Indocyanine Green Method Research Articles

Hepatic hemodynamics and cell functions in human and experimental sepsis.

Hepatic hemodynamics and cell functions in human and experimental sepsis.

Detection of histamine-induced capillary protein leakage and hypovolaemia by determination of indocyanine green and glucose dilution method in dogs.

The plasma volume of histamine-induced protein capillary leakage may be overestimated when this is determined using the indocyanine green (ICG) dilution method (Vd-ICG), since this dye binds to plasma proteins. The initial distribution volume of glucose (IDVG) has been shown to indicate the central extracellular fluid volume including plasma. Accordingly, the overestimation would be detected by a higher Vd-ICG/IDVG ratio. Our study was intended to examine whether the simultaneous measurement of these two variables can evaluate histamine-induced protein leakage and associated hypovolaemia. Prospective animal study. Institutional animal research laboratory. Twenty-four anaesthetized and ventilated mongrel dogs. Anaesthetized animals were mechanically ventilated and received infusions of normal saline (n = 8), histamine 50 microg/kg per h (n = 8), or histamine 100 microg/kg per h. The Vd-ICG and IDVG were calculated using a one-compartment model by simultaneous administration of ICG 0.5 mg/kg, and glucose 100 mg/kg followed by serial arterial blood sampling. In both histamine groups, a significant elevation of haematocrit and a decrease of plasma albumin concentration were found (p<0.05). Although the IDVG decreased following histamine administration (p<0.05), the Vd-ICG remained unchanged. The Vd-ICG/IDVG ratio increased in a dose-dependent manner after histamine administration (p<0.05), but remained unchanged following normal saline administration. The results suggest that the Vd-ICG/IDVG ratio and the IDVG are useful in evaluating the magnitude of the leakage and hypovolaemia.

Does hepato-splanchnic VO2/DO2 dependency exist in critically ill septic patients?

Since the gradient between the mixed venous and hepatic vein oxygen saturation (DSO2) is often increased in septic patients, we suspected these patients may have an imbalance between oxygen supply and demand in the hepato-splanchnic area. In 42 septic patients, hepato-splanchnic blood flow was determined by the indocyanine green clearance method with hepatic vein catheterization. The relationships between hepato-splanchnic oxygen delivery (DO2spla) and consumption (VO2spla) were analyzed during an increase in blood flow induced by a dobutamine infusion at doses up to 10 microg/kg x min. In 14 patients, positive end-expiratory pressure (PEEP) was also increased up to 20 cm H2O. The patients were separated according to their DSO2 (Group I: DSO2 < 10%, n = 13; and Group II: DSO2 > 10%, n = 29). Although DO2spla increased similarly in both groups, VO2spla only increased in Group II (from 45+/-22 to 59+/-39 ml/min x M2, p < 0.01). The slope of the VO2spla/DO2spla relationship was higher in Group II than in Group I (31.2+/-16.7 versus 10.4+/-5.1%, p < 0.001) and was similar during dobutamine and PEEP (21.9+/-14.2 versus 21.9+/-14.0%, p = NS). In conclusion, VO2spla increased only in septic patients with an increased DSO2 indicating splanchnic dysoxia. The similar slope observed with dobutamine and PEEP suggests that a thermogenic effect was unlikely.

Effects of R80122, a New Phosphodiesterase Inhibitor, on Liver and Global Haemodynamics in Patients Undergoing Coronary Artery Bypass Surgery

R80122 (0.3 mg/kg body weight), a new phosphodiesterase inhibitor, was tested in ten patients undergoing coronary artery bypass surgery. Haemodynamic measurements were made and hepatic blood flow assessed by the indocyanine green infusion method using liver vein catheterization. Cardiac index increased by 63% and systemic vascular resistance decreased by 47%. Hepatic blood flow and intestinal vascular resistance were not significantly affected; nor was hepatic oxygen consumption. It is concluded that R80122 is a highly cardioselective phosphodiesterase inhibitor and that the reduction in systemic vascular resistance by this drug is not an effect of extensive intestinal vasodilatation.

Measurement of circulating blood volume in vivo after trauma-hemorrhage and hemodilution.

Although cardiac output (CO) and other hemodynamic variables are used to assess the adequacy of fluid resuscitation after hemorrhage, it is not known whether there is any correlation between restoration of CO and circulating blood volume (CBV). To determine this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximum bleedout volume was returned in the form of Ringer lactate (RL). The animals were then resuscitated with four or five times the volume of maximum bleedout in the form of RL. CO and hepatocellular function were measured using an in vivo hemoreflectometer. CBV was monitored by using in vivo indocyanine green clearance. A good correlation between the values of blood volume obtained by this method and the 125I-albumin method indicates that the indocyanine green method is also a reliable technique for measuring CBV. Results indicate that resuscitation after hemorrhage improved the decreased CBV but did not restore it to control levels despite the fact that CO was restored and central venous pressure was more than doubled. A good correlation between depressed CBV and hepatocellular dysfunction was also observed under such conditions. Thus measurement of CBV appears to be useful for evaluating the adequacy of fluid resuscitation after trauma-hemorrhage and hemodilution.

Clinical applications of ICG Finger Monitor in patients with liver disease

The indocyanine green (ICG) Finger Monitor system is a non-invasive indication of ICG concentrations in the blood. In this study, significant correlation was found between the sensor signal voltage and plasma ICG concentrations ranging from 0.04 mg/dl to 1.0 mg/dl (r = 0.998, P < 0.001) in vivo. The ICG clearance curve showed an initial sharp rise 20-30 s after bolus injection, followed by a small rise. The concentration then deceased exponentially. In 196 patients with chronic liver disease, there was a close correlation between the KICG (plasma disappearance rate) and R15 (blood retention ratio at 15 min) (r = 0.886, P < 0.001, r = 0.912, P < 0.001) and corresponding values calculated by the conventional ICG method. In 263 cases with chronic liver disease, the plasma disappearance rates calculated using this monitor (mean +/- S.D.) were 0.156 +/- 0.064 (n = 20) in the control group, 0.129 +/- 0.060 (n = 92) in the chronic hepatitis group, 0.048 +/- 0.025 (n = 59) in the cirrhosis group and 0.059 +/- 0.03, (n = 92) in the group with hepatocellular carcinoma. A significant difference in the plasma disappearance rate and blood retention ratios 15 min after injection of ICG using this system was observed between control cases and the chronic hepatitis and cirrhosis groups (P < 0.0001). In 36 cases, the time from injection to the appearance of ICG in the fingertip significantly decreased in the cirrhosis group (P < 0.01). The ICG Finger Monitor system was shown to be useful clinically as well as for research due to its accuracy and non-invasive nature.

Combined evaluation of total and functional liver plasma flows and intrahepatic shunting

A diagnostic protocol was studied, designed to evaluate the main parameters of liver circulation in man. A water solution of D-sorbitol (S) and indocyanine green (ICG) was infused intravenously in six controls and nine cirrhotics. Steady-state renal and hepatic S clearances as well as hepatic ICG clearance were calculated. In controls the values (mean +/- SD) of the independent measurements of S and ICG hepatic clearance were 978 +/- 107 and 519 +/- 142 ml/min, respectively, while in cirrhotic patients they were 554 +/- 238 and 231 +/- 90 ml/min. Owing to the kinetic properties of S, its hepatic clearance may be regarded as a measure of functional liver plasma flow (FLPF). The total liver plasma flow (TLPF) values (mean +/- SD), calculated according to Fick's principle, were 1091 +/- 157 ml/min (S method) and 1033 +/- 153 ml/min (ICG method) in controls, and 1251 +/- 554 and 1284 +/- 677 ml/min in cirrhotics. In controls, FLPF was found to be very close to TLPF. In cirrhotic patients the difference between TLPF and FLPF (ranging from 169 to 2093 ml/min when measured by S method) was considered as an approximate estimate of intrahepatic shunting. The procedure is safe and simple and may add a new dimension to the investigation of hepatic circulation.

Effect of receptor up-regulation on insulin pharmacokinetics in streptozotocin-treated diabetic rats.

The present study investigated the mechanism by which the disposition of insulin is altered in streptozotocin (STZ)-treated diabetic rats as compared with 48-hr-fasted normal (control) rats. It was shown by an indocyanine green infusion method that the hepatic plasma flow rate (QH) in diabetic rats (1.64 ml/min/g liver) is significantly higher than that in control rats (0.982 ml/min/g liver). The portal injection technique revealed that the unidirectional clearance (CLon), which represents the binding of A14-125I-insulin to surface receptors in the liver, is significantly elevated in diabetic rats, suggesting an increase in the surface receptor number (RT), i.e., up-regulation in the liver. In both control and diabetic rats, the total-body clearance (CLtot) and steady-state volume of distribution (Vdss) of labeled insulin decreased significantly with a simultaneous injection of unlabeled insulin (8 U/kg), confirming that the disposition of insulin is affected largely by specific, saturable receptor-mediated processes. The CLtot and Vdss increased significantly in diabetic rats, while nonspecific portions of these parameters were not changed. From the increases in CLtot (80%) and QH (67%) in diabetic rats, a pharmacokinetic analysis has revealed a 40% increase in the hepatic intrinsic clearance (CLint,sp) of A14-125I-insulin via a specific mechanism in diabetic rats. In conclusion, we have provided in vivo evidence for a small increase in CLint,sp of insulin in STZ-diabetic rats compared with control rats, which may be caused by an increase in the surface receptor number in the livers of diabetic rats.

Increased extravascular lung water in patients with low pulmonary artery occlusion pressure after acute myocardial infarction

To evaluate the clinical characteristics of increased extravascular lung water (EVLW) in patients with low pulmonary artery occlusion pressure (PAOP) in the early phase of acute myocardial infarction. Consecutive sample for descriptions of the clinical features of medical disorders. A general medicine group practice in a university hospital. Sixteen patients with low PAOP (less than 18 mm Hg) on the initial measurement obtained within 12 hr of chest pain onset. EVLW was measured by the thermal indocyanine green dye double-indicator dilution method. QRS score was obtained on hospital day 7 from the Selvester's QRS Scoring System. Eleven (69%) patients had increased EVLW greater than 7 mL/kg despite low PAOP. EVLW had no significant correlation with PAOP and the difference between plasma colloid osmotic pressure and PAOP, but did have a significant correlation with pulmonary vascular resistance index (r2 = .31, p less than .05), and QRS score (r2 = .45, p less than .005). Larger infarcts led to increased EVLW even with low PAOP, and the accumulation of increased EVLW around the small arterioles might have led to increased pulmonary vascular resistance.

Assessment of the sensitivity of hydrogen inhalation in the detection of left‐to‐right shunting

For the detection of left-to-right intracardiac shunting, the oximetric and standard indocyanine green techniques are relatively insensitive, in that neither can reliably detect a shunt with a ratio of pulmonary to systemic flow (Qp/Qs) less than 1.3 (percentage shunt, 23%). Although the hydrogen inhalation method is said to be much more sensitive in this regard, no previous study has measured its sensitivity. Accordingly, in 15 patients (4 men, 11 women, aged 38 to 67 years) without intracardiac shunting, hydrogen inhalation was performed 1) without and 2) with an artificially created femoral arteriovenous shunt of known size, and cardiac output was measured by thermodilution. For the 15 subjects with cardiac outputs of 3.64 to 8.10 liters/min, shunts of 22 to 248 ml/min were created, so that the shunts ranged from 0.5% to 3.3%. Hydrogen inhalation detected all shunts greater than or equal to 1.3% (Qp/Qs greater than or equal to 1.01). Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods.

Detection of intracardiac left-to-right shunting in adults: A prospective analysis of the variability of the standard indocyanine green technique in patients without shunting

Intracardiac left-to-right shunting may be detected and quantitated by an oximetric analysis of blood from the right-sided cardiac chambers and prominent early recirculation of indocyanine green after it is injected into the central venous circulation and sampled from a systemic artery. Although the variability of oximetric measurements has been established in patients without shunting and a range of normal has been determined for the technique, the variability of the indocyanine green method among persons without shunting has not been clarified; as a result, a range of normal for indocyanine green has not been established. In 66 adult patients in whom hydrogen inhalation (an extremely sensitive technique for detecting even very small intracardiac left-to-right shunts) revealed no shunting, indocyanine green curves were generated by injection into the pulmonary artery as blood was sampled from a systemic artery. In these patients the percentage left-to-right shunt (that is, the percentage of pulmonary blood flow reaching the lungs through an intracardiac shunt) (determined with the equation of Carter et al) ranged from −9% to +26% (+7 ± 8%, mean ± standard deviation). There was no definable relation between the percentage left-to-right shunt and the indicator dilution measurement of cardiac output. Thus, these data establish a range of normal for the indocyanine green technique of detecting and measuring intracardiac left-to-right shunting. If this technique is to be used reliably to detect shunting, its results must demonstrate a percentage shunt in excess of +26%.

Role of acidosis in regulating hepatic nitrogen metabolism during fasting in conscious dog.

This study was designed to investigate the role that acidosis plays in the metabolic responses to fasting. Eighteen conscious dogs with surgically implanted catheters in the femoral artery and in the hepatic, portal, and renal veins were studied. Six were fasted for 24 h and 12 were fasted for 4 days (96 h). On the day of the study, six 4-day fasted dogs were infused intravenously with NaHCO3 (10 mumol X kg-1 X min-1) for 3 h, while the rest received saline and acted as controls. Splanchnic balances of glutamine, alanine, blood urea nitrogen, ammonia, lactate, beta-hydroxybutyrate, and acetoacetate were estimated using the Fick principle. Blood flow to the splanchnic and renal beds were estimated using indocyanine green and p-aminohippurate extraction methods, respectively. The infusion of NaHCO3 nearly abolished the base deficit associated with fasting and normalized arterial bicarbonate levels but did not alter blood pH. It suppressed but did not abolish hepatic glutamine output by 60%. This was associated with a shift in cytoplasmic and mitochondrial redox potentials of the hepatocyte as evident by a decrease in hepatic production of beta-hydroxybutyrate and an increase in hepatic production of acetoacetate and a decrease in hepatic lactate utilization. Concomitantly, renal glutamine uptake decreased. Glutamine release of skeletal muscle was unchanged. The data suggest that hepatic glutamine synthesis and release seen with 4-day fasting has two components: a bicarbonate-dependent component that is influenced by the redox potential of the hepatocyte and a bicarbonate-independent component, the nature of which is not yet clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Interorgan relationships of alanine and glutamine during fasting in the conscious dog

This study was designed to assess the interorgan relationships of glutamine and alanine in the conscious, overnight fasted dog, and to determine changes which occur with progressive fasting. Dogs were fasted for 18 hr ( n = 6), 48 hr ( n = 6), and 96 hr ( n = 6) prior to the study. Catheters had been previously implanted in the femoral artery, renal vein, portal vein, and hepatic vein, and were used for blood sampling at 30-min intervals during the 3-hr experimental period. Hepatic and renal blood flows were determined by indocyanine green and para-aminohippuric acid (PAH) extraction methods, respectively. Balance data (micromoles/kilogram/minute) were estimated by multiplying the appropriate arteriovenous concentration differences by blood flows. Hepatic uptake of glutamine decreased 50% after a 48-hr fast, and by 96 hr, the liver became a net producer of glutamine. Gut utilization remained constant throughout fasting. The kidney's utilization gradually increased with fasting. The hepatic extraction of alanine fell with fasting, declining to 40% of its original uptake at 96 hr. The gut's production of alanine fell during the first 48 hr of fasting, but remained stable thereafter. The kidney's production of alanine increased throughout the period of starvation. The arterial concentration of glutamine rose with fasting, while that of alanine fell even with a 48 hr fast. The liver, by becoming a net producer of glutamine, and the kidney, by increasing its production of alanine, decrease demands for peripheral release of these two amino acids, and thus may have protein-sparing actions during fasting.

Cardiac output distribution in the laying hen during shell formation

1. 1. During shell formation the organs of the laying hen received the following percentages of the cardiac output: kidneys (arterial), 9·96; shell gland, 8·58; liver (arterial), 7·05; heart, 5·78; magnum, 5·70; duodenum, 4·81; femora, 4·08; spleen, 3·37; tibiae, 2·62; isthmus, 1·06; pancreas, 0·70; colon, 0·40; metatarsi, 0·10; cerebellum, 0·09; parathyroids, 0·06; thyroids, 0·04; adrenals, 0·03. 2. 2. The Evans Blue method gave consistently higher estimates of cardiac output (277 ± 16 ml/kg per min) than the indocyanine green method (177 ± 11 ml/kg per min). 3. 3. On a weight basis, the parathyroids received the highest blood flow (13·5 ml/g per min), possibly because they may include the carotid body. Blood flow rates to the duodenum and bones were higher than in mammals.

Determination of Cardiac Output by Indocyanine Green-Dilution Method and Its Clinical Applications

A new method of serial determination of cardiac output has been employed to evaluate the cardiac function. It is based on the indocyanine green dye-dilution method with sampling from the systemic artery after injection of the dye into the right atrium. The purpose of the present study is to verify the reliability and reproducibility of this method, and to investigate the influence of cardiac glycoside and adrenergic β-receptor blockade upon the cardiac and renal functions, and also to determine the hemodynamic effect of electrical conversion of atrial fibrillation to sinus rhythm in patients with operated mitral stenosis. Part I. The Basic Studies for the Determination of Cardiac Output by Indocyanine Green-Dilution Method Materials and Methods. Indocyanine green in doses of I to 1.5 mg was injected into the right atrium through a 7F Lehman catheter inserted into the antecubital vein. Blood was sampled from the brachial or femoral artery through an indwelling arterial needle employing a Gilford constant withdrawal pump (Model 105S) and a cuvette densitometer (Model 1031R). The dye dilution curve was recorded on an 8-channel photographic recorder (Sanborn 4568A) with an electrocardiogram. The dye concentrations were replotted on a semilogarithmic paper. The curve was calibrated by whole blood and integrated sampling methods. The cardiac output was calculated according to Hamilton's formula. Two successive determinations of cardial indicies within 3 to 5 minutes were made in a total of 31 cases with or without heart disease. Results and Discussion: Fick and dye determination of cardiac output were carried out in 16 subjects. The average dye cardiac index was 2.74 ± 0.20 L/min/m2 and the Fick was 2.94 ± 0.23 L/min/m2. The correlation coefficient for Fick to dye was 0.88 (P <0.001). There was no significant difference between the mean values of these two groups. These results showed reliability of the dye method. The average cardiac index in the first determination of the two successive measurements within 3 to 5 minutes in 31 subjects was 2.86 ± 0.15 L/min/m2. The average in the second determination was 2.88 ± 0.16 L/min/m2. The percent difference between two successive determinations ranged from -13.3 to ± 10.5%. About 94% of all determinations were within ± 10% of the line of identity. The correlation coefficient was 0.99 (P <0.001). These results revealed good reproducibility of the dye-dilution method. The differences may be mainly due to the physiological changes rather than technical errors.