Indocyanine Green Blood Research Articles

Preputial pedicle flap ICG blood flow assessment during proximal hypospadias repair: Development of a standardized protocol

Blood supply to preputial flap drives outcomes ofhypospadias repair. Unfortunately, we onlyhave surgeon's subjective assessment to evaluate flap perfusion which may not be accurate. Indocyanine green (ICG) has been used inamultitude of surgeries for perfusion assessment,however, no standardized protocol has been described for use of ICG in hypospadiasrepairs. The aim of this study is to develop a standardized protocol of ICG use in proximal hypospadias and establish perfusion patterns ofpreputial flaps. A pilot study was conducted using ICG in patientswith proximal hypospadias undergoing first stage repair with a preputial flap. The Stryker SPY PHI system and novel quantification software, SPY-QP, were used for ICG imaging. An adaptive approach was taken to develop and implement a standardized protocol (Summary Figure). Per the protocol, ICG was administered at 3 time points which were felt to be critical for assessment of flap perfusion. Of the study patients who have undergone second stage repair, ICG was also usedto reassess the flap prior to tubularization ofthe urethra. A total of 14 patients underwent first stage hypospadias repair with preputial flaps and intraoperative use of ICG. Median ICG uptake of the prepuce after degloving (dose 1) was 58.5% (IQR 43-76). ICG uptake decreased after flap harvest and mobilization (dose 2) with a median ICG uptake of 34% (IQR 26-46). ICG uptake remained stable after securing the flap in place and closing the skin (dose 3) with a median ICG uptake of 34% (IQR 25-48). ICG was able to delineate subtle findings in the preputial flaps not visible to the naked eye and in one case impacted intraoperative decision making. To date, 5 patients have undergone second stage repair. Flap assessment prior to tubularization of the urethra showed hypervascularity with a median ICG uptake of 159%. A standardized protocol for ICG use in proximal hypospadias was successfully developed and implemented. ICG uptake in the preputial flap decreased with increasing manipulation and mobilization of the flap. ICG was able to detect changes to flap perfusion which were not able to be seen with the naked eye. Reliance on surgeon'ssubjective assessment of flap perfusion may be inadequate and ICG could provide a useful tool for surgeons to improve preputial flap outcomes. ICG may also enhance the learning experience for trainees and early career urologists in these complex surgeries.

A novel imaging technology to assess tissue oxygen saturation and its correlation with indocyanine green in the gastric conduit during thoracic esophagectomy

BackgroundAnastomotic leakage in esophagectomy is a serious complication, and assessing blood perfusion in the conduit can help minimize this risk. Indocyanine green is the most widely used method to assess tissue blood flow; however, this technique has disadvantages. Evaluating tissue oxygen saturation in the gastric conduit during thoracic esophagectomy compared with indocyanine green blood perfusion assessment addresses these disadvantages and can be performed easily and repeatedly. MethodsThis was a prospective study of patients with esophageal cancer who underwent thoracic esophagectomy. Intraoperative tissue oxygen saturation and indocyanine green measurements were obtained to determine the anastomotic site and to compare the correlation between the 2 methods. Tissue oxygen saturation and indocyanine green values were obtained at the tip of the gastric conduit, the demarcation line indicating visible perfusion, and the end of the right gastroepiploic artery. ResultsFifty-seven patients were enrolled in this study; 3 developed anastomotic leakage, and all 3 underwent robotic thoracic surgery. The tissue oxygen saturation value decreased gradually toward the tip of the conduit, as did congestion, and was significantly decreased at the tip compared with the value at the demarcation line (P = .001). Mean tissue oxygen saturation differed significantly between the leakage and no-leakage groups at the anastomosis site (P = .04). We found a negative correlation between tissue oxygen saturation and indocyanine green values at the end of the right gastroepiploic artery (r = −0.361; P = .03). ConclusionTissue oxygen saturation imaging was useful in determining the anastomotic site and addressed the disadvantages associated with indocyanine green.

A TMVP1-modified near-infrared nanoprobe: molecular imaging for tumor metastasis in sentinel lymph node and targeted enhanced photothermal therapy

BackgroundTMVP1 is a novel tumor targeting polypeptide screened by our laboratory with a core sequence of five amino acids LARGR. It specially binds to vascular endothelial growth factor receptor-3 (VEGFR-3), which is mainly expressed on neo-lymphatic vessels in sentinel lymph node (SLN) with tumor metastasis in adults. Here, we prepared a targeted nanoprobe using TMVP1-modified nanomaterials for tumor metastasis SLN imaging.ResultsIn this study, TMVP1-modified polymer nanomaterials were loaded with the near-infrared (NIR) fluorescent dye, indocyanine green (ICG), to prepare a molecular imaging TMVP1-ICG nanoparticles (NPs) to identify tumor metastasis in SLN at molecular level. TMVP1-ICG-NPs were successfully prepared using the nano-precipitation method. The particle diameter, morphology, drug encapsulation efficiency, UV absorption spectrum, cytotoxicity, safety, and pharmacokinetic properties were determined. The TMVP1-ICG-NPs had a diameter of approximately 130 nm and an ICG loading rate of 70%. In vitro cell experiments and in vivo mouse experiments confirmed that TMVP1-ICG-NPs have good targeting ability to tumors in situ and to SLN with tumor metastasis by binding to VEGFR-3. Effective photothermal therapy (PTT) with TMVP1-ICG-NPs was confirmed in vitro and in vivo. As expected, TMVP1-ICG-NPs improved ICG blood stability, targeted tumor metastasis to SLN, and enhanced PTT/photodynamic (PDT) therapy, without obvious cytotoxicity, making it a promising theranostic nanomedicine.ConclusionTMVP1-ICG-NPs identified SLN with tumor metastasis and were used to perform imaging-guided PTT, which makes it a promising strategy for providing real-time NIR fluorescence imaging and intraoperative PTT for patients with SLN metastasis.

Association between indocyanine green fluorescence blood flow speed in the gastric conduit wall and superior mesenteric artery calcification: predictive significance for anastomotic leakage after esophagectomy.

Near-infrared fluorescence using indocyanine green (ICG) has been applied as a real-time navigation tool to observe blood flow in gastric conduit wall after esophagectomy. Atherosclerosis might impair the blood flow of the systemic organs. The aim of the study was to investigate the significances of ICG blood flow speed in the gastric conduit wall and atherosclerotic calcification for the prediction of anastomotic leakage after esophagectomy. The 109 esophageal cancer patients were prospectively enrolled. ICG fluorescence blood flow speed in the gastric conduit wall and abdominal aortic calcification index (ACI), celiac artery (CA) calcification, and superior mesenteric artery (SMA) calcification were determined. Then, the correlation between ICG fluorescence blood flow speed and anastomotic leakage as well as ACI, CA, and SMA calcification were evaluated. Anastomotic leakage occurred in 15 patients. ACI ranged from 0 to 65. CA calcification and SMA calcification were present in 25 and 12 patients. Multivariate analysis demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall of 2.07cm/s or less (P < 0.001) and SMA calcification (P = 0.026) were the significant independent predictors of anastomotic leakage. Only SMA calcification was significantly associated with ICG fluorescence blood flow speed in the gastric conduit wall (P = 0.026). This study demonstrated that ICG fluorescence blood flow speed in the gastric conduit wall can predict anastomotic leakage after esophagectomy and microvascular perfusion of capillary vessels of the gastric conduit might be impaired by systemic atherosclerosis.

Use of finger-piece method for indocyanine green clearance test.

The indocyanine green (ICG) finger-piece method (FPM), which allows measurement of the ICG concentration by mounting a light sensor onto a finger, is used to assess liver function. We compared the ICG FPM with the conventional ICG blood sampling method (BSM) in patients with liver disorders. Ninety consecutive patients simultaneously underwent the ICG BSM and ICG FPM. After ICG administration, blood samples were collected at 5, 10, and 15min for the ICG BSM. The ICG concentration was measured through the finger piece by an ICG clearance meter. Seventy-one patients (78.9%) had Child-Pugh class A liver disease, and 19 (21.1%) had class B or C. The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values (r = 0.886, P <0.001). Bland-Altman analysis showed good agreement between the two methods (mean difference, 0.012 ± 0.018). The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values both in patients with Child-Pugh class A liver disease (r = 0.821, P <0.001) and class B or C liver disease (r = 0.859, P <0.001). The ICG FPM may be an alternative to the ICG BSM for liver function assessment.

Age-related changes in pial arterial structure and blood flow in mice

Age-related cerebral blood flow decreases are thought to deteriorate cognition and cause senescence, although the related mechanism is unclear. To investigate the relationships between aging and changes in cerebral blood flow and vasculature, we obtained fluorescence images of young (2-month-old) and old (12-month-old) mice using indocyanine green (ICG). First, we found that the blood flow in old mice's brains is lower than that in young mice and that old mice had more curved pial arteries and fewer pial artery junctions than young mice. Second, using Western blotting, we determined that the ratio of collagen to elastin (related to cerebral vascular wall distensibility) increased with age. Finally, we found that the peak ICG intensity and blood flow index decreased, whereas the mean transit time increased, with age in the middle cerebral artery and superior sagittal sinus. Age-related changes in pial arterial structure and composition, concurrent with the observed changes in the blood flow parameters, suggest that age-related changes in the cerebral vasculature structure and distensibility may induce altered brain blood flow.

Relationship between Indocyanine Green Clearance Test and Feed Intake and Impaired Hepatic Function in Dairy Cows

The purposes of this study were 1) to examine changes in the indocyanine green (ICG) clearance by feeding and 4-day fasting in dry cows, and (2) to investigate the relationship between ICG clearance and blood chemistry profile in postpartum cows. In 3 dry cows, post-feeding ICG half-life (T(1/2)) was shorter than the pre-feeding value, and post-fasting T(1/2) was longer than pre-feeding and post-feeding values. In 16 lactating cows, T(1/2) value at 2 weeks postpartum showed positive correlations with AST, T-Bil and γ-GTP. These results suggested that ICG clearance correlated with T-Bil and liver enzymes can be sensitive and accurate diagnostic marker for impaired liver function in dairy cows. In addition, ICG clearance is greatly affected by feeding and fasting.

Indocyanine green clearance varies as a function of N-acetylcysteine treatment in a murine model of acetaminophen toxicity

Standard assays to assess acetaminophen (APAP) toxicity in animal models include determination of ALT (alanine aminotransferase) levels and examination of histopathology of liver sections. However, these assays do not reflect the functional capacity of the injured liver. To examine a functional marker of liver injury, the pharmacokinetics of indocyanine green (ICG) were examined in mice treated with APAP, saline, or APAP followed by N-acetylcysteine (NAC) treatment.Male B6C3F1 mice were administered APAP (200 mg/kg IP) or saline. Two additional groups of mice received APAP followed by NAC at 1 or 4 h after APAP. At 24 h, mice were injected with ICG (10 mg/kg IV) and serial blood samples (0, 2, 10, 30, 50 and 75 min) were obtained for determination of serum ICG concentrations and ALT. Mouse livers were removed for measurement of APAP protein adducts and examination of histopathology. Toxicity (ALT values and histology) was significantly increased above saline treated mice in the APAP and APAP/NAC 4 h mice. Mice treated with APAP/NAC 1 h had complete protection from toxicity. APAP protein adducts were increased in all APAP treated groups and were highest in the APAP/NAC 1 h group. Pharmacokinetic analysis of ICG demonstrated that the total body clearance (Cl T) of ICG was significantly decreased and the mean residence time (MRT) was significantly increased in the APAP mice compared to the saline mice. Mice treated with NAC at 1 h had Cl T and MRT values similar to those of saline treated mice. Conversely, mice that received NAC at 4 h had a similar ICG pharmacokinetic profile to that of the APAP only mice. Prompt treatment with NAC prevented loss of functional activity while late treatment with NAC offered no improvement in ICG clearance at 24 h. ICG clearance in mice with APAP toxicity can be utilized in future studies testing the effects of novel treatments for APAP toxicity.

The Adaptive Response of the Reticuloendothelial System to Major Liver Resection in Humans

To evaluate the contribution of the liver to total circulatory reticuloendothelial system (RES) phagocytosis capacity in patients undergoing liver resection and to compare it with values in end-stage chronic liver disease. The mechanism whereby major liver resection is associated with a high incidence of infection is unknown. Significant impairment of RES phagocytosis has been described in liver failure, rendering such patients susceptible to infection; and we hypothesized that similar impairment might occur following major liver resection. A prospective study was conducted in which Tc-albumin microspheres blood clearance served as a parameter for RES phagocytosis and was studied together with indocyanine green blood clearance, actual liver volume measured by three-dimensional image analysis, and a clinical score of hepatic dysfunction in 17 patients undergoing liver resection and in 8 patients with end-stage chronic liver disease assessed for liver transplantation. When expressed relative to volume unit of residual liver, microspheres clearance increased significantly in the immediate postoperative period (day 1) following major (0.009% versus 0.022% min(-1) mL(-1), P < 0.001), but not minor liver resection. In contrast, the absolute rate of microsphere clearance decreased following major resection (15% min(-1) versus 10% min(-1), P < 0.001) and was comparable with the rate observed in end-stage chronic liver disease (9% min(-1)). This decrease in circulatory microspheres clearance after resection paralleled a decrease in indocyanine green clearance (R2 = 0.511, P = 0.006), and there was a trend for those with moderate liver dysfunction to have lower microspheres clearance rates (P = 0.068). Preservation of a minimum volume of functioning liver is a prerequisite for adequate RES phagocytosis capacity, and failure of this system may predispose patients undergoing major liver resection to infection as observed in clinical studies.

Relation between indocyanine green (ICG) plasma disappearance rate and ICG blood clearance in critically ill patients

In contrast to indocyanine green (ICG) blood clearance, the plasma disappearance rate (PDR) of ICG does not require absolute ICG blood concentrations and today can be assessed transcutaneously. In this study, we analyzed the relation between ICG disappearance rate and ICG blood clearance as parameters of liver function in critically patients. Observational, clinical study. Retrospective analysis. Operative intensive care unit of a university hospital. 209 patients (139 male, 70 female, age 10-88 years, 53+/-19 years) who underwent liver function monitoring for clinical indication. Patients suffered from sepsis (n=99), acute respiratory distress syndrome (n=31), severe head injury (n=38), hemorrhagic shock (n=19), intracranial hemorrhage (n=19), and cerebral infarction (n=3). All patients were sedated and mechanically ventilated via an endotracheal tube. All patients were monitored by the transpulmonary double-indicator (thermo-dye dilution) technique using a thermistor and calibrated fiber-optic system (Pulsiocath 4F, PV 2024L, Pulsion Medical Systems, Munich, Germany). For each measurement, a dosage of 0.3 mg/kg ICG was injected central-venously. Transpulmonary ICG concentration curves were analyzed automatically using a computer system (COLD-Z021, Pulsion Medical Systems, Munich, Germany). By using the first ICG measurement in each patient after admission to the ICU, we analyzed 209 pairs of ICG disappearance rate and ICG blood clearance. Linear regression analysis revealed a correlation of r2=0.77 between ICG-PDR and ICG blood clearance. ICG-PDR does reflect ICG blood clearance with sufficient accuracy in critically ill patients and may be used as a surrogate.

Monitoring global volume-related hemodynamic or regional variables after initial resuscitation: What is a better predictor of outcome in critically ill septic patients?*

Regional variables of organ dysfunction are thought to be better monitoring variables than global pressure-related hemodynamic variables. Whether a difference exists between regional and global volume-related variables in critically ill patients after resuscitation is unknown. Prospective diagnostic test evaluation. University-affiliated mixed intensive care unit. Twenty-eight critically ill patients. Using standardized resuscitation, hemodynamic optimization was targeted at mean arterial pressure, heart rate, occlusion pressure, cardiac output, systemic vascular resistance, and urine output. Primary outcome variable was in-hospital mortality. During resuscitation, global volume-related hemodynamic variables were measured simultaneously and compared with regional variables. At admission no variable was superior as a predictor of outcome. During resuscitation, significant changes were seen in mean arterial pressure, central venous pressure, oxygen delivery, systemic vascular resistance, total blood volume, right heart and ventricle end-diastolic volume, right ventricle ejection fraction, right and left stroke work index, intramucosal carbon dioxide pressure, gastric mucosal pH, mucosal-end tidal Pco2 gap, indocyanine green blood clearance, indocyanine green plasma clearance, and plasma disappearance rate. Multivariate analysis identified lactate, gastric mucosal pH, mucosal-end tidal Pco2 gap, mucosal-arterial Pco2 gap, indocyanine green plasma clearance, and plasma disappearance rate of dye as nondependent predictors of outcome. Patients who subsequently died had a significantly lower gastric mucosal pH, higher intramucosal carbon dioxide pressure and mucosal-end tidal Pco2 gap, and lower indocyanine green blood clearance, indocyanine green plasma clearance, plasma disappearance rate, and right ventricular end-diastolic volume index, of which gastric mucosal pH, mucosal-end tidal Pco2 gap, and indocyanine green blood clearance were the most important predictors of outcome. Initial resuscitation of critically ill patients with shock does not require monitoring of regional variables. After stabilization, however, regional variables are the best predictors of outcome.

Estimation of circulating blood volume in infants using the pulse dye densitometry method

Estimation of hemodynamics is important for critically ill infants. Pulse dye densitometry (PDD) using indocyanine green (ICG), which enables measurements of circulating blood volume at the bedside, has recently been developed for adults. We conducted a basic investigation to determine whether this method can be applied to infants and measured circulating blood volume in 25 infants whose gestational ages ranged from 24 to 40 weeks (median, 32 weeks). At first, to validate the accuracy of measurements, arterial ICG concentrations determined by blood sample measurements were compared using a spectrophotometer ([ICG blood]) and by noninvasive measurement using PDD ([ICG pdd]) in seven infants. Next, blood volumes in 25 infants were estimated by the PDD method. There was a positive relationships between [ICG blood] and [ICG pdd] (r = 0.913, P < 0.0001). Using Bland Altman analysis, the bias between the two methods was 0.24 +/- 0.30 mg.l(-1) (95% confidence interval: 0.39-0.09 mg.l(-1)) and the limits of agreement (2 sd) were -0.36 and 0.84 mg.l(-1), respectively. Mean (sd) blood volume was 94.9 ml.kg(-1) (24.3). The values obtained by this study are almost the same as previously reported values obtained by using other methods. PDD using ICG can be used to monitor of hemodynamics in infants.

Thermal injury decreases hepatic blood flow and the intrinsic clearance of indocyanine green in the rat.

The influence of severe thermal injury (full-thickness burns involving 50% of the body surface area) on hepatic blood flow in the rat was assessed using the tricarbocyanine dye indocyanine green (ICG). In a randomized crossover fashion, rats received sequential infusions of ICG through both the femoral vein and the portal vein, allowing the estimation of total hepatic plasma clearance and transhepatic extraction of the dye. These two parameters, along with the hematocrit, were used to calculate intrinsic hepatic clearance of ICG and hepatic blood flow. Animals were examined at 0 (control), 0.5, 12, or 24 hr following infliction of scald burns. Hepatic blood flow was decreased significantly by 0.5 hr postburn and remained approximately 20% below normal throughout the remainder of the study. The intrinsic efficiency of the liver in removing ICG from the systemic circulation was also decreased by thermal injury. The potential mechanisms involved in these two physiologic perturbations are discussed.

Effects of Single‐Dose and Short‐Term Oral Nifedipine on Indocyanine Green Clearance as Assessed by Spectrophotometry and High Performance Liquid Chromatography

The effects of single-dose (10 mg) and short-term (10 mg tid) nifedipine treatment on apparent hepatic blood flow, as assessed by indocyanine green (ICG) clearance, were studied in ten healthy male subjects. ICG was measured by both spectrophotometric and high performance liquid chromatography (HPLC) assay methods. Blood clearance of ICG and apparent hepatic blood flow were increased by 30 and 50%, respectively, after single-dose nifedipine, whereas after 4 days' treatment these values were 12 and 30%. The spectrophotometric assay significantly overestimated ICG plasma concentrations from 7 minutes onwards. Although the spectrophotometric and HPLC assay showed marked differences in calculated half-lives and volume of distribution of ICG, the ICG clearance values were similar for the two assay methods.

Changes in hepatic blood volume on galactose and indocyanine green uptake by cat liver.

The liver has important functions as a blood volume reserve and in uptake and metabolism of many substrates. This study examines whether changes in hepatic blood volume modify the uptakes of model substrates galactose and indocyanine green (ICG) in cats anesthetized with pentobarbital sodium. A hepatic venous long-circuit technique with an extracorporeal reservoir was used to control hepatic flow and venous pressure and to allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic blood volume was measured by plethysmography. Galactose and ICG were infused intravenously at constant rates for 200 min in each of three series of experiments. The first series were time controls. In the second series, hepatic blood volume was increased by raising hepatic venous pressure. In the third series hepatic blood volume was decreased by hepatic nerve stimulation and infusions of norepinephrine and angiotensin. Hepatic congestion resulted in small increases in blood galactose levels, suggesting mild impairment of hepatic galactose metabolism. Decreases in liver blood volume did not modify hepatic galactose metabolism. Increases in hepatic blood volume facilitated while decreases inhibited ICG uptake, but the effects were small. Sinusoidal velocity and transit time have minor effects on uptake even for protein-bound substrates. In summary, large changes in hepatic blood volume had minor effects on galactose and ICG blood concentrations, suggesting that the metabolic functions of the liver are essentially independent of the blood reservoir function.

The influence of verapamil and nifedipine on hepatic indocyanine green clearance in patients with HBsAg-positive cirrhosis and ascites.

The influence of verapamil and nifedipine on hepatic indocyanine green kinetics was studied in 12 patients with HBsAg-positive cirrhosis and ascites. Hepatic clearance and its two biologic determinants, hepatic blood flow and metabolic activity (intrinsic clearance [maximum velocity/metabolite elimination rate constant, or Vmax/km]), were determined from hepatic indocyanine green elimination at steady state in patients with cirrhosis. Acute intravenous administration 10 mg verapamil significantly increased the hepatic indocyanine green blood flow (p less than 0.05), but significantly decreased the hepatic clearance (p less than 0.05), extraction ratio (p less than 0.05) and Vmax/km (p less than 0.05). However, acute sublingual administration of 10 mg nifedipine resulted in no significant change in any parameters of hepatic elimination function. These results show that verapamil, but not nifedipine, might impair the transhepatic extraction activity of hepatocytes in patients with HBsAg-positive cirrhosis and ascites.

Effect of carbohydrates on estimated hepatic blood flow.

Recent experiments suggest that propranolol taken orally with a carbohydrate-rich meal increases its apparent bioavailability by reducing first-pass metabolism. It has been postulated that this increase in bioavailability may be secondary to a transient increase in hepatic blood flow (QH). To examine this hypothesis, we examined the effect of one of the carbohydrate meals (potato) tested in other propranolol studies on QH by measuring blood clearance (ClB) of indocyanine green (ICG). Ten minutes after eating 200 gm cooked potato, mean ICG blood clearance (ClB) in six subjects rose by 12% (range -13% to +41%). There also was a 10% mean increase (range -13% to +23%) in ICG ClB 60 min after the meal. It was then postulated that a larger carbohydrate meal might induce a more consistent and substantial increase in ICG ClB; therefore, five of the subjects were restudied after 400 gm potato. The increase in ICG ClB was of the order of that after 200 gm. Changes in QH of this magnitude would be expected to make a negligible contribution to the mean 50% increase in propranolol bioavailability reported by several investigators. It thus appears that factors other than change in QH play a dominant role in the reduced first-pass metabolism of propranolol after a meal rich in carbohydrates.

Blood clearance tests for detecting 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatotoxicity in rats and rabbits.

The objective was to determine if a blood clearance test would detect liver dysfunction in rats and rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Guinea pigs were included as a negative control, because TCDD does not produce detectable hepatotoxicity in this species. TCDD was given as a single dose to male rats (25 microgram/kg, po), rabbits (25 microgram/kg, ip) and guinea pigs (2 microgram/kg, ip) and liver function was assessed 10 days later by determining blood clearance of indocyanine green (ICG) and ouabain. Activity in serum of sorbitol dehydrogenase (SDH), glutamic pyruvic transaminase (SGPT) and gamma glutamyl transpeptidase (gamma GTP) were also measured and light microscopy performed on the liver. The results showed that hepatotoxicity in the rabbit could be detected by a reduction in ICG blood clearance and an elevation in SDH activity. In the rat, ouabain blood clearance was reduced and SDH activity elevated. None of the liver function tests were altered in the guinea pig. These results underline the usefulness of blood clearance tests using ICG and ouabain in detecting TCDD hepatotoxicity in animals.

Effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin on indocyanine green blood clearance in rhesus monkeys

To assess effects of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) on liver function adult male rhesus monkeys were treated with a single oral dose of acetone/corn oil (control) or 5, 25, or 75 μg/kg TCDD. Each monkey was used as its own control and indocyanine green (ICG) blood clearance and the following serum enzymes: glutamic pyruvate transaminase (SGPT), sorbitol dehydrogenase (SDH) and gamma glutamyl transpeptidase (γGTP), were measured at regular intervals for 4 weeks before and 17 weeks after treatment. In control monkeys ICG blood clearance and serum enzymes were similar before and after treatment. However, in the monkey that received 5 μg/kg TCDD there was a mild increase in ICG blood clearance followed by a slight decrease. The magnitude of this biphasic change was greater in monkeys that received 25 and 75 μg/kg TCDD and the decrease in clearance was invariably associated with a 1–2-week period before the monkeys died. SDH and SGPT activities were elevated at some time during the course of intoxication in TCDD-treated monkeys but γGTP activity was not altered. The monkey treated with 5 μg/kg TCDD survived but monkeys treated with 25 and 75 μg/kg died 4–6 weeks after treatment. Light microscopy of the livers of TCDD-treated monkeys that died revealed fatty infiltration with minimal hepatocellular necrosis.