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Biomedical subjects

D J Legare

Publications and source records attributed to D J Legare.

31 records · Page 2Linked to original sources
PubMed1990

Evaluation of hepatic venous balloon occluder to estimate portal pressure.

The hepatic venous balloon occluder method of estimating portal venous pressure (PVP) was evaluated in cats and dogs, during basal state and active vasoconstriction, and during passive presinusoidal resistance elevation in cats. In the dog, the balloon catheter measured a pressure not different from PVP when the balloon was inflated both in basal state and during active vasoconstriction induced by hepatic nerve stimulation, intraportal infusion of histamine or norepinephrine, regardless of whether the balloon was distal or proximal to hepatic venous sphincters. In the cat, the inflated balloon measures a pressure not different from PVP in basal state but slightly overestimated PVP during nerve stimulation or norepinephrine infusion in some protocols. Blood clots were injected intraportally in cats to produce a pure, passive presinusoidal resistance as shown by unchanged intrahepatic pressure but elevated PVP. The balloon method accurately measured PVP in this condition and clearly cannot differentiate pre- from postsinusoidal resistance sites in cats or dogs. The balloon method and the classical wedged pressure method will represent PVP when resistance is primarily postsinusoidal; they provide different measurements when resistance is presinusoidal, the wedged method representing intrahepatic pressure but the balloon method reflecting portal pressure. These differences require confirmation in human presinusoidal cirrhosis.

Animals↗
PubMed1988

Adenosine modulation of vasoconstrictor responses to stimulation of sympathetic nerves and norepinephrine infusion in the superior mesenteric artery of the cat.

Vasoconstriction induced by sympathetic nerve stimulation and by norepinephrine infusion in the superior mesenteric artery of cats anesthetized with pentobarbital was inhibited by adenosine infusions in a dose-related way. The responses to nerve stimulation were not inhibited to a greater extent than the responses to norepinephrine, thus suggesting no presynaptic modulation of sympathetic nerves supplying the resistance vessels of the feline intestinal vascular bed. Blockade of adenosine receptors using 8-phenyltheophylline did not alter the degree of constriction induced by nerve stimulation or norepinephrine infusion, indicating that in the fasted cat, endogenous adenosine co-released or released subsequent to constriction does not affect the peak vasoconstriction reached. Isoproterenol caused similar degrees of vasodilation as adenosine but did not show significant antagonism of the pooled responses to nerve stimulation or norepinephrine infusion; there was no tendency for the degree of dilation induced by isoproterenol to correlate with the inhibition of constrictor responses. Thus, the effect of adenosine on nerve- and norepinephrine-induced constriction is not secondary to nonspecific vasodilation.

Adenosine↗
PubMed1988

Vascular escape from vasoconstriction and post-stimulatory hyperemia in the superior mesenteric artery of the cat.

Vascular escape is seen as a partial recovery from initial vasoconstriction despite continued constrictor stimuli. Escape in the feline intestine (superior mesenteric artery) occurred for i.a. norepinephrine (NE) infusions (56% escape for low dose, 40% for high dose NE) and for sympathetic nerve stimulation (SNS) (65% for 1 Hz, 49% for 3 Hz, 44% for 9 Hz). Adenosine infusion or blockade of adenosine receptors (8-phenyltheophylline) did not alter the escape, showing that endogenous adenosine levels are unlikely to play any role in the mechanism of escape. Other aspects of escape were studied: equiconstrictor doses of NE given i.a. or i.v. lead to similar degrees of escape; propranolol and ouabain did not alter escape; the degree of escape was significantly greater for the low dose NE and the 1-Hz SNS than for higher intensities of stimulation, however, escape did not inversely correlate significantly with the initial degree of vasoconstriction when all data were pooled. Post-stimulatory hyperemia occurs upon cessation of vasoconstrictor stimuli, reaches a peak conductance within 1 min, and returns to baseline within about 3 min. Hyperemia was quantitated from the peak vasodilation and from the area under the flow-hyperemia curve. The hyperemias were not related to NE dose or SNS frequency nor did they correlate with initial vasoconstriction or extent of vascular escape. Contrary to the hypothesis that adenosine may mediate hyperemia, adenosine infusions reduced the response and adenosine receptor antagonism tended to elevate the response. Propranolol and ouabain did not produce significant effects on post-stimulatory hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1987

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↗
PubMed1987

Hepatic venous resistance site in the dog: localization and validation of intrahepatic pressure measurements.

Intrahepatic pressure (9.4 +/- 0.3 mmHg; 1 mmHg = 133.32 Pa), measured proximal to a hepatic venous resistance site, was insignificantly different from portal venous pressure (9.6 +/- 0.4 mmHg). This lobar venous pressure is not wedged hepatic venous pressure as it is measured from side holes in a catheter with a sealed tip. Validation of the lobar venous pressure measurement was done in a variety of ways and using different sizes and configurations of catheters. The site of hepatic venous resistance in the dog is localized to a narrow sphincterlike region about 0.5 cm in length and within 1-2 cm (usually within 1 cm) of the junction of the vena cava and hepatic veins. Sinusoidal and portal venous resistance appears insignificant in the basal state and large increases in liver blood volume (histamine infusion or passive vena caval occlusion) or large decreases in liver blood volume (passive vascular occlusion) do not alter the insignificant pressure gradient between portal and lobar venous pressures. Norepinephrine infusion (1.25 microgram X kg-1 X min-1 intraportal) and hepatic sympathetic nerve stimulation (10 Hz) led to a significantly greater rise in portal venous pressure than in lobar venous pressure, indicating some presinusoidal (and (or) sinusoidal) constriction and this indicates that lobar venous pressure cannot be assumed under all conditions to accurately reflect portal pressure. However, most of the rise in portal venous pressure induced by intraportal infusion of norepinephrine or nerve stimulation and virtually all of the pressure rise induced by histamine could be attributed to the postsinusoidal resistance site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of hepatic venous sphincter contraction on transmission of central venous pressure to lobar and portal pressure.

In dogs anesthetized with pentobarbital, central vena caval pressure (CVP), portal venous pressure (PVP), and intrahepatic lobar venous pressure (proximal to the hepatic venous sphincters) were measured. The objective was to determine some characteristics of the intrahepatic vascular resistance sites (proximal and distal to the hepatic venous sphincters) including testing predictions made using a recent mathematical model of distensible hepatic venous resistance. The stimulus used was a brief rise in CVP produced by transient occlusion of the thoracic vena cava in control state and when vascular resistance was elevated by infusions of norepinephrine or histamine, or by nerve stimulation. The percent transmission of the downstream pressure rise to upstream sites past areas of vascular resistance was elevated. Even small increments in CVP are partially transmitted upstream. The data are incompatible with the vascular waterfall phenomenon which predicts that venous pressure increments are not transmitted upstream until a critical pressure is overcome and then further increments would be 100% transmitted. The hepatic sphincters show the following characteristics. First, small rises in CVP are transmitted less than large elevations; as the CVP rises, the sphincters passively distend and allow a greater percent transmission upstream, thus a large rise in CVP is more fully transmitted than a small rise in CVP. Second, the amount of pressure transmission upstream is determined by the vascular resistance across which the pressure is transmitted. As nerves, norepinephrine, or histamine cause the hepatic sphincters to contract, the percent transmission becomes less and the distensibility of the sphincters is reduced. Similar characteristics are shown for the "presinusoidal" vascular resistance and the hepatic venous sphincter resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of histamine, norepinephrine, and nerves on vascular pressures in dog liver.

In the control state, lobar venous pressure (LVP) measured proximal to a hepatic venous sphincter in dog liver (9.9 +/- 0.3 mmHg) is insignificantly different from portal venous pressure (PVP = 9.9 +/- 0.3 mmHg). Essentially all of the pressure drop occurs across the hepatic veins. Intraportal infusion of histamine constricts the hepatic venous sphincter and leads to similar elevations of LVP and PVP, indicating that all of the rise in PVP (except at small doses = 1 microgram X kg-1. min-1) can be accounted for by hepatic venous sphincter constriction. Norepinephrine at doses from 0.25 to 1.25 micrograms X kg-1. min-1 (intraportal) caused both hepatic venous sphincter constriction and constriction proximal to hepatic venous sphincters to roughly equal proportions, with approximately 44% of the rise in PVP due to hepatic sphincter constriction. Hepatic nerves activated both resistance sites, with 90% of the rise in PVP due to hepatic venous constriction at 2 Hz stimulation. By 4 Hz stimulation, the postsinusoidal sphincters were nearly maximally activated, but the "presinusoidal" resistance continued to increase until, at 10 Hz, the hepatic venous sphincter component accounted for only 59% of the rise in PVP. The proportion of PVP rise accounted for by hepatic venous sphincter resistance was not significantly altered by prior occlusion of the hepatic artery.

Animals↗
PubMed1986

Adenosine modulation of hepatic arterial but not portal venous constriction induced by sympathetic nerves, norepinephrine, angiotensin, and vasopressin in the cat.

Intrinsic regulation of hepatic arterial blood flow depends upon local concentrations of adenosine. The present data show that i.a. infusions of adenosine cause dilation of the hepatic artery and inhibition of arterial vasoconstriction induced by norepinephrine, vasopressin, angiotensin, and hepatic nerve stimulation. Vasoconstriction induced by submaximal nerve stimulation (2 Hz) and norepinephrine infusions (0.25 and 0.5 micrograms X kg-1 X min-1, i.p.v.) were equally inhibited by adenosine. Supramaximal nerve stimulation (8 Hz) was inhibited to a lesser extent. The data are consistent with the hypotheses that (a) adenosine causes nonselective inhibition of vasoconstrictor influences on the hepatic artery; and (b) adenosine antagonizes neurally induced vasoconstriction by a purely postsynaptic effect and does not decrease norepinephrine release. In contrast with the hepatic artery, the intrahepatic portal resistance vessels are not affected by even large doses of adenosine; neither responses in basal tone nor antagonism of vasoconstrictor effects of nerve stimulation, norepinephrine, or angiotensin could be demonstrated. The data are consistent with the hypothesis that the smooth muscle of the portal resistance vessels does not contain adenosine receptors, whereas adenosine receptors on the smooth muscle of the hepatic arterial resistance vessels are of major regulatory importance. Whether endogenous levels of adenosine can reach sufficient concentration to modulate endogenous constrictors remains to be determined.

Adenosine↗
PubMed1986

Localization of intrahepatic portal vascular resistance.

The pressure drop from the portal vein to the vena cava occurs primarily across a postsinusoidal site localized to a narrow segment (less than 0.5 cm) of hepatic veins (roughly 1.5 mm diam) in the anesthetized cat. Portal venous pressure (PVP = 8.9 +/- 0.3 mmHg) and lobar hepatic venous pressure (LVP = 8.7 +/- 0.4 mmHg) are insignificantly different, and pressure changes imposed from the presinusoidal or postsinusoidal side are equally transmitted to both pressure sites. Several types of experiments were done to validate the LVP measurement. The portal vein, hepatic sinusoids, and hepatic veins proximal to the resistance site are all under a similar pressure. Previously reported calculations of hepatic vascular resistance are in error because of incorrect assumptions of sinusoidal pressure and localization of the portal resistance site as presinusoidal. Stimulation of hepatic sympathetic nerves for 3 min caused LVP and PVP to increase equally, showing that the increased "portal" resistance is postsinusoidal across the same region of the hepatic veins that was previously localized as the site of resistance in the basal state.

Animals↗
PubMed1985

The use of 8-phenyltheophylline as a competitive antagonist of adenosine and an inhibitor of the intrinsic regulatory mechanism of the hepatic artery.

Reduction of portal blood flow results in compensatory vasodilation of the hepatic artery, the hepatic arterial buffer response. The hypothesis tested is that the regulation of the buffer response is mediated by adenosine, where the local concentration of adenosine in the region of the hepatic arterial resistance vessels is regulated by washout of adenosine into portal venules that are in intimate contact with hepatic arterioles. In anesthetized cats, portal flow was reduced to zero by complete occlusion of all arterial supply to the guts. The resultant dilation of the hepatic artery compensated for 23.9 +/- 4.9% of the decrease in portal flow. Dose-response curves were obtained for the effect of intraportal adenosine infusion on hepatic arterial conductance in doses that did not lead to recirculation and secondary effects on the hepatic artery via altered portal blood flow. The dose to produce one-half maximal response for adenosine is 0.19 mg X kg-1 X min-1 (intraportal) and the estimated maximal dilation is equivalent to an increase in hepatic arterial conductance to 245% of the basal (100%) level. The adenosine antagonist, 8-phenyltheophylline, produced dose-related competitive antagonism of the dilator response to infused adenosine (but not to isoproterenol) and a similar, parallel antagonism of the hepatic arterial buffer response. If supramaximal blocking doses were used, the hepatic artery showed massive and prolonged constriction with blood flow decreasing to zero. The data strongly support the hypothesis that intrinsic hepatic arterial buffer response is mediated entirely by local adenosine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1985

Adenosine as putative regulator of hepatic arterial flow (the buffer response).

In anesthetized cats, reduction of portal flow by occlusion of the superior mesenteric artery results in rapid increase in hepatic arterial (HA) flow that compensates for (buffers) 25.5 +/- 2.7% of the decreased portal flow. The hypothesis tested is that adenosine concentration produced near the HA resistance vessels is regulated by washout into portal vessels in intimate contact with the HA. Reduced portal flow leads to accumulation of adenosine and HA dilation. Several criteria for this hypothesis are met. First, adenosine is a potent dilator of the HA. Second, portal blood has access to HA resistance vessels as shown by a marked dilator effect of adenosine infused into the portal vein; it is therefore possible for adenosine produced locally to diffuse into portal blood. Third, dipyridamole potentiated the dilator response to adenosine as well as potentiating the buffer response from a 23% compensation for reduced portal flow to 34%. Fourth, 1-methyl-3-isobutylxanthine (MIX) antagonized exogenous adenosine and reduced the buffer response from 19% down to 5%. These data strongly support the hypothesis that the hepatic arterial buffer response is mediated by local concentrations of adenosine that are controlled by the rate of washout into portal blood.

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

The comparative effect of administration of substances via the hepatic artery or portal vein on hepatic arterial resistance, liver blood volume and hepatic extraction in cats.

Compounds reaching the liver do so via either the hepatic artery or the portal vein. This paper reports on the effectiveness of administration of compounds into these alternate routes for their effects on the hepatic parenchymal cells, the hepatic arterial resistance vessels (blood flow) and hepatic capacitance (blood volume responses). All tests were done on cats under pentobarbital anesthesia. Perfusion of the parenchymal cell mass was assessed by comparing the hepatic elimination of indocyanine green (ICG) administered via the two vascular routes. The ICG uptake was assessed by measuring relative areas under the hepatic venous outflow curve obtained following bolus injections of ICG into the artery and portal vein. In a separate series, using different methods, the hepatic venous levels reached early (2 min) and later (5 min) during a constant infusion were compared during administration via the two routes and found to be equal. Parenchymal cell functions (ICG extraction, bile salt stimulation of bile flow) indicate that blood from the artery and portal vein supplies the hepatic parenchymal cells equally well. This suggests a well-mixed blood supply prior to exposure of either blood stream to parenchymal cells. Substances being processed by the liver are thus equally well handled if reaching the liver via either the arterial or portal blood stream. This has significance in validating the use of some isolated liver perfusion methods that perfuse only via the portal vein. Access of vasoactive compounds in the two blood streams to hepatic arterial resistance vessels was assessed using electromagnetic flow probes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗