Ann Thorac Surg 2002;73:549-555
© 2002 The Society of Thoracic Surgeons
Original article: cardiovascular
Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation
Takafumi Masai, MDa,
Yoshiki Sawa, MDa,
Shigeaki Ohtake, MDa,
Toshirou Nishida, MDa,
Motonobu Nishimura, MDa,
Norihide Fukushima, MDa,
Takashi Yamaguchi, MDa,
Hikaru Matsuda, MD*a
a Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Accepted for publication November 6, 2001.
* Address reprint requests to Dr Matsuda, Department of Surgery, Osaka University Graduate School of Medicine (E1), 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
e-mail: matsuda{at}surg1.med.osaka-u.ac.jp
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Abstract
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Background. In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma.
Methods. Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups.
Results. Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis.
Conclusions. Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.
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Introduction
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Salvaging the patients with profound heart failure by mechanical circulatory support has been a well-accepted therapeutic option, and the ventricular assist devices (VADs) have become the most commonly used and reliable tools for such patients, including postcardiotomy shock [1] or bridge to heart transplantation [2, 3]. The average salvaging ratio has been from 20% to 30% in a group of postcardiotomy shock, and 60% to 70% in other chronic heart failure such as idiopathic or ischemic cardiomyopathy [1–3]. This is mainly contributed to by the development of sophisticated left (L)VADs and also patient management. However, the obstacles to improve the outcome of LVAD support remain, particularly in a cohort of high-risk patients. Multiple organ failure (MOF) has been the main cause of death, besides other complications, such as bleeding, thromboembolism, and infection [1–3]. Regarding MOF in VADs, some authors have emphasized that the degree of hepatic injury induced by heart failure before the institution of mechanical circulation is the key to determining outcome in patients on VAD [2–4]. Furthermore, deterioration of hepatic function often is observed even after improved hemodynamics are achieved under VAD. The crucial issue has been why cardiac-induced hepatic dysfunction advances despite adequate hemodynamics with mechanical circulatory support. The pathophysiology of MOF after major surgery and trauma recently has been investigated by examining the relation between inflammatory responses activated by surgical intervention or infection and induction of chemical mediators and their relation to organ perfusion [5–7]. We therefore hypothesized that the pathogenesis of aggravating hepatic dysfunction in LVAD patients might be similar to that of MOF after surgery or trauma because LVAD insertion itself is regarded as a major surgical intervention. In this study, we clinically evaluated factors, including inflammatory response and relation to liver perfusion, in patients who developed hepatic dysfunction after the implantation of LVAD.
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Material and methods
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Patients
We followed a consecutive 16 patients who received LVAD support between April 1992 and February 2000 at our institution. This cohort does not include acute heart failure after cardiac surgery. The mean age of patients was 48 years (range 18 to 64 years); 1 patient was a woman and the others were men. The basic cardiac lesions were dilated cardiomyopathy in 9, hypertrophied cardiomyopathy in 4, and ischemic cardiomyopathy in 3. As the devices used as the first choice, pneumatic extracorporeal left ventricular assist systems (LVASs) (Toyobo, Inc, Osaka, Japan) were implanted in 13 patients, and wearable Novacor LVASs (World Heart Inc, Oakland, CA) were implanted in 3 patients. In 3 of 13 patients who received Toyobo LVAS, the device subsequently converted to the HeartMate 1000 IP LVAD (Thermo Cardiosystems, Inc, Woburn, MA) in 1 patient and Novacor LVAS in 2 patients after 66 to 463 days (median 93 days) of support of the Toyobo LVAS. Cannulation of LVAD was carried out through the left atrium in all patients with the Toyobo LVAS and through the left ventricle in patients with the Novacor or TCI LVAD. Descriptions of the Toyobo LVAS and details of the clinical course and management for these patients have been reported previously [8]. Biventricular assistance was indicated if LVAD output could not be maintained above a cardiac index of 2.5 L/min/m2 with central venous pressure (CVP) greater than 20 mm Hg despite the support with prostaglandin E1 and inhalation of nitric oxide.
All 16 patients had end-stage heart failure requiring two or more inotropic agents, and 12 of the patients required other mechanical circulatory devices before starting LVAD. Six of these 12 patients were supported only by an intraaortic balloon pump (IABP), 4 by both IABP and percutaneous cardiopulmonary support (PCPS), 1 by both percutaneous LVAS (PLVAS) and IABP, and 1 by IABP followed by resuscitation with PCPS. Average durations of inotropic support and IABP support were 29 days (range 7 to 64 days) and 9.5 (range 4 to 16 days), respectively.
Of the 16 patients, 5 developed severe hepatic failure early in the postoperative period after LVAD insertion and died from MOF after hepatic failure after 20 to 73 days (median 46 days) of LVAD support. These 5 patients are referred to as group 1. The remaining 11 patients who did not develop fatal hepatic failure after the LVAD implantation were designated as group 2. In this group, 2 survived after heart transplantation, one discharged on device, and 8 died of other causes after LVAD support for periods ranging from 52 to 580 days (median 124 days). Two patients in group 2 developed transient hepatic failure resulting in complete recovery within 20 days after LVAD implantation. Demographics of the two groups are shown in Tables 1 and 2.
Hemodynamics, hepatic function, and inflammatory responses, including infection, were compared between the two groups before and during the period of LVAD support until postoperative day (POD) 20. All blood samples were taken from the radial artery. In the 4 patients supported by PCPS before LVAD insertion, pre-LVAD data were collected before the institution of PCPS.
Hepatic function
Serum total bilirubin (T-Bil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), and albumin concentrations were measured before and every 2 days after the implantation of LVAD. In 12 patients (4 in group 1 and 8 in group 2), the arterial ketone body ratio (AKBR), which is a known indicator of redox potential of liver mitochondria and decreases in parallel with the progression of hepatocellular hypoxia [9], was calculated before and every 2 days after LVAD insertion. A poor prognosis has been indicated when this ratio persistently drops below 0.4 [9].
Infection and inflammatory response
In all patients, white blood cell count and C reactive protein (CRP) levels were measured before and each day after LVAD insertion. In 12 patients (4 in group 1 and 8 in group 2), serum endotoxin, interleukin (IL)-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assay before and at 2, 4, 6, 10, and 20 days after LVAD implantation.
Serum hyaluronan
In the last 7 patients (2 in group 1 and 5 in group 2), serum hyaluronan concentration, which is a known indicator of hepatic sinusoidal endothelial function [10], was determined perioperatively until POD 20 by sandwich binding protein assay for evaluation of hepatic sinusoidal microcirculation.
Statistical analysis
Hemodynamic data are shown as mean ± SD. Other laboratory data are shown as mean ± SEM. Serum hyaluronan values did not distribute normally and were analyzed after logarithmic transformation. Statistical analysis was done with StatView Version J 4.02 (Abacus Concepts Inc, Berkeley, CA). Mean differences were analyzed by a nonparametric Mann-Whitney U test. Correlations between T-Bil levels and serum hyaluronan were analyzed by univariate linear regression and Pearson correlation coefficients, and corresponding p values were calculated. Differences were considered statistically significant at a p value of less than 0.05.
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Results
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Perioperative hemodynamics
There were no significant differences between the two groups in cardiac index (CI), pulmonary capillary pressure (PC), and CVP before LVAD implantation (Table 1). Fifteen of the 16 patients were able to maintain adequate LVAD output above a cardiac index of 2.5 L/min/m2 with LVAD support alone. One patient in group 1 required right ventricular support by centrifugal pump for 10 days in addition to LVAD (Table 1). His LVAD flow was satisfactorily maintained at more than 3.0 L/min/m2, keeping CVP within the normal limit under biventricular support. Flow rates achieved by LVAD and postoperative CVP did not differ significantly between the groups on any given POD (Fig 1).
No patients required dialysis during study period until POD 20.
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Fig 1. Perioperative hemodynamics. Flow rates achieved by left ventricular assist device (LVAD) and postoperative central venous pressure (CVP) did not differ significantly between two groups on any given postoperative day (POD). Error bars represent standard deviation.
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Hepatic function
The T-Bil levels before LVAD were significantly higher in group 1 (5.1 ± 1.4 mg/dL) than in group 2 (1.9 ± 0.3 mg/dL) (p < 0.05) (Table 3).
In group 1, T-Bil levels increased abruptly to a mean of 35 mg/dL at POD 20. In contrast, T-Bil levels in group 2 improved to almost normal by POD 20, whereas they showed a transient increase immediately after LVAD implantation (Fig 2).
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Fig 2. Changes in serum total bilirubin (T-Bil) levels. T-Bil levels were significantly higher in group 1 than in group 2 before (Pre) left ventricular assist device and from postoperative day (POD) 4 to POD 20. Error bars represent SEM. *p less than 0.05 versus group 2.  p less than 0.01 versus group 2.
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There were no significant differences in AST, ALT, ChE, or albumin values between the groups preoperatively (Table 3) and after LVAD implantation.
Preoperative AKBR was significantly lower in group 1 (1.0 ± 0.10) than in group 2 (2.3 ± 0.31) (p < 0.05) (Table 3). The mean AKBR, however, was maintained at more than 1.0 before and after LVAD implantation in both groups (evidence of no severe hepatic hypoxia), and showed no significant differences between the groups during any postoperative period.
Inflammatory responses
There were no significant differences in white blood cell counts or endotoxin levels between the groups preoperatively (Table 3) and after LVAD implantation. The CRP level before LVAD was significantly higher (p < 0.05) in group 1 (15 ± 5.3 mg/dL) than it was in group 2 (5.9 ± 1.2 mg/dL) (Table 3). The postoperative CRP levels were also higher in group 1 than in group 2, and significant differences were observed between these two groups at POD 6, 10, and 20 (p < 0.05) (Fig 3).
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Fig 3. Perioperative inflammatory responses. C reactive protein (CRP), interleukin-6 (IL-6), and interleukin-8 ( IL-8) levels are compared between two groups before (Pre) and 2, 4, 6, 10, and 20 days after left ventricular assist device implantation. Error bars represent SEM. *p less than 0.05 versus group 2. p less than 0.01 versus group 2.
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IL-8 levels before LVAD were significantly higher (p < 0.05) in group 1 than in group 2 (Table 3). After LVAD insertion, both IL-6 and IL-8 levels were higher in group 1 than in group 2, and significant differences were observed from POD 4 to POD 20 in IL-6 and throughout the postoperative period in IL-8 (Fig 3). Both IL-6 and IL-8 values increased transiently immediately after LVAD insertion in group 2, however, were nearly normal by POD 20. In contrast, both IL-6 and IL-8 levels elevated markedly in group 1 after LVAD insertion and remained high throughout postoperative period (Fig 3).
Serum hyaluronan level
Serum hyaluronan levels measured in 7 patients (2 in group 1 and 5 in group 2) were significantly correlated with the levels of T-Bil (r = 0.60, p < 0.05 in group 1 and r = 0.68, p < 0.0001) (Fig 4).
Furthermore, higher levels of serum hyaluronan were observed in group 1 than in group 2. In group 2, 2 patients who showed transient elevations and improvements of T-Bil levels (recovery case) showed higher levels of serum hyaluronan than another 3 patients who did not develop hepatic dysfunction (Fig 4).
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Fig 4. Relation between serum hyaluronan and serum total bilirubin (T-Bil) levels. The data of serum hyaluronan are analyzed after logarithmic transformation. Serum hyaluronan levels measured in 7 patients from each group show a significant correlation (ar = 0.60, p less than 0.05 in group 1 and br = 0.68, p less than 0.0001 in group 2) with T-Bil levels for the first 20 days after left ventricular assist device implantation.
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Comment
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In patients undergoing cardiac surgery, postoperative hepatic dysfunction has been reported in association with postoperative low cardiac output and high central venous pressure [11, 12]. In our series, however, hepatic dysfunction advanced despite adequate LVAD flow and normal central venous pressure levels during the entire postoperative periods. Other etiologies besides hemodynamics require investigation to understand the pathogenesis of the postimplant aggravation of hepatic dysfunction.
Recently, the inflammatory networks activated by organ hypoperfusion or infection have been reported to play an important role in the development of MOF, and several inflammatory substances such as endotoxin and inflammatory cytokines have been known to cause organ tissue damage directly or indirectly through impaired tissue perfusion [5–7, 13–15]. IL-6 is a cytokine induced from fibroblasts, macrophages, and Kupffer cells under infection or surgical stress, and is known as marker of inflammation [13, 14, 16]. IL-8 is a cytokine that stimulates neutrophil chemotaxis and the release of lysosomal enzymes. IL-8 is made by several types of cells, including fibroblasts, Kupffer cells, and hepatocytes. In our preliminary study, CRP, IL-6, and IL-8 levels were significantly correlated with T-Bil levels in patients with LVAD [17]. In this series, we investigated perioperative changes in these inflammatory factors and found significantly higher levels of these factors in the patients with declining hepatic function (group 1) throughout the study period. Our data suggest that the inflammatory reaction may participate in the etiology of deteriorating hepatic function after the implantation of LVAD, and that preoperative inflammatory indices, as well as preoperative T-Bil levels, could be diagnostic markers predicting outcome in these patients.
It is still unclear how these inflammatory reactions cause hepatic cell damage. It has been suggested that IL-6 and lysosomal enzymes released by IL-8 injure hepatocytes directly [13, 15, 16]. Several authors have demonstrated involvement of impaired hepatic microcirculation, especially in the liver sinusoid, in septic liver injury [18–21]. These reports suggest that inflammatory cytokines and chemical mediators, such as nitric oxide, endothelin, and prostaglandins induced from endotoxicemia, influence the hepatic microcirculation by directly injuring the sinusoidal endothelial cells [13–15, 21] or by acting as vasoactive substances within the portal venous bed [18–21], for example, in the regulation of sinusoidal sphincter function observed in Kupffer cells [21] and Ito cells [20]. Some authors have demonstrated histologically that hepatic microcirculation is impaired by thrombus formation in the sinusoid that is observed in cases of disseminated intravascular coagulation with endotoxemia by affecting monocyte-macrophagic lineage and endothelial cells as well as cytokines released from these cells [16, 21]. We observed similar histologic changes with endotoxemia in a patient in our progressive dysfunction group (group 1) (Fig 5).
Further studies are required regarding the contribution of endotoxin in MOF during LVAD support.
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Fig 5. Light microscopy findings from a liver specimen obtained through transvenous biopsy in a group 1 patient who died from hepatic failure after implantation of left ventricular assist device. Fibrous deposits (solid arrow) and degenerated hepatic cell (open arrow) were observed in the hepatic sinusoid as well as findings of intrahepatic cholestasis and moderate fibrosis. Serum hyaluronan was markedly elevated to 2,225 ng/mL at the time of biopsy. (H&E, x200)
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Hyaluronan is an unbranched high-molecular weight polysaccharide in the extracellular matrix that is synthesized mainly by mesenchymal cells and is widely distributed in the body. More than 90% of serum hyaluronan in the human body is degraded in the liver from endocytosis by hepatic sinusoidal endothelial cells with a half-life of 2.5 to 5.5 minutes [10, 23]. Therefore, serum hyaluronan levels are known to reflect liver sinusoidal endothelial cell function [24]. Quantification of serum hyaluronan has been evaluated for assessing the severity of hepatic injury, especially in cirrhotic liver disease, and recently as an index of rejection in liver transplantation [10]. Also, serum hyaluronan levels have been correlated with indocianin green clearance ratio, which is an indicator of hepatic sinusoidal blood flow [24, 25]. Because serum hyaluronan concentration may indicate the liver sinusoidal microcirculation, we measured serum hyaluronan levels in 7 patients perioperatively. Levels in these patients showed significant correlation with T-Bil levels as previously reported [17]. Furthermore, the higher serum hyaluronan levels were observed in patients with hepatic failure. Our findings suggest that impaired hepatic sinusoidal microcirculation may participate in the hepatic failure of LVAD patients (Fig 6).
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Fig 6. Speculated mechanism for aggravation of hepatic function. Activation of inflammatory substances such as cytokines and chemical mediators caused by liver hypoperfusion, infection, or surgical intervention before and after left ventricular assist device implantation may play an important role in aggravation of hepatic function by impairing hepatic microcirculation directly or indirectly. (NO = nitric oxide.)
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Our results are still tentative and require confirmation by further investigation including histologic and molecular biological studies in a larger patient population. Furthermore, future studies should be conducted to prove not only an association between inflammatory response and liver failure but also the direction of those chain reactions to have better understanding for the pathogenesis of liver failure in LVAD patients. Such studies also shed light on the possibility of treating patients with anticytokine therapy using monoclonal antibodies against cytokines or antiinflammatory cytokines such as IL-10 [26], which may contribute to the improvement of hepatic microcirculation.
In summary, patients with hyperbilirubinemia and activated inflammatory status before LVAD implantation showed further increase of serum bilirubin, inflammatory cytokine, and hyaluronan levels despite adequate circulatory support with LVAD. Inflammatory responses may play an important role in subsequent aggravation of hepatic dysfunction, probably with derangement in hepatic sinusoidal microcirculation even under systemic circulatory support. These results suggest that implantation of LVAD should be done before significant hyperbilirubinemia and an advanced stage of inflammatory response develops, and that some kinds of antiinflammatory therapy may allow a better chance to survive such hepatic failure and subsequent MOF in VAD patients [22].
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Acknowledgments
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We are deeply grateful to Dr O. H. Frazier of the Texas Heart Institute, Houston, TX, for reviewing the manuscript and for his thoughtful and encouraging comments.
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References
|
|---|
-
Pae W.E., Miller C.A., Matthews Y., Pierce W.S. Ventricular assist devices for postcardiotomy cardiogenic shock. A combined registry experience. J Thorac Cardiovasc Surg 1992;104:541-553.[Abstract]
-
Frazier O.H., Rose E.A., Macmanus Q., et al. Multicenter clinical evaluations of the HeartMate 1000IP ventricular assist device. Ann Thorac Surg 1992;53:1080-1090.[Abstract/Free Full Text]
-
MaCarthy P.M., Smedira N.O., Vargo R.L., et al. One hundred patients with the HeartMate left ventricular assist device: evolving concepts and technology. J Thorac Cardiovasc Surg 1998;115:904-912.[Abstract/Free Full Text]
-
Kawaguchi A.T., Cabrol C., Pavie A., et al. Survival prediction in staged heart transplantation using Jarvik-7 artificial heart. Circulation 1992;86(Suppl 2):311-315.[Abstract/Free Full Text]
-
Baigrie R.J., Lamont P.M., Kwiatkowski D., Dallman M.J., Morris P.J. The systemic cytokine response after major surgery. Br J Surg 1992;79:757-760.[Medline]
-
Guillou P.J. Biological variation in the development of sepsis after surgery or trauma. Lancet 1993;342:217-220.[Medline]
-
Takala J. Determinants of splanchnic blood flow. Br J Anaesth 1996;77:50-58.[Free Full Text]
-
Masai T., Shimazaki Y., Kadoba K., et al. Clinical experience with long-term use of the Toyobo left ventricular assist system. ASAIO J 1995;41:M522-M525.[Medline]
-
Ozawa K., Aoyama H., Yasuda K., et al. Metabolic abnormalities associated with postoperative organ failure: a redox theory. Arch Surg 1983;118:1245-1251.[Medline]
-
Laurent T.C., Laurent U.B., Frazer J.R.E. Serum hyaluronan as a disease marker. Ann Med 1996;28:241-253.[Medline]
-
Matsuda H., Covino E., Hirose H., et al. Acute liver dysfunction after modified Fontan operation for complex cardiac lesions: analysis of contributing factors and its relation to the early prognosis. J Thorac Cardiovasc Surg 1988;96:219-226.[Abstract]
-
Takano H., Matsuda H., Kadoba K., et al. Monitoring of hepatic venous oxygen saturation for predicting acute liver dysfunction after Fontan operations. J Thorac Cardiovasc Surg 1994;108:700-708.[Abstract/Free Full Text]
-
Callerly M.P., Kamei T., Flye M.W. Endotoxin stimulates interleukin-6 production by human Kupffer cells. Circ Shock 1992;37:185-188.[Medline]
-
Steinger R., Roth E., Fugger R., et al. Transhepatic metabolism of TNF-
, IL-6, and endotoxin in the early hepatic reperfusion period after human liver transplantation. Transplantation 1994;58:179-182.[Medline]
-
Hill D.B., Marsano L.S., McClain C.J. Increased plasma interleukin-8 concentrations in alcoholic hepatitis. Hepatology 1993;18:576-580.[Medline]
-
Takeuchi M., Nakashima Y., Miura Y., et al. The localization of lipopolysaccharide in an endotoxemic rat liver and its relation to sinusoidal thrombogenesis. Path Res Pract 1994;190:1123-1133.
-
Yamaguchi T., Sawa Y., Masai T., et al. Hepatic sinusoid endothelial dysfunction plays a role in hyperbilirubinemia in patients following implantation of an LVAD. ASAIO J 1997;43:M449-M452.[Medline]
-
Nishida J., McCuskey R.S., McDonnell D., Fox B.S. Protective role of NO in hepatic microcirculation during endotoxemia. Am J Physiol 1994;267:G1135-G1141.[Abstract/Free Full Text]
-
Oshita M., Takei Y., Kawano S., et al. Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in the rat liver. J Clin Invest 1993;91:1337-1342.
-
Kawada N., Klein H., Decker K. Contraction and relaxation of hepatic stellete cells in culture. In: Knook D.L., Leiden E.W., eds. . Cells of the hepatic sinusoid. Leiden, The Netherlands: Kupffer Cell Foundation, 1993:161-164.
-
McCuskey R.S. Hepatic microvascular responses to endotoxemia and sepsis. Prog Appl Microcirc 1993;19:76-84.
-
Deitch E.A. Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg 1992;216:117-134.[Medline]
-
McGray C.T., Raja R.H., Weigel P.H. Endocytosis of hyaluronic acid by rat liver endothelial cells. Biochem J 1989;257:875-884.[Medline]
-
Gibson P.R., Frazer J.R.E., Brown T.J., et al. Hemodynamic and liver function predictors of serum hyaluronan in alcoholic liver disease. Hepatology 1992;15:1054-1059.[Medline]
-
Gibson P.R., Frazer J.R.E., Colman J.C., et al. Change in serum hyaluronan: a simple index of short-term drug-induced changes in hepatic sinusoidal perfusion. Gastroenterology 1993;105:470-474.[Medline]
-
Van Dissel J.T., van Langerelde P., Westendorp R.G.J., Kwappenberg K., Frolich M. Anti-inflammtory cytokine profile and mortality in febrile patients. Lancet 1998;351:950-953.[Medline]
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Abstract
Introduction
