of the liver are essentially independent of the blood reservoir function.

Animals↗

Rapid measurement of blood ethanol concentrations using the alcohol oxidase membrane technique.

The alcohol oxidase membrane technique is available for measurement of ethanol in commercial fluids. In this paper we examined its usefulness for cat and human blood in comparison with gas-liquid chromatography (GLC). The membrane method proved to be simple, reproducible, accurate, and inexpensive. Analysis took 1-2 min per sample and required only 25 microL of whole blood for measurement of concentrations between 0.05 and 1.0 mM (0.25-5 mg/dL) and 10 microL of whole blood for measurement of concentrations between 1.0 and 40 mM (5-190 mg/dL). Background concentrations were undetectable in cats after extraneous sources of alcohols were removed. The alcohol oxidase membrane technique is less specific than GLC, but it may be useful when ethanol is administered after background samples have shown an absence of other nonspecific reactants. Its high sensitivity is useful for kinetic studies where blood ethanol concentrations are below or close to those required for maximal hepatic ethanol metabolism.

Alcohol Oxidoreductases↗

Hepatic blood flow: estimation from clearances of very low dose infusions of ethanol in cats.

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from systemic clearances of ethanol during very low dose (8 mumol.min-1.kg-1) infusions of ethanol in anesthetized cats. Systemic clearances were compared with directly measured hepatic blood flow using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial, portal, and hepatic venous blood samples without depletion of the animal's blood volume. In 18 cats, Vmax for ethanol was 93 +/- 7 mumol.min-1 per 100 g liver or 21 +/- 2 mumol.min-1.kg body weight-1 and Km was 144 +/- 19 microM in terms of logarithmic mean sinusoidal concentration. At the dose of 8 mumol.min-1.kg body weight-1 used for estimation of hepatic blood flow, extraction was 0.95 +/- 0.07 (mean +/- SD). Systemic clearance of ethanol overestimated directly measured hepatic blood flow by 15 +/- 16%. Hepatic blood flow changes expressed as percentages of the control level were accurately estimated from systemic ethanol clearance (100 +/- 10%). Since 73 +/- 12% of the infused ethanol was eliminated by the liver and 83 +/- 11% was eliminated by the splanchnic bed, an extrasplanchnic uptake of 17% accounted for the overestimation of hepatic blood flow. Estimation of hepatic blood flow from systemic clearances of ethanol during very low dose infusions may have advantages over other clearance methods. Its use in cats was illustrated in a separate series of experiments and it was shown that surgery significantly reduced hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Distensibility of hepatic venous resistance sites and consequences on portal pressure.

Hepatic venous resistance was measured in cats anesthetized with pentobarbital sodium during changes in hepatic blood flow and in inferior vena cava (IVC) pressure, in an attempt to explain the variable and partial transmission of pressure from IVC to portal vein. Problems with earlier explanations based on a "vascular waterfall" or a "Starling resistor" are discussed. Our data and previously published data can be explained by the hypothesis that hepatic venous resistance decreases as the resistance site is distended by the pressure within the resistance vessels. The product of resistance and distending pressure was a constant. This constant equals the resistance at unit-distending pressure, and it is an index of active contraction of the resistance sites in acute experiments. It is increased during infusions of norepinephrine, and it is higher in innervated than in denervated livers. A distensible hepatic venous resistance is a passive mechanism for partial autoregulation of portal pressure. It also serves as a mechanism for regulation of the splanchnic capacitance response to changes in IVC pressure.

Animals↗

Effect of hepatic nerves, norepinephrine, angiotensin, and elevated central venous pressure on postsinusoidal resistance sites and intrahepatic pressures in cats.

Portal venous pressure was controlled by resistance localized to specific sites in hepatic lobar veins in cats. All of the pressure drop from the portal vein to the vena cava occurred across postsinusoidal vessels; portal pressure, lobar venous pressure, and, therefore, sinusoidal pressure were not significantly different. Norepinephrine and angiotensin infusions (intraportal) caused elevation in portal pressure due to constriction of hepatic venous resistance sites as well as some constriction of presinusoidal (portal or sinusoidal) resistance sites. At low doses of norepinephrine presinusoidal constriction dominated whereas at higher doses the postsinusoidal constriction increased proportionately more. Hepatic nerve stimulation produced a similar response measured at an early time (1 min), but by 3 min the presinusoidal constriction showed complete escape so that elevated portal pressure was entirely due to hepatic venous constriction. The same site that provided basal vascular resistance also provided the increased hepatic venous resistance with nerve stimulation and infusion of angiotensin and norepinephrine. Rapid elevation of central venous pressure (CVP) caused elevated sinusoidal pressure. At high CVP (16 mm Hg), 75% of a rise in CVP was transmitted whereas at normal CVP (less than 4.5 mm Hg) less than 20% transmission occurred. The presence of a high resistance in the hepatic veins protected intrahepatic pressure from the effects of normal fluctuation of CVP.

Angiotensin II↗

Hepatic blood flow: accuracy of estimation from infusions of indocyanine green in anaesthetized cats.

Experiments were performed to determine the accuracy of the estimation of hepatic blood flow from infusions of indocyanine green (ICG) in anaesthetized cats. The estimated flows were compared to hepatic blood flows measured directly in a hepatic venous long-circuit preparation. This preparation allowed direct measurement and alteration of hepatic blood flows, and collection of arterial and mixed hepatic venous blood samples without depletion of blood volume in the animal. Mean hepatic plasma flows estimated during infusions of 3.22 and 6.44 nmol kg-1 min-1 were reliable indicators of true hepatic flow at three different flow levels, provided that a sufficiently long time (greater than 30 min) was allowed for distribution equilibrium and that data from several animals were pooled to reduce random variability. Variability arose through subtraction of plasma arterial and hepatic venous levels to obtain the arteriovenous difference. Estimations of hepatic plasma flow by intravenous infusions of ICG were more accurate and reliable than estimations from bolus injections of ICG, or intravenous infusions of galactose studied previously. The kinetics of hepatic uptake of ICG are complex. Extraction and clearance of ICG fell steadily with time during the infusions and constant plasma ICG levels were not attained during 150 min infusions. This is attributed to the effects of accumulation of ICG within the liver cells since hepatic uptake substantially exceeded biliary excretion rate. Total ICG concentrations in sinusoid and liver cells increased in parallel. The concentration in the liver cell was 88 (60-115) times the concentration in the sinusoid but we have no data on whether or not the free concentrations in plasma and cell were in equilibrium.

Anesthesia↗