Development of a percutaneous fiberoptic hepatic venous localization catheter.

OBJECTIVE: To develop a liver-specific biosensor system/catheter assembly that can be used to localize and cannulate the hepatic venous system without the need for fluoroscopic imaging. This would permit the bedside placement of a hepatic venous catheter for monitoring purposes without radiographic guidance. DESIGN: Experimental, in vitro. STUDY SETTING: Experimental laboratory at a university center. SUBJECT: This was a simulation study to evaluate the ability of a cardiovascular monitoring catheter mounted with a liver-specific biosensor to anatomically identify a side arm tributary. The experimental system used for this study mimics the hepatic vein draining into the inferior vena cava and allows its localization without the need for assisted imaging. The biosensor design and catheter/sensor assembly function were studied in this in vitro model. INTERVENTIONS: A liver-specific biosensor was developed by housing a homogeneous affinity fluorescence assay system sensitive to galactose in a microdialysis hollow fiber receptacle. A polyvinyl chloride tube containing a side arm was constructed to mimic the confluence of a venous tributary (i.e., the hepatic vein) with a major vascular channel (i.e., the vena cava). In this simulation, the side arm was continuously perfused with a liver-sensitive analyte (galactose) and the main channel was perfused with galactose-free buffer. A cardiovascular catheter containing a fiberoptic waveguide mounted with a galactose-sensitive fluorescent probe was advanced along the main conduit to assess its ability to identify the location of the galactose side arm infusion site. MEASUREMENTS AND MAIN RESULTS: The response of the fiberoptic sensor to different galactose concentrations was assessed and found to be almost linear over the concentration range of 0 to 2 mM, which encompasses the expected utilization range of this system. The variability in identifying the galactose infusion point (simulated hepatic vein) in a 15-cm conduit was 1.7 to 2.8 mm, or 1.1% to 1.9%. CONCLUSIONS: The construction of a catheter/sensor system with the ability to provide accurate spatial/anatomical localization data for the hepatic venous system is feasible. This assembly will eliminate the need for ancillary imaging systems for catheter/sensor delivery to an individual organ system and potentially can be positioned at the bedside in a fashion similar to the pulmonary artery flotation catheter.

Independent origins of the internal and external carotid arteries--a case report.

A case illustrating a congenital anomaly in the development of the left carotid artery is presented. The common carotid artery was found to be absent, with both internal and external carotid arteries arising separately from the aortic arch. This is a rare occurrence that is described angiographically and embryologically.

The influence of hepatic venous oxygen saturation on the liver's synthetic response to metabolic stress.

Hepatic oxygen consumption (HVO2) and hepatic venous oxygen saturation (ShvO2) were assessed in the isolated perfused rat liver under conditions that mimic critical illness in an effort to assess their utility in predicting the functional status of the liver. Flow rates were adjusted over the physiologic range of oxygen transport as indicated by the hepatic venous O2 saturation range of 10%-75%. HVO2 was found to be transport (HDO2) dependent only when perfusate conditions contained an increased counterregulatory hormone (glucagon, epinephrine, dexamethasone) stimulus or a high lactate concentration. In the absence of a metabolic load, (substrate and hormone-free perfusate), HVO2 was transport independent even at an ShvO2 as low as 10%. Although transport dependency of HVO2 is frequently used to infer tissue ischemia, hepatic oxygen consumption was poorly correlated with synthetic function under all conditions. In contrast, hepatic albumin production was directly related to ShvO2 at all levels of HDO2 and under all perfusion conditions indicating that this metabolic process is particularly sensitive to reductions in oxygen availability, which is more reliably predicted by venous saturation measurements. However, glucose and urea synthesis were almost independent of ShvO2. These findings indicate that various hepatic processes are affected differentially by stress conditions and flow alterations that may exist during critical illness, and protein synthesis is particularly sensitive to oxygen deprivation. Additionally, hepatic venous oxygen saturation measurement, but not HVO2, serves as a useful surrogate marker for hepatic albumin production suggesting that regional venous oximetry may play an important role in the detection of hepatic functional impairment.

Systemic and splanchnic metabolic response to exogenous human growth hormone.

BACKGROUND: Evidence exists indicating that growth hormone (GH) resistance in some disease states such as hypercatabolic conditions may limit the metabolic benefit associated with recombinant human growth hormone (rhGH) administration. It was the purpose of this study to compare the systemic and splanchnic effects of rhGH in patients with sepsis exhibiting systemic inflammatory response syndrome (SIRS) with the response observed in normal volunteers. Because insulin-like growth factor I (IGF-I) is believed to be the dominant factor responsible for the anabolic effects of rhGH, particular attention was given to this secondary effector. METHODS: The systemic and splanchnic effects of rhGH (0.15 mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I, urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and splanchnic oxygen exchange were measured after a 48-hour course of rhGH. RESULTS: Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF-I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and Sepsis/SIRS + Nutrition groups, respectively, compared with normal control subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined by a similar magnitude in all three groups. Hepatic blood flow remained unaffected, but rhGH administration increased splanchnic oxygen consumption in all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p < 0.05 relative to corresponding basal) resulting in a decline of basal to end therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%; Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55% +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that rhGH may induce centrilobular hepatic hypoxia, which may contribute to the diminished IGF-I response. CONCLUSIONS: Although critically ill patients exhibit an IGF-I increase in response to exogenous rhGH, the rise is markedly attenuated compared with healthy volunteers, indicating the presence of GH resistance. Unexpectedly, the changes in the anabolic hormone IGF-I did not appear to be related to the reduction in urea excretion. This may provide some additional evidence for IGF-I resistance. Finally, rhGH is associated with an augmented splanchnic oxygen consumption but no corresponding increase in regional blood flow. As a result, regional tissue hypoxia may arise and contribute to the impaired or suboptimal IGF-I response pattern.

Functional characteristics of the hypermetabolic isolated perfused liver.

Clinically, hypermetabolism of the liver accompanies the systemic response associated with trauma and sepsis. Although increased metabolism is generally considered a beneficial response, a markedly increased hepatic oxygen consumption (HVO2) may be associated with adverse consequences such as induction of centrilobular hypoxia. We studied the effects of lactate and glucagon as inducers of increased HVO2 in the isolated perfused rat liver to determine if hepatic functional derangements could be precipitated by these trauma-associated factors at high metabolic rates. HVO2 rose by 27%, 52%, and 70% in response to 5 mM lactate/1 mM pyruvate, 20 nM glucagon, or both, respectively. In response to these stimuli at a fixed perfusion rate, hepatic venous oxygen saturation declined to 48 +/- 4% at the highest HVO2, and this was associated with a reduced hepatic adenosine triphosphate content and fibrinogen secretion. These findings indicate that hepatic metabolic disturbances can result from hepatocellular hypoxia due to increased HVO2.

Metabolic function of the isolated perfused rat liver in chronic sepsis.

Significant alterations of liver function have been identified in experimental sepsis including changes in protein and glucose production. The specific changes which are evident in vivo appear to depend upon the specific experimental model and probably represent the relative contribution of hepatocellular function and extrahepatic influences as well as the time course of the septic process. Relatively few studies have focused on function of the whole organ. In an effort to study intrinsic hepatic function during chronic sepsis, control and septic animals (intraabdominal abscess) were studied using the isolated perfused liver model. Basal hepatic oxygen utilization was mildly elevated compared to that in control livers and the oxygen consumption response to a metabolic load was found to be essentially identical to that in control and septic livers. Glucose and albumin production were not substantially different in these two groups. These findings suggest that alterations in liver function following the induction of sepsis may result from extra hepatic factors, since intrinsic liver function appears to be normal.

Hepatic metabolic response to injury and sepsis.

BACKGROUND: Experimental reports have indicated that hepatic oxidative and synthetic metabolism may become depressed in sepsis. Because the mechanism of infection-related liver dysfunction has not been established, further study of these functional alterations could contribute to the therapeutic management of septic organ failure syndromes. However, recently controversy has arisen over the existence of these derangements that must be reconciled before further progress in this field can be made. METHODS: Splanchnic balance studies for the measurement of glucose output and oxygen consumption were used to assess hepatic function in fasted normal volunteers (n = 18), injured patients (n = 10), and patients with sepsis (n = 18). The liver's contribution to splanchnic metabolism was estimated from a comparison of splanchnic oxygen utilization in response to increases in the liver-specific process of glucogenesis. In addition, in vivo liver albumin production was determined by using the [14C] carbonate technique. RESULTS: Glucose output after injury and sepsis was increased by 12.8% and 76.6%, respectively, compared with controls. On the basis of substrate balance studies, gluconeogenesis was estimated to account for 46%, 87%, and 93%, respectively, of splanchnic glucose output in each of the three groups. In patients with sepsis glucose output was also noted to be linearly related to regional oxygen consumption, indicating that these processes were coupled and increases in the respiratory activity of the splanchnic cellular mass could be accounted for by increases in new glucose output and gluconeogenic substrate clearance. The mean albumin synthetic rate increased during injury and sepsis by 22% and 29%, respectively, compared with normal volunteers. CONCLUSIONS: These studies cast doubt on the commonly held notion that tissue respiratory dysfunction may occur during sepsis. On the contrary, hepatic function is accelerated during hyperdynamic sepsis, and evidence indicating oxidative or synthetic functional depression is lacking.

Splanchnic metabolism associated with liver metastasis.

Metastatic liver disease can modify the metabolic response to critical illness. Systemic lactic acidosis may arise from an increased production due to inadequate peripheral tissue oxygen transport, altered metabolic function such as depressed pyruvate oxidation or insufficient hepatic clearing capacity due to tumor replacement of functional liver mass. Hepatic venous catheterization in a patient with extensive metastatic melanoma to the liver and adult respiratory distress syndrome indicated a marked disparity between whole body and liver oxygenation which may arise due to a markedly stepped up splanchnic oxygen utilization unmatched by a proportionate rise in regional oxygen delivery. Since some neoplasms may exhibit increased metabolic activity, it is suspected that these metastatic lesions may have contributed to the observed regional hypermetabolism thereby worsening hepatic hypoxia and exacerbating lactic acidosis. This case also illustrates the difficulties in interpreting global indicators of metabolic function and oxygenation in critically ill patients.

Effects of tumor necrosis factor-alpha on glucose and albumin production in primary cultures of rat hepatocytes.

Tumor necrosis factor-alpha (TNF) is known to alter significantly in vivo hepatic glucose and albumin metabolism. However, it remains unclear whether the observed effects represent direct actions of this factor or secondary responses due to the recruitment of other mediator systems. The present study was designed to investigate direct actions of TNF on glucose and albumin production in primary cultures of rat hepatocytes. Addition of TNF to the culture medium resulted in a 45% to 50% reduction in glucose production from a control level of 239 +/- 15 nmol/plate.h. This effect was reversed by addition of anti-TNF monoclonal antibody. In glycogen-depleted cells, short-term (5-hour) incubation with TNF did not affect hepatocyte albumin secretion, which was 8.13 +/- 0.29 microgram/plate.h. However, in cells exposed to insulin or in non-glycogen-depleted cells, addition of TNF resulted in a 10% to 25% reduction in albumin production. These findings indicate that TNF exerts direct inhibitory effects on hepatocyte glucose and albumin production, but the effects on the latter process are modest. A notable aspect of the findings is that the albumin effects are insulin or glucose substrate-dependent, which may have implications regarding liver function during nutritional support in critical illness.

Oxygen transport-dependent splanchnic metabolism in the sepsis syndrome.

OBJECTIVE: Total body oxygen consumption (VO2) may be pathologically oxygen delivery (DO2)-dependent in critically ill patients exhibiting the sepsis syndrome. This observation has been used to infer the presence of occult tissue or organ ischemia that potentially can be eradicated by augmenting DO2. We examined this hypothesis by determining the VO2-DO2 relationship and lactate metabolism in the splanchnic region. DESIGN: Before and after intervention trial. SETTING: University-affiliated Veterans Affairs Medical Center, Allen Park, Mich. PATIENTS: Eighteen surgical patients exhibiting the sepsis syndrome. INTERVENTION: Systemic and splanchnic oxygen exchange and lactate uptake measurements before and after augmentation of DO2 with blood transfusion. MAIN OUTCOME MEASURES: Changes in oxygen exchange and lactate metabolism. RESULTS: The splanchnic VO2 index rose 9% in association with a 26% regional DO2 index increase indicating an oxygen transport dependency (P < .05). Splanchnic O2 extraction (0.47 +/- 0.04) was significantly greater than the mean systemic level (0.31 +/- 0.02) and showed a greater decline following DO2 index augmentation (0.41 +/- 0.04 vs 0.28 +/- 0.03, respectively). However, splanchnic lactate uptake was not changed significantly in response to the increased DO2 index. CONCLUSIONS: Although splanchnic oxygen transport dependency and elevated extraction ratios suggest the presence of regional ischemia that should be relieved with an increased DO2 index, the observed changes in lactate uptake do not support this conclusion. The significance of the VO2-DO2 relationship, its role in the pathophysiology of the sepsis syndrome, and its place in the clinical care of the septic surgical patient are in doubt.

Factors affecting secretory protein production in primary cultures of rat hepatocytes.

Previous studies suggest that protein synthesis in the liver may be influenced by alterations in hepatic proteolysis and gluconeogenesis. Since proteolysis and gluconeogenesis are accelerated in acute stress states (especially when associated with nutrient deprivation), these alterations may substantially affect hepatic protein synthesis, the integrity of which is important for host survival. In the present study, we have investigated albumin secretion and glucose production in primary cultures of rat hepatocytes in response to nutrient-limiting conditions, including amino acid depletion, proteolysis inhibition, and augmented gluconeogenesis. In nonlimiting nutrient culture medium containing 10 times the normal plasma amino acid concentrations, hepatocytes produced 8.05 +/- 1.62 micrograms/plate-hr of albumin. Short-term (5 hr) inhibition of cellular protein degradation with the lysosomal protease inhibitor leupeptin did not influence albumin production, but caused a profound reduction (17-41%) when amino acid supply was reduced to the physiologic range (1.5-0.5 times, respectively). This indicates the need for active proteolysis for the maintenance of secretory protein production during nutrient limitation. Similarly, leupeptin inhibited glucose production by 22-30% at physiologic (1.5 times and 0.5 times, respectively) amino acid concentrations. Additionally, hepatocyte glucose production could be augmented 168% by epinephrine (2 microM) in 10 times medium, but this response was markedly depressed by leupeptin. Similar catecholamine-mediated effects, but of a smaller magnitude, were noted at lower medium amino acid concentrations. These findings indicate that hepatocyte albumin and glucose production are associated with the common factor of active cellular proteolysis, probably through the regulation of amino acid supply. However, protein synthesis exhibits a higher priority, since stimulated hepatocyte glucose production did not substantially alter albumin secretion.

The isolated perfused rat liver as an experimental model.

Intrinsic liver function may be specifically studied using the isolated perfused liver system. In this report, the metabolic characteristics of the perfused rat liver are described in response to lactate (5 mM) and ammonia (10 mM) loading. These conditions are analogous to the increased substrate availability that accompanies some acute disease states such as trauma. Glucose production (490 +/- 85 nm/gm liver/min) was constant during a 90-minute perfusion whereas albumin secretion exhibited a biphasic kinetic profile in the absence of exogenous amino acids. Liver oxygen consumption (VO2) was responsive to substrate loading as evidenced by a 20 to 60 per cent initial increase in VO2. The authors conclude that a large portion of hepatic VO2 may normally be directed toward substrate clearance. Additionally, although hepatic secretory protein synthesis persists despite the limitation of nutrient amino acid supply, the kinetics of secretion are complex.

Renal functional response to dopamine during and after arteriography in patients with chronic renal insufficiency.

The potential renal vasodilatory effect of dopamine in improving renal function after arteriography was studied. Sixty patients with preexisting renal insufficiency were prospectively randomized into two groups. Patients in the treated group (n = 30) received an infusion of dopamine for 12 hours starting at the beginning of arteriography. Patients who received placebo infusion with arteriography (n = 30) served as controls. The study was conducted in two different time intervals. In the first interval, serum creatinine levels and 12-hour creatinine clearance values were obtained before and immediately after arteriography in 12 patients in the dopamine group and 13 patients in the control group. In the second interval, the same variables were measured before arteriography and for 3 consecutive days after arteriography in 18 patients in the dopamine group and 17 patients in the control group. Serum creatinine levels became significantly elevated in the control group on the 1st day and remained so on the 3rd day after arteriography, whereas the dopamine group did not show significant elevation of these levels. Creatinine clearance decreased in the control group on the 1st day, but this deterioration was not sustained on the 3rd day. In the dopamine group, there was no deterioration in creatinine clearance on either day, and mean effective renal plasma flow during and after arteriography was greater.

Hepatic parenchymal oxygen tension following injury and sepsis.

Hepatic blood flow and splanchnic oxygen consumption were measured in 16 injured (n = 6) or septic (n = 10) patients and compared with values in 16 normal volunteers. Sepsis and injury appeared to stimulate an increase in blood flow and oxygen utilization, with the highest levels observed in the septic group. Patients with sepsis exhibited a 72% and 60% increase in hepatic blood flow and splanchnic oxygen consumption, respectively, compared with normal volunteers. Application of these data to the Krogh-Erlang tissue model indicates that despite an increase in oxygen delivery to the splanchnic bed during sepsis, it becomes more sensitive to hypoxic/ischemic events compared with other patient groups. This is indicated by a reduced centrilobular and increased critical oxygen tension. The major factor responsible for this is the regional hypermetabolism present in sepsis. This analysis emphasizes the critical importance of maintaining oxygen transport in critically ill patients with sepsis.