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Biomedical subjects

B R Davidson

Publications and source records attributed to B R Davidson.

At least 55 records · Page 3Linked to original sources
PubMed2000

In vivo evaluation of an implantable portal pump system for augmenting liver perfusion.

BACKGROUND: Increasing portal inflow in cirrhosis using a mechanical pump reduces portal venous pressure and improves liver function. A pump has been developed for portal vein implantation in human cirrhosis. This study describes the initial in vivo evaluation in a porcine model. METHODS: Five Large White pigs underwent laparotomy and exposure of the liver. Flow in the hepatic artery, portal vein and hepatic microcirculation was monitored continuously. Hepatic tissue oxygenation was measured by near-infrared spectroscopy. After baseline measurements the pump was inserted into the portal vein. Pump flow rate was then increased stepwise to 50 per cent over the baseline value for a period of 2 h. The pump was then stopped for 20 min and left in situ while continuing to collect systemic and hepatic haemodynamic data. The animal was killed and biopsies for histological examination were taken from the liver, small intestine and spleen. RESULTS: The baseline total hepatic blood flow was 626(39) ml/min; the hepatic artery supplied 18.4(2.1) per cent and the portal vein 81.6(2.1) per cent. The pump was inserted successfully in all animals without surgical complications. During surgical insertion of the pump, the temporary portal vein occlusion resulted in a significant rise in hepatic artery blood flow (22(3) per cent; P < 0.01 versus baseline). Portal vein flow was augmented by pumping; there was a significant correlation between the pump motor speed and portal vein flow (P < 0.0001). This inflow correlated directly with flow in the hepatic microcirculation and hepatic tissue oxygenation (P < 0.001). The pump ran satisfactorily throughout the study. Histological examination revealed no evidence of structural damage to the liver or ischaemic changes in the small intestine or spleen. CONCLUSION: It is technically possible and safe to insert an implantable pump in the portal vein. Portal venous blood flow can be increased up to 50 per cent with a resultant increase in flow in the hepatic microcirculation and hepatic oxygenation and without adverse effects on either hepatic or systemic haemodynamics.

Animals↗
PubMed2000

Portal flow augmentation for liver cirrhosis.

BACKGROUND: Portal hypertension due to chronic liver disease is a major cause of death worldwide. Orthotopic liver transplantation offers the best therapeutic option but is available to only a minority of patients. In the past few years mechanically pumping portal venous inflow has been reported to reduce portal hypertension and improve liver function. METHODS: A review of the published data on augmented portal perfusion for the treatment of portal hypertension in cirrhosis was carried out by searching Medline and other online databases. From each published study portal pressure and blood flow data before and after augmented portal perfusion were used to calculate the change in mean intrahepatic portal vascular resistance (IHPR). The standardized data were then combined to allow meta-analysis. RESULTS: Seven papers were identified on normal and cirrhotic animal and human livers with augmented flow (50% to fourfold over baseline) for 30-180 min. Meta-analysis revealed that the increased portal venous inflow was associated with a significant rise in portal venous pressure on the hepatic side (P < 0.001), a significant reduction on the mesenteric side (P < 0.001) and a significant reduction in IHPR (P = 0.013). Limited data were available to support improved liver function. CONCLUSION: Detailed in vivo cirrhotic liver studies on augmented portal flow in experimental models assessing haemodynamic and functional changes are required before clinical evaluation.

Animals↗
PubMed2000

Predicting early mortality following percutaneous stent insertion for malignant biliary obstruction: a multivariate risk factor analysis.

BACKGROUND: Percutaneous stent placement is an accepted method of palliation in malignant biliary obstruction. Factors predicting early mortality after this procedure have not been identified. METHODS: We performed a retrospective study of 141 patients with malignant biliary obstruction who underwent percutaneous stent placement for biliary decompression to identify the risk factors associated with early mortality (< or = 30 days). RESULTS: Of 14 clinicopathological and laboratory variables analysed blood urea, albumin, haemoglobin and alkaline phosphatase were found to be significant on univariate analysis. The age and gender of the patient along with cancer type, level of obstruction, presence of pyrexia and bilirubin level had no influence on early mortality. Stepwise logistic regression identified the haemoglobin level and blood urea to be independently significant in predicting early mortality. Overall 30-day mortality was 20.5% (29/141). Patients with blood urea over 4.3 mmol/l and a haemoglobin less than 10.9 g/dl had a mortality rate of 52% (12/23) compared with 14% (17/118) in the remainder. Using these two variables a regression equation has been derived which allows calculation of the probability of survival at 30 days after the percutaneous procedure. CONCLUSIONS: Laboratory variables in patients with malignant obstructive jaundice can be used to predict mortality following percutaneous stent insertion.

Adult↗
PubMed2000

Measurement of hepatic tissue hypoxia using near infrared spectroscopy: comparison with hepatic vein oxygen partial pressure.

Hepatic hypoxia occurs during liver surgery and transplantation. The critical level associated with irreversible hepatocellular damage is unknown. Measurement of hepatic tissue oxygenation and hepatic vein oxygen partial pressure (HVPO(2)) reflects oxygen supply and consumption. Near infrared spectroscopy (NIRS) can be used to monitor hepatic oxyhaemoglobin (HbO(2)), deoxyhaemoglobin (Hb) and cytochrome oxidase (Cyt Ox) oxidation. This study compared regional hepatic tissue oxygenation (HbO(2), Hb and Cyt Ox) using NIRS with HVPO(2). The use of tissue oxygenation measured by NIRS and HVPO(2) as indicators of hepatic tissue hypoxia was also investigated. Large Landrace pigs (n = 5) underwent laparotomy and liver exposure. Systemic and hepatic haemodynamics were monitored continuously. NIRS probes were placed on the liver to record continuously HbO(2), Hb and Cyt Ox. Graded hypoxaemia was achieved by stepwise reduction of the fraction of inspired oxygen (FiO(2)) from 30% (baseline) to 4%. A significant decrease in hepatic arterial blood flow and total hepatic blood flow was seen with severe hypoxaemia while there was no significant change to portal vein blood flow. Oxygen partial pressures in the hepatic artery, portal vein and hepatic vein decreased progressively with all grades of hypoxaemia. There was an immediate reduction of hepatic HbO(2) and simultaneous increase in hepatic Hb with all grades of hypoxaemia. Hepatic Cyt Ox was reduced significantly only with FiO(2) < or =10%. A significant correlation (p<0.001) was found between the changes in hepatic oxygenation parameters measured by NIRS and HVPO(2). HVPO(2) measurement did not predict the reduction in intracellular tissue oxygenation demonstrated by NIRS with a decrease of Cyt Ox oxidation. In conclusion there was a good correlation between the tissue oxygenation parameters measured by NIRS and HVPO(2). However, the reduction of intracellular oxygenation found with severe hypoxaemia was demonstrated only by NIRS.

Animals↗
PubMed2000

The effect of human organ preservation and albumin flush solution on in vitro cell metabolic activity.

In liver transplantation, the organ during the recipient's operation is traditionally flushed with 4.5% of human albumin solution to wash away the potassium-rich University of Wisconsin (UW) solution. It has been argued whether albumin could be useful at this stage. We used a new simple non-toxic assay to determine cell viability in vitro. Alamar Blue incorporates a redox indicator which changes colour from blue (oxidised form) to magenta (reduced form) in response to metabolic activity. Cultured human hepatocyte and HUVEC cell lines were exposed for 3, 6, 12 or 24 hours to plain medium, UW solution, human albumin 4.5% solution, UW-containing effluents before and after preservation as well as albumin flushes from different transplantation cases. After addition of Alamar Blue the optical density was measured at 570 nm and the background measured at 600 nm was subtracted. The studies showed a significantly lower metabolic rate of the cells exposed to albumin and albumin-containing flushes at all time periods, even after a short exposure such as 3 hours (p < 0.001). On the other hand, there was no significant difference of growth and metabolic activity rate between cells exposed to UW solution, different UW-containing flushes and medium for up to 12 hours. In conclusion, human albumin is a very poor solution for cell maintenance. In contrast, UW solution has comparable results with the full growth medium for up to 12 hours of exposure.

Albumins↗
PubMed2000

Radioimmunoguided surgery in colorectal cancer using a genetically engineered anti-CEA single-chain Fv antibody.

In radioimmunoguided surgery (RIGS), a radiolabeled antibody is given i.v. before surgery and a hand-held gamma-detecting probe is used to locate tumor in the operative field. The rapid blood clearance and good tumor penetration of single-chain Fv antibodies (scFv) offer potential advantages over larger antibody molecules used previously for RIGS. A Phase I clinical trial is reported on RIGS with scFv (MFE-23-his) to carcinoembryonic antigen (CEA). Thirty-four patients undergoing surgery for colorectal carcinoma (17 primary tumors, 16 liver metastases, and 1 anastomotic recurrence) and 1 patient with liver metastases of pancreatic carcinoma received 125I-labeled MFE-23-his scFv (125I-MFE-23-his) 24, 48, 72, or 96 h before operation. 125I-MFE-23-his showed biexponential blood clearance with alpha and beta half-lives of 0.32 and 10.95 h, respectively. The abdomen was scanned during surgery with a hand-held gamma detecting probe (Neoprobe Corp.). 125I-MFE-23-his showed good tumor localization; comparison with histology showed overall accuracy of 84%. Highest median ratios for tumor:normal tissue and tumor:blood were recorded 72 or 96 h after scFv injection for patients undergoing resection of liver metastases. High levels of radioactivity were found in the kidneys. Five patients had grade 1 fever, and three had a grade 1 rise in blood pressure according to the Common Toxicity Criteria. There was a significant correlation between these ratios and those measured in excised tissues using a laboratory gamma counter (P < 0.001). MFE-23-his scFv antibody localizes in CEA-producing carcinomas. The short interval between injection and operation, the lack of significant toxicity, and the relatively simple production in bacteria make MFE-23-his scFv suitable for RIGS.

Adult↗
PubMed1999

A pilot study of immunosuppressive monotherapy in liver transplantation: tacrolimus versus microemulsified cyclosporin.

BACKGROUND: Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years. The question now arises whether, in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus, routine administration of steroids posttransplant is necessary at all. This single center pilot study reports on the feasibility, safety, and efficacy of single agent immunosuppression "ab initio" with either Neoral or Tacrolimus, and no routine or maintenance steroids. METHODS: A total of 64 adult patients receiving first liver grafts for a variety of indications were randomized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally. Liver biopsies were performed on postoperative days 5 and 10, and whenever else clinically indicated. Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days. A further episode of rejection after two courses of Methylprednisolone was considered to be monotherapy failure, and consequently other immunosuppressive agents, usually Prednisolone 1 mg/kg/day, was started on a regular basis, tapering slowly. RESULTS: Actuarial 1 year survival was 85% for Tacrolimus patients, and 78% for Neoral patients (P = NS), with 80% for Tacrolimus and 73.5% for Neoral at 30 months. Graft survival at 1 and 2.5 years was 73 and 62% for Tacrolimus and Neoral, respectively (P = NS). Two-thirds of patients in both groups showed biopsy evidence of acute cellular rejection. Rejection severity measured by a histological scoring system was similar for both patient groups. Additional longterm immunosuppressive therapy was necessary in 36% of patients receiving Neoral, compared with 13% of Tacrolimus patients (P = NS). No graft was lost on account of acute or chronic rejection. Short-term pulse steroid therapy to treat acute rejection was necessary for 60% of Tacrolimus patients and 40% of Neoral patients. CONCLUSION: Tacrolimus or Neoral monotherapy after liver transplantation provides adequate immunosuppression for 87% of Tacrolimus patients and 64% of Neoral patients. In this study, 33% of patients in both groups showed no evidence of acute rejection, either clinically, biochemically or histologically, and were not exposed to steroids at any time. Evaluation of the long-term morbidity related to the side effects of the immunosuppressants given as monotherapy, for example, renal impairment and posttransplant lymphoproliferative disorder, and the effect on recurrent viral hepatitis in the graft, would be suitable areas for further study.

Adult↗
PubMed1999

The effect of graded steatosis on flow in the hepatic parenchymal microcirculation.

BACKGROUND: Steatosis is a major cause of microcirculatory impairment and graft dysfunction after liver transplantation. The mechanism of this circulatory compromise is unclear. The aim of this study was to evaluate in vivo the effect of steatosis on parenchymal microcirculation and on total hepatic blood flow in an animal model. METHODS: Four groups of New Zealand White rabbits (n=24) were investigated. Group 1 were fed on normal diet (controls). In groups 2, 3, and 4 graded steatosis was induced by feeding on a high cholesterol diet (1.5%) for 4, 8, and 12 weeks, respectively. After laparotomy and exposure of the liver, total hepatic blood flow (THBF) and the hepatic parenchymal microcirculation (HPM) were measured. These parameters were correlated with the degree of histological fat infiltration classified as mild (<30%), moderate (30-60%), or severe (>60%). RESULTS: The 4-, 8-, and 12-week cholesterol diets resulted in mild, moderate, and severe steatosis, respectively. There was an inverse correlation between the degree of fat infiltration and both HPM (Spearman r=-0.967, P<0.0001) and THBF (r=-0.893, P<0.0001). THBF was 137+/-6 ml/min in controls, which reduced to 121+/-3, 99+/-5, and 63+/-5 ml/min in steatotic livers of groups 2, 3, and 4, respectively. HPM was 226+/-5 flux units in the controls and 197+/-7, 119+/-8, and 37+/-9 flux units in steatotic livers of groups 2, 3, and 4 respectively. Comparing with controls using analysis of covariance, the fall in HPM and THBF was found to be significant (P<0.002) in the moderate and severe groups, but not significant (P>0.050) in the mild group. Parenchymal perfusion was reduced to a greater extent than total liver blood flow in moderate and severe grades of steatosis. CONCLUSIONS: Fatty infiltration reduces hepatic blood flow and parenchymal microcirculation. The latter is more markedly reduced with severe steatosis. This may explain the development of microcirculatory impairment and graft failure after transplantation of fatty livers despite adequate liver blood flow.

Animals↗
PubMed1999

Improved preservation solutions for organ storage: a dynamic study of hepatic metabolism.

BACKGROUND: Organ cold storage times may be extended by modifications to organ preservation solutions. METHODS: Three preservation solutions were investigated for their ability to maintain viable hepatic bioenergetics in stored pig livers: modified University of Wisconsin (mUW); mUW+adenosine (1.34 g/L), and mUW+ iloprost (10(-8)mol/L), a prostacyclin analogue. Using human liver retrieval and storage techniques, pig livers were stored on ice for either 2 or 16 hr, after which phosphorus-31 spectra were collected every 2 min during the period of cold ischemia and hypothermic reperfusion (HtR). During HtR, metabolite concentration changes associated with phosphomonoesters, inorganic phosphate, gamma-nucleotide triphosphate (NTP), and beta-NTP were measured for all solutions. RESULTS: After a 2-hr storage, beta-NTP regeneration in mUW+iloprost produced +57.7% (P<0.01) more beta-NTP, at a faster initial rate of +66.3% (P<0.001), compared with mUW, and mUW+adenosine regenerated +35.6% (P<0.05) more beta-NTP, compared with mUW. Storage for 16 hr did not slow the rates of regeneration, and the total NTP produced during the course of the experiment remained unchanged for the respective preservation solutions. Cessation of HtR invoked a net accumulation of nucleotide diphosphate, indicating differential kinetics of adenine nucleotide hydrolysis. CONCLUSION: This large animal model study suggests significant improvements to human organ preservation solutions using prostacyclin analogues and adenosine with respect to hepatic bioenergetics.

Adenine Nucleotides↗
PubMed1999

Evolution of genetic abnormalities in hepatocellular carcinomas demonstrated by DNA fingerprinting.

Hepatocellular carcinomas (HCC) often contain subpopulations of cells showing heterogeneous differentiation within each tumour. The majority of HCCs first appear as well-differentiated lesions and proliferate with gradual dedifferentiation. The present study was designed to investigate the clonal diversity which is seen with progression in neoplasms. The degree of genomic heterogeneity of HCC nodules was assessed using the arbitrarily primed-polymerase chain reaction technique. Two or more sectors of 31 HCC nodules were needle-microdissected and amplified with two different arbitrary primers in appropriate conditions. In every HCC less than 6 mm in diameter (n=18, range 3-6 mm, mean diameter 4.7 mm), all sectors of each of these lesions had the same DNA fingerprint. All HCC nodules greater than 6 mm diameter (n=13, range 7-30 mm, mean diameter 15.4 mm) showed distinct DNA fingerprints in each sector sampled (p< 0. 05, compared with size less than 6 mm in diameter). When synchronous HCCs were present, no two tumour nodules had the same DNA fingerprint. These results suggest that a process of clonal evolution occurs in expanding HCC, with neoplasms more than 6 mm in diameter developing as multiple clones. The advent of laser capture microdissection technology makes such analysis much more rapid and easily applied. Studies of clonality in HCCs, including borderline cases, are made possible by the combination of these novel techniques.

Carcinoma, Hepatocellular↗
PubMed1999

Incorporation of metabolite prior knowledge for data analysis: biochemical implications of dynamic 31P NMR ex vivo pig liver studies.

A semi-automated, metabolite prior-knowledge-based, lineshape fitting analysis has been developed to assess the dynamic biochemical changes found in ex vivo 31P NMR pig liver preservation studies. Due to the inherent experimental limitations of the ex vivo study and the complexity of the composite phosphorus resonances, metabolite information obtained in vitro was incorporated into the ex vivo analysis. This approach has allowed complete metabolite analysis (phosphomonoesters, inorganic phosphate, phosphodiesters and nucleotide triphosphates) in over 2000 spectra in a fraction of the time compared with more conventional analysis methods. The developed analysis will enable complete and rapid assessment of the biochemical changes in ongoing cold preservation studies of the pig liver which will result in thousands of ex vivo 31P NMR spectra. It is also envisaged that comparative studies on human donor livers will be carried out, in which this type of analysis would be the method of choice. Moreover, this kind of analysis approach could be advantageous in many complex in vivo NMR spectroscopy applications.

Animals↗
PubMed1999

The effect of mechanically enhancing portal venous inflow on hepatic oxygenation, microcirculation, and function in a rabbit model with extensive hepatic fibrosis.

Enhancing the portal venous blood flow (PVBF) has been shown to reduce portal pressure and intrahepatic vascular resistance and to improve liver function in isolated cirrhotic rodent livers in vitro. The aim of this study was to assess the short-term effect of mechanically pumping the portal inflow on hepatic microcirculation (HM), oxygenation, and function in an animal model of extensive hepatic fibrosis. New Zealand white rabbits underwent laparotomy and exposure of the liver: group 1 (n = 7) were normal controls; group 2 (n = 7) had hepatic fibrosis. Total hepatic blood flow (THBF) and HM was measured along with continuous monitoring of intrahepatic tissue oxygenation using near infrared spectroscopy (NIRS). Baseline hepatic hemodynamics and liver function were measured in both groups. PVBF was then increased by 50% over a 3-hour period in the hepatic fibrosis group using a miniature portal pump designed for human implantation, and the hemodynamics were monitored continuously. Liver function tests were repeated after portal pumping. In comparison with normal controls, animals with hepatic fibrosis had a higher portal pressure (13.0 +/- 3.6 vs. 3.7 +/- 1.4 mm Hg, P <.001, mean +/- SD vs. controls), reduced PVBF (52.4 +/- 24.6 vs. 96.9 +/- 21.1 mL/min, P =.003), and increased portal vascular resistance (P =. 001). THBF and flow in the HM was lower than in controls, and liver function tests were abnormal. After a 3-hour period of enhanced portal flow in animals with hepatic fibrosis, the portal pressure greatly reduced (13.0 +/- 3.6 to 2.5 +/- 1.1 mm Hg, P <.001) as did the intrahepatic portal resistance (0.32 +/- 0.18 to 0.04 +/- 0.03 mm Hg/mL/min, P =.006). Flow in the HM improved (143 +/- 16 to 173 +/- 14 flux units, P =.006) and was associated with improved hepatic tissue oxygenation, tissue oxy-hemoglobin (HbO2) and cytochrome oxidase being increased by 24.4 +/- 7.5 and 5.65 +/- 2.30 micromol/L above the baseline value (P <.001), respectively. A 3-hour period of mechanical portal pumping produced a dramatic improvement in liver function, bilirubin (41.1 +/- 25.9 to 10.0 +/- 5.9 micromol/L, P =. 040), aspartate transaminase (AST) (135.5 +/- 52.3 to 56.3 +/- 19.8 U/L, P =.006) and lactate dehydrogenase (LDH) (2,030.1 +/- 796.3 to 1,309.8 +/- 431.6 IU/L, P =.006; prepumping vs. postpumping, all P <. 050). In conclusion, portal pumping in this rabbit model with extensive hepatic fibrosis improved liver parenchymal perfusion, oxygenation, and function.

Animals↗
PubMed1999

Prolonged lactic acidosis after extended hepatectomy under in situ hypothermic perfusion.

A 46-year-old woman underwent right extended hepatectomy under total vascular occlusion with in situ hypothermic perfusion for colorectal metastasis. Immediately after surgery, she developed severe lactic acidosis, which required correction with sodium bicarbonate solution and ventilatory support for 36 hours. After 2 days, her lactate normalized, and the acidosis was corrected. She made an uneventful recovery. Persistent lactic acidosis after major hepatic resection under in situ hypothermic perfusion is a rare but reversible problem.

Acidosis, Lactic↗
PubMed1999

Effect of graded hypoxia on hepatic tissue oxygenation measured by near infrared spectroscopy.

BACKGROUND/AIMS: In liver transplantation ischaemia-reperfusion injury of the graft reduces hepatic tissue oxygenation which has prognostic value for patient survival. Near infrared spectroscopy (NIRS) can measure extracellular (haemoglobin oxygenation) and intracellular tissue oxygenation (cytochrome oxidase oxidation). However, it has not been validated for measuring hepatic tissue oxygenation in an experimental model with graded hypoxia. METHODS: New Zealand White rabbits (2.9+/-0.3 kg, n=9) underwent laparotomy for liver exposure. Heart rate, blood pressure, temperature, arterial blood pH and blood gas partial pressures were monitored during the experiments. Near infrared spectroscopy probes were placed on the liver surface to record continuously hepatic oxyhaemoglobin, deoxyhaemoglobin and cytochrome oxidase oxidation. Graded hypoxia was achieved by stepwise reduction of the inspired oxygen from 15 to 4%. During recovery from hypoxia 30% oxygen was administered. RESULTS: There was an immediate reduction of hepatic oxyhaemoglobin with hypoxia and a simultaneous increase of hepatic deoxyhaemoglobin. Hepatic oxyhaemoglobin showed a positive correlation with arterial oxygen pressure (r=0.77, p<0.001). Hepatic deoxyhaemoglobin showed a negative correlation with arterial oxygen pressure (r=-0.75, p<0.001). Hepatic cytochrome oxidase decreased significantly with an inspired oxygen of 10% or less and showed a positive correlation with arterial oxygen pressure (r= 0.90, p<0.001). CONCLUSIONS: Near infrared spectroscopy is an effective method for monitoring hepatic extracellular and intracellular tissue oxygenation.

Animals↗
PubMed1999

Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation.

BACKGROUND: Biliary reconstruction is the Achilles heel of liver transplantation. Side-to-side anastomosis of donor and recipient bile duct has been claimed to be superior to end-to-end anastomosis in uncontrolled studies. METHODS: A total of 100 consecutive patients undergoing orthotopic liver transplantation were randomized after commencement of the transplant procedure to end-to-end or side-to-side anastomosis. No T tube drainage was employed. Endoscopic retrograde cholangiography was performed 2 weeks after transplantation and findings were reported by an experienced endoscopist as normal, leak or stricture. Median follow-up was 53 (range 35-63) months. RESULTS: Patient age, sex, the graft preservation time and indication for transplantation were similar in both groups. Sixty patients received end-to-end and 40 side-to-side anastomosis. Ten patients randomized to side-to-side anastomosis had an end-to-end procedure. The total number of biliary complications was similar in both groups (end-to-end 32 per cent versus side-to-side 30 per cent) as were the number of leaks (17 versus 18 per cent) and biliary strictures (15 versus 12 per cent). There was no difference in the number of biliary complications that required interventional treatment (22 per cent in both groups). CONCLUSION: Side-to-side and end-to-end biliary anastomosis at liver transplantation are equally effective.

Adolescent↗
PubMed1999

Experimental study of liver dysfunction evaluated by direct indocyanine green clearance using near infrared spectroscopy.

BACKGROUND: Blood clearance of indocyanine green (ICG) is an objective test of liver function. Hepatic ICG clearance can now be measured directly using near infrared spectroscopy (NIRS). The aim of this study was to evaluate measurement of hepatic ICG clearance by NIRS in an animal model of acute hepatic dysfunction. METHODS: New Zealand white rabbits (n = 36) underwent laparotomy for liver exposure. Hepatic blood flow and microcirculation were measured along with hepatic ICG concentration by NIRS. Hepatic ICG clearance was measured in groups of six animals after reduction of the hepatic blood flow by hepatic artery occlusion and portal vein partial occlusion, lobar ischaemia and reperfusion (I/R), colchicine administration and bile duct ligation. Hepatic ICG uptake and excretion rates were calculated by a non-linear least square curve fitting method from the ICG concentration-time curve. RESULTS: There was a significant positive correlation between hepatic ICG rate of uptake and both hepatic blood flow and microcirculation (r = 0.79, P = 0.0001; r = 0.59, P = 0.005 respectively). I/R resulted in a significant reduction of both the rates of ICG uptake (mean(s.d.) 0. 85(0.59) min-1; P = 0.0002 versus control) and ICG excretion (0. 020(0.006) min-1; P = 0.02 versus control). Colchicine decreased the rate of hepatic ICG excretion (0.030(0.010) min-1; P = 0.02 versus control) as did bile duct ligation (0.002(0.001) min-1; P = 0.01 versus control). CONCLUSION: Measurement of hepatic ICG clearance by NIRS is a promising technique for assessing hepatic parenchymal dysfunction and may have application in liver surgery and transplantation.

Animals↗