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A T Blei

Publications and source records attributed to A T Blei.

88 records · Page 5Linked to original sources
PubMed1984

Portal-systemic shunting and the hemodynamic effects of nitroglycerin in the rat.

A hemodynamic response to oral nitroglycerin has been used recently to estimate the extent of portal systemic shunts in humans. We studied the hemodynamic effects of this drug in the rat with partial portal vein ligation, a model in which portal hypertension develops and the extent of portal-systemic collaterals can be measured. Two to ten days after the initial procedure, shunted and sham-operated controls received a continuous infusion of nitroglycerin into a jugular vein, the ileocolic vein, or intrajejunally. The response of systolic arterial pressure to intravenous nitroglycerin was similar in shunted and sham animals. The cumulative dose-response curve showed an earlier and more pronounced response in shunted rats receiving nitroglycerin intraportally, suggesting a marked increase in bioavailability. When the arterial response to nitroglycerin, infused intraportally at 1 microgram/kg X min, was compared to the extent of ileocolic shunting, measured with radioactive microspheres, a close correlation (r = 0.84) was seen; shunting values ranged from 0% (sham) to 97%. Additionally, in shunted rats a more pronounced response to intraportal, compared to intrajejunal, infusion suggested a contribution of the intestine to the first-pass elimination of the drug. The bioavailability of intraportal and intrajejunal nitroglycerin is influenced by the extent of portal systemic collaterals. A significant reduction in portal vein pressure in response to nitroglycerin seen in this animal model supports its testing as a therapeutic agent in portal hypertension.

Animals↗
PubMed1984

Distribution of portal blood flow in the liver of the rat: a microsphere study.

We sought to determine whether streamlining of portal venous blood occurs in normal anaesthetized rats under basal conditions and with variations in hepatic blood flow. We catheterized the ileocolic vein and injected 15 micron microspheres labeled with 85Sr and 141Ce into this vein and into the spleen, respectively. The hepatic lobar distribution of microspheres was studied in a group under basal conditions and after hepatic blood flow was increased (infusions of nitroglycerin or glucagon) or decreased (infusion of vasopressin or ligation of the superior mesenteric artery); this blood flow was measured with a constant infusion of indocyanine green. Measured results (expressed as proportion of total liver counts per minute) were compared with a reference group in which the portal vein of rats had been partially ligated 10 days prior to study and in which similarly injected microspheres that lodged in the liver were assumed to be completely mixed with portal blood. No differences were seen within groups and between the reference and experimental groups. We conclude that under these experimental conditions, portal venous blood flow appears to be distributed homogeneously between hepatic lobes.

Animals↗
PubMed1982

Insulin resistance and insulin receptors in hepatic cirrhosis.

To explore the influence of extrahepatic factors in the pathogenesis of insulin resistance in hepatic cirrhosis, we studied 125I-insulin binding to erythrocytes and monocytes of 14 clinically stable cirrhotic individuals and compared the results with a normal control group. All patients had fasting normoglycemia at the time of the study but abnormal glucose tolerance was detected in 7 of 9 cirrhotic patients after an oral glucose load. Seven patients (group N) had normal fasting serum insulin levels, and 7 patients (group H) manifested fasting hyperinsulinemia. However, all patients had elevated insulin levels after oral glucose. Insulin binding to erythrocytes was significantly decreased in both cirrhotic subgroups; monocyte studies in 5 hyperinsulinemic patients revealed a similar decrease in binding. Scatchard analysis in monocytes suggests that this decreased binding is secondary to a decrease in the receptor number per cell. No correlation between insulin binding and fasting plasma insulin, glucagon, or growth hormone levels was seen. Sera from 4 patients were examined for the presence of a non-specific inhibitor of insulin binding, but no evidence for such a factor was found. We conclude that the decrease in insulin binding is mediated in the monocyte by a reduction of receptor concentration; in the erythrocyte the mechanism for decreased binding could not be clearly delineated. The insulin resistance seen in cirrhosis may result in part from decreased binding of insulin to target tissues; an additional postreceptor defect cannot be excluded in hyperinsulinemic individuals.

Adult↗
PubMed1980

Comparison of vasopressin and triglycyl-lysine vasopressin on splanchnic and systemic hemodynamics in dogs.

Triglycyl-lysine vasopressin (tGLVPP) is activated in the circulation when the N-triglycyl residue of the molecule is cleaved by endothelial peptidases, releasing lysine vasopressin. We compared the effect of an intravenous bolus dose of tGLV (20 micrograms/kg) with a constant infusion (2.75 mU/kg/min) of arginine and lysine vasopressin (Pitressin) in normal mongrel dogs. Portal pressure was artifactually increased by a constricting flow probe. Baseline values were similar in both groups; at the time of near-maximal reduction in portal pressure, both drugs equally reduced portal venous pressure (38 +/- 4 vs 39 +/- 4%), superior mesenteric arterial blood flow (40 +/- 8 vs 39 +/- 9%), portal venous flow (35 +/- 4 vs 40 +/- 5%), and heart rate (9 +/- 2 vs 11 +/- 7%. Cardiac output obtained 10-30 min after tGLVP administration was similar that of VP, and each drug reduced cardiac output significantly when compared with its own baseline (18 +/- 4 vs 21 +/- 7%). Mean arterial pressure increased similarly with both drugs (11 +/- 3 vs 11 +/- 3%). The only difference observed was the hepatic arterial flow response. While tGLVP increased HAF 34 +/- 11%, the physiologic autoregulatory response to a decrease in portal venous flow and pressure; vasopressin was associated with no such compensatory response (1 +/- 6%). Whether this advantage of tGLVP and its more prolonged reduction of portal venous pressure (mean 103 min) are beneficial in the clinical setting requires additional studies.

Animals↗
PubMed1979

A controlled comparison of continuous intraarterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices.

Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.

Adult↗
PubMed1979

Wedged and free hepatic venous pressure measured with a balloon catheter.

The accuracy and reliability of a balloon catheter for measuring wedged hepatic venous pressure (WHVP) were evaluated in 82 simultaneous determinations using the balloon catheter technique and the direct measurement of portal venous pressure. These measurements showed a close positive correlation (r = 0.97) over a wide range of pressures in 12 normal and 4 cirrhotic dogs. Studies were then performed in 13 cirrhotic patients in whom the balloon catheter was introduced using the Seldinger technique. Free hepatic venous pressure (FHVP) was measured with the balloon undistended. By distending the balloon to occlude the hepatic vein, the WHVP was recorded. Comparison of FHVP and WHVP with the conventional and balloon techniques revealed a close positive correlation (r = 0.89 and 0.93, respectively). The correlation was virtually perfect for the hepatic venous pressure gradient (WHVP-FHVP, r = 0.98). The balloon technique offers many advantages over the conventional approach, including the ease of achieving and demonstrating the wedged position from the femoral approach, the ability to measure the free and wedged pressure repeatedly without manipulating the catheter, and the measurement of pressure in a larger, more representative segment of the liver.

Animals↗
PubMed1978

Portal pressure reduction induced by partial mechanical obstruction of the superior mesenteric artery in the anesthetized dog.

In an effort to avoid the potentially dangerous side effects of vasopressin infusions, we attempted to reproduce mechanically the splanchnic hemodynamic changes induced by vasopressin without its systemic effects. Superior mesenteric arterial pressure was reduced to 50 to 70 mm Hg for 30 to 60 min in 10 normal dogs by partial balloon obstruction of the superior mesenteric artery. Balloon inflation caused a decrease in portal venous pressure (5.6 +/- 0.6 versus 2.8 +/- 0.7 mm Hg), hepatic vein wedge pressure (4.8 +/- 0.4 versus 2.3 +/- 0.5 mm Hg), and portal vein flow 424 +/- 53 versus 275 +/- 52 ml per min), and an increase in hepatic arterial blood flow (172 +/- 19 versus 217 +/- 29 ml per min). Total hepatic blood flow and oxygen delivery to the liver were unchanged. Partial balloon obstruction caused an increase in cardiac output (1950 +/- 203 versus 2317 +/- 376 ml per min) and mean arterial pressure 138 +/- 6 versus 151 +/- 7 mm Hg), whereas heart rate did not change. Partial balloon obstruction of the superior mesenteric artery caused similar changes in splanchnic hemodynamics to those of vasopressin infusions into the superior mesenteric artery, but without the potential deleterious effects of vasopressin on systemic hemodynamics.

Animals↗
PubMed1978

Pharmacological vs. mechanical reduction in portal pressure: a comparative study.

Previous studies have shown that decreasing blood flow in the superior mesenteric artery (SMA) by the infusion of intra-arterial vasopressin into or partial mechanical obstruction of the SMA by a balloon catheter (partial balloon obstruction) causes similar alterations in splanchnic hemodynamics, but divergent changes in systemic hemodynamics. The effects of these two methods of reducing SMA blood flow were compared in each of six anesthetized normal dogs. Vasopressin and partial balloon obstruction induce similar reductions in portal pressure (-54 +/- 12% vs. -46 +/- 11%), wedge hepatic vein pressure (-54 +/- 13% vs. -53 +/- 18%), and portal venous flow (-34 +/- 7% vs. -37 +/- 7%). Significantly different effects between intra-arterial vasopressin and partial balloon obstruction were observed, however, in cardiac output (a decrease of -24 +/- 5% vs. an increase of +12 +/- 4%) (P less than 0.001), heart rate (-8 +/- 3% vs. 0) (P less than 0.05), and systemic vascular resistance (+36 +/- 8% vs. -2 +/- 2%) (P less than 0.005), respectively. These results indicate that the two procedures are equally effective in reducing portal venous pressure and blood flow. Partial balloon obstruction, however, does not induce the potentially deleterious systemic hemodynamic effects seen with vasopressin infusion. In fact, some of the changes observed with partial balloon obstruction, especially the increase in cardiac output, are considered to be beneficial. In an additional five dogs, partial balloon obstruction was maintained for 5 hours. Throughout, the reduction in portal venous pressure (hepatic venous wedge minus hepatic venous free pressure) was maintained at less than half of the baseline levels (4.75 +/- 0.43 vs. 2.25 +/- 0.32 mm Hg), and the mean arterial pressure at baseline values. All of the dogs survived and were well at 1 week after the prolonged partial obstruction. No abnormalities were observed in the anatomical or histological studies of the small intestine. This study suggests that partial balloon obstruction of the SMA has theoretical therapeutic advantages over intra-arterial vasopressin for reducing portal venous pressure.

Animals↗
PubMedDate not supplied

Pharmacokinetic-hemodynamic interactions between vasopressin and nitroglycerin: comparison between intravenous and cutaneous routes of nitrate delivery.

Addition of nitroglycerin (NTG) improves the hemodynamic response to vasopressin and may thus be useful in the treatment of gastrointestinal hemorrhage. We studied in the rat the influence of vasopressin on the disposition of a constant intravenous infusion of NTG and the cutaneous absorption of NTG ointment. The effect of NTG on the pharmacokinetics of vasopressin was also determined. Animals were divided into four groups: control, NTG, vasopressin and vasopressin + NTG. Infusions (or ointments) were maintained for 70 min; cardiac output and regional blood flows were determined with the microsphere technique. Both intravenous and cutaneous NTG resulted in similar hemodynamic responses. Vasopressin caused generalized vasoconstriction, while the addition of NTG reversed the deleterious systemic hemodynamic effects of vasopressin. Addition of vasopressin to NTG did not alter NTG systemic clearance nor did NTG affect vasopressin clearance. Of note, the systemic clearance of NTG was directly correlated with the cardiac output (r = 0.804), supporting a model of NTG distribution where blood vessels and/or extrahepatic tissues are the site of elimination of the drug. The marked reduction in skin blood flow by vasopressin did not decrease the steady-state plasma concentration of NTG nor the estimated cutaneous absorption rate of NTG ointment, indicating that cutaneous blood flow is not an important determinant in the absorption of NTG ointment. The skin is an appropriate route of delivery for NTG when combined with vasopressin.

Animals↗
PubMedDate not supplied

Isosorbide dinitrate in experimental portal hypertension: a study of factors that modulate the hemodynamic response.

Isosorbide dinitrate, a long-acting vasodilator, has been tested in human portal hypertension with conflicting results. In order to determine some of the factors that could affect the individual response to this drug, we infused isosorbide dinitrate at a low dose (10 to 25 micrograms per kg per min) and a high dose (100 micrograms per kg per min) to rats with portal vein stenosis. Under pentobarbital anesthesia, portal pressure was measured with an ileocolic vein catheter while cardiac output and regional blood flows were measured with the microsphere technique. At a dose that decreased arterial pressure by approximately 10%, cardiac output remained unchanged while portal vein inflow decreased significantly; portal pressure was not reduced (10.7 +/- 0.2 vs. 10.0 +/- 0.3 mm Hg), indicating a rise in portal vascular resistance. At a high dose of isosorbide dinitrate, arterial pressure and cardiac output fell markedly; portal pressure decreased only modestly (11.3 +/- 0.3 vs. 9.8 +/- 0.6 mm Hg, p less than 0.05), but portal flow was unchanged, indicating a reduction in portal vascular resistance. In addition, portal hypertensive rats received a constant i.v. infusion of N-acetyl-cysteine; the combination of the latter and isosorbide dinitrate markedly potentiated the effects on arterial pressure. Thus, the dose of the drug and the presence of cysteine-containing compounds appear to modulate the hemodynamic response to isosorbide dinitrate. Clinical testing with this drug should be undertaken with consideration of these factors.

Acetylcysteine↗
PubMedDate not supplied

Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: ultrastructure and integrity of the blood-brain barrier.

Brain edema is a major complication of fulminant hepatic failure and is responsible for death in a large percentage of patients. We previously demonstrated the progressive accumulation of water in grey matter areas of the brain in the rabbit with galactosamine-induced fulminant hepatic failure. We now report the electron microscopic morphology of the brain in the same model of acute hepatic failure following the intravenous injection of horseradish peroxidase, an intravascular tracer which forms an electron-dense reaction product. Rabbits with both mild and severe encephalopathy had normal blood pressures and blood gases at the time of study. Fixation of brain tissue was obtained by whole-body perfusion. Marked swelling of the cytoplasm, perineuronal and perivascular processes of astrocytes were noted in cortical gray, but not white, matter areas; the other cellular components of the brain had normal morphology. Capillary endothelial cells were normal, and there was no evidence of horseradish peroxidase in endothelial cell vesicles, basement membranes or the brain parenchyma, suggesting that the blood-brain barrier was impermeable to large molecules. Histologic evidence of brain edema is seen in this model, with swelling of astrocytes as the primary manifestation of the accumulation of water. Damage to astrocytes or inhibition of their function may contribute to the pathogenesis of hepatic encephalopathy in this model.

Animals↗