Doppler sonographic assessment of functional response of the right and left portal venous branches to a meal

PURPOSE: The aim of our study was to quantitate by Doppler sonography the blood flow in the right and left portal vein branches before and after a standard meal. We also assessed the functional response of the right and left lobes of the liver. METHODS: Portal blood flow was measured by Doppler sonography in the left and right portal vein branches and main portal trunk in 20 healthy volunteers in both fasting and postprandial states. The ratio between portal blood flow and liver volume (determined by MRI) was the portal flow index (PFI). RESULTS: Before the meal, a statistically significant difference in portal blood flow volume was observed between the right and left portal branches (p < 0.01). The right PFI (0.83 ml/minute/cm3) and left PFI (1.1 ml/minute/cm3) were also significantly different (p < 0.01). The increase in portal venous blood flow after a meal was found to be greater in the left portal branch (128%) than in the right portal branch (78%). The postprandial PFI also differed significantly (right, 1.54 ml/minute/cm3; left, 2.5 ml/minute/cm3). CONCLUSIONS: These findings suggest that the left lobe of the liver has a better postprandial compliance than the right lobe has.     

The temporary alar suspension stitch: a refinement in forehead flap reconstruction of nasal defects

Experimental and clinical studies have led to the hypothesis that the phosphodiester signal obtained by 31P magnetic resonance (MR) spectroscopy may be a specific marker for the hepatic induction of oxidative metabolism (P450 induction) by phenobarbitone or ethanol. Systematic studies in humans are lacking. Therefore, we studied 10 volunteers who received rifampin (600 mg/d) for 6 days, resulting in a documented induction of oxidative metabolism as measured by an increase in urinary 6-beta-hydroxycortisol output in all volunteers (P = .0004). 31P-MR spectroscopy and 1H-MR relaxometry were performed before and after hepatic P450 induction. As shown by 31P-MR spectroscopy, the median phosphomonoester concentration (PME) relative to nucleoside triphosphate (NTP) increased by 21% from 0.63 (range, 0.40-0.89) before induction to 0.76 (0.49-1.67) after induction (P = .0451). The median level of phosphodiesters (PDE) relative to NTP increased by 28% from 4.82 (3.41-6.67) before induction to 6.18 (4.63-11.63) after induction (P = .0091). An increase in the level of inorganic phosphates (Pi) relative to NTP was observed, but changes were not significant. As shown by 1H-MR relaxometry, a nonsignificant trend of the liver parenchyma to shorter relaxation times was observed after P-450 induction. In conclusion, both PME/NTP and PDE/NTP ratios (measured by in vivo 31P-MR spectroscopy) increased significantly after hepatic induction with rifampin. Further clinical studies with 31P-MR spectroscopy must take into account the potential effects of P450-inducing agents.     

Responses of older men with and without chronic obstructive pulmonary disease to prolonged ozone exposure

Measurement of cardiac output by Doppler echocardiography were compared to simultaneous measurements by thermodilution in 9 conscious horses. In the Doppler technique, mean blood flow velocities for estimation of cardiac output were recorded from the aorta and pulmonary artery. The flow area of each vessel was calculated from the vessel diameter, measured from a 2-dimensional ultrasound image. Differences in the site and method of measuring the vessel diameter altered the estimation of cardiac output by the Doppler method. Cardiac output was modified by the i.v. infusion of 4 micrograms/kg bwt/min dopamine and 4 micrograms/kg bwt/min dobutamine and by the i.v. administration of 10 micrograms/kg bwt detomidine and 20 micrograms/kg bwt butorphanol. Doppler measurements of cardiac output correlated closely with measurement by thermodilution. Measurements from the aortic outflow correlated more closely with thermodilution, than those from the pulmonary artery (r = 0.89 and r = 0.77, respectively). Doppler measurements when the mean flow velocity was recorded from the aorta and the flow area was measured from the ascending aorta using the leading edge method. There was no significant bias between the 2 techniques when Doppler flow velocities were recorded by this method and the limits of agreement were narrow (+/- 12.26 l/min). The differences between the 2 methods increased with increasing cardiac output. Doppler echocardiography is a safe noninvasive method of measuring cardiac output in horses. The agreement between Doppler echocardiography and thermodilution in this study is similar to that reported in man and is similar to that reported between thermodilution and other techniques in man.     

Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats

The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 micrograms/kg twice daily, subcutaneously). Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and fibronectin mRNA contents, and serum hyaluronate. Systemic and splanchnic hemodynamic changes were also evaluated, including the splenorenal shunt blood flow by the transit-time ultrasound (TTU) technique. In both models, splenorenal shunt blood flow was significantly lower in the octreotide groups than in the placebo group (P <.05), while portal pressure was not significantly decreased. There was a significant decrease in fibrosis by octreotide in the CCl4 model only: area of fibrosis: 13.9% +/- 3.7% vs. 9.8% +/- 2.5% (P <.01), hydroxyproline: 1.8 +/- 0.6 vs. 1.3 +/- 0.4 mg/g wet liver (P <.05), respectively, placebo vs. octreotide 10 micrograms/kg. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r =.87 in the biliary model and r =.91 in the CCl4 model; P <.0001). The early and chronic administration of octreotide prevents the development of portocollateral blood flow without reducing portal pressure in two models of liver fibrosis and the development of liver fibrosis in the CCl4 model.     

Study of FHIT transcripts in normal and malignant breast tissue

The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.     

Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis

BACKGROUND/AIMS: Cirrhosis with portal hypertension is associated with changes in the splanchnic and systemic haemodynamics, and subsequent complications, such as bleeding from oesophageal varices, have led to the introduction of long-acting somatostatin analogues in the treatment of portal hypertension. However, reports on the splanchnic and systemic effects of octreotide are contradictory and therefore the aim of the present study was to assess the effects of continuous infusion of octreotide on central and systemic haemodynamics, portal pressures, and hepatic blood flow. METHODS: Thirteen patients with cirrhosis underwent liver vein catheterisation. Portal and arterial blood pressures were determined at baseline and 10, 30, and 50 min after a bolus injection of octreotide 100 micrograms, followed by continuous infusion of octreotide 100 micrograms/ h for 1 h. Hepatic blood flow, cardiac output, central and arterial blood volume, and central circulation time were determined at baseline and 50 min after the start of the octreotide infusion. RESULTS: The mean arterial blood pressure increased during the first 10 min (p < 0.0005), but returned to baseline after 50 min. The central and arterial blood volume (-16%, p < 0.005) and the central circulation time (-8%, p < 0.05) were significantly decreased after 50 min, whereas the cardiac output did not change significantly. The hepatic venous pressure gradient and the hepatic blood flow did not change significantly at any time after infusion of octreotide. CONCLUSIONS: Octreotide does not affect the portal pressure or hepatic blood flow, whereas it may further contract the central blood volume and thereby exert a potentially harmful effect on central hypovolaemia in patients with cirrhosis. However, these early effects do not exclude the possibility that administration of longacting somatostatin analogues over a longer period may have a beneficial effect.     

Portal hemodynamics after large-volume paracentesis in patients with liver cirrhosis and tense ascites

Large-volume paracentesis with a plasma expander has been extensively evaluated and shown to be an effective and safe therapy. While hepatic and systemic hemodynamics have been studied extensively, there is little information on portal hemodynamics by duplex Doppler. Portal vein diameter, portal flow velocity, and portal blood flow were measured with duplex Doppler in 11 cirrhotic patients before and 24 hr after large volume paracentesis. There were no significant changes in the portal vein diameter (9.88+/-2.62 mm vs 10.09+/-2.73 mm), portal flow velocity (10.65+/-2.60 vs 10.01+/-2.58 cm/sec), and portal blood flow (488+/-288.9 vs 502+/-73.38 ml/min), before and 24 hr after large-volume paracentesis. Thus, significant changes in portal hemodynamics do not occur after large-volume paracentesis.     

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.     

One-stage reconstruction of post-electrical burn forearm and hand defects using microsurgical transfer of an ulnar neuromyotendinocutaneous unit

Epirubicin is known to be metabolized in the liver. Therefore, drugs such as cimetidine, which inhibit the cytochrome P-450 enzyme system or reduce liver blood flow, may reduce the plasma clearance of epirubicin. In a small study, epirubicin 100 mg/m2 every 3 weeks was administered intravenously to eight patients, who also received oral cimetidine (400 mg b.d. for 7 days starting 5 days before chemotherapy) with either the first or second cycles. Epirubicin pharmacokinetics and liver blood flow (idocyanine green clearance) were assessed at each course. The areas under the plasma concentration time curves (AUCs) were used to compare the systemic exposure to epirubicin and its metabolites with each course. The estimated median percentage increase (95% confidence interval CI) in the AUC with cimetidine were: epirubicin 50% (95% CI -18 to 193, epirubicinol 41% (95% CI 1 to 92). Despite the small numbers studied, the increase in the active metabolite epirubicinol was significant (P < 0.05). These changes in exposure were not explained by reduced cytochrome P-450 activity as the 7-deoxy-doxorubicinol aglycone AUC was not reduced (357% increase: 95% CI 17 to 719) or by a decrease in liver blood flow (17% increase: 95% CI -39 to 104). Cimetidine is likely to be coprescribed or self-administered with epirubicin and therefore clinicians should be aware of this potential interaction.     

Modulation of cytochrome P-450-dependent monooxygenases, glutathione and glutathione S-transferase in rat liver by geniposide from Gardenia jasminoides

Geniposide is an iridoid glycoside extracted from the fruits of Gardenia jasminoides, which are used as a food colorant and as a traditional Chinese medicine for treatment of hepatic and inflammatory diseases. The effects of geniposide and G. jasminoides fruit crude extract on liver cytochrome P-450 (P-450)-dependent monooxygenases, glutathione and glutathione S-transferase were investigated using rats treated orally with the iridoid glycoside (0.1 g/kg body weight/day) or the fruit crude extract (2 g/kg/day) for 4 days. The treatments decreased serum urea nitrogen level but increased liver to body weight ratio, total hepatic glutathione content and hepatic cytosolic glutathione S-transferase activity. Treatments with geniposide and G. jasminoides decreased P-450 content, benzo[a]pyrene hydroxylation, 7-ethoxycoumarin O-deethylation, and erythromycin N-demethylation activities in liver microsomes without affecting aniline hydroxylation activity. The natural products had no effect on glutathione content and monooxygenase activities in kidney microsomes. Immunoblotting analyses of liver microsomal proteins using mouse monoclonal antibody 2-13-1 to rat P4503A1/2 revealed that geniposide and G. jasminoides crude extract decreased the intensity of a P4503A-immunorelated protein. Protein blots probed with mouse monoclonal antibody 1-12-3 to rat P4501A1 and rabbit polyclonal antibody against human P4502E1 showed that both treatments had little or no effect on P4501A and 2E proteins. The present findings demonstrate that geniposide from G. jasminoides has the ability to inhibit a P4503A monooxygenase and increase glutathione content in rat liver.     

Anti-GBM glomerulonephritis in mice lacking nitric oxide synthase type 2

To determine the relationship between quantitative Doppler parameters of portal, hepatic, and splanchnic circulation and hepatic venous pressure gradient (HVPG), variceal size, and Child-Pugh class in patients with alcoholic cirrhosis, we studied forty patients with proved alcoholic cirrhosis who underwent Doppler ultrasonography, hepatic vein catheterization, and esophagoscopy. The following Doppler parameters were recorded: time-averaged mean blood velocity, volume flow of the main portal vein flow, and resistance index (RI) of the hepatic and of the superior mesenteric artery. Doppler findings were compared with HVPG, presence and size of esophageal varices, and Child-Pugh class. There was a significant inverse correlation between portal velocity and HVPG (r = -.69), as well as between portal vein flow and HVPG (r = -.58). No correlation was found between RI in the hepatic artery or superior mesenteric artery and HVPG. No correlation was found between portal vein measurements and presence and size of varices. Severe liver failure was associated with lower portal velocity and flow. In patients with alcoholic cirrhosis, only portal vein blood velocity and flow, but neither hepatic nor mesenteric artery RI, are correlated to the severity of portal hypertension and to the severity of liver failure.     

Usefulness of Doppler ultrasound in predicting the effect of gonadotropin-releasing hormone agonist (GnRHa) on myoma uteri

This paper shows the value of Doppler ultrasound of the uterine blood flow in predicting the effect of GnRHa on myoma uteri. Thirty-eight patients with myoma uteri were divided into two groups by Doppler ultrasound before treatment: a group with positive arterial blood flow in or around the myoma nodule, and another group with negative arterial blood flow. Histological examinations which were performed in thirty patients demonstrated that the myoma in the negative blood flow group showed higher hyalinization with poor vascularization. In fifteen patients treated with GnRHa (Buserelin 900 micrograms/day), a significant increase (p < 0.01) in the resistance index of the uterine arteries was induced and suppressed the serum estradiol concentration in all cases during GnRHa therapy. The size of the myoma nodules also decreased in all 6 patients in the positive blood flow group, but in only 3 of the 9 patients in the negative blood flow group during GnRHa therapy. These results indicated that Doppler assessments of the arterial blood flow in myoma would be useful in predicting the effect of GnRHa on myoma uteri.     

Accuracy of portal and forearm blood flow measurements in the assessment of the portal pressure response to propranolol

BACKGROUND/AIMS: The portal pressure response to propranolol varies significantly in individual patients with cirrhosis. At present, propranolol responders can be identified only by measuring the hepatic venous pressure gradient. The aims of this study were: 1) to investigate whether the noninvasive monitoring of portal blood flow by pulsed Doppler ultrasound and forearm blood flow by strain-gauge plethysmography can predict the hepatic venous pressure gradient response to propranolol in patients with cirrhosis, and 2) to analyze the factors that may influence this response. METHODS: Hemodynamic measurements were undertaken in 80 patients with cirrhosis before and after receiving propranolol (0.15 mg/kg i.v., n = 60) or placebo (n = 20). RESULTS: No changes were observed in the placebo group. Propranolol lowered (p < 0.01) hepatic venous pressure gradient from 17.6 +/- 3.8 to 14.7 +/- 3.8 mmHg, portal blood flow from 1122 +/- 363 to 897 +/- 332 ml/min and forearm blood flow from 7.52 +/- 3.1 to 6.12 +/- 2.3 ml/min%. Changes in hepatic venous pressure gradient were correlated (p < 0.01) with those of portal blood flow (r = 0.82) and forearm blood flow (r = 0.54). The reduction in hepatic venous pressure gradient was > 20% in 23 patients ("responders"). The accuracy of portal Doppler flowmetry in identifying responders was higher than that of forearm plethysmography (88.3 vs. 68.3%, p < 0.05). Multivariate analysis proved that previous variceal bleeding was the only factor independently associated with a lack of response to propranolol (relative risk 3.42, 95% CI 1.5-7.4, p < 0.01). Hepatic venous pressure gradient reduction by propranolol was higher in non-bleeders than in bleeders (-19.9 +/- 9.4 vs. -11.3 +/- 8.6%, p < 0.01). CONCLUSIONS: Portal Doppler ultrasound can be used as a reliable surrogate indicator of the hepatic venous pressure gradient response to acute propranolol administration. In addition, our study indicates that this response is mainly influenced by previous variceal hemorrhage.     

Effect of a new rifamycin derivative, rifalazil, on liver microsomal enzyme induction in rat and dog

1. The effect of a new rifamycin derivative, rifalazil (KRM-1648), on liver microsomal enzyme induction was studied in rat and dog with repeated oral administration of the compound. Relative liver weight, cytochrome b5 and P450 contents, enzyme activities of NADPH-cytochrome c reductase, aniline hydroxylase, p-nitroanisole O-demethylase, aminopyrine N-demethylase, and erythromycin N-demethylase were measured. 2. In rat, rifalazil treatment at 300 mg/kg/day for 10 days increased cytochrome b5 content but it did not affect liver weight, P450 content or enzyme activities. In contrast, rifampicin and rifabutin increased relative liver weights, cytochrome contents and enzyme activities under similar conditions. 3. In dog, rifalazil did not affect any parameters at 30 or 300 mg/kg/day for 13 weeks. 4. These findings indicate that rifalazil is not an enzyme inducer in rat and dog. This property differs from other rifamycin derivatives such as rifampicin and rifabutin.     

Neuro-otologic findings in the lightning-injured patient

To determine whether endoplasmic reticulum (ER) proliferation in hepatocytes after phenobarbital (PB) administration relates closely to cytochrome P-450 (P-450) increase, we have measured the amount of total P-450 per unit cytoplasmic volume (P-450 content) by microphotometry and estimated the area of ER per unit cytoplasmic volume (ER area) by morphometry in periportal, midzonal, and perivenular hepatocytes of mice injected daily with PB (100 mg/kg), or with PB (100 mg/kg) plus cobalt chloride (50 mg/kg) for three days. After injection of PB, the P-450 content and ER area increased in hepatocytes of the three sublobular zones. In mice treated with PB plus cobalt chloride, however, the ER area increased, but the P-450 content decreased or remained unchanged in hepatocytes of the three zones. We conclude that cobalt chloride inhibits the increase in total P-450 but has no effect on the proliferation of ER of hepatocytes in mice treated with PB, indicating a dissociation of ER proliferation and P-450 increase after administration of PB.     

Vasodilatory effects of propylthiouracil in patients with alcoholic cirrhosis

BACKGROUND/AIMS: An experimental study has shown that propylthiouracil increases portal blood flow in normal rats. Whether propylthiouracil has a similar effect in patients with alcoholic cirrhosis remains to be demonstrated. The aim of this study was to evaluate the effects of oral propylthiouracil (300 mg) on systemic and portal hemodynamics in patients with alcoholic cirrhosis. METHODS: Plasma propylthiouracil levels were also measured by high performance liquid chromatography in five patients with alcoholic cirrhosis. In eight patients with cirrhosis, mean arterial pressure, cardiac output and portal blood flow were evaluated before and after placebo and propylthiouracil administration. Hemodynamic measurements were performed by the Doppler technique. The plasma peak level of propylthiouracil was achieved at 1.4 +/- 0.1 h in patients with alcoholic cirrhosis. This time was chosen to express hemodynamic changes. RESULTS: Propylthiouracil administration caused a significant increase in portal blood flow (+16.5%, p < 0.05) in patients with alcoholic cirrhosis. This effect was associated with a mild and significant rise in cardiac output (from 5.8 +/- 0.2 to 6.1 +/- 0.3 l/min, p < 0.05) and a decrease in peripheral vascular resistance (from 1171 +/- 69 to 1070 +/- 67 dyn . s-1 . cm-5, p < 0.01). A significant correlation was observed between changes in portal blood flow and peripheral vascular resistance (r = 0.79, p < 0.05). No significant changes were observed after placebo. CONCLUSIONS: Our findings show that propylthiouracil has a vasodilatory effect in patients with alcoholic cirrhosis. We postulate that this effect could be the mechanism by which propylthiouracil decreases hypermetabolic state, and increases oxygen delivery to the liver, in patients with alcoholic liver diseases.     

New perspectives on the clinical applications of functional radiology of the liver

Preliminary results of "new clinical applications" of functional imaging of the liver are reported. In 20 healthy volunteers portal flow measurement with Doppler US at the level of right, left portal branch and main portal trunk, showed the preferential distribution in baseline conditions of portal flow to the right liver (about 68%) as compared to the left portal branch. This influenced MRI volumetry of right liver as compared to left liver. After meal intake, flow increase was significantly higher at the level of left portal branch suggestive for a "functional reserve" in left liver. Portal flow physiology was examined in preparation of portal imaging before and after portal vein embolization, a procedure performed preoperatively before enlarged hepatectomies.     

Liver injury as a model of uncontrolled hemorrhagic shock: resuscitation with different hypertonic regimens

OBJECTIVE: To study if metabolic stress modifies the thermogenic effect of dobutamine. DESIGN: Prospective, increasing dose, pharmacologic study. SETTING: Laboratory of the Department of Intensive Care Unit at a university hospital. SUBJECTS: Twelve normal volunteers. INTERVENTIONS: Dobutamine hydrochloride was infused to 12 healthy male volunteers starting at a dose of 2 micrograms/min/kg and gradually increased to 4 and 6 micrograms/min/kg. Each dose of dobutamine was infused for 20 mins. Metabolic stress was induced in six of the 12 volunteers using a triple hormone infusion (epinephrine, cortisol, and glucagon) before dobutamine, and was continued at a constant rate during the dobutamine infusion. The remaining six volunteers served as the control group and received only dobutamine. MEASUREMENTS AND MAIN RESULTS: Oxygen consumption (VO2) was measured using a metabolic monitor. Arterial blood pressure was measured noninvasively, and cardiac output was monitored by Doppler echocardiography. Plasma concentrations of dopamine, norepinephrine, and epinephrine were measured in both groups. In the triple hormone group, blood was sampled to measure concentrations of insulin, glucagon, cortisol, free fatty acids, and glycerol to ensure the presence of a metabolic stress reaction. At the maximum dose, dobutamine induced a 19% increase (from 140 +/- 17 to 166 +/- 17 mL/min/m2) in VO2 in the control group and an 11% increase (from 167 +/- 10 to 184 +/- 13 mL/min/m2) in the triple hormone group (p < .05 between the two groups) compared with baseline. No change in the respiratory exchange ratio was seen. The triple hormone infusion alone induced hypermetabolism, a marked hemodynamic response, and increased lipolysis. CONCLUSIONS: Stress, induced by a triple hormone infusion, diminishes the thermogenic effect of dobutamine. In the clinical setting, a > 10% to 15% increase in VO2 in response to dobutamine may not be explained just by the thermogenic effect of the drug.     

Vascular and cardiac effects of amlodipine in acute heart failure in dogs

BACKGROUND: Amlodipine improves exercise capacity in patients with chronic congestive heart failure (HF), but the mechanisms of this effect are unknown. OBJECTIVE: To test the hypothesis, in a canine model of acute, ischemic HF, that amlodipine increases vascular capacitance and reduces cardiac filling pressures. METHODS: Amlodipine was given to 13 anesthetized, splenectomized dogs (six controls and seven with HF). Aortic, left ventricular end-diastolic (LVEDP) and portal venous (Pportal) pressures, cardiac output, portal flow (ultrasonic probe) and intestinal blood volume (IBV, 99mTc blood-pool scintigraphy) were measured. Intestinal vascular conductance (= 1/resistance) and vascular capacitance (CAP) were measured before and 15 mins after repetitive 150 micrograms/kg dosages of amlodipine (maximum cumulative dosage, 1000 micrograms/kg). Pportal-IBV curves were obtained by impeding portal flow (pneumatic cuff), and change in CAP was defined by the change in IBV at Pportal = 7.5 mmHg. HF was induced by microsphere embolization of the left coronary artery. RESULTS: CAP increased in the control group (+ 28%, P < 0.01) but decreased (-9%, P < 0.05) in the HF group. Left ventricular stroke work increased in the control group (P < 0.05), while it decreased (P < 0.05) in the HF group, suggesting a negative inotropic effect. In the control group, LVEDP increased after amlodipine was given (P < 0.05) but did not change significantly in the HF group. CONCLUSIONS: In the acute experimental HF model, amlodipine failed to increase intestinal vascular CAP or decrease filling pressures, and may have had a negative inotropic effect. The experiment failed to demonstrate a beneficial hemodynamic effect of amlodipine in acute HF, and the mechanism of benefit of this agent in chronic HF remains unclear.     

Doppler US of helical flow in the portal vein

In helical portal venous blood flow, the usual laminar flow in the portal vein is replaced by a spiral. This changes the color Doppler ultrasound (US) appearance to one of alternating or parallel red and blue bands. Duplex US may appear to show hepatopetal, hepatofugal, or simultaneous bidirectional flow depending on placement of the cursor within the helix. Helical portal venous flow is unusual in normal individuals (2.2% of 135 patients). Its presence should prompt further scrutiny for signs of liver disease, particularly portosystemic shunts, as in 20% of 41 patients who subsequently underwent liver transplantation. It is a normal finding immediately after liver transplantation (43% of 35 patients) and transjugular intrahepatic portosystemic shunt (TIPS) creation (28% of 36 patients). In both liver transplant and TIPS recipients, helical flow is usually transient. Its persistence long after transplantation in association with a prolonged increase in portal venous velocity is a useful sign of portal vein stenosis. Helical flow may also occur in cases of neoplastic invasion or displacement of the portal vein.