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Biomedical subjects

W W Lautt

Publications and source records attributed to W W Lautt.

At least 19 recordsLinked to original sources
PubMed1992

Arterial and venous plasma concentrations of adenosine during haemorrhage.

A haemorrhage model was used to impose severe metabolic stress in anaesthetized cats by removing blood (15.3 ml min-1) to attain an arterial pressure of ca. 50 mmHg for a 2 h period. Adenosine levels in central venous blood rose by 5 min, reached a peak of about 3.5 times control levels by 15 min and then returned to the basal level (1 microM) by 60 min. However, the adenosine concentration in arterial blood remained unchanged for the entire 2 h period of hypotension. These data demonstrate that haemorrhage results in rapid adenosine release, but the released adenosine is not able to serve a role as a systemic circulating vasodilator even in this severe model.

Adenosine↗
PubMed1992

Evaluation of hepatic venous resistance responses using index of contractility.

Hepatic vascular responses to 1.25 micrograms.kg-1.min-1 norepinephrine, infused into the hepatic artery, and 8-Hz nerve stimulation were monitored in anesthetized cats using a recently introduced index of contractility (IC). IC was validated in that it did not change passively in response to passive changes in portal flow or distending blood pressure, whereas the distensible venous resistance sites showed dramatic changes in resistance. Resistance is altered by both active contractile responses and passive distensibility; IC is not altered passively but is affected by changes in vascular tone. Resistance was a less sensitive index of vasoconstriction because, although the constriction increased resistance, the subsequent elevation in portal and intrahepatic pressure counteracted the constriction; the extent of active neurogenic response using resistance as the index was grossly underestimated due to venous distensibility. IC showed that pre- and postsinusoidal constriction occurred to both norepinephrine and nerves; extensive vascular escape from neurogenic constriction occurred for the portal vein so that by 5 min almost all the rise in portal pressure was due to hepatic venous constriction.

Animals↗
PubMed1992

Passive autoregulation of portal venous pressure: distensible hepatic resistance.

Hepatic resistance to portal blood flow is extremely low and both the pre- and postsinusoidal resistance sites are distensible. Both isolated in situ and in vivo vascular circuitry were used in cats to demonstrate the principle of distensible resistance as a mechanism for the observation that blood flow was able to be decreased from 50 to 20 ml.min-1 x kg-1 while intrahepatic pressure decreased by only 1.4 +/- 0.2 mmHg and portal pressure by 2.0 +/- 0.4 mmHg. Presinusoidal resistance increased by 226% and hepatic venous resistance by 57%, thus accounting for passive autoregulation of portal pressure. The relation between vascular resistance and the distending blood pressure that acts on the resistance is predictable from the relationship IC = R.Pd3, where IC is the index of contractility (does not change passively, but does change with active vascular tone changes), R is vascular resistance (changes actively and passively), and Pd is distending blood pressure (estimated as the average of pressure on either side of the resistance vessels). The relatively minor effect of portal flow on portal pressure is accounted for by a combination of factors including the low basal resistance, the distensible resistance, the hepatic arterial buffer response, and hepatic blood volume compliance. By calculation of IC, the venous distensibility can be quantified and the passive effect of flow changes on portal and intrahepatic pressure determined.

Animals↗
PubMed1992

Expression of vascular escape: conductance or resistance?

Vascular escape is that phenomenon whereby a tachyphylaxis occurs in the vasoconstriction of an arteriole to a constant sympathetic stimulation. Vascular escape, in vivo, is primarily a blood flow event. Calculated resistance, as an index of vascular tone, does not consistently describe the responses of the arterioles undergoing vascular escape. Conductance, which is the inverse of resistance, obviates several of the errors produced by the use of resistance. In this study, we illustrate this issue using hypothetical and experimental data. Escape responses were calculated in terms of resistance and conductance and plotted against blood flow escape responses. Resistance escape responses were nonlinearly related to blood flow escapes and overestimated vascular escape with both hypothetical and experimental data. Conductance escape responses were linearly related to flow escape responses and consistently described vascular escape. We therefore conclude that conductance is a better index of vascular tone to express vascular escape.

Animals↗
PubMed1991

Dilazep-induced vasodilation is mediated through adenosine receptors.

Administration of dilazep, an inhibitor of adenosine uptake, significantly reduced systemic arterial blood pressure and increased superior mesenteric arterial conductance without affecting the plasma adenosine levels of femoral arterial or portal venous blood. Administration of a bolus dose of 8-phenyltheophylline (8-PT), an antagonist of adenosine receptors, blocked adenosine-mediated autoregulation of the superior mesenteric artery. After the blockade of adenosine receptors by 8-PT, dilazep did not produce vasodilation. These data suggest that dilazep has a vasodilating effect in vivo that is mediated by adenosine.

Adenosine↗
PubMed1991

Effect of adenosine and glucagon on hepatic blood volume responses to sympathetic nerves.

Hepatic blood volume responses were studied in cats using in vivo plethysmography. The maximal response (Rmax) to sympathetic nerve stimulation and to infusions of norepinephrine into the hepatic artery or portal vein was similar (12-14 mL expelled per liver in 2.9-kg cats; average liver weight, 76.8 +/- 6.8 g). The ED50 for norepinephrine intraportal (0.44 +/- 0.13) and intrahepatic arterial infusions (0.33 +/- 0.08 micrograms.kg-1.min-1) were similar indicating equal access of both blood supplies to the capacitance vessels. Adenosine (2.0 mg.kg-1.min-1) did not cause significant volume changes but produced a mild (27%) suppression of Rmax due to nerve stimulation with no change in the frequency (3.4 Hz) needed to produce 50% of Rmax. Rmax tended (not statistically significant) to decrease during glucagon (1.0 micrograms.kg-1.min-1) infusion but the nerve frequency needed to produce 50% of Rmax rose to 5.6 Hz. Thus both adenosine and glucagon produced modulation of sympathetic nerve-induced capacitance responses without having significant effects on basal blood volume. Adenosine, by virtue of its marked effects on arterial resistance vessels (at substantially lower doses than those used here) and the relative lack of effect on venous capacitance vessels, may be useful for producing clinical afterload reduction without venous pooling.

Adenosine↗
PubMed1991

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↗
PubMed1991

Improved high-pressure liquid chromatographic-fluorometric assay for measurement of adenosine in plasma.

A high-pressure liquid chromatographic system using fluorescence detection was characterized for the determination of adenosine levels in plasma from anesthetized cat, rat, dog, mouse, rabbit, and guinea pig. The optimal concentration of chloroacetaldehyde necessary to convert physiological levels of adenosine to its fluorescent derivative 1,N6-ethenoadenosine (ethenoadenosine) was in excess of 220 mM. As little as 0.2 pmol of ethenoadenosine could be measured, and detection was linear up to 200 pmol. Derivatization of adenosine into ethenoadenosine was highly dependent on temperature and time. However, ethenoadenosine showed thermal instability in that levels dropped sharply after 30 min at 100 degrees C, 2 h at 80 degrees C, and 24 h at 55 degrees C. Adenosine nucleotides were extracted from plasma samples with an efficiency of greater than 91% to prevent adenosine formation from ATP and AMP that would have otherwise occurred during the derivatization procedure. Plasma levels (microM) of adenosine in venous blood were 0.31 in dog, 0.54 in cat, 0.71 in guinea pig, 1.03 in mouse, 1.04 in rat, and 1.68 in rabbit. Plasma levels of adenosine in arterial blood were not significantly different from levels in venous blood. This method can be used to measure even very low levels of adenosine without interference from nucleotide breakdown.

Adenosine↗
PubMed1991

Dilazep potentiation of adenosine-mediated superior mesenteric arterial vasodilation.

The present study investigated the effects of dilazep, an inhibitor of adenosine uptake, on adenosine-mediated vasodilation in vivo. Intravenous and intraportal venous infusions of exogenous adenosine (0.04-1.0 mg/kg/min) did not recirculate to cause increases in superior mesenteric arterial conductance (SMAC) or arterial plasma adenosine levels except at the higher doses tested (0.4-1.0 mg/kg/min). After administration of dilazep, however, even low doses (0.04-0.1 mg/kg/min) of exogenous adenosine significantly increased SMAC and elevated arterial plasma adenosine concentration. The increased adenosine levels were highly correlated with the increased percentage of change of SMAC and values for Rmax and EC50 were 193.4 +/- 27.3% change of SMAC and 2.8 +/- 1.3 microM, respectively. Administration of bolus doses of 8-phenyltheophylline abolished the ability of dilazep to potentiate vasodilation, but did not affect isoproterenol-induced relaxation. Together, these results suggest that potentiation of the vasodilating effect of exogenous adenosine by dilazep is mediated through inhibition of adenosine uptake in vivo which increases the availability of plasma adenosine to act on adenosine receptors.

Adenosine↗
PubMed1991

Glucagon pharmacodynamics and modulation of sympathetic nerve and norepinephrine-induced constrictor responses in the superior mesenteric artery of the cat.

The aim of this study was to assess whether the pancreatic peptide glucagon was capable of inhibiting nerve- and norepinephrine-induced vasoconstrictor responses in the superior mesenteric artery of the anesthetized cat. Intra-arterial dose-response curves for glucagon and norepinephrine were analyzed by nonlinear regression to estimate the maximal response (maximal dilation, 163%; maximal constriction, 110%) in terms of percent change in superior mesenteric artery conductance and dose of glucagon or norepinephrine required to produce 50% of the maximal response (0.98 and 0.38 micrograms/kg/min, respectively). Constrictor responses (3-min duration) were only weakly inhibited by glucagon. Peak constrictor responses induced by low-dose i.a. infusions of norepinephrine were significantly inhibited (39%) by the high dose of glucagon, whereas the high-dose norepinephrine peak constrictor responses were unaffected by any dose of glucagon. Intermediate and high doses of glucagon significantly inhibited the low-frequency (2 Hz) nerve-induced peak constrictions (19% and 34%, respectively). The higher frequency (6 Hz) nerve-induced peak constrictor responses were not significantly affected by glucagon. Vascular escape from nerve- and norepinephrine-induced peak constrictor responses was not related to the degree of initial constriction nor were they affected by glucagon. Glucagon levels produced by our i.a. infusions were estimated to be well outside the pathophysiological range. We conclude that glucagon is not an effective inhibitor of constrictor responses in the superior mesenteric artery and is unlikely to have such an effect at physiological levels.

Animals↗
PubMed1990

Quantitation of the hepatic arterial buffer response to graded changes in portal blood flow.

Hepatic arterial blood flow changes inversely in response to altered portal blood flow. The hepatic arterial capacity to buffer portal flow changes was studied over a wide range of portal flow with arterial pressure held steady (the active buffer response) or uncontrolled. The active component of the buffer response led to nearly full dilation of the hepatic artery at low portal flows as shown by inability to dilate further in response to adenosine infusion; at high portal flows the hepatic artery was nearly fully constricted as shown by lack of further constriction to norepinephrine. With pressure uncontrolled, active and passive effects combined to produce an increased compensation with similar efficiency (44% +/- 4%) over the full range of portal blood flows. Thus, although the active component of the hepatic arterial buffer response becomes less efficient at very high and low portal flows, the combination of active and passive effects leads to a larger buffer capacity which is equally efficient over a wide range of portal blood flow changes.

Adenosine↗
PubMed1990

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↗
PubMed1990

Hypoxia-induced vasodilation of the feline superior mesenteric artery is not adenosine mediated.

The role of adenosine in hypoxia-induced vasodilation was examined in the intestine of pentobarbital sodium-anesthetized cats. A hollow-fiber fetal oxygenator was used to selectively reduce the PO2 of the blood supplying the superior mesenteric artery, thereby inducing hypoxia in the intestines. Decreasing the PO2 from 109 to 38 Torr caused vascular resistance to decrease from 10.2 to 7.5 Torr.kg.min.ml-1, a decrease of 2.7 Torr.kg.min.ml-1 or 24%. During selective adenosine receptor blockade with 8-phenyltheophylline, the same decrease in PO2 (from 109 to 40 Torr) produced a similar decrease in resistance from 5.7 to 3.4 Torr.kg.min.ml-1 or a difference of 2.3 Torr.kg.min.ml-1 (-36%). Thus adenosine is not the mediator of hypoxia-induced vasodilation in the feline intestine because blockade of the vasodilating effects of exogenous and presumably endogenous adenosine did not affect the observed decrease in resistance.

Adenosine↗